Evaluation of Pancreatic Disease Crystal Byerly, MEd, PA-C Seton Hill University PA Program
Evaluation of Pancreatic Disease
Crystal Byerly, MEd, PA-CSeton Hill University PA Program
Learning Objectives
• Identify the various types of pancreatic cysts and masses
• Discuss the diagnostic studies used in the evaluation of pancreatic cysts and masses
• Explain the treatment options of pancreatic cysts and masses
A PA’s common questions about the basics....
• How do we know which pancreatic cysts and masses have a bad prognosis and which are safe to “watch”???
• What diagnostic testing will give us the best information on this pancreatic abnormality??
• Which cysts and masses require treatment and which can be left alone???
Pancreatic cysts and masses
Pancreatic mass on
CT
60+ yr old female gets CT scan for unrelated reason with incidental finding of pancreatic
mass
Patient presents with symptoms of abdominal
pain, wt. loss, maybe vomiting or jaundice. No etiology found on EGD so CT ordered which
reveals pancreatic massPatient with persistent or recurrent abdominal
pain. PMH of Acute Pancreatitis, Chronic
Pancreatitis, or trauma.
CLASSIFICATION OF PANCREATIC CYSTS AND MASSES
How do we know which pancreatic cysts and masses have a bad prognosis and which are safe to “watch”???
Pancreatic cyst and mass etiologies• Congenital
– “True” cysts of the pancreas– Neither neoplastic nor result of prior inflammation– Distinguished from other cysts only by epithelial lining
• Inflammatory– “Pseudocysts” and Pancreatic abcesses– Result from acute or chronic pancreatitis or pancreatic trauma– Lack epithelial lining; often with fibrous wall after 4+ weeks– Fairly rapid evolution size– Contains fluid (near water-attenuation) contents
• Pancreatic juices, necrotic debris, hemorrhage
• Neoplastic Processes– Benign neoplasms/ Non-neoplastic pancreatic cysts (NNPCs)
• Cystic teratoma, Lymphoepithelial cysts, Serous Cystadenoma
– Pancreatic cystic neoplasms (PCNs)• Malignant/Premalignant:
– Mucinous cystic neoplasm, aka Mucinous cystadenoma– Solid and Papillary Epithelial Neoplasms, aka Pseudopapillary neoplasm, Intraductal papillary mucinous
neoplasm
PSEUDOCYSTSNNPCS• True cysts• Retention cysts• Mucinous NON-
neoplastic cysts• Lymphoepithelial
cysts
PCNs• IPMNs• Mucinous
cystadenoma• Serous cyst tumor• Solid
pseudopapillary neoplasm
PANCREATIC NEOPLASMS• Ductal Carcinoma• Acinar Cell
Adenocarcinoma• Panreatoblastoma• Islet Cell tumors
BENIGN ???? MALIGNANT
Benign Pseudocysts
• Lack of epithelial lining • is what distinguishes pseudocysts from true cystic lesions of the
pancreas
• No vascularized soft-tissue elements present • if vascularized elements are seen within a cystic lesion on
contrast-enhanced MR images, the lesion is not a pseudocyst
• May be single, multiple, variable in size• Located inside or outside of pancreas• Most communicate with pancreatic ductal system • Most contain high concentrations of digestive enzymes
Benign Pseudocysts
• Recognition of pseudocyst resulting from known inflammation (pancreatitis, trauma) makes dx more obvious
• If no known inflammatory process, findings can be difficult to distinguish from the neoplastic IPMN (Intraductal papillary mucinous neoplasm)
• Even mature pseudocysts may resolve spontaneously
Benign/Non-neoplastic Pancreatic cysts (NNPCs)
• Rare• Often asymptomatic• Elderly patients with incidental CT finding even though
may have been congenital etiology• Usually NO pancreatic ductal communication seen• Includes:
– True cysts– Retention cysts– Mucinous NON-neoplastic cysts– Lymphoepithelial cysts
PSEUDOCYSTSNNCPS• True cysts• Retention cysts• Mucinous NON-
neoplastic cysts• Lymphoepithelial
cysts
PCNs• IPMNs• Mucinous
cystadenoma• Serous cyst tumor• Solid
pseudopapillary neoplasm
PANCREATIC NEOPLASMS• Ductal Carcinoma• Acinar Cell
Adenocarcinoma• Panreatoblastoma• Islet Cell tumors
BENIGN ???? MALIGNANT
Pancreatic cystic neoplasms (PCNs)
• Females > Males• 5th decade• Incidental finding on CT• Abdominal pain, weight loss, possibly vomiting• Each of the 4 subtypes have benign and malignant forms
and are categorized using the WHO histological classification:
• Intraductal papillary mucinous neoplasm (*38%)• Mucinous cystic neoplasm/mucinous cystadenoma (*23%)• Serous cystic tumor (*16%)• Solid pseudopapillary neoplasm (*3%)
» *Study of 851 patients underwent surgical resection for cystic lesion of pancreas between 1978-2011
PCN most common type:Intraductal papillary mucinous neoplasms (IPMNs)
• Over 50 yrs old, F=M presentation• Mucin-producing papillary neoplasms of the
pancreatic ductal system• Excellent prognosis when lesions showing only
adenomatous and borderline atypia cytology• Poor prognosis when invasive carcinoma
present
Common PCN type:Mucinous cystic neoplasm/
mucinous cystadenoma
• Exclusively females > 40• Well circumscribed masses, thick-walled, and usually
unilocular (or less than 6 septa)• Like IPMNs: cellular atypia and secrete mucin• Unlike IPMNs: have ovarian-like stroma and do NOT
communicate with pancreatic duct• Resection recommended due to moderate malignancy
potential• Poor prognosis when invasive adenocarcinoma is
present, but resection can be curative
PCN type: Serous cystadenomas
• Most benign• Females over 60• Imaging appearance is sponge-like or
honeycomb (thin septal segments)• Unless symptomatic, can follow conservatively
due to low malignancy potential• Actual carcinoma is rare, resection curative
PCN type: Solid pseudopapillary neoplasms
• Aka solid and papillary epithelial neoplasms, solid and cystic tumors
• Young women ~20’s; usually under 35• Mixed features of solid mass with fluid and
hemorrhage; necrotic debris• Well-circumscribed mass that’s slow growing• Moderate to high malignancy potential• Resection yields excellent prognosis
We’ve covered the benign and the questionable... Now here’s the definite bad ones
PSEUDOCYSTSNNCPS• True cysts• Retention cysts• Mucinous NON-
neoplastic cysts• Lymphoepithelial
cysts
PCNs• IPMNs• Mucinous
cystadenoma• Serous cyst tumor• Solid
pseudopapillary neoplasm
PANCREATIC NEOPLASMS• Ductal Carcinoma• Acinar Cell
Adenocarcinoma• Panreatoblastoma• Islet Cell tumors
BENIGN ???? MALIGNANT
“Pancreatic Neoplasms”
• Exocrine Pancreatic Neoplasms:• Ductal adenocarcinoma (85% of all pancreatic
neoplasms)• Acinar cell cystadenocarcinoma• Pancreatoblastoma
• Endocrine Pancreatic Neoplasms:• Islet cell tumors
Ductal adenocarcinoma
• Cancer• Slight male predominance • 60’s- 70’s• VERY rare <1%• Dismal prognosis
Acinar cell cystadenocarcinoma
• Cancer• Aggressive neoplasm• Males 60’s-70’s• VERY rare <1%• Similar to solid type• Poor prognosis
Pancreatoblastoma
• Rare pancreatic tumor with distinct acinar and squamoid cell differentiation that generally affects infants and young children
• Presenting usually with abdominal mass
Islet Cell Tumors
• Neuroendocrine• Less than 5% of pancreatic neoplasms
PSEUDOCYSTSNNCPS• True cysts• Retention cysts• Mucinous NON-
neoplastic cysts• Lymphoepithelial
cysts
PCNs• IPMNs• Mucinous
cystadenoma• Serous cyst tumor• Solid
pseudopapillary neoplasm
PANCREATIC NEOPLASMS• Ductal Carcinoma• Acinar Cell
Adenocarcinoma• Panreatoblastoma• Islet Cell tumors
BENIGN ???? MALIGNANT
How do we know which pancreatic cysts and masses have a bad prognosis and which are safe to “watch”???
DIAGNOSTIC STUDIES USED IN EVALUATION OF PANCREATIC CYSTS AND MASSES
What diagnostic testing will give us the best information on this pancreatic abnormality??
CTThe good guy or the bad guy depending on how we look at it
GOOD GUY• Initially reveals the
pancreatic abnormality • Finds more pancreatic
cancers than in past• Can depict small pancreatic
cysts• Better demonstrates
calcifications
BAD GUY• Increased incidental findings lead
to more tests, patient worry, professional liability concerns, higher healthcare costs
• Limited evaluation of internal septa of cysts
• Presence or absence of calcifications is NOT a critical diagnostic indicator in differentiation of pancreatic cysts
*Preferred initial testing in pts with epigastric pain and wt loss without jaundice.*Provides local and regional disease extent, which determines resectability as well as metastatic potential. *”Pancreas Protocol CT”
Suspicious vs. Benign cystic features on CT
• The typical CT appearance of an exocrine pancreatic cancer is an ill-defined, hypoattenuating mass within the pancreas.
• If cyst is <5mm, asymptomatic, and lacks concerning features on imaging, its reasonable to repeat cross-sectional imaging in one year.
• Additional evaluation (EUS) is required for most other cysts and for pts with small cysts who develop symptoms or cyst enlargement.
MRI
• Best suited for many distinguishing features of the pancreas– Cyst morphology- clearer depiction of septa and
other cyst contents (fluid, necrotic debris)– Communication with pancreatic ductal system– Good soft tissue contrast
BOTH CT and MRI???
• Combining CT with MRI offers little that can not be achieved by one alone.
• “The choice of MRI or CT for pancreatic diagnosis depends on level of locally available expertise and the clinician’s comfort with one or the other” per UpToDate July 2013
MRCP
• Uses MR technology to create a 3D image of the pancreatobiliary tree, liver, and vascular structures
• Better than CT for biliary and pancreatic duct anatomy
• At least same sensitivity to ERCP for detecting pancreatic CA
• Doesn’t require contrast into ductal system like ERCP but lacks the therapeutic capability
ERCP
• Permits visualization of biliary neoplasms while providing diagnostic and therapeutic opportunities– Collection of tissue samples by
• Forcep biopsy• Brush cytology
• Great for biliary-specific dx but not for a pancreatic mass that may be applying external obstruction to the biliary tract.
• Sensitivity is lower than EUS-FNA for detecting pancreatic malignancy
• Invasive with complication risks• Much more expensive than US or CT
Transabdominal Ultrasound
– Commonly utilized as initial screening due to low cost and wide availability
– If + for pancreatic mass, then abdominal CT typically done to confirm extent of disease
• High sensitivity for detecting tumors >3cm but much lower for small tumors
– A pancreatic carcinoma will appear as a focal, hypoechoic, hypovascular, solid mass with irregular margins. May also have +/- dilated bile ducts.
– Lacks spacial resolution– Lack of soft tissue contrast resolution– Limited visualization in larger patients
EUS
• Invasive ultrasound• Allows better visualization of pancreas• May be used as alternative to contrast-enhanced CT
for the staging of pancreatic CA• Any lesions that are visible only on EUS should be
biopsied to confirm dx prior to surgical exploration.
• EUS FNA is best modality when inconclusive CT findings for pancreatic malignancy – (87% sensitivity/ 98% specificity in study 116 pts)
ENDOSCOPIC ULTRASOUND (EUS)
Pancreatic mass biopsies
• EUS-guided biopsy • Not required if definite
resectable mass– Is required if inconclusive
CT findings for malignancy
• 90% sensitivity and 96% specificity for dx of pancreatic CA
• Less likely to cause peritoneal spread than percutaneous bx
• Percutaneous fine needle aspiration
• Pancreatic mass bx done by either US or CT guidance
• ?? Possibility of intraperitoneal tumor cell dissemination???
Tumor Markers
• CA19-9– Used as prognostic marker and not a screening tool– Low specificity due to other cancer types and
various benign pancreatobiliary disorders that would elevate
– Sensitivity closely related to tumor size and of limited usefulness in small cancers
• CEA level of cyst fluid (not blood test)– Best studied and most accurate tumor marker for
diagnosis of a mucinous pancreatic cystic neoplasm (PCN)
Tumor Markers in future
• Several markers are candidates in studies at this time, but none have replaced the two mentioned to date– Might be seeing more about Macrophage
inhibitory cytokine-1
Molecular genetic analysis
• Molecular markers of cyst fluid DNA has been used to differentiate PCNs from other pancreatic lesions
• The addition of molecular genetic analysis are not routine component of diagnostic evaluation at present– Assay for K-ras– P53 gene mutations
TREATMENT OPTIONS
Which cysts and masses require treatment and which can be left alone???
Cystic lesion treatment
• If cyst is – <5mm– asymptomatic– and lacks concerning features on imaging=
textbook NNPCs• its reasonable to repeat cross-sectional
imaging in one year.
Pseudocyst follow up
• Watchful waiting recommendations vary:• Beyond 13 weeks without resolution is linked to higher
complication rate
– Abdominal ultrasound, CT, or MRI q 3-6m sometimes followed by conservative specialists
• ERCP usually done before attempting drainage• No malignancy potential• Surgical management only if symptomatic
Symptomatic Pseudocyst Treatment
• Intervention required for persistent, symptomatic cysts (abdominal pain or early satiety)
• ERCP usually done before attempting drainage• Symptomatic tx options include:
– Percutaneous catheter drainage– Endoscopic drainage (transpapillary or transmural)– Surgical drainage (cystenterostomy)
Principles of EUS-directed Pseudocyst Drainage
•Cautery access•Wire placement•Contrast injection•Site dilation•Stent placement
Barthet M, Lamblin G, Gasmi M, Vitton V, Desjeux A, Grimaud JC.Clinical usefulness of a treatment algorithm for pancreatic pseudocysts.Gastrointest Endosc. 2008 Feb;67(2):245-52.
Introducer
Balloon dilation
Pig Tail Stent
Surgical resection• Pancreatic neoplasms
• Solid pseudopapillary neoplasm• Mucinous cystic neoplasm/mucinous cystadenoma
• Pancreatic Adenocarcinoma
• If patient is a reasonable surgical candidate, and if the clinical presentation is typical for a resectable pancreatic adenocarcinoma, surgical resection is done without a pre-op tissue diagnosis
• Complete surgical resection is only potentially curative modality for treatment of pancreatic CA
• Pt is not resection candidate if there is vascular invasion, particularly of the SMA
Mucinous cystic neoplasm
• Resection advised• Imaging suggests malignancy with descriptions such
as: mural nodularity, enhancement, calcification, possible ductal obstruction,thick-walled cystic mass
• Mucinous content on CT or MRI is viscous due to proteinaceous fluid
• EUS w FNA yields thick mucinous fluid and elevated CEA level
• DNA with mutations within the fluid accurately predicted presence of malignancy
• Molecular analysis used as adjunct testing where available
Serous cystadenoma evaluation
• Can be watched due to low malignancy potential if classic appearance
• MRI > CT for septal features, and MRI better for revealing fluid content of the mass
• EUS provides high-resolution imaging that highlights the sponge-like/honeycomb appearance
• FNA no longer done if mass has classic appearance
• Actual carcinoma is rare
Solid pseudopapillary neoplasms
• Mixed features of solid mass with fluid, hemorrhage, necrotic debris
• Often not dx until large mass (>10cm avg!!)• EUS w FNA provides accurate pre-op dx if
CT/MRI questionable• Resection advised due to high malignancy
potential• Possible liver metastases and lymph node
involvement later in disease
EUS-Guided Injection of Chemotherapy
• OncoGel (ReGel/Paclitaxel) • designed for intralesional injection with a sustained paclitaxel
delivery over approximately 6 weeks• OncoGel was injected into 18 superficially accessible advanced
solid cancerous lesions among 16 adult patients for whom no curative therapy
• OncoGel injections were generally well tolerated. There was one report of grade 3 injection site pain.
• stable disease was noted among 6/14 patients and progressive disease among 8 patients.
Cryo-Therm Ablation of the Pancreas
• Flexible bipolar probe--RFA energy input (16 W) and simultaneous cryogenic cooling with carbon dioxide (650 psi)
• Application time range was 120 - 900 seconds in 14 pigs• Good correlation between RFA time and size of ablation• 2/14 pigs showed histochemical pancreatitis, which was
clinically overt in one. • Necropsy additionally revealed one burn to the gastric wall
and four gut adhesions.• EUS – guided RFA provides pancreatic ablation
Carrara S, Arcidiacono PG, Albarello L, Addis A, Enderle MD, Boemo C, Campagnol M, Ambrosi A, Doglioni C, Testoni PA.
Endoscopic ultrasound-guided application of a new hybrid cryotherm probe in porcine pancreas: a preliminary study.
Endoscopy. 2008 Apr;40(4):321-6.
A PA’s common questions about the basics....
• How do we know which pancreatic cysts and masses have a bad prognosis and which are safe to “watch”???
• What diagnostic testing will give us the best information on this pancreatic abnormality??
• Which cysts and masses require treatment and which can be left alone???
REFERENCES• Chang KJ, Lee JG, Holcombe RF, Kuo J, Muthusamy R, Wu ML. Endoscopic ultrasound delivery of an
antitumor agent to treat a case of pancreatic cancer. Nat Clin Pract Gastroenterol Hepatol. 2008 Feb; 5(2): 107-11.
• Federle MP, McGrath KM. Cystic Neoplasms of the Pancreas. Gastroenterol Clin N Am, 2007; 36: 365-376.
• Khalid, A, Brugge, Wr. ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts. Am J Gastroenterol 2007; 102:2339.
• Oh HC, Seo DW, Lee TY, Kim JY, Lee SS, Lee SK, Kim MH. New treatment for cystic tumors of the pancreas: EUS-guided ethanol lavage with paclitaxel injection. Gastrointest Endosc. 2008 Apr;67(4):636-42.
• Valsangkar NP, Morales-Oyarvide V, Thayer SP, et al. 851 resected cystic tumors of the pancreas: a 33-year experience at the Massachusetts General Hospital. Surgery 2012; 152:S4.
• Wang W, Shpaner A, Krishna SG, et al. Use of EUS-FNA in diagnosing pancreatic neoplasm without a definitive mass on CT. Gastrointest Endosc 2013.
• Yusuf TE, Matthes K, Brugge WR. EUS-guided photodynamic therapy with verteporfin for ablation of normal pancreatic tissue: a pilot study in a porcine model. Gastrointest Edosc. 2008 May; 67 (6): 957-61.
• Zamboni G, Kloeppel G, Hruban RH, et al. Mucinous cystic neoplasms of the pancreas. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System, Aaltonen LA, Hamiltion SR (Eds), IARC Press, Lyon, France 2000. p. 234.