Pancreas

Acute Pancreatitis

• Most common causes = ETOH, Gallstones
• Gallstone pancreatitis: Clear the duct (ERCP vs IOC) → cholecystectomy during same admission <4 weeks >4 weeks Non-necrotizing Acute peri- pancreatic fluid collection Pseudocyst Necrotizing Acute necrotic collection Walled off necrosis (you WON an operation) Table 1 - Revised Atlanta Classification for post pancreatitis fluid collections
• Necrotizing pancreatitis
• Antibiotics?
• No for pancreatitis
• No for necrotizing pancreatitis
• Yes, for necrotizing pancreatitis with signs of infection
• Clinical signs: fever, elevated WBC
• CT guided FNA with organisms
• Imipenem is antibiotic of choice
• Step-up approach — Answer for infected pancreatic necrosis used to be immediate OR for open debridement — 2010 JAMA article showed improved outcomes with delayed OR with “step-up” approach

Figure 1: Step-Up Approach for Infected Pancreatic Necrosis Chronic Pancreatitis

• Secondary to longstanding ETOH abuse, biliary tract disease, autoimmune, or idiopathic
• What are the symptoms of chronic pancreatitis?
• Persistent abdominal pain, weight loss, pancreatic insufficiency (malabsorption, steatorrhea, diabetes) with hx of one or more bouts of pancreatitis
• What is the preferred imaging and findings?
• CT can confirm diagnosis - demonstrates fibrosis, atrophy, and calcification of the gland
• Chronic pancreatitis increases risk of pancreatic cancer

• Non-operative management — pain control, nutritional management, abstaining from ETOH, pancreatic enzyme replacement

• Two main categories of operations for chronic pancreatitis: Decompress obstructed ductal system and resection of diseased tissue (Or combination of both) — several variations and very complex topic but main operations for the ABSITE are:
• Puestow Procedure — Longitudinal pancreaticojejunostomy
• Beger Procedure — Resection of pancreatic head up to wall of duodenum with either end to end or side to side pancreaticojejunostomy (Duodenum preserving pancreatic head resection)
• Frey Procedure — Lateral longitudinal pancreaticojejunostomy with an excavation of the pancreatic head (Core out head of pancreas but avoid pancreatic transection required of Beger procedure)
• Operative intervention depends on particular morphology of disease
• For dilated pancreatic duct (6mm or greater) would go with Peustow, so long as pancreatic head is normal
• If pancreatic head dominant disease with or without duct dilation → Frey procedure
• If distal pancreatic duct stricture with side branch changes and normal pancreatic head → distal pancreatectomy
• Minimal change pancreatitis → Resection and/or drainage will not help → denervation operation (bilateral thoracoscopic splanchnicectomy) Pseudocyst
• More common with chronic pancreatitis, however, can occur after acute pancreatitis
• Most will resolve spontaneously → manage expectantly for at least 6 weeks (ideally 3mo) . Most will resolve in this time period, wait time also allows wall to mature . Consider intervention if >6cm or symptomatic .

• Often associated with pancreatic duct abnormality → Need ERCP or MRCP prior to intervention

• Available approaches include transpapillary endoscopic stenting, endoscopic transluminal drainage, open cystgastrostomy, laparoscopic cystgastrostomy
• How I would answer: If given a patient with persistent abdominal pain following pancreatitis and contained fluid collection on CT → Image ductal system FIRST (ERCP or MRCP), then if it’s been at least 6 weeks open or lap cystgastrostomy . Cystic Neoplasms of the Pancreas
• Many found incidentally on abdominal CTs done for other reasons → MRCP will provide better characterization and duct anatomy .
• EUS is helpful as well and allows for aspiration for cyst fluid analysis (CEA and Amylase)
• Management based on cyst characteristics and patient symptoms
• CEA >192 c/w mucinous cyst
• High amylase indicates ductal communication (pseudocyst or IPMN)
• Serous cystadenoma
• Predominantly benign
• Well circumscribed with characteristic central stellate scar on imaging
• Low CEA
• Resect only if symptomatic or growing on serial imaging
• Mucinous cystic neoplams (MCN)
• One of two mucinous lesions of the pancreas (along with IPMN)
• Have malignant potential
• Elevated CEA on FNA
• Radiographically: thick walled, single cyst with internal septations

• All MCNs should be resected in fit patients

• Intraductal Papillary Mucinous Neoplasm (IPMN)
• Classification: Main Duct IPMN and Branch Duct IPMN (Mixed type managed like MD)
• Main Duct IPMN — higher risk of malignancy than BD-IPMN
• Endoscopic visualization of mucin secreting from a patulous “fish mouth” papilla is pathognomonic for MD IPMN
• Surgical resection is recommended for all main duct and mixed type IPMNs
• Branch Duct IPMN — lower risk of malignancy than MD- IPMN
• Management based on Fukuoka guidelines
• Decision to resect based on fitness of patient for surgery, risk tolerance of patient, and individual cyst characteristics
• Consider resection for:
• “Worrisome Features” — cyst size >3cm, thickened cyst wall, nonenhancing mural nodules, lyphadenopathy, MPD >10mm, abrupt change in MPD size with distal atrophy
• EUS with mural nodules, main duct involvement, or suspicious cytology
• Young patient with cyst >2cm owing to cumulative risk of malignancy
• Age can indicate likely lesion
• Daughter → solid pseudopapillary
• Mother → mucinous
• Grandmother → serous

Neuroendocrine Tumors of the Pancreas (PNETs) Figure 2: PNET Distribution

• Comprise 1-2% of pancreatic tumors
• Frequently non-functional, but can also elaborate a number of bioactive peptides (gastrin, glucagon, somatostatin, insulin, VIP)
• If functional, clinical presentation is characteristic of hormone elaborated
• Nonfunctional pancreatic neuroendocrine tumor
• Majority (60-90%) of nonfunctional PNETs are malignant
• Most discovered late due to asymptomatic nature . Can be discovered incidentally or 2/2 symptoms from mass effect - Generally large at time of discovery with high metastasis rate
• MC in head of pancreas
• Tumors IN the head of the pancreas: insulINoma, gastrINoma, somatostatINoma

• Patients with locoregional disease should undergo resection

• Insulinoma
• Most common functional PNET
• Insulin secreted by beta-cells
• Most are benign (90%)
• Located throughout pancreas
• Associated with “Whipple Triad”
• Fasting hypoglycemia
• Neuroglycopenic symptoms (confusion, combativeness, seizures, visual changes, loss of consciousness)
• Relief of symptoms with administration of glucose
• Biochemical diagnosis and confirmation tests - If meet the below criteria, localization studies should be done
• Symptoms with plasma glucose <55mg/dL
• Insulin >18pmol/L
• C-peptide > 0 .6 ng/mL
• Proinsulin > 5 pg/mL
• Beta-hydroxybutyrate < 2 .7mmol/L
• An increase in plasma glucose of at least 25 mg/dL after administration of glucagon
• Localization studies
• 1 - Triphasic CT or MRI
• 2 - Endoscopic US
• 3 - If above unable to localize → Selective intra-arterial calcium injection with hepatic venous sampling for insulin
• Somatostatin scintigraphy is NOT effective
• Treatment
• Depends on location, suspicion for malignancy, and presence of other tumors
• Solitary, benign appearing tumors can be treated with enucleation
• Distal tumors may be treated with distal spleen preserving pancreatectomy

• Suspicion for malignancy requires formal resection

• Gastrinoma
• Gastrin stimulates acid secretion from parietal cells
• Mostly malignant (60-90%)
• 2/3rd are located in Gastrinoma Triangle, a triangle formed by:
• Junction of the cystic duct and CBD
• Junction of the 2nd and 3rd portions of the duodenum
• Junction of the neck and body of the pancreas
• Associated with classic triad (abdominal pain, diarrhea, weight loss) in the presence of PUD
• Diagnostic and confirmatory tests
• Elevated fasting serum gastrin level - must be with a low gastric pH or high basal acid output (as use of PPI or H2 blockers will raise gastrin levels)
• Fasting gastrin level >1000 pg/mL is diagnostic
• Elevated levels <1000 pg/mL → secretin stimulation test
• Gastrinoma will have a paradoxical effect from secretin (Increase >200 pg/mL with administration of secretin is diagnostic)
• Localization studies
• 1 . Triphasic CT or MRI
• 2 . Somatostatin receptor scintigraphy (SRS)
• 3 . EUS
• 4 . Possible selective intra-arterial calcium injection with hepatic venous sampling for gastrin (institution specific)
• Unable to localize → Exploration with the following maneuvers
• Intraoperative U/S
• Transduodenal palpation
• Intraoperative upper endoscopy with transduodenal illumination

• Duodenotomy with palpation

• Treatment
• Tumor in duodenal mucosa → enucleation and periduodenal lymph node dissection
• Noninvasive tumors 5cm or smaller in head of pancreas → enucleation with periduodenal lymph node dissection
• Tumors >5cm or invasive in head of pancreas → Whipple
• Tumor in body and tail → distal pancreatectomy
• Glucagonoma
• Glucagon secreted from alpha islet cells and acts on hepatocytes and adipose tissue to increase gluconeogenesis and glycogenolysis
• Mostly malignant (90%)
• MC location is tail of pancreas
• Associated with 4 D’s - dermatitis, diabetes, depression, and DVT
• DVT 2/2 a factor X-like antigen secreted by tumor
• Characteristic skin rash = necrolytic migratory erythema
• Diagnostic and confirmatory tests
• Glucose intolerance + fasting glucagon levels between 1,000-5,000 pg/mL
• Localization studies
• Triphasic CT or MRI
• Somatostatin receptor Scintigraphy
• EUS
• Selective visceral angiography
• Treatment
• Resection with regional lymphadenectomy (no enucleation due to high malignant potential

• Usually distal pancreatectomy

• What else is needed?
• Cholecystectomy (d/t possible need for prolonged somatostatin therapy)
• Somatostatinoma
• Somatostatin has a broad spectrum of inhibitory activity in the GI tract
• Mostly malignant
• MC location is head of pancreas (duodenal location also common)
• Associated with cholecystitis, DM, malabsorption, steatorrhea
• Localization studies
• Triphasic CT or MRI
• Somatostatin receptor scintigraphy
• EUS
• Selective arteriography
• Treatment
• Resection with regional lymphadenectomy (No enucleation due to high malignant potential)
• AND…?
• Cholecystectomy
• VIPoma
• VIP is neuropeptide that stimulates secretion of fluids and electrolytes into lumen, also inhibits gastric acid secretion
• Mostly malignant
• MC location is body or tail of pancreas (extra-pancreatic locations also possible: adrenal, retroperitoneum, mediastinum)
• Associated with WDHA syndrome (watery diarrhea, hypokalemia, achlorhydria)
• Diagnostic tests

• Elevated fasting VIP levels when diarrhea is present

• Localization studies
• Triphasic CT of MRI
• Somatostatin receptor scintigraphy
• EUS
• Selective arteriography
• Treatment
• Resection with regional lymphadenectomy (no enucleation due to high malignant potential
• AND???
• Cholecystectomy (d/t possibly need for prolonged somatostatin therapy) Table 21: High-Yield PNET Pancreatic Adenocarcinoma
• Risk factors: cigarette smoking, heavy ETOH use, chronic pancreatitis, increased BMI, longstanding DM
• Imaging
• Pancreatic protocol CT
• EUS can be complimentary to CT in patients with questionable involvement of lymph nodes or blood vessels
• PET/CT used selectively if suspicion for metastasis
• Role of staging laparoscopy? - Controversial . Used routinely by some, selectively by others only in patients at high risk for disseminated disease (borderline resectable, high CA 19-9, large primary tumor, large regional nodes, highly symptomatic)
• Biopsy?
• Pathologic diagnosis NOT required prior to resection
• Needed prior to neoadjuvant therapy or if unresectable, prior

to definitive chemotherapy

• Role of preoperative biliary drainage?
• No effect on survival; associated with increased wound infections rates
• For resectable disease and not undergoing neoadjuvant therapy → Consider only if significant pruritis, cholangitis, coagulopathic .
• For patients undergoing neoadjuvant therapy → drain if jaundiced
• What kind of stent?
• Self-expanding metal stents are preferred because they are easy to place without dilation, have longer patency than plastic stents, and do not interfere with resection
• Resectability
• Resectable
• No arterial tumor contact
• <180-degree contact with SMV or PV without vein contour irregularity
• Borderline Resectable
• Tumor contact with SMA or celiac <180 degrees
• Tumor contact with common hepatic only (no celiac or proper hepatic involvement) allowing for resection and reconstruction
• Involvement of SMV or PV that is amenable to resection and reconstruction
• Tumor contact with IVC
• Unresectable
• Distant metastasis

• 180-degree contact with SMA or celiac

• Unreconstructable involvement of SMV or PV
• Treatment

• Primary Surgery

• Distal tumors present late and are usually too advanced at time of diagnosis for resection → Distal pancreatectomy and splenectomy if resectable
• Head of pancreas tumor → pancreaticoduodenectomy (Whipple procedure)
• If found to be unresectable at time of operation → consider palliative biliary bypass, gastrojejunostomy, and/ or celiac plexus neurolysis depending on individual tumor characteristics and patient symptoms
• In absence of frank venous occlusion PV or SMV resection and reconstruction may be performed in order to obtain R0 resection
• Perioperative therapy
• Recurrence rates are high, even with R0 resection → Everyone gets adjuvant therapy
• FOLFIRINOX (FOLinic acid, Fluorouricil, IRINotecan, OXaliplatin)
• Neoadjuvant chemoradiation should be considered for those with borderline resectable disease (requires EUS with FNA for pathologic confirmation first) Quick Hits
• Patient with history of multiple episodes of pancreatitis now presents with hematemesis . Diagnosis and management?
• Gastric varices from splenic vein thrombosis
• Treatment = Splenectomy
• Patient with multiple branch duct IPMNs on imaging . There are multiple small benign appearing cysts throughout proximal pancreatic body with larger dominant one more distally with worrisome features . Management?
• Resect distal lesion, okay to leave smaller benign ones behind but will need surveillance
• 48-year-old patient incidentally diagnosed with 2cm branch chain IPMN on abdominal CT . Microcytic anemia noted on laboratory w/u . What else does he/she need as part of work up?
• Colonoscopy — IPMN patients have higher incidence of

extra-pancreatic malignancies (MC - Colon adenocarcinoma)

• Syndromes associated with PNETs?
• MEN I
• Usually multiple PNETs - can be functional or non- functional
• MC pancreatic tumor?
• Nonfunctional
• MC functional tumor?
• Gastrinoma
• Patient presents with episodes of fasting hypoglycemia and dizziness that resolves with glucose administration . C-peptide is checked and is low . Diagnosis?
• Exogenous (factitious) insulin administration
• Medical management of functional neuroendocrine tumors of pancreas?
• Octreotide; except for…Insulinoma
• Somatic mutations associated with pancreatic adenocarcinoma?
• KRAS, TP53, CDKN2A, SMAD4
• Biomarkers associated with pancreatic adenocarcinoma?
• Many, but CA 19-9 is best validated and most clinically useful
• During pancreaticoduodenectomy for pancreatic adenocarcinoma, a clinically positive lymph node is encountered outside the field of resection. Should you:
• A . Leave it alone
• B . Perform regional lymphadenectomy
• C . Sample the node but not perform complete regional lymphadenectomy
• Answer = C . Nodal metastasis are a marker of systemic disease and removal is unlikely to alter overall survival . Outside of a clinical trial a regional lymphadenectomy should not be performed during Whipple procedure .

Figures