Small Bowel Small Bowel Transplantation Transplantation Keith Thatch, M.D. Keith Thatch, M.D. St. Luke’s-Roosevelt St. Luke’s-Roosevelt Hospital Center Hospital Center May 16 May 16 th th , 2007 , 2007
Dec 17, 2015
Small Bowel Small Bowel TransplantationTransplantation
Keith Thatch, M.D. Keith Thatch, M.D.
St. Luke’s-Roosevelt Hospital St. Luke’s-Roosevelt Hospital CenterCenter
May 16May 16thth, 2007, 2007
Intestinal Intestinal TransplantationTransplantation
Small-intestine transplantation Small-intestine transplantation continues to evolve as a surgical continues to evolve as a surgical procedure used in the management of procedure used in the management of intestinal failure in children and adultsintestinal failure in children and adults
Intestinal transplantation offers the Intestinal transplantation offers the hope of increased longevity & hope of increased longevity & improved quality of life to patients with improved quality of life to patients with intestinal failure and life-threatening intestinal failure and life-threatening complications of chronic TPNcomplications of chronic TPN
Intestinal Intestinal TransplantationTransplantation
Over the last three decades, intestinal Over the last three decades, intestinal transplantation has evolved from transplantation has evolved from experimental to a standard therapeutic experimental to a standard therapeutic option for intestinal failure patientsoption for intestinal failure patients
Primarily a pediatric procedure with Primarily a pediatric procedure with ~2/3s performed on children~2/3s performed on children
Remains less successful to other solid Remains less successful to other solid organ transplantation -> presumably due organ transplantation -> presumably due to the preponderance of lymphocytes in to the preponderance of lymphocytes in the bowel (strong stimulus for rejection)the bowel (strong stimulus for rejection)
Intestinal Intestinal TransplantationTransplantation
Indications include:Indications include: Short-bowel syndrome with complications Short-bowel syndrome with complications
associated with parenteral nutritionassociated with parenteral nutrition Irreversible intestinal failureIrreversible intestinal failure End-stage liver disease for combined liver and End-stage liver disease for combined liver and
small-intestine transplantationsmall-intestine transplantation Congenital mucosal disordersCongenital mucosal disorders Chronic pseudo-obstruction of intestineChronic pseudo-obstruction of intestine Locally invasive tumors at the base Locally invasive tumors at the base
Transplant options include:Transplant options include: Isolated intestinal (cadaveric or living-related)Isolated intestinal (cadaveric or living-related) Multivisceral transplantation (combined liver Multivisceral transplantation (combined liver
and multivisceral)and multivisceral)
Intestinal Intestinal TransplantationTransplantation
Patient survival & graft survival rates Patient survival & graft survival rates have improved with have improved with The introduction of tacrolimus (FK506)–The introduction of tacrolimus (FK506)–
based immunosuppression (calcineurin based immunosuppression (calcineurin inhibitor)inhibitor)
Used in combination with Used in combination with Decontamination protocolsDecontamination protocols Antibiotic regimensAntibiotic regimens Antiviral measures against cytomegalovirus Antiviral measures against cytomegalovirus
(CMV) and Epstein-Barr virus (EBV). (CMV) and Epstein-Barr virus (EBV). Pre-tacrolimus – pt survival 0-28% and Pre-tacrolimus – pt survival 0-28% and
graft survival 0-11%graft survival 0-11% With tacrolimus – pt & graft survival With tacrolimus – pt & graft survival
exceed 50%exceed 50%
History of the Procedure History of the Procedure
Lillehei et al reported the first case of Lillehei et al reported the first case of human bowel transplantation in human bowel transplantation in October 1967October 1967
Alexis Carrel was the first one to Alexis Carrel was the first one to perform it in an animal modelperform it in an animal model
Before 1970, 8 clinical cases of small-Before 1970, 8 clinical cases of small-intestine transplantation were intestine transplantation were reportedly performed worldwidereportedly performed worldwide maximum graft survival time was 79 daysmaximum graft survival time was 79 days All patients died of technical All patients died of technical
complications, sepsis, or rejectioncomplications, sepsis, or rejection
History of the Procedure History of the Procedure
This continued until the early 1980s, with the advent of This continued until the early 1980s, with the advent of cyclosporine, immunosuppressive medications cyclosporine, immunosuppressive medications (azathioprine), steroids, and antilymphocyte globulin (azathioprine), steroids, and antilymphocyte globulin (ALG)(ALG) However, clinical results with cyclosporine were disappointing However, clinical results with cyclosporine were disappointing
(most grafts lost to rejection)(most grafts lost to rejection) Deltz reported the first successful long-term Deltz reported the first successful long-term
transplantation in Germanytransplantation in Germany 1988 - 42-year-old woman received a segment of her sister's 1988 - 42-year-old woman received a segment of her sister's
jejunum and ileumjejunum and ileum The graft survived until 1992 -> lost to chronic rejectionThe graft survived until 1992 -> lost to chronic rejection
Goulet reported on 9 patients in 1990 (including a 9-Goulet reported on 9 patients in 1990 (including a 9-month-old infant who received 2 intestinal transplants) month-old infant who received 2 intestinal transplants) with poor success rates under cyclosporine-based with poor success rates under cyclosporine-based immunosuppressionimmunosuppression Graft survival time ranged from 10 days to 49 months. Graft survival time ranged from 10 days to 49 months.
History of the Procedure History of the Procedure
The most significant advance in the The most significant advance in the development of intestinal transplantation development of intestinal transplantation was the introduction of was the introduction of TACROLIMUSTACROLIMUS (1990)(1990)
The Starzl group (1998) reported that in 55 The Starzl group (1998) reported that in 55 children who underwent small-intestine children who underwent small-intestine transplantations with tacrolimus transplantations with tacrolimus 28 girls and 27 boys28 girls and 27 boys Median age = 3.2 years of ageMedian age = 3.2 years of age Patient survival rates were 55%Patient survival rates were 55% Graft survival rates were 52%Graft survival rates were 52%
Greater understanding of the unique Greater understanding of the unique immunologic properties of the intestine has immunologic properties of the intestine has furthered the advancement of small-furthered the advancement of small-intestine transplantationintestine transplantation
History of the Procedure History of the Procedure
As a result of these advances and a As a result of these advances and a growing appreciation of the growing appreciation of the phenomenon of chimerism, the number phenomenon of chimerism, the number of intestinal transplants has steadily of intestinal transplants has steadily increasedincreased
More than 100 intestinal transplants More than 100 intestinal transplants being performed each year in the being performed each year in the United StatesUnited States
Most active programs in North America:Most active programs in North America: Univ of Pittsburgh, Univ of Nebraska, Univ Univ of Pittsburgh, Univ of Nebraska, Univ
of Miami, and the Toronto Hospitalof Miami, and the Toronto Hospital
Intestinal Transplantation Intestinal Transplantation FrequencyFrequency
Difficult to measure the incidence of intestinal Difficult to measure the incidence of intestinal failure 2failure 2ndary ndary to complications of TPN to complications of TPN Studies demonstrate the incidence of irreversible Studies demonstrate the incidence of irreversible
intestinal failure is ~ 2-3 cases per million per yearintestinal failure is ~ 2-3 cases per million per year Success of intestine transplantation was first Success of intestine transplantation was first
reported reported 1987 - Multivisceral transplantation (University of 1987 - Multivisceral transplantation (University of
Pittsburgh)Pittsburgh) 1988 - Isolated bowel transplantation (University of 1988 - Isolated bowel transplantation (University of
Kiel, Germany)Kiel, Germany) 1988 – Liver-small bowel transplantation (London 1988 – Liver-small bowel transplantation (London
Health Sciences Center)Health Sciences Center) 1989 – Total small bowel transplantation (Hopital 1989 – Total small bowel transplantation (Hopital
Necker-Enfants-Malades, Paris)Necker-Enfants-Malades, Paris)
Intestinal Transplantation Intestinal Transplantation FrequencyFrequency
As of November 2005, the As of November 2005, the United Network for Organ United Network for Organ Sharing (UNOS) database listed Sharing (UNOS) database listed 190 patients awaiting intestinal 190 patients awaiting intestinal transplantationtransplantation
In 2003, 116 small-intestine In 2003, 116 small-intestine transplantations were performed transplantations were performed in adult and pediatric patients in in adult and pediatric patients in the United States the United States
Intestinal Transplantation Intestinal Transplantation FrequencyFrequency
Graft survival rates at 1 and 5 years Graft survival rates at 1 and 5 years have been reported to be as high as 84% have been reported to be as high as 84% and 63%, respectivelyand 63%, respectively
Waiting times were relatively brief (for a Waiting times were relatively brief (for a suitable small intestine) from 1993-97, suitable small intestine) from 1993-97, yet the mortality rate was 66% for yet the mortality rate was 66% for intestinal failure patients on the waiting intestinal failure patients on the waiting listlist
Currently >150 patients waiting, but, Currently >150 patients waiting, but, unfortunately, very few cadaveric unfortunately, very few cadaveric donors are suitable for intestinal donors are suitable for intestinal transplantation transplantation
Intestinal Transplantation - Intestinal Transplantation - EtiologyEtiology
TPN = current standard of care for TPN = current standard of care for patients unable to maintain patients unable to maintain adequate nutrition via the intestinal adequate nutrition via the intestinal tract alonetract alone
Patients with poor intestinal function Patients with poor intestinal function who cannot be maintained on TPN who cannot be maintained on TPN are potential candidates for are potential candidates for transplantationtransplantation
Intestinal Transplantation - Intestinal Transplantation - EtiologyEtiology
Intestinal failure—defined as the Intestinal failure—defined as the inability to maintain sufficient inability to maintain sufficient electrolyte, nutrient, and fluid balance electrolyte, nutrient, and fluid balance for more than 1 month without TPN for more than 1 month without TPN and no adaptive potential to meet and no adaptive potential to meet these needs in the futurethese needs in the future May result from surgical short-bowel May result from surgical short-bowel
syndrome or intestinal dysfunction in syndrome or intestinal dysfunction in children children
Intestinal Transplantation - Intestinal Transplantation - EtiologyEtiology
Worldwide, the leading cause of intestinal failure Worldwide, the leading cause of intestinal failure is short-bowel syndrome caused by surgical is short-bowel syndrome caused by surgical removalremoval ~10-20cm of small bowel needed with an ileocecal ~10-20cm of small bowel needed with an ileocecal
valvevalve 40cm without a ileocecal valve40cm without a ileocecal valve
Conditions leading to short-bowel syndrome Conditions leading to short-bowel syndrome include include Midgut volvulusMidgut volvulus GastroschisisGastroschisis TraumaTrauma Necrotizing enterocolitis (NEC)Necrotizing enterocolitis (NEC) IschemiaIschemia Crohn’s diseaseCrohn’s disease
Short Bowel Short Bowel SyndromeSyndrome
In patients with short In patients with short bowel syndrome, bowel syndrome, absorption of nutrients is absorption of nutrients is significantly altered, significantly altered, leading to electrolyte and leading to electrolyte and mineral imbalances and mineral imbalances and inadequate delivery of inadequate delivery of calories (severe calories (severe dehydration and dehydration and malnourishment)malnourishment)
Symptoms are common: Symptoms are common: persistent diarrhea, muscle persistent diarrhea, muscle wasting, poor growth, wasting, poor growth, frequent infections, weight frequent infections, weight loss, fatigue, and loss, fatigue, and dehydration dehydration
Intestinal Transplantation - Intestinal Transplantation - EtiologyEtiology
Other causes of intestinal dysfunction Other causes of intestinal dysfunction areare Absorptive disordersAbsorptive disorders
Microvillus inclusionMicrovillus inclusion Secretory diarrheaSecretory diarrhea Autoimmune enteritisAutoimmune enteritis
Dysmotiliy disordersDysmotiliy disorders Pseudo-obstructionPseudo-obstruction Hirschsprung diseaseHirschsprung disease Visceral neuropathyVisceral neuropathy A tumor (desmoid tumor and familial polyposis A tumor (desmoid tumor and familial polyposis
(eg, Gardner disease))(eg, Gardner disease))
Intestinal Transplantation - Intestinal Transplantation - EtiologyEtiology
Leading causes of Leading causes of intestinal failure in intestinal failure in children (in order of children (in order of decreasing decreasing frequency) frequency) Intestinal atresia Intestinal atresia Gastroschisis Gastroschisis Crohn’s disease Crohn’s disease Microvillus involution Microvillus involution
disease disease NEC NEC Midgut volvulus (leading Midgut volvulus (leading
to infarction)to infarction) Chronic intestinal Chronic intestinal
pseudo-obstruction pseudo-obstruction Massive resection Massive resection
secondary to tumor secondary to tumor Hirschsprung diseaseHirschsprung disease
Leading causes of Leading causes of intestinal failure in intestinal failure in adultsadults Crohn’s disease Crohn’s disease Superior mesenteric Superior mesenteric
artery thrombosis artery thrombosis Superior mesenteric Superior mesenteric
vein thrombosis vein thrombosis Trauma Trauma Desmoid tumor Desmoid tumor Volvulus Volvulus Pseudo-obstruction Pseudo-obstruction Massive resection Massive resection
secondary to tumor secondary to tumor Radiation enteritisRadiation enteritis
Intestinal Transplantation - Intestinal Transplantation - EtiologyEtiology
Intestinal transplantation is reserved Intestinal transplantation is reserved for TPN-dependent patients with for TPN-dependent patients with permanent intestinal insufficiencypermanent intestinal insufficiency Pts become intolerant of TPN -> which Pts become intolerant of TPN -> which
manifests in potentially fatal manifests in potentially fatal complicationscomplications Recurrent sepsisRecurrent sepsis Thrombosis of access sitesThrombosis of access sites Metabolic disordersMetabolic disorders CholestasisCholestasis Hepatic dysfunction Hepatic dysfunction
Intestinal Transplantation - Intestinal Transplantation - EtiologyEtiology
Isolated intestinal graftingIsolated intestinal grafting Poor venous access or moderate hepatic dysfunction Poor venous access or moderate hepatic dysfunction
and for those who develop severe fluid and and for those who develop severe fluid and electrolyte abnormalities that cannot be managed electrolyte abnormalities that cannot be managed with TPNwith TPN
Combined small-intestine and liver Combined small-intestine and liver transplantationtransplantation Intestinal insufficiency & irreversible hepatic failure Intestinal insufficiency & irreversible hepatic failure
or coagulopathy or coagulopathy Multivisceral transplantsMultivisceral transplants (ie, combined (ie, combined
stomach, duodenum, pancreas, small intestine) stomach, duodenum, pancreas, small intestine) Following extensive surgical resection of abdominal Following extensive surgical resection of abdominal
organs for aggressive tumor or severe abdominal organs for aggressive tumor or severe abdominal traumatrauma
Preoperative evaluation and Preoperative evaluation and selection selection
Preoperative evaluation requires a Preoperative evaluation requires a complete multidisciplinary complete multidisciplinary assessmentassessment to clearly define the cause to clearly define the cause of isolated intestinal or of isolated intestinal or intestinal/hepatic failureintestinal/hepatic failure
Evaluation of comorbidities and organ Evaluation of comorbidities and organ dysfunctiondysfunction Optimization of preoperative morbid Optimization of preoperative morbid
conditions (infection, malnutrition) can conditions (infection, malnutrition) can significantly affect outcome significantly affect outcome
Preoperative evaluation and Preoperative evaluation and selection selection
Sixth International Small Bowel Transplant Sixth International Small Bowel Transplant Symposium – referral criteria:Symposium – referral criteria: Intestinal failure with impending life-threatening Intestinal failure with impending life-threatening
complications (i.e. end-stage liver disease)complications (i.e. end-stage liver disease) Recurrent sepsis (bacterial translocation 2Recurrent sepsis (bacterial translocation 2ndary ndary
chronic TPN)chronic TPN) Impending loss of central venous access Impending loss of central venous access Locally invasive tumors of the abdomen Locally invasive tumors of the abdomen
(desmoid)(desmoid) Rescue therapy for visceral vascular Rescue therapy for visceral vascular
thrombosis, primary intestinal graft loss, thrombosis, primary intestinal graft loss, and poor quality of life secondary to and poor quality of life secondary to intestinal failureintestinal failure
Preoperative evaluation and Preoperative evaluation and selection selection
Referring patients before the onset of Referring patients before the onset of hepatic dysfunction is importanthepatic dysfunction is important Progression of liver injury, as manifested by Progression of liver injury, as manifested by
jaundice, significantly influences life jaundice, significantly influences life expectancyexpectancy
Bilirubin concentrations >3 mg/dL have 1- Bilirubin concentrations >3 mg/dL have 1- and 2-year survival rates of 42% and 20% and 2-year survival rates of 42% and 20%
Bilirubin <3 mg/dL have a survival rate of Bilirubin <3 mg/dL have a survival rate of 80% 80%
pT >15 and pTT >40 also associated with pT >15 and pTT >40 also associated with poorer outcomespoorer outcomes
Isolated intestinal Isolated intestinal transplantation transplantation
Transplantation may not be indicated Transplantation may not be indicated for patients who have complications of for patients who have complications of their disease but maintain a borderline their disease but maintain a borderline length of intestinelength of intestine May respond to intensive medical May respond to intensive medical
managementmanagement Medical management may involve Medical management may involve
Modified administration of TPNModified administration of TPN Selective gut decontaminationSelective gut decontamination Optimized enteral feedings ( at least 20-Optimized enteral feedings ( at least 20-
30% caloric needs)30% caloric needs)
Isolated intestinal Isolated intestinal transplantation transplantation
Must evaluate liver functionMust evaluate liver function Suspected progression of liver Suspected progression of liver
dysfunction requires prompt dysfunction requires prompt evaluation for intestinal evaluation for intestinal transplantation and a liver biopsy to transplantation and a liver biopsy to determine whether a combined liver determine whether a combined liver and small-intestine transplantation is and small-intestine transplantation is neededneeded
Isolated Intestinal Isolated Intestinal Transplantation Transplantation
Combined liver and small-Combined liver and small-intestine transplantation intestine transplantation
Patients with end-stage liver disease (often Patients with end-stage liver disease (often TPN-related liver disease) & intestinal failure TPN-related liver disease) & intestinal failure The highest mortality rate of all patients on the The highest mortality rate of all patients on the
waiting lists for organ transplantationswaiting lists for organ transplantations Chronic TPN -> cholestatic liver disease (esp. Chronic TPN -> cholestatic liver disease (esp.
children)children) Very few size-match quality organs are Very few size-match quality organs are
available, and these patients are competing available, and these patients are competing for organs with patients on longer waiting for organs with patients on longer waiting lists who are waiting for an isolated liver lists who are waiting for an isolated liver transplantationtransplantation Represent only 2% of the patients on the liver Represent only 2% of the patients on the liver
waiting listwaiting list Do not rank well in the MELD (model for end-stage Do not rank well in the MELD (model for end-stage
liver disease) and PELD (pediatric end-stage liver liver disease) and PELD (pediatric end-stage liver disease) scoring systemdisease) scoring system
Multivisceral Multivisceral transplantation transplantation
Pts with permanent intestinal Pts with permanent intestinal dysfunction, those with TPN dysfunction, those with TPN dependency with complications, and dependency with complications, and those with a systemic motility disorder those with a systemic motility disorder (e.g., chronic pseudo-obstruction, (e.g., chronic pseudo-obstruction, traumatic loss of the stomach or traumatic loss of the stomach or duodenum)duodenum)
Can receive a stomach, duodenum, Can receive a stomach, duodenum, pancreas, and small intestine, with or pancreas, and small intestine, with or without the liver without the liver
Intestinal Transplantation Intestinal Transplantation ContraindicationsContraindications
Absolute contraindicationsAbsolute contraindications Congenital immunodeficiency syndromes, systemic Congenital immunodeficiency syndromes, systemic
malignancy, metastatic disease, AIDs, cardiopulmonary malignancy, metastatic disease, AIDs, cardiopulmonary insufficiency & overwhelming sepsisinsufficiency & overwhelming sepsis
Because of the risk of unrestrained graft versus host Because of the risk of unrestrained graft versus host disease (GVHD)disease (GVHD)
Relative contraindicationsRelative contraindications are evolving, but are evolving, but concern about transplantation from CMV- or EBV-concern about transplantation from CMV- or EBV-positive donors to CMV- or EBV-negative positive donors to CMV- or EBV-negative recipients, weight (<5kg) and elderly pts recipients, weight (<5kg) and elderly pts High morbidity & mortality rates associated with the High morbidity & mortality rates associated with the
development of CMV or lymphoproliferative disease in development of CMV or lymphoproliferative disease in pediatric intestinal transplantspediatric intestinal transplants
Although critically ill patients should be excluded, a Although critically ill patients should be excluded, a history of multiple abdominal surgeries is not a history of multiple abdominal surgeries is not a contraindication for transplantationcontraindication for transplantation
No clear lower age limit for pediatric patients No clear lower age limit for pediatric patients (better results >2yrs of age)(better results >2yrs of age)
Intestinal Transplantation Intestinal Transplantation Pediatric RecommendationsPediatric Recommendations Hakim (1999) recommended cadaveric Hakim (1999) recommended cadaveric
tranplantations from a donor with a tranplantations from a donor with a beating heart 20% smaller than the beating heart 20% smaller than the recipientrecipient Designed to ensure that the pediatric Designed to ensure that the pediatric
recipient (who is likely to have a contracted recipient (who is likely to have a contracted peritoneal cavity) can accommodate the graftperitoneal cavity) can accommodate the graft
The shortage of potential donors because of The shortage of potential donors because of size constraints is prompting development of size constraints is prompting development of novel harvesting and grafting techniquesnovel harvesting and grafting techniques
Intestinal Transplantation - Intestinal Transplantation - WorkupWorkup
Preoperative workup: Preoperative workup: All potential transplant recipients All potential transplant recipients
require a review of require a review of ComorbiditiesComorbidities Relevant laboratoryRelevant laboratory Imaging studiesImaging studies
Intestinal Transplantation - Intestinal Transplantation - WorkupWorkup
Laboratory studies include the following:Laboratory studies include the following: CBC CBC Chem-20 Chem-20 Prothrombin time (PT) Prothrombin time (PT) Activated partial thromboplastin time (aPTT) Activated partial thromboplastin time (aPTT) Blood group and screen Blood group and screen Serologic testing for HIV, hepatitis B virus (HBV), Serologic testing for HIV, hepatitis B virus (HBV),
hepatitis C virus (HCV), CMV, EBV, syphilis, blood hepatitis C virus (HCV), CMV, EBV, syphilis, blood group system (ABO), and human leukocyte group system (ABO), and human leukocyte antigen (HLA) status antigen (HLA) status
When indicated, a hypercoagulable workup (i.e., When indicated, a hypercoagulable workup (i.e., protein C, protein S, antithrombin III, factor V protein C, protein S, antithrombin III, factor V mutation)mutation)
Intestinal Transplantation - Intestinal Transplantation - WorkupWorkup
Imaging Studies: Imaging Studies: Perform Perform angiography and or additional angiography and or additional
Duplex studiesDuplex studies Assess the vascular supply for potential Assess the vascular supply for potential
isolated living-related intestine donorsisolated living-related intestine donors Angiography helps evaluate the SMA to ensure a Angiography helps evaluate the SMA to ensure a
normal vascular intestinal distribution normal vascular intestinal distribution Duplex and Doppler studies help asses for possible Duplex and Doppler studies help asses for possible
inflow/outflow stenosisinflow/outflow stenosis Adequate assessment & preservation of Adequate assessment & preservation of
the descending branch of the right colic the descending branch of the right colic artery are important to provide adequate artery are important to provide adequate blood supply to the areas of the terminal blood supply to the areas of the terminal ileum and ileocecal valveileum and ileocecal valve
Intestinal Transplantation - Intestinal Transplantation - WorkupWorkup
Diagnostic Procedures: Diagnostic Procedures: Dysmotility disordersDysmotility disorders require assessment of require assessment of
the stomach to exclude functional abnormalitiesthe stomach to exclude functional abnormalities Manometry of the stomach, esophagus, and rectum Manometry of the stomach, esophagus, and rectum
may be required to exclude sphincter achalasia and may be required to exclude sphincter achalasia and gastroparesisgastroparesis
Pediatric pseudo-obstructionPediatric pseudo-obstruction pts require pts require urologic assessmenturologic assessment Up to 1/3 may have a dysfunctional urinary tractUp to 1/3 may have a dysfunctional urinary tract
NECNEC -> full neurologic and pulmonary workup -> full neurologic and pulmonary workup Exclude the possibility of associated intraventricular Exclude the possibility of associated intraventricular
hemorrhage & bronchopulmonary dysplasiahemorrhage & bronchopulmonary dysplasia Liver biopsyLiver biopsy in patients with intestinal failure in patients with intestinal failure
and hepatic insufficiency and hepatic insufficiency
Transplantation – Transplantation – Preoperative DetailsPreoperative Details
Cadaveric small-intestine procurementCadaveric small-intestine procurement Choose smaller donors than the intended recipientChoose smaller donors than the intended recipient Preferentially direct CMV– donors to CMV– recipientsPreferentially direct CMV– donors to CMV– recipients
Perform selective gut decontamination with Perform selective gut decontamination with antibiotic and antifungal preparations antibiotic and antifungal preparations administered via a NGT along with standard IV administered via a NGT along with standard IV antibiotic prophylaxisantibiotic prophylaxis
Use University of Wisconsin Universal Organ Use University of Wisconsin Universal Organ Preservation (UW) solution for both in situ Preservation (UW) solution for both in situ flushing and cold storageflushing and cold storage
Polyethylene glycol electrolyte solutionPolyethylene glycol electrolyte solution Obtain wide exposure to the abdominal cavity, and Obtain wide exposure to the abdominal cavity, and
encircle the abdominal aorta distally for encircle the abdominal aorta distally for subsequent insertion of the infusion cannula and subsequent insertion of the infusion cannula and proximally above the celiac axis for cross-clampingproximally above the celiac axis for cross-clamping
Transplantation – Transplantation – Preoperative DetailsPreoperative Details
Cadaveric small-intestine procurementCadaveric small-intestine procurement Perform dissection, in situ cooling of abdominal Perform dissection, in situ cooling of abdominal
organs, and exsanguination before removing organs, and exsanguination before removing the organs to the back table for preparation. the organs to the back table for preparation.
Mobilize and devascularize the cecum and Mobilize and devascularize the cecum and ascending colon with care to preserve the ileal ascending colon with care to preserve the ileal branches of the ileocolic artery.branches of the ileocolic artery.
Divide and close the ileum with the GIA stapler near Divide and close the ileum with the GIA stapler near the ileocecal valvethe ileocecal valve
Devascularize the colon by ligating and dividing Devascularize the colon by ligating and dividing the middle colic, left colic, and inferior the middle colic, left colic, and inferior mesenteric arteries near their originmesenteric arteries near their origin
After transection of the gastrocolic ligament After transection of the gastrocolic ligament and transection of the stapled sigmoid colon, and transection of the stapled sigmoid colon, remove the large bowel and greater omentumremove the large bowel and greater omentum
Transplantation – Transplantation – Preoperative DetailsPreoperative Details
Cadaveric small-intestine procurementCadaveric small-intestine procurement Free the small-bowel mesentery from its Free the small-bowel mesentery from its
retroperitoneal attachments retroperitoneal attachments Expose the mesenteric root, abdominal aorta, and Expose the mesenteric root, abdominal aorta, and
infrahepatic vena cava (including renal veins entry) infrahepatic vena cava (including renal veins entry) Divide the highest jejunal vascular arcadesDivide the highest jejunal vascular arcades
Preserve the vascular supply to the fourth part of Preserve the vascular supply to the fourth part of the duodenum and the proximal part of the jejunum. the duodenum and the proximal part of the jejunum.
Transect the proximal jejunum after mobilizing and Transect the proximal jejunum after mobilizing and dividing the ligament of Treitz and the IMV dividing the ligament of Treitz and the IMV
Suture the jejunal end of the intestine to help orient the Suture the jejunal end of the intestine to help orient the allograftallograft
At this stage, the intestine is attached to the At this stage, the intestine is attached to the donor only by the superior mesenteric pedicle donor only by the superior mesenteric pedicle (SMA & SMV)(SMA & SMV)
Divide the mesenteric root distal to the level of the ligated Divide the mesenteric root distal to the level of the ligated middle colic vesselmiddle colic vessel
Transplantation – Intra-Transplantation – Intra-operative Detailsoperative Details
In situ organ cooling and removalIn situ organ cooling and removal Transaortic cooling requires perfusion Transaortic cooling requires perfusion
with UW solution, 50-100 mL/kg, for with UW solution, 50-100 mL/kg, for pediatric donorspediatric donors
Remove the small-intestine graft by Remove the small-intestine graft by dissection of the SMA & SMV below the dissection of the SMA & SMV below the origin of the inferior pancreaticoduodenal origin of the inferior pancreaticoduodenal arteryartery
Excise a large Carrel patch from the Excise a large Carrel patch from the anterior aortic wall containing the celiac anterior aortic wall containing the celiac axis and superior mesenteric artery. axis and superior mesenteric artery.
Procure iliac and carotid arteries and veins as Procure iliac and carotid arteries and veins as potential vascular graftspotential vascular grafts
Transplantation – Intra-Transplantation – Intra-operative Detailsoperative Details
Back-table preparation of organsBack-table preparation of organs Small-intestine grafts require little Small-intestine grafts require little
revisionrevision If the pedicle of the superior mesenteric If the pedicle of the superior mesenteric
artery is too short, it may be lengthened artery is too short, it may be lengthened with free vascular grafts with free vascular grafts
The anastomoses are made to the The anastomoses are made to the recipient aorta and portal vein or recipient aorta and portal vein or vena cavavena cava
An isolated intestine being prepared on the back An isolated intestine being prepared on the back
table prior to implantationtable prior to implantation
Transplantation – Intra-Transplantation – Intra-operative Detailsoperative Details
Transplantation surgical therapyTransplantation surgical therapy Isolated living-related intestinal Isolated living-related intestinal
grafting requires as much as grafting requires as much as 150-200 150-200 cm of distal jejunum and ileumcm of distal jejunum and ileum to to ensure that the recipient has a ensure that the recipient has a sufficient amount of small bowel to be sufficient amount of small bowel to be completely free of TPNcompletely free of TPN
Transplantation – Intra-Transplantation – Intra-operative Detailsoperative Details
Transplantation surgical therapyTransplantation surgical therapy Carefully preservation of the vascular pedicle Carefully preservation of the vascular pedicle
comprising the ileocolic artery & vein with end-to-comprising the ileocolic artery & vein with end-to-side anastomoses to the recipient's infrarenal side anastomoses to the recipient's infrarenal aorta & vena cava aorta & vena cava
For cadaveric intestinal grafting, arteries are For cadaveric intestinal grafting, arteries are anastomosed directly to the infrarenal aorta with anastomosed directly to the infrarenal aorta with a Carrel patch a Carrel patch
Venous drainage through an anastomosis or patch to the Venous drainage through an anastomosis or patch to the recipient's IVC (combined)recipient's IVC (combined)
Isolated cadaveric intestinal grafting -> preferred Isolated cadaveric intestinal grafting -> preferred venous drainage =portal vein venous drainage =portal vein
In addition, a gastrostomy or jejunostomy is In addition, a gastrostomy or jejunostomy is usually performed for continuous enteral feedingusually performed for continuous enteral feeding
Graft ileostomy permits frequent endoscopic and Graft ileostomy permits frequent endoscopic and histologic postoperative monitoringhistologic postoperative monitoring
Transplantation – Transplantation – Postoperative DetailsPostoperative Details
Require ICU monitoring postoperativelyRequire ICU monitoring postoperatively Induction therapy with tacrolimus and steroids Induction therapy with tacrolimus and steroids
is typically begun most often in conjunction with is typically begun most often in conjunction with an interleukin-2 (IL-2) receptor antibodyan interleukin-2 (IL-2) receptor antibody Maintain high levels of immunosuppression early in Maintain high levels of immunosuppression early in
the postoperative period (risk of rejection is greatest)the postoperative period (risk of rejection is greatest) Then follow with a lower dose for maintenance Then follow with a lower dose for maintenance
therapy therapy Consider the variable absorption and bioavailability of whichever immunosuppression Consider the variable absorption and bioavailability of whichever immunosuppression
regimen is used (ie, tacrolimus, cyclosporine microemulsion)regimen is used (ie, tacrolimus, cyclosporine microemulsion) Because the bioavailability of these drugs depends on intestinal surface area and transit Because the bioavailability of these drugs depends on intestinal surface area and transit
time, the function of the grafts directly affects drug availability time, the function of the grafts directly affects drug availability
In addition, multiple immunosuppressive agents are used (as in other organ In addition, multiple immunosuppressive agents are used (as in other organ transplants) to minimize toxicity and to maximize therapeutic efficacytransplants) to minimize toxicity and to maximize therapeutic efficacy
Intestinal Intestinal Transplantation – Transplantation –
Follow-up careFollow-up care At regular intervals, perform At regular intervals, perform
CMV antigenemiaCMV antigenemia Quantitative EBV polymerase chain Quantitative EBV polymerase chain
reaction (PCR) surveillancereaction (PCR) surveillance Routine culturesRoutine cultures Transplant ileostomal endoscopy & Transplant ileostomal endoscopy &
biopsy (as often as twice weekly)biopsy (as often as twice weekly) Additionally, monitor fluid status, Additionally, monitor fluid status,
stool losses, and serum electrolytesstool losses, and serum electrolytes
Intestinal Transplantation - Intestinal Transplantation - ComplicationsComplications
Infectious complications account for ~60% of Infectious complications account for ~60% of intestinal graft lossesintestinal graft losses Bacterial and fungal infections in intestinal Bacterial and fungal infections in intestinal
transplantation are similar to those found in other transplantation are similar to those found in other solid-organ transplantationssolid-organ transplantations
Rejection and technical errors accounting for Rejection and technical errors accounting for a further 36%a further 36%
An autopsy series found 94% had a coexisting An autopsy series found 94% had a coexisting infection, even in cases in which sepsis was infection, even in cases in which sepsis was not the immediate cause of deathnot the immediate cause of death
Post-transplant lymphoproliferative disease Post-transplant lymphoproliferative disease and graft rejection can lead to breakdown of and graft rejection can lead to breakdown of the mucosal barrier, resulting in bacteremia the mucosal barrier, resulting in bacteremia or fungemiaor fungemia
Intestinal Transplantation - Intestinal Transplantation - ComplicationsComplications
CMV infectionCMV infection Immunosuppression is maintained to avoid Immunosuppression is maintained to avoid
breakthrough rejection but is decreased if the breakthrough rejection but is decreased if the patient's condition worsens. patient's condition worsens.
~ 15-30% of patients~ 15-30% of patients (most often involves an (most often involves an allograft intestine) allograft intestine)
One of the most serious infections that can occur, One of the most serious infections that can occur, because it can lead to loss of the transplanted organ because it can lead to loss of the transplanted organ and even deathand even death
Incidence is highest in CMV-negative recipients who Incidence is highest in CMV-negative recipients who receive CMV-positive grafts (thus avoided)receive CMV-positive grafts (thus avoided)
Infection is diagnosed by measuring CMV Infection is diagnosed by measuring CMV antigenemia and by findings on endoscopic antigenemia and by findings on endoscopic examinationexamination
Endoscopy shows superficial ulcers, and histopathology Endoscopy shows superficial ulcers, and histopathology confirms CMV inclusion bodiesconfirms CMV inclusion bodies
Intestinal Transplantation - Intestinal Transplantation - ComplicationsComplications
CMV infectionCMV infection Treatment consists of IV ganciclovir in Treatment consists of IV ganciclovir in
combination with CMV immune globulin combination with CMV immune globulin (CytoGam) and valganciclovir (Valcyte) tablets(CytoGam) and valganciclovir (Valcyte) tablets Valganciclovir is the oral prodrug of ganciclovir Valganciclovir is the oral prodrug of ganciclovir
(ester prodrug converted by intestinal & hepatic (ester prodrug converted by intestinal & hepatic esterases)esterases)
Valganciclovir delivers the same active drug Valganciclovir delivers the same active drug ingredient with up to 10 times more bioavailability ingredient with up to 10 times more bioavailability
Ganciclovir is a synthetic analogue of 2'-Ganciclovir is a synthetic analogue of 2'-deoxyguanosine, which inhibits replication of deoxyguanosine, which inhibits replication of human CMV human CMV
Intestinal Transplantation - Intestinal Transplantation - ComplicationsComplications
EBV-associated lymphoproliferative diseaseEBV-associated lymphoproliferative disease Posttransplantation lymphoproliferative disease Posttransplantation lymphoproliferative disease
occurs more often in children > adults (29% vs. 11%)occurs more often in children > adults (29% vs. 11%) Occurs more commonly within 24 months after multivisceral Occurs more commonly within 24 months after multivisceral
transplantation than after isolated intestinal transplantationtransplantation than after isolated intestinal transplantation Linked to EBV infection in association with the use of anti-Linked to EBV infection in association with the use of anti-
CD3 monoclonal antibody (OKT3) and steroidsCD3 monoclonal antibody (OKT3) and steroids The high incidence in small-intestine recipients is The high incidence in small-intestine recipients is
presumably caused by the large amount of presumably caused by the large amount of immunosuppression necessary to prevent transplant immunosuppression necessary to prevent transplant rejectionrejection
EBV may lead to a wide spectrum of clinical disease, EBV may lead to a wide spectrum of clinical disease, ranging from a benign mononucleosis syndrome to a ranging from a benign mononucleosis syndrome to a polyclonal proliferative tumor or monoclonal type polyclonal proliferative tumor or monoclonal type lymphoma. lymphoma.
Present with fever, abdominal pain, & either Present with fever, abdominal pain, & either lymphadenopathy or masses on abdominal imaginglymphadenopathy or masses on abdominal imaging
In addition, low-grade EBV infections often precede In addition, low-grade EBV infections often precede posttransplantation lymphoproliferative diseaseposttransplantation lymphoproliferative disease
Intestinal Transplantation - Intestinal Transplantation - ComplicationsComplications
EBV-associated lymphoproliferative EBV-associated lymphoproliferative diseasedisease Treatment of posttransplantation Treatment of posttransplantation
lymphoproliferative disease involves lymphoproliferative disease involves Reduction of immunosuppressionReduction of immunosuppression Administration of ganciclovir (10 mg/kg/d) Administration of ganciclovir (10 mg/kg/d)
Mortality has decreased with improved Mortality has decreased with improved early diagnosisearly diagnosis In situ hybridization staining for EBV In situ hybridization staining for EBV Early ribonucleic acid (RNA) and EBV PCR Early ribonucleic acid (RNA) and EBV PCR
surveillancesurveillance Combined with early interventionCombined with early intervention
Intestinal Transplantation - Intestinal Transplantation - ComplicationsComplications
Acute allograft rejectionAcute allograft rejection Early diagnosis of allograft rejection, a major contributor Early diagnosis of allograft rejection, a major contributor
to both the high morbidity and the high mortality to both the high morbidity and the high mortality associated with small-intestine transplantation, is essentialassociated with small-intestine transplantation, is essential
Allograft rejection incidence rates as high as 87% have Allograft rejection incidence rates as high as 87% have been reportedbeen reported
Manifests clinicallyManifests clinically FeverFever abdominal painabdominal pain increased output from the ostomyincreased output from the ostomy abdominal distentionabdominal distention AcidosisAcidosis Malabsorption and electrolyte abnormalities occur in some Malabsorption and electrolyte abnormalities occur in some
patientspatients Bacterial & fungal sepsis can be life threatening because Bacterial & fungal sepsis can be life threatening because
of the intestine's loss of barrier function, making early of the intestine's loss of barrier function, making early diagnosis and effective treatment of the rejection vitaldiagnosis and effective treatment of the rejection vital
Intestinal Transplantation - Intestinal Transplantation - ComplicationsComplications
Acute allograft rejectionAcute allograft rejection Rejection is diagnosed by endoscopic intestinal biopsy Rejection is diagnosed by endoscopic intestinal biopsy
Diagnosis can be difficult because of the patchy nature of Diagnosis can be difficult because of the patchy nature of rejection and the presence of bleeding & perforation rejection and the presence of bleeding & perforation complicationscomplications
Histologic evidence -> mucosal necrosis and loss of Histologic evidence -> mucosal necrosis and loss of villous architecture with transmural cellular infiltratevillous architecture with transmural cellular infiltrate
Histopathology -> crypt cell apoptosis, cryptitis or crypt loss, Histopathology -> crypt cell apoptosis, cryptitis or crypt loss, necrosis, and endotheliitis necrosis, and endotheliitis
Treatment -> Treatment -> IV bolus of methylprednisolone (10 mg/kg), followed by IV bolus of methylprednisolone (10 mg/kg), followed by
steroid recycle and optimization of the tacrolimus level steroid recycle and optimization of the tacrolimus level OKT3 therapy may be used to treat steroid-resistant rejection OKT3 therapy may be used to treat steroid-resistant rejection
Some centers report that combined liver-intestine Some centers report that combined liver-intestine transplantation provides a greater protective benefit transplantation provides a greater protective benefit (i.e., lower incidence and severity of acute rejection) (i.e., lower incidence and severity of acute rejection) than intestinal transplantation. than intestinal transplantation.
Intestinal Transplantation - Intestinal Transplantation - ComplicationsComplications
Chronic allograft rejectionChronic allograft rejection With improvements in immunosuppressive drugs, With improvements in immunosuppressive drugs,
chronic rejection has become an increasingly chronic rejection has become an increasingly important cause of late allograft dysfunctionimportant cause of late allograft dysfunction
Little is known of the clinical and pathophysiologic Little is known of the clinical and pathophysiologic course of chronic intestinal rejectioncourse of chronic intestinal rejection
In 1990, Goulet reported muscular fibrosis & chronic In 1990, Goulet reported muscular fibrosis & chronic infiltrate with intact mucosal and epithelial structures in infiltrate with intact mucosal and epithelial structures in a small-intestine transplant removed from a 17-month-old a small-intestine transplant removed from a 17-month-old infantinfant
Obliterative arteritis, atrophic Peyer patches and mesenteric Obliterative arteritis, atrophic Peyer patches and mesenteric lymph nodes lymph nodes
Possibly caused by injury to the vascular endothelium, Possibly caused by injury to the vascular endothelium, with a complex inflammatory cascade occurring in the with a complex inflammatory cascade occurring in the vessel wallvessel wall
Therefore, prevention and treatment of chronic intestinal Therefore, prevention and treatment of chronic intestinal rejection are difficult rejection are difficult
Intestinal Transplantation - Intestinal Transplantation - ComplicationsComplications
Graft versus host diseaseGraft versus host disease Small intestine = immunocompetent organ Small intestine = immunocompetent organ
Population of lymphoid cells can mount an immunologic Population of lymphoid cells can mount an immunologic response to the host—a GVHD reaction response to the host—a GVHD reaction
Although animal models have shown that GVHD is a Although animal models have shown that GVHD is a common occurrence and GVHD has not been a significant common occurrence and GVHD has not been a significant clinical problemclinical problem
Acute GVHD presents 1-8 weeks post-transplantation with Acute GVHD presents 1-8 weeks post-transplantation with FeverFever LeukopeniaLeukopenia DiarrheaDiarrhea RashRash Other symptoms may include malaise, anorexia, arthralgia, Other symptoms may include malaise, anorexia, arthralgia,
and abdominal pain. and abdominal pain. Confirm diagnosis by biopsy Confirm diagnosis by biopsy Treatment -> high-dose steroids & antithrombocyte Treatment -> high-dose steroids & antithrombocyte
globulin or with OKT3globulin or with OKT3
Intestinal Transplantation - Intestinal Transplantation - ComplicationsComplications
Technical errorsTechnical errors (up to 50%) (up to 50%) More common in children than in adults More common in children than in adults May cause graft loss May cause graft loss The errors include The errors include
Anastomotic leaksAnastomotic leaks Hepatic artery thrombosisHepatic artery thrombosis Biliary anastomosis leaks or strictureBiliary anastomosis leaks or stricture Intra-abdominal hemorrhageIntra-abdominal hemorrhage Intra-abdominal abscessIntra-abdominal abscess Chylous ascitesChylous ascites
Intestinal Intestinal Transplantation - Transplantation -
Outcome and PrognosisOutcome and Prognosis In 1999, Mazariegos reported a 55% patient In 1999, Mazariegos reported a 55% patient
survival rate and 52% graft survival rate at 5 survival rate and 52% graft survival rate at 5 years following intestinal transplantationyears following intestinal transplantation Matched group of patients (no transplantation) Matched group of patients (no transplantation)
demonstrated 30% 1-year and 22% 2-year survival demonstrated 30% 1-year and 22% 2-year survival ratesrates
Isolated intestinal grafts reportedly provide Isolated intestinal grafts reportedly provide better patient and graft survival rates than better patient and graft survival rates than multivisceral grafts multivisceral grafts
Graft and patient survival rates are improving as Graft and patient survival rates are improving as centers gain experience (51 worldwide centers)centers gain experience (51 worldwide centers) Main centers – U of Pittsburgh, U of Nebraska, U of Main centers – U of Pittsburgh, U of Nebraska, U of
Miami, Hopital Necker-Enfants-Malades, & London Miami, Hopital Necker-Enfants-Malades, & London Health Sciences Center Health Sciences Center
Intestinal Intestinal Transplantation - Transplantation -
Outcome and PrognosisOutcome and PrognosisAuthorAuthor TransplanTransplan
t typet typeGraft 1 Yr Graft 1 Yr %%
Patient 1 Patient 1 Yr %Yr %
Graft 5 Yr Graft 5 Yr %%
Patient 5 Patient 5 Yr %Yr %
Lagnas(NLagnas(Neb)eb)
Liver & Liver & S.I.S.I.
6161 7676
Reyes Reyes (Pitt)(Pitt)
AllAll 6363 7373
GrantGrant S.I.S.I. 5555 6969
Liver & Liver & S.I.S.I.
6363 6666
MultiviscMultivisceraleral
6363 6363
MazariegMazariegosos
AllAll 5252 5555
ControlControl 3030
MadariagMadariagaa
MultiviscMultivisceraleral
5454 4242
FarmerFarmer AllAll 7777 9090
Intestinal Transplantation - Intestinal Transplantation - Outcome and PrognosisOutcome and Prognosis
University of Miami University of Miami experienceexperience
Type of GraftType of Graft 8/94 – 8/94 – 6/956/95
7/95-7/95-12/9712/97
1/98-1/98-9/999/99
Isolated small Isolated small bowelbowel
0%0% 50%50% 80%80%
Liver-small bowel Liver-small bowel 40%40% 30%30% 48%48%
MultivisceralMultivisceral 27%27% 27%27% 27%27%
Intestinal Intestinal Transplantation - Transplantation -
Outcome and PrognosisOutcome and Prognosis Small-intestine transplantation has Small-intestine transplantation has
higher incidences of rejection, sepsis, higher incidences of rejection, sepsis, and post-transplantation and post-transplantation lymphoproliferative disease than other lymphoproliferative disease than other organ transplantationsorgan transplantations These outcomes may be secondary to These outcomes may be secondary to
bacterial translocationbacterial translocation Overall, 78% of intestinal transplant Overall, 78% of intestinal transplant
patients can be expected to be free of patients can be expected to be free of TPN and to tolerate oral nutrition TPN and to tolerate oral nutrition following surgeryfollowing surgery
Intestinal Intestinal Transplantation - Transplantation -
Outcome and PrognosisOutcome and Prognosis One study demonstrates 50% normal One study demonstrates 50% normal growth in pediatric patients who growth in pediatric patients who receive intestinal transplantsreceive intestinal transplants
Sudan et al (2000) reportedSudan et al (2000) reported 11% of patients maintained pre-transplant 11% of patients maintained pre-transplant
growth at less than the 10th percentilegrowth at less than the 10th percentile 15% demonstrated catch-up growth15% demonstrated catch-up growth 84% of these children were able to return 84% of these children were able to return
to day care, preschool, or school at the to day care, preschool, or school at the appropriate level for their development appropriate level for their development
Intestinal Intestinal Transplantation – Transplantation –
Outcome and Prognosis Outcome and Prognosis The introduction of tacrolimus The introduction of tacrolimus immunosuppression, in combination immunosuppression, in combination with decontamination protocols, with decontamination protocols, antibiotic regimens, and antiviral antibiotic regimens, and antiviral measures against CMV and EBV, has measures against CMV and EBV, has improved patient and graft survival improved patient and graft survival ratesrates
Survival rates at 1 year as high as 90% Survival rates at 1 year as high as 90% have been achieved for patients have been achieved for patients receiving isolated intestinal grafts receiving isolated intestinal grafts 3 year survival > 70%3 year survival > 70%
Intestinal Intestinal Transplantation – Transplantation –
Future and ControversiesFuture and Controversies Outcomes may improve with further work Outcomes may improve with further work
to overcome the lack of suitable organ to overcome the lack of suitable organ donors through living-related intestinal donors through living-related intestinal transplantation, improved transplantation, improved immunosuppression, and infection immunosuppression, and infection surveillancesurveillance
Promising procedures, although still Promising procedures, although still unproven, include new immunosuppressive unproven, include new immunosuppressive drugs and regimens, as well as unmodified drugs and regimens, as well as unmodified donor bone marrow infusions to induce donor bone marrow infusions to induce chimerism and to promote graft chimerism and to promote graft acceptanceacceptance
Intestinal Intestinal Transplantation – Transplantation –
Future and ControversiesFuture and Controversies Cost analyses of continued medical Cost analyses of continued medical management versus early liver-intestine management versus early liver-intestine and intestinal transplantation requires and intestinal transplantation requires further study to help guide policyfurther study to help guide policy
According to Dr. Abu-Elmagd of the Univ According to Dr. Abu-Elmagd of the Univ of Pittsburgh “the data …(has)… shown of Pittsburgh “the data …(has)… shown that the total cost is unequivocally cost-that the total cost is unequivocally cost-effective. It pays for itself in the effective. It pays for itself in the following two years — exactly the same following two years — exactly the same as in kidney transplantation." as in kidney transplantation."
Future and ControversiesFuture and Controversies Current Research led by Dr. Marshall Schwartz at Current Research led by Dr. Marshall Schwartz at
St. Christopher’s Pediatric Hospital Center St. Christopher’s Pediatric Hospital Center Can Parenteral Nutrition Induced Liver Injury Can Parenteral Nutrition Induced Liver Injury
Be Prevented in Children with Short Bowel Be Prevented in Children with Short Bowel Syndrome?Syndrome? Investigating the potential role of growth factors on Investigating the potential role of growth factors on
enhancing the function of the residual small intestine in enhancing the function of the residual small intestine in SBS and thereby preventing liver injurySBS and thereby preventing liver injury
Esp. Hepatocyte Growth Factor (believed to be the most Esp. Hepatocyte Growth Factor (believed to be the most potent)potent)
The use of novel quantum dot technology in the The use of novel quantum dot technology in the early detection of graft rejection and the role of early detection of graft rejection and the role of a growth factor on amelioration of bowel injury a growth factor on amelioration of bowel injury following small bowel transplantationfollowing small bowel transplantation Inorganic fluorophores use to detect surface molecular Inorganic fluorophores use to detect surface molecular
attachment and epidermal receptor function – minimally attachment and epidermal receptor function – minimally invasive evaluation for possible acute rejectioninvasive evaluation for possible acute rejection
Thomas E. Starzl Thomas E. Starzl Transplant Institute – 13 Transplant Institute – 13
year survival datayear survival data Abu-Elmagd et al reported on the status Abu-Elmagd et al reported on the status
96 children who received 102 allografts 96 children who received 102 allografts (29 intestine, 60 liver & intestine, & 13 (29 intestine, 60 liver & intestine, & 13
multivisceral) multivisceral) Since 1990, 54% still alive with an Since 1990, 54% still alive with an
overall 5 yr survival rate of 58% & 5yr overall 5 yr survival rate of 58% & 5yr graft survival of 50%graft survival of 50%
Quality of life is also greatly improved Quality of life is also greatly improved with re-institution of enteral feedingwith re-institution of enteral feeding
Intestinal Transplant Intestinal Transplant PatientsPatients
Transplant:Transplant: MB has a MB has a small bowel transplant small bowel transplant for Near Total for Near Total Hirschsprung's DiseaseHirschsprung's Disease
Requires 24-hours a dayRequires 24-hours a day Performed at Children's Performed at Children's
Hospital of Pittsburgh Hospital of Pittsburgh Continues to receive Continues to receive
continual medical testing continual medical testing and care and care
Intestinal Transplant Intestinal Transplant PatientsPatients
SR was only 5 months SR was only 5 months old when she received a old when she received a bowel-liver-stomach-bowel-liver-stomach-pancreas transplant pancreas transplant (1997)(1997)
London Health Sciences London Health Sciences CenterCenter
Here she is at the age of Here she is at the age of 4 4
Intestinal Transplant Intestinal Transplant PatientsPatients
AC small bowel AC small bowel transplant 2ndary to transplant 2ndary to obstructive tumor obstructive tumor (gardiner’s (gardiner’s syndrome), s/p syndrome), s/p previous colectomyprevious colectomy
Dr. Fishbein and the Dr. Fishbein and the Georgetown Univ Georgetown Univ Transplant teamTransplant team
AC became to eat AC became to eat again after a few again after a few post-operative weeks post-operative weeks
Intestinal Transplant Intestinal Transplant PatientsPatients
AG received a liver AG received a liver and small bowel and small bowel transplant when he transplant when he was just three years was just three years old and has also old and has also undergone two heart undergone two heart operations in operations in ScotlandScotland
Currently 10 years, Currently 10 years, he enjoys many of the he enjoys many of the same activities as his same activities as his peerspeers
References References Abu-Elmagd K, Fung J, Bueno J: Logistics and technique for procurement of intestinal, Abu-Elmagd K, Fung J, Bueno J: Logistics and technique for procurement of intestinal,
pancreatic, and hepatic grafts from the same donor. Ann Surg 2000 Nov; 232(5): 680-7pancreatic, and hepatic grafts from the same donor. Ann Surg 2000 Nov; 232(5): 680-7[Medline][Medline]. .
Beath SV, Protheroe SP, Brook GA: Early experience of paediatric intestinal transplantation in Beath SV, Protheroe SP, Brook GA: Early experience of paediatric intestinal transplantation in the United Kingdom, 1993 to 1999. Transplant Proc 2000 Sep; 32(6): 1225the United Kingdom, 1993 to 1999. Transplant Proc 2000 Sep; 32(6): 1225[Medline][Medline]. .
Benedetti E, Baum C, Raofi V: Living related small bowel transplantation: progressive Benedetti E, Baum C, Raofi V: Living related small bowel transplantation: progressive functional adaptation of the graft. Transplant Proc 2000 Sep; 32(6): 1209functional adaptation of the graft. Transplant Proc 2000 Sep; 32(6): 1209[Medline][Medline]. .
Bueno J, Ohwada S, Kocoshis S: Factors impacting the survival of children with intestinal Bueno J, Ohwada S, Kocoshis S: Factors impacting the survival of children with intestinal failure referred for intestinal transplantation. J Pediatr Surg 1999 Jan; 34(1): 27-32; discussion failure referred for intestinal transplantation. J Pediatr Surg 1999 Jan; 34(1): 27-32; discussion 32-332-3[Medline][Medline]. .
Carrel A: La technique des anastomese vasculaires et la transplantation des visceres. Lyon Carrel A: La technique des anastomese vasculaires et la transplantation des visceres. Lyon Med 1902; 98: 859. Med 1902; 98: 859.
Cicalese L, Sileri P, Green M: Bacterial translocation in clinical intestinal transplantation. Cicalese L, Sileri P, Green M: Bacterial translocation in clinical intestinal transplantation. Transplant Proc 2000 Sep; 32(6): 1210Transplant Proc 2000 Sep; 32(6): 1210[Medline][Medline]. .
Deltz E, Schroeder P, Gebhardt H: [First successful clinical small intestine transplantation. Deltz E, Schroeder P, Gebhardt H: [First successful clinical small intestine transplantation. Tactics and surgical technic]. Chirurg 1989 Apr; 60(4): 235-9Tactics and surgical technic]. Chirurg 1989 Apr; 60(4): 235-9[Medline][Medline]. .
Farmer DG, McDiarmid SV, Yersiz H: Improved outcome after intestinal transplantation: an 8-Farmer DG, McDiarmid SV, Yersiz H: Improved outcome after intestinal transplantation: an 8-year, single-center experience. Transplant Proc 2000 Sep; 32(6): 1233-4year, single-center experience. Transplant Proc 2000 Sep; 32(6): 1233-4[Medline][Medline]. .
Filston HC, Colombani PM: Preliminary experience with intestinal transplantation in infants Filston HC, Colombani PM: Preliminary experience with intestinal transplantation in infants and children. Pediatrics 1996 Apr; 97(4): 583-4and children. Pediatrics 1996 Apr; 97(4): 583-4[Medline][Medline]. .
Finn L, Reyes J, Bueno J: Epstein-Barr virus infections in children after transplantation of the Finn L, Reyes J, Bueno J: Epstein-Barr virus infections in children after transplantation of the small intestine. Am J Surg Pathol 1998 Mar; 22(3): 299-309small intestine. Am J Surg Pathol 1998 Mar; 22(3): 299-309[Medline][Medline]. .
Frezza EE, Tzakis A, Fung JJ: Small bowel transplantation: current progress and clinical Frezza EE, Tzakis A, Fung JJ: Small bowel transplantation: current progress and clinical application. Hepatogastroenterology 1996 Mar-Apr; 43(8): 363-76application. Hepatogastroenterology 1996 Mar-Apr; 43(8): 363-76[Medline][Medline]. .
Giraldo M, Martin D, Colangelo J: Intestinal transplantation for patients with short gut Giraldo M, Martin D, Colangelo J: Intestinal transplantation for patients with short gut syndrome and hypercoagulable states. Transplant Proc 2000 Sep; 32(6): 1223-4syndrome and hypercoagulable states. Transplant Proc 2000 Sep; 32(6): 1223-4[Medline][Medline]. .
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Transplant Registry. Transplantation 1999 Apr 15; 67(7): 1061-4Transplant Registry. Transplantation 1999 Apr 15; 67(7): 1061-4[Medline][Medline]. . Grebe SC, Streilein JW: Graft-versus-Host reactions: a review. Adv Immunol 1976; 22: 119-Grebe SC, Streilein JW: Graft-versus-Host reactions: a review. Adv Immunol 1976; 22: 119-
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standardized surgical technique. Transplantation 1997 Dec 15; 64(11): 1605-7standardized surgical technique. Transplantation 1997 Dec 15; 64(11): 1605-7[Medline][Medline]. . Hakim NS, Papalois VE: Small bowel transplantation. Int Surg 1999 Oct-Dec; 84(4): 313-7Hakim NS, Papalois VE: Small bowel transplantation. Int Surg 1999 Oct-Dec; 84(4): 313-7
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Pharmacol Ther 1993; 62: 2. Pharmacol Ther 1993; 62: 2. Lillehei RC, Idezuki Y, Feemster JA: Transplantation of stomach, intestine, and pancreas: Lillehei RC, Idezuki Y, Feemster JA: Transplantation of stomach, intestine, and pancreas:
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1999 Nov; 20(11): 363-75[Medline]. 1999 Nov; 20(11): 363-75[Medline]. Mazariegos GV, Kocoshis S: Patient selection for intestinal transplantation. Curr Mazariegos GV, Kocoshis S: Patient selection for intestinal transplantation. Curr
Opin Organ Transplant 1998; 3: 293-97. Opin Organ Transplant 1998; 3: 293-97. Nalesnik M, Jaffe R, Reyes J: Posttransplant lymphoproliferative disorders in small Nalesnik M, Jaffe R, Reyes J: Posttransplant lymphoproliferative disorders in small
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16(2): 293-312. 16(2): 293-312. Roberts CA, Radio SJ, Markin RS: Histopathologic evaluation of primary intestinal Roberts CA, Radio SJ, Markin RS: Histopathologic evaluation of primary intestinal
transplant recipients at autopsy: a single-center experience. Transplant Proc 2000 transplant recipients at autopsy: a single-center experience. Transplant Proc 2000 Sep; 32(6): 1202-3[Medline]. Sep; 32(6): 1202-3[Medline].
Sudan DL, Kaufman S, Horslen S: Incidence, timing, and histologic grade of acute Sudan DL, Kaufman S, Horslen S: Incidence, timing, and histologic grade of acute rejection in small bowel transplant recipients. Transplant Proc 2000 Sep; 32(6): rejection in small bowel transplant recipients. Transplant Proc 2000 Sep; 32(6): 1199[Medline]. 1199[Medline].
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Thompson JS: Intestinal transplantation. Experience in the United States. Eur J Thompson JS: Intestinal transplantation. Experience in the United States. Eur J Pediatr Surg 1999 Aug; 9(4): 271-3[Medline]. Pediatr Surg 1999 Aug; 9(4): 271-3[Medline].
Todo S, Tzakis A, Abu-Elmagd K: Current status of intestinal transplantation. Adv Todo S, Tzakis A, Abu-Elmagd K: Current status of intestinal transplantation. Adv Surg 1994; 27: 295-316[Medline]. Surg 1994; 27: 295-316[Medline].