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VALUTAZIONE CLINICA E DIAGNOSI PRECOCE
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VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

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Page 1: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

VALUTAZIONE CLINICA E

DIAGNOSI PRECOCE

ENDOMETRIOSIS IS A GYNECOLOGIC PATHOLOGY THAT IS CONSIDERED

ldquoENIGMATICrdquo It is defined by the presence of a tissue similar to uterine endometrium that is located

in places other than physiologically appropriate most commonly in the pelvic cavity including the ovaries the uterosacral ligaments and the pouch of Douglas These endometrial heterotopic islets contain glands and stroma and are functionally capable of responding to exogenous endogenous or local hormonal stimuli

Obstet Gynecol 2013

Endometriosis A Disease That Remains Enigmatic P Acien and IVelasco

THE INVESTIGATION AND MANAGEMENT OF ENDOMETRIOSIS (2006)

The condition is predominantly found in women of reproductive age from all ethnic and social groups

The associated symptoms can impact on general physical mental and social wellbeing

DIAGNOSI

Accurata raccolta dellrsquoanamnesi Esame ginecologico Ecografia Risonanza Magnetica Nucleare Dosaggio plasmatico del Ca-125 Laparoscopia Conferma istologica

Rev Bras Ginecol Obstet 2013 Jun35(6)262-7

Correlation between serum Ca-125 levels and surgical findings in women with symptoms evocative of endometriosis

Zomer MT1 Ribeiro R Trippia CH Cavalcanti TC Hayashi RM Kondo W

Based on clinical and patient experience endometriosis can cause the

following symptoms

Severe dysmenorrhoea

Deep dyspareunia

Chronic pelvic pain

Ovulation pain

Cyclical or perimenstrual symptoms with or without abnormal bleeding or pain

Infertility

Chronic fatigue

Dyschezia

Dysuria

Irritable bowel syndrome

DOLORE

helliplrsquoaggravamento della mia malattia che mentre nessuno la scopriva mi divorava dallrsquointerno galoppandohellip

hellipil dolore si faceva insopportabile non riuscivo nemmeno a camminare piugrave non riuscivo a stare sdraiata seduta riuscivo solo a piangerehellip

hellippiango rimango buttata sul divano per ore mordo i cuscini mi deprimohellip

hellipmestruazioni dolorose e abbondanti hanno sempre flagellato la mia esistenzahellip

hellipa volte il dolore egrave cosigrave forte che non sapevo se sbattere la testa contro il muro o buttarmi dal balconehellip

DISPAREUNIA PROFONDA

Dovuta allo stretching degli impianti endometriosici nel Douglas o nel setto retto-vaginale Descritta come dolore acuto lancinante profondo Si manifesta durante il rapporto sessuale e dura fino a 24-48 ore dopo Compare talora durante ogni coito talora solo in certi periodi del ciclo mestruale

Deep endometriosis of the rectovaginal septum is associated with the most severe forms of dyschezia and dyspareunia Seracchioli et al 2008

La dispareunia profonda puograve essere il primo sintomo di unrsquoendometriosi ancora altrimenti silente Vercellini Graziottin 2010

Clinicians may consider the diagnosis of deep endometriosis in women with (painful) induration andor nodules of the rectovaginal wall found during clinical examination or visible vaginal nodules in the posterior vaginal fornix

Clinicians may consider the diagnosis of ovarian endometrioma in women with adnexal masses detected during clinical examination

Deeply infiltrating nodules are most reliably detected when clinical examination is performed during menstruation

bull

Endometriosis in adolescents is a hidden progressive and severe disease that deserves attention not just compassion Medicine Human Reproduction Volume 28 Issue 8 Pp 2026-31 April 2013

I Brosens S Gordts and G Benagiano

Notwithstanding the difficulty in drawing any definite conclusions from incomplete evidence and occasionally even contradictory results recent findings indicate that

An early onset of chronic pelvic pain at the time of menarche represents a risk factor for severe endometriosis during adolescence

An early identification of the disease may go a long way in slowing or preventing progression

DIAGNOSI PRECOCE

Clinicians may consider the diagnosis of endometriosis in women suspected of the disease

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 2: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

ENDOMETRIOSIS IS A GYNECOLOGIC PATHOLOGY THAT IS CONSIDERED

ldquoENIGMATICrdquo It is defined by the presence of a tissue similar to uterine endometrium that is located

in places other than physiologically appropriate most commonly in the pelvic cavity including the ovaries the uterosacral ligaments and the pouch of Douglas These endometrial heterotopic islets contain glands and stroma and are functionally capable of responding to exogenous endogenous or local hormonal stimuli

Obstet Gynecol 2013

Endometriosis A Disease That Remains Enigmatic P Acien and IVelasco

THE INVESTIGATION AND MANAGEMENT OF ENDOMETRIOSIS (2006)

The condition is predominantly found in women of reproductive age from all ethnic and social groups

The associated symptoms can impact on general physical mental and social wellbeing

DIAGNOSI

Accurata raccolta dellrsquoanamnesi Esame ginecologico Ecografia Risonanza Magnetica Nucleare Dosaggio plasmatico del Ca-125 Laparoscopia Conferma istologica

Rev Bras Ginecol Obstet 2013 Jun35(6)262-7

Correlation between serum Ca-125 levels and surgical findings in women with symptoms evocative of endometriosis

Zomer MT1 Ribeiro R Trippia CH Cavalcanti TC Hayashi RM Kondo W

Based on clinical and patient experience endometriosis can cause the

following symptoms

Severe dysmenorrhoea

Deep dyspareunia

Chronic pelvic pain

Ovulation pain

Cyclical or perimenstrual symptoms with or without abnormal bleeding or pain

Infertility

Chronic fatigue

Dyschezia

Dysuria

Irritable bowel syndrome

DOLORE

helliplrsquoaggravamento della mia malattia che mentre nessuno la scopriva mi divorava dallrsquointerno galoppandohellip

hellipil dolore si faceva insopportabile non riuscivo nemmeno a camminare piugrave non riuscivo a stare sdraiata seduta riuscivo solo a piangerehellip

hellippiango rimango buttata sul divano per ore mordo i cuscini mi deprimohellip

hellipmestruazioni dolorose e abbondanti hanno sempre flagellato la mia esistenzahellip

hellipa volte il dolore egrave cosigrave forte che non sapevo se sbattere la testa contro il muro o buttarmi dal balconehellip

DISPAREUNIA PROFONDA

Dovuta allo stretching degli impianti endometriosici nel Douglas o nel setto retto-vaginale Descritta come dolore acuto lancinante profondo Si manifesta durante il rapporto sessuale e dura fino a 24-48 ore dopo Compare talora durante ogni coito talora solo in certi periodi del ciclo mestruale

Deep endometriosis of the rectovaginal septum is associated with the most severe forms of dyschezia and dyspareunia Seracchioli et al 2008

La dispareunia profonda puograve essere il primo sintomo di unrsquoendometriosi ancora altrimenti silente Vercellini Graziottin 2010

Clinicians may consider the diagnosis of deep endometriosis in women with (painful) induration andor nodules of the rectovaginal wall found during clinical examination or visible vaginal nodules in the posterior vaginal fornix

Clinicians may consider the diagnosis of ovarian endometrioma in women with adnexal masses detected during clinical examination

Deeply infiltrating nodules are most reliably detected when clinical examination is performed during menstruation

bull

Endometriosis in adolescents is a hidden progressive and severe disease that deserves attention not just compassion Medicine Human Reproduction Volume 28 Issue 8 Pp 2026-31 April 2013

I Brosens S Gordts and G Benagiano

Notwithstanding the difficulty in drawing any definite conclusions from incomplete evidence and occasionally even contradictory results recent findings indicate that

An early onset of chronic pelvic pain at the time of menarche represents a risk factor for severe endometriosis during adolescence

An early identification of the disease may go a long way in slowing or preventing progression

DIAGNOSI PRECOCE

Clinicians may consider the diagnosis of endometriosis in women suspected of the disease

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 3: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

THE INVESTIGATION AND MANAGEMENT OF ENDOMETRIOSIS (2006)

The condition is predominantly found in women of reproductive age from all ethnic and social groups

The associated symptoms can impact on general physical mental and social wellbeing

DIAGNOSI

Accurata raccolta dellrsquoanamnesi Esame ginecologico Ecografia Risonanza Magnetica Nucleare Dosaggio plasmatico del Ca-125 Laparoscopia Conferma istologica

Rev Bras Ginecol Obstet 2013 Jun35(6)262-7

Correlation between serum Ca-125 levels and surgical findings in women with symptoms evocative of endometriosis

Zomer MT1 Ribeiro R Trippia CH Cavalcanti TC Hayashi RM Kondo W

Based on clinical and patient experience endometriosis can cause the

following symptoms

Severe dysmenorrhoea

Deep dyspareunia

Chronic pelvic pain

Ovulation pain

Cyclical or perimenstrual symptoms with or without abnormal bleeding or pain

Infertility

Chronic fatigue

Dyschezia

Dysuria

Irritable bowel syndrome

DOLORE

helliplrsquoaggravamento della mia malattia che mentre nessuno la scopriva mi divorava dallrsquointerno galoppandohellip

hellipil dolore si faceva insopportabile non riuscivo nemmeno a camminare piugrave non riuscivo a stare sdraiata seduta riuscivo solo a piangerehellip

hellippiango rimango buttata sul divano per ore mordo i cuscini mi deprimohellip

hellipmestruazioni dolorose e abbondanti hanno sempre flagellato la mia esistenzahellip

hellipa volte il dolore egrave cosigrave forte che non sapevo se sbattere la testa contro il muro o buttarmi dal balconehellip

DISPAREUNIA PROFONDA

Dovuta allo stretching degli impianti endometriosici nel Douglas o nel setto retto-vaginale Descritta come dolore acuto lancinante profondo Si manifesta durante il rapporto sessuale e dura fino a 24-48 ore dopo Compare talora durante ogni coito talora solo in certi periodi del ciclo mestruale

Deep endometriosis of the rectovaginal septum is associated with the most severe forms of dyschezia and dyspareunia Seracchioli et al 2008

La dispareunia profonda puograve essere il primo sintomo di unrsquoendometriosi ancora altrimenti silente Vercellini Graziottin 2010

Clinicians may consider the diagnosis of deep endometriosis in women with (painful) induration andor nodules of the rectovaginal wall found during clinical examination or visible vaginal nodules in the posterior vaginal fornix

Clinicians may consider the diagnosis of ovarian endometrioma in women with adnexal masses detected during clinical examination

Deeply infiltrating nodules are most reliably detected when clinical examination is performed during menstruation

bull

Endometriosis in adolescents is a hidden progressive and severe disease that deserves attention not just compassion Medicine Human Reproduction Volume 28 Issue 8 Pp 2026-31 April 2013

I Brosens S Gordts and G Benagiano

Notwithstanding the difficulty in drawing any definite conclusions from incomplete evidence and occasionally even contradictory results recent findings indicate that

An early onset of chronic pelvic pain at the time of menarche represents a risk factor for severe endometriosis during adolescence

An early identification of the disease may go a long way in slowing or preventing progression

DIAGNOSI PRECOCE

Clinicians may consider the diagnosis of endometriosis in women suspected of the disease

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 4: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

DIAGNOSI

Accurata raccolta dellrsquoanamnesi Esame ginecologico Ecografia Risonanza Magnetica Nucleare Dosaggio plasmatico del Ca-125 Laparoscopia Conferma istologica

Rev Bras Ginecol Obstet 2013 Jun35(6)262-7

Correlation between serum Ca-125 levels and surgical findings in women with symptoms evocative of endometriosis

Zomer MT1 Ribeiro R Trippia CH Cavalcanti TC Hayashi RM Kondo W

Based on clinical and patient experience endometriosis can cause the

following symptoms

Severe dysmenorrhoea

Deep dyspareunia

Chronic pelvic pain

Ovulation pain

Cyclical or perimenstrual symptoms with or without abnormal bleeding or pain

Infertility

Chronic fatigue

Dyschezia

Dysuria

Irritable bowel syndrome

DOLORE

helliplrsquoaggravamento della mia malattia che mentre nessuno la scopriva mi divorava dallrsquointerno galoppandohellip

hellipil dolore si faceva insopportabile non riuscivo nemmeno a camminare piugrave non riuscivo a stare sdraiata seduta riuscivo solo a piangerehellip

hellippiango rimango buttata sul divano per ore mordo i cuscini mi deprimohellip

hellipmestruazioni dolorose e abbondanti hanno sempre flagellato la mia esistenzahellip

hellipa volte il dolore egrave cosigrave forte che non sapevo se sbattere la testa contro il muro o buttarmi dal balconehellip

DISPAREUNIA PROFONDA

Dovuta allo stretching degli impianti endometriosici nel Douglas o nel setto retto-vaginale Descritta come dolore acuto lancinante profondo Si manifesta durante il rapporto sessuale e dura fino a 24-48 ore dopo Compare talora durante ogni coito talora solo in certi periodi del ciclo mestruale

Deep endometriosis of the rectovaginal septum is associated with the most severe forms of dyschezia and dyspareunia Seracchioli et al 2008

La dispareunia profonda puograve essere il primo sintomo di unrsquoendometriosi ancora altrimenti silente Vercellini Graziottin 2010

Clinicians may consider the diagnosis of deep endometriosis in women with (painful) induration andor nodules of the rectovaginal wall found during clinical examination or visible vaginal nodules in the posterior vaginal fornix

Clinicians may consider the diagnosis of ovarian endometrioma in women with adnexal masses detected during clinical examination

Deeply infiltrating nodules are most reliably detected when clinical examination is performed during menstruation

bull

Endometriosis in adolescents is a hidden progressive and severe disease that deserves attention not just compassion Medicine Human Reproduction Volume 28 Issue 8 Pp 2026-31 April 2013

I Brosens S Gordts and G Benagiano

Notwithstanding the difficulty in drawing any definite conclusions from incomplete evidence and occasionally even contradictory results recent findings indicate that

An early onset of chronic pelvic pain at the time of menarche represents a risk factor for severe endometriosis during adolescence

An early identification of the disease may go a long way in slowing or preventing progression

DIAGNOSI PRECOCE

Clinicians may consider the diagnosis of endometriosis in women suspected of the disease

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 5: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Based on clinical and patient experience endometriosis can cause the

following symptoms

Severe dysmenorrhoea

Deep dyspareunia

Chronic pelvic pain

Ovulation pain

Cyclical or perimenstrual symptoms with or without abnormal bleeding or pain

Infertility

Chronic fatigue

Dyschezia

Dysuria

Irritable bowel syndrome

DOLORE

helliplrsquoaggravamento della mia malattia che mentre nessuno la scopriva mi divorava dallrsquointerno galoppandohellip

hellipil dolore si faceva insopportabile non riuscivo nemmeno a camminare piugrave non riuscivo a stare sdraiata seduta riuscivo solo a piangerehellip

hellippiango rimango buttata sul divano per ore mordo i cuscini mi deprimohellip

hellipmestruazioni dolorose e abbondanti hanno sempre flagellato la mia esistenzahellip

hellipa volte il dolore egrave cosigrave forte che non sapevo se sbattere la testa contro il muro o buttarmi dal balconehellip

DISPAREUNIA PROFONDA

Dovuta allo stretching degli impianti endometriosici nel Douglas o nel setto retto-vaginale Descritta come dolore acuto lancinante profondo Si manifesta durante il rapporto sessuale e dura fino a 24-48 ore dopo Compare talora durante ogni coito talora solo in certi periodi del ciclo mestruale

Deep endometriosis of the rectovaginal septum is associated with the most severe forms of dyschezia and dyspareunia Seracchioli et al 2008

La dispareunia profonda puograve essere il primo sintomo di unrsquoendometriosi ancora altrimenti silente Vercellini Graziottin 2010

Clinicians may consider the diagnosis of deep endometriosis in women with (painful) induration andor nodules of the rectovaginal wall found during clinical examination or visible vaginal nodules in the posterior vaginal fornix

Clinicians may consider the diagnosis of ovarian endometrioma in women with adnexal masses detected during clinical examination

Deeply infiltrating nodules are most reliably detected when clinical examination is performed during menstruation

bull

Endometriosis in adolescents is a hidden progressive and severe disease that deserves attention not just compassion Medicine Human Reproduction Volume 28 Issue 8 Pp 2026-31 April 2013

I Brosens S Gordts and G Benagiano

Notwithstanding the difficulty in drawing any definite conclusions from incomplete evidence and occasionally even contradictory results recent findings indicate that

An early onset of chronic pelvic pain at the time of menarche represents a risk factor for severe endometriosis during adolescence

An early identification of the disease may go a long way in slowing or preventing progression

DIAGNOSI PRECOCE

Clinicians may consider the diagnosis of endometriosis in women suspected of the disease

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 6: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

DOLORE

helliplrsquoaggravamento della mia malattia che mentre nessuno la scopriva mi divorava dallrsquointerno galoppandohellip

hellipil dolore si faceva insopportabile non riuscivo nemmeno a camminare piugrave non riuscivo a stare sdraiata seduta riuscivo solo a piangerehellip

hellippiango rimango buttata sul divano per ore mordo i cuscini mi deprimohellip

hellipmestruazioni dolorose e abbondanti hanno sempre flagellato la mia esistenzahellip

hellipa volte il dolore egrave cosigrave forte che non sapevo se sbattere la testa contro il muro o buttarmi dal balconehellip

DISPAREUNIA PROFONDA

Dovuta allo stretching degli impianti endometriosici nel Douglas o nel setto retto-vaginale Descritta come dolore acuto lancinante profondo Si manifesta durante il rapporto sessuale e dura fino a 24-48 ore dopo Compare talora durante ogni coito talora solo in certi periodi del ciclo mestruale

Deep endometriosis of the rectovaginal septum is associated with the most severe forms of dyschezia and dyspareunia Seracchioli et al 2008

La dispareunia profonda puograve essere il primo sintomo di unrsquoendometriosi ancora altrimenti silente Vercellini Graziottin 2010

Clinicians may consider the diagnosis of deep endometriosis in women with (painful) induration andor nodules of the rectovaginal wall found during clinical examination or visible vaginal nodules in the posterior vaginal fornix

Clinicians may consider the diagnosis of ovarian endometrioma in women with adnexal masses detected during clinical examination

Deeply infiltrating nodules are most reliably detected when clinical examination is performed during menstruation

bull

Endometriosis in adolescents is a hidden progressive and severe disease that deserves attention not just compassion Medicine Human Reproduction Volume 28 Issue 8 Pp 2026-31 April 2013

I Brosens S Gordts and G Benagiano

Notwithstanding the difficulty in drawing any definite conclusions from incomplete evidence and occasionally even contradictory results recent findings indicate that

An early onset of chronic pelvic pain at the time of menarche represents a risk factor for severe endometriosis during adolescence

An early identification of the disease may go a long way in slowing or preventing progression

DIAGNOSI PRECOCE

Clinicians may consider the diagnosis of endometriosis in women suspected of the disease

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 7: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

helliplrsquoaggravamento della mia malattia che mentre nessuno la scopriva mi divorava dallrsquointerno galoppandohellip

hellipil dolore si faceva insopportabile non riuscivo nemmeno a camminare piugrave non riuscivo a stare sdraiata seduta riuscivo solo a piangerehellip

hellippiango rimango buttata sul divano per ore mordo i cuscini mi deprimohellip

hellipmestruazioni dolorose e abbondanti hanno sempre flagellato la mia esistenzahellip

hellipa volte il dolore egrave cosigrave forte che non sapevo se sbattere la testa contro il muro o buttarmi dal balconehellip

DISPAREUNIA PROFONDA

Dovuta allo stretching degli impianti endometriosici nel Douglas o nel setto retto-vaginale Descritta come dolore acuto lancinante profondo Si manifesta durante il rapporto sessuale e dura fino a 24-48 ore dopo Compare talora durante ogni coito talora solo in certi periodi del ciclo mestruale

Deep endometriosis of the rectovaginal septum is associated with the most severe forms of dyschezia and dyspareunia Seracchioli et al 2008

La dispareunia profonda puograve essere il primo sintomo di unrsquoendometriosi ancora altrimenti silente Vercellini Graziottin 2010

Clinicians may consider the diagnosis of deep endometriosis in women with (painful) induration andor nodules of the rectovaginal wall found during clinical examination or visible vaginal nodules in the posterior vaginal fornix

Clinicians may consider the diagnosis of ovarian endometrioma in women with adnexal masses detected during clinical examination

Deeply infiltrating nodules are most reliably detected when clinical examination is performed during menstruation

bull

Endometriosis in adolescents is a hidden progressive and severe disease that deserves attention not just compassion Medicine Human Reproduction Volume 28 Issue 8 Pp 2026-31 April 2013

I Brosens S Gordts and G Benagiano

Notwithstanding the difficulty in drawing any definite conclusions from incomplete evidence and occasionally even contradictory results recent findings indicate that

An early onset of chronic pelvic pain at the time of menarche represents a risk factor for severe endometriosis during adolescence

An early identification of the disease may go a long way in slowing or preventing progression

DIAGNOSI PRECOCE

Clinicians may consider the diagnosis of endometriosis in women suspected of the disease

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 8: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

DISPAREUNIA PROFONDA

Dovuta allo stretching degli impianti endometriosici nel Douglas o nel setto retto-vaginale Descritta come dolore acuto lancinante profondo Si manifesta durante il rapporto sessuale e dura fino a 24-48 ore dopo Compare talora durante ogni coito talora solo in certi periodi del ciclo mestruale

Deep endometriosis of the rectovaginal septum is associated with the most severe forms of dyschezia and dyspareunia Seracchioli et al 2008

La dispareunia profonda puograve essere il primo sintomo di unrsquoendometriosi ancora altrimenti silente Vercellini Graziottin 2010

Clinicians may consider the diagnosis of deep endometriosis in women with (painful) induration andor nodules of the rectovaginal wall found during clinical examination or visible vaginal nodules in the posterior vaginal fornix

Clinicians may consider the diagnosis of ovarian endometrioma in women with adnexal masses detected during clinical examination

Deeply infiltrating nodules are most reliably detected when clinical examination is performed during menstruation

bull

Endometriosis in adolescents is a hidden progressive and severe disease that deserves attention not just compassion Medicine Human Reproduction Volume 28 Issue 8 Pp 2026-31 April 2013

I Brosens S Gordts and G Benagiano

Notwithstanding the difficulty in drawing any definite conclusions from incomplete evidence and occasionally even contradictory results recent findings indicate that

An early onset of chronic pelvic pain at the time of menarche represents a risk factor for severe endometriosis during adolescence

An early identification of the disease may go a long way in slowing or preventing progression

DIAGNOSI PRECOCE

Clinicians may consider the diagnosis of endometriosis in women suspected of the disease

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 9: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Clinicians may consider the diagnosis of deep endometriosis in women with (painful) induration andor nodules of the rectovaginal wall found during clinical examination or visible vaginal nodules in the posterior vaginal fornix

Clinicians may consider the diagnosis of ovarian endometrioma in women with adnexal masses detected during clinical examination

Deeply infiltrating nodules are most reliably detected when clinical examination is performed during menstruation

bull

Endometriosis in adolescents is a hidden progressive and severe disease that deserves attention not just compassion Medicine Human Reproduction Volume 28 Issue 8 Pp 2026-31 April 2013

I Brosens S Gordts and G Benagiano

Notwithstanding the difficulty in drawing any definite conclusions from incomplete evidence and occasionally even contradictory results recent findings indicate that

An early onset of chronic pelvic pain at the time of menarche represents a risk factor for severe endometriosis during adolescence

An early identification of the disease may go a long way in slowing or preventing progression

DIAGNOSI PRECOCE

Clinicians may consider the diagnosis of endometriosis in women suspected of the disease

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 10: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

bull

Endometriosis in adolescents is a hidden progressive and severe disease that deserves attention not just compassion Medicine Human Reproduction Volume 28 Issue 8 Pp 2026-31 April 2013

I Brosens S Gordts and G Benagiano

Notwithstanding the difficulty in drawing any definite conclusions from incomplete evidence and occasionally even contradictory results recent findings indicate that

An early onset of chronic pelvic pain at the time of menarche represents a risk factor for severe endometriosis during adolescence

An early identification of the disease may go a long way in slowing or preventing progression

DIAGNOSI PRECOCE

Clinicians may consider the diagnosis of endometriosis in women suspected of the disease

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 11: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

DIAGNOSI PRECOCE

Clinicians may consider the diagnosis of endometriosis in women suspected of the disease

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 12: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Clinicians may consider the diagnosis of endometriosis in women suspected of the disease

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 13: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in the presence of gynecological symptoms such as

bull dysmenorrhea

bull non-cyclical pelvic pain

bull deep dyspareunia

bull infertility

bull fatigue in the presence of any of the above

bull The GDG recommends that clinicians should consider the diagnosis of endometriosis in women of reproductive age with non-gynecological cyclical symptoms

bull dyschezia

bull dysuria

bull hematuria

bull rectal bleeding

bull shoulder pain

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 14: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

However the included studies all had retrospective design and

did not show a predictive value of these symptoms

for the presence of endometriosis

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 15: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

The predictive value of any one symptom or set of symptoms remains uncertain as each of these symptoms can have other causes and a significant proportion of affected women are asymptomatic

Establishing the diagnosis of endometriosis on the basis of symptoms alone can be difficult because the presentation is so variable and there is considerable overlap with other conditions such as irritable bowel syndrome and pelvic inflammatory disease

Even though endometriosis has been researched extensively it is a complex disease that can be challenging to diagnose and treat Many symptoms of endometriosis ndash severe painful menstrual cramps painful intercourse and gastrointestinal upsets such as diarrhea constipation and nausea ndash are similar to those for a wide variety of other conditions As well each woman with endometriosis will experience symptoms differently depending on the location and extent of her endometriosis

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 16: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Whatrsquos the delay A qualitative study of womenrsquos experiences of reaching a diagnosis of endometriosis Ballard KD Lowton K Wright JT Fertil Steril 2006861296-1301

This paper reports the findings of an interview-based study where they set out to investigate womenrsquos experiences of endometriosis and in particular the events that lead to a diagnosis of endometriosis

The study confirmed the findings of others showing that there continues to be a delayed diagnosis

of endometriosis

of around 8 frac12 years

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 17: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

AUTORE RIVISTA ANNO NAZIONE RITARDO (anni)

HADFLELD R Hum Reprod 1996 UK USA 1173 +- 905

GUNHILD KELLEBERG H Acta obst Gynec Scand 2003 Norvegia 67 +- 62

ARRUDA MS Hum Reprod 2003 Brasile 12

BALLARD KD Fertil Steril 2006 UK 8

BALLARD KD Fertil Steril 2006 Norvegia 67

NNOAHAM KE Fertil Steril 2011 Italia 7-10

NNOAHAM KE Fertil Steril 2011 Spagna 8

NNOAHAM KE Fertil Steril 2011 IrlandaBelgio 4-5

HUDELIST G Hum Reprod 2012 GermaniaAustria 104

PERLOE M Georgia Repr Spec 2013 North America 928

Australian Endom Soc 2013 44

New Zeland Endon 2013 10

DELAY OF DIAGNOSIS

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 18: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Le donne spesso ritardano nel raccontare il loro dolore considerandolo spesso NORMALE e ritenendosi SFORTUNATE non volendo apparire deboli ed incapaci di affrontare il dolore

Queste percezioni sono spesso confermate dalle donne della famiglia che hanno o hanno avuto sintomi simili

I medici talora affrontano il laquoproblema dismenorrearaquo come se fosse NORMALE limitandosi ad invitare la donna ad assumere antalgici o un estroprogestinico

Siffatte laquoindicazioniraquo mediche portano spesso la giovane donna a credere che il dolore laquoegrave nella propria testaraquo

Se a ciograve si aggiunge talvolta ci si limita ad eseguire una ecografia per lo piugrave trans-addominale che spesso risulta negativa ecco che

il concetto di NORMALITArsquo si rafforza ehellip

il ritardo diagnostico si incrementa

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 19: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Mysterious Pain

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 20: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Developing symptom-based predictive models of endometriosis as a clinical screening tool results from a multicenter study Nnoaham KE Hummelshoj L Kennedy SH Jenkinson C Zondervan KT World Endometriosis Research Foundation Womens Health Symptom Survey Consortium

Fertil Steril 2012 Sept 98 (3) 692-701

wwwendometriosisfoundationorgWERF- WHSS-Questionnaire-Englishpdf

Our symptom-based models predict any-stage endometriosis relatively poorly and stage III and IV disease with good accuracy Predictive tools based on such models could help to prioritize women for surgical investigation in clinical practice and thus contribute to reducing time to diagnosis

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 21: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Peripheral biomarkers of endometriosis a systematic review

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674 KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

A careful examination of the blood or urine may avoid the need for an invasive procedure (Brosens et al 2003a b) or at least could allow symptomatic women to be screened It has previously been suggested that a biomarker may be more clinical use in specific subgroups of women with endometriosis (DHooghe et al 2006)

We therefore decided to conduct a systematic review of the literature to determine which biomarkers have been proposed over the past 25 years as a potential diagnostic tests

The search identified more than 100 possible biomarkers that have been investigated however none of these has been clearly shown to be of clinical use

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 22: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

KE Maggio SA Conduit-Hulbert J Villar S Kirtley SH Kennedy e CM Becker

Hum Reprod Update 2010 Nov-Dec 16 (6) 651-674

One biomarker that has been used in clinical practice during the last 20 years is CA-125

However in a meta-analysis published in 1998 Mol et al (1998) have convincingly demonstrated that the performance of biomarker in the diagnosis of endometriosis was low although it has shown some promise in detecting more serious disease

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 23: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Postgenomic technologies for Identification of novel serum of

Endometrial markers are likely to

revolutionize future diagnosis of endometriosis

Curr Opin Obstet Gynecol 2003 Dec15(6)519-22

Non-invasive methods of diagnosis of endometriosis Brosens I Puttemans P Campo R Gordts S Brosens J

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 24: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

CONCLUSIONS The concomitant dosage of CA 125 CA 199 and IL-6

does not add significant information in respect to the CA 125 test alone in diagnosing either early or advances stages of endometriosis

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 25: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Am J Reprod Immunol 2013 Dec70(6)497-558

Increased nuclear expression of nuclear factor kappa-B p65 subunit in the eutopic endometrium and ovarian endometrioma of women with advanced stage endometriosis Kim SH1 Ihm HJ Oh YS Chae HD Kim CH Kang BM

Int J Med Sci 2013 Jul 3010(9)1199-208

Increased expression of pattern recognition receptors and nitric oxide synthase in patients with endometriosis Yeo SG1 Won YS Lee HY Kim YI Lee JW Park DC

Arch Gynecol Obstet 2013 Oct288(4)805-14

Diagnostic accuracy of interleukin-6 levels in peritoneal fluid for detection of endometriosis Wickiewicz D1 Chrobak A Gmyrek GB Halbersztadt A Gabryś MS Goluda M Chełmońska-Soyta A

J Reprod Immunol 2013 Mar97(1)95-103

Inducers of G-protein coupled estrogen receptor (GPER) in endometriosis potential implications for macrophages and follicle maturation Heublein S1 Vrekoussis T Kuhn C Friese K Makrigiannakis A Mayr D Lenhard M Jeschke U

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 26: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Identification and Validation of Novel Serum Markers for Early Diagnosis of Endometriosis R Gajbhiye A Sonawani S Khan A Suryawanshi S Kadam N Warty V Raut V Khole Hum Reprod 201227(2)408-417

The 2D Western Blot analysis resulted in the identification of three endometrial antigens tropomyosin 3 (TPM3) stomatin-like protein 2 (SLP2) and tropomodulin 3 (TMOD3) Serum levels of antibodies against the epitopes from the immunodominant region of proteins TPM3 SLP2 and TMOD3 were significantly elevated in endometriosis patients when compared with controls

Our results indicate that TPM3 SLP2 and TMOD3 could be potential biomarkers for the early detection of minimal-mild endometriosis due to high sensitivity specificity and accuracy with respect to other reported markers Based on the results we conclude that we have a serum assay for endometriosis which would utilize a combination of dominant antigenic epitopes of the three target proteins

Our results indicate that this assay could be a reliable preliminary screening test for patients suspected of having endometriosis

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 27: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis Nabeta M1 Abe Y Haraguchi R Kito K Kusanagi Y Ito M Fertil Steril 2010 Dec94(7)2552-7

Several autoAbs were identified ELISAs were established and serum autoAb titlers were estimated Among those identified anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients

Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis This study validates further clinical evaluation of this novel marker

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 28: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Our study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR (Nuclear Magnetic Resonance spectroscopy for the analysis of biofluids and tissues) based metabonomics

Considering the immense potential of this branch of lsquoomicsrsquo our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using 1H-NMR

Metabonomics is defined as lsquolsquothe quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modificationsrsquorsquo

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 29: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

We here report for the first time a comprehensive analysis of global metabolic patterns of endometriosis The results not only indicate that metabonomic methods have sufficient sensitivity and specificity in distinguishing endometriosis from controls but also have the potential to be developed into a clinically useful diagnostic tool for contributing towards an improved understanding of a disease mechanism

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 30: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

For a definitive diagnosis of endometriosis visual inspection of the pelvis at

laparoscopy is the gold standard investigation unless disease is visible in the posterior vaginal fornix or elsewhere

Positive histology confirms the diagnosis of endometriosis negative histology does not exclude it Whether histology should be obtained if peritoneal disease alone is present is controversial Visual inspection is usually adequate but histological confirmation of at least one lesion is ideal In cases of ovarian endometrioma (greater than 3 cm in diameter) and in deeply infiltrating disease histology should be obtained to identify endometriosis and to exclude rare instances of malignancy

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 31: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

The GDG recommends that clinicians perform a laparoscopy to diagnose endometriosis although evidence is lacking that a positive laparoscopy without histology proves the presence of disease

The GDG recommends that clinicians confirm a positive laparoscopy by histology since positive histology confirms the diagnosis of endometriosis even though negative histology does not exclude it

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 32: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

The lesions most likely to be positive for endometriosis (75) were those gt10 mm in width and gt5 mm in depth mixed in color and located in the cul-de-sac ovarian fossa or on the utero-sacral ligaments

We found that most endometriosis lesions were subtle in color rather than the traditionally described black powder-burned appearance Furthermore all single-color lesions contained biopsy-confirmed endometriosis at about 60

However even surgeons knowledgeable and experienced in the characteristics of endometriosis lesions were able to correctly identify lesions with confirmed endometriosis only 64 of the time

Using location color size and depth to characterize and identify endometriosis lesions in a cohort of 133 women Barbara J Stegmann MD MPHa Ninet Sinaii PhD MPHb Shannon Liua James Segars MDa Maria Merino MDc Lynnette K Nieman MDa and Pamela Stratton MDa Fertil Steril 2008 June 89(6) 1632ndash1636

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 33: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Most gynecologists are familiar with the common black brown or blue powder burn appearance of peritoneal endometriosis however this manifestation accounts for only a minority of lesions (Becker amp Nezhat 2008) Endometrial implants may appear in a number of different ways including subtle red or white lesions clear bubble lesions small hemorrhagic cysts or white fibrotic lesions (Kennedy ESHRE 2005)

Video-assisted laparoscopy for the detection and diagnosis of endometriosis

safety reliability and invasiveness Erica Schipper1 and Camran Nezhat2 Int J Womens Health 2012 4 383ndash393 -

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 34: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

Indigo carmine is derived from a blue plant dye (indigo) and a red coloring agent (carmine) This deep blue stain is not absorbed by the epithelium in the gastrointestinal tract it pools in crevices between epithelial cells and highlights small or flat lesions and defines irregularities in mucosal architecture

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine A contrast stain such as indigo carmine is not absorbed by epithelial cells but accumulates in pits and valleys between cells highlighting the peritoneal architecture

revealing occult areas of endometriosis

that would have escaped the surgeonrsquos eye under normal circumstances

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 35: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine a new technique J Alejandro Rauh-Hain Marc R Laufer Department of Obstetrics and Gynecology Brigham and Womens Hospital Harvard Medical School Boston Massachusetts USA Fertil Steril 032011 95(3)1113-4

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 36: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surface during laparoscopy to detect loss of peritoneal integrity in patient with pelvic pain and suspected endometriosis During LS methylene blue dye (mixed 1200 with sterile saline solution) was sprayed into peritoneal surfaces then aspirated and rinsend with Lactated Ringer solution Areas of localizated dye uptake were evaluated for the presence of visible endometriotic lesions Areas of intense staining were resected [hellip] and examinated by scanning electron microscopy [hellip] revealed endometriosis and loss of peritoneal cell-cell contact compared to normal

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 37: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

Blue dye uptake was more common in women with endometriosis and cronic pelvic pain (85 vs 40) Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP Subjective pain relief was reported in 80 of subjects

This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at LS and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy

Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity

GRAZIE PER LrsquoATTENZIONE

Page 38: VALUTAZIONE CLINICA E DIAGNOSI PRECOCEsichig.it/wp-content/uploads/2011/06/BARDI.pdf · including the ovaries, the uterosacral ligaments, and the pouch of Douglas. These endometrial

GRAZIE PER LrsquoATTENZIONE