Exocrine Pancreatic Neoplasms

Pancreatic Ductal Adenocarcinoma

1. Epidemiology
• ~ 57,600 cases in the U.S.
• 4th most common cause of cancer deaths in the U.S.
• 90% of patients die within one year of diagnosis
• 5-year survival < 5%
• risk factors: blacks > whites, males > females, smokers > nonsmokers


2. Pathogenesis
1. Environmental Causes
• smokers have up to a threefold risk of developing pancreatic cancer
• obese patients also have 3X the risk
• less clear risk factors are alcohol abuse, chronic pancreatitis, diabetes


2. Hereditary Risk Factors
• between 5% and 10% of patients with pancreatic cancer have a familial form
• 20% of hereditary pancreatic cancer is associated with known genetic syndromes: hereditary pancreatitis (PRSS1), BRCA2, Lynch syndrome, familial atypical mole and melanoma (CDKN2A)
• the remaining 80% do not have an identifiable genetic syndrome (familial pancreatic cancer)


3. Pathology
• originates from pancreatic duct cells
• majority (75%) occur in the head of the pancreas, the rest in the body and tail
• may be impossible to distinguish pancreatic head cancer from ampullary carcinoma, duodenal carcinoma, and distal common bile duct carcinoma


1. Distal Common Duct Carcinoma
• 2nd most common periampullary cancer
• 5-year survival rates between 20% to 40% after resection


2. Ampulla of Vater Carcinoma
• 3rd most common periampullary cancer
• found earlier than pancreatic cancers because they cause obstructive jaundice earlier
• 5-year survival rates between 35% to 55% after resection


3. Duodenal Carcinoma
• rare; accounts for 5% of periampullary cancers
• has the most favorable prognosis: 5-year survival rates between 40% to 60% after resection


4. Clinical Manifestations
1. Symptoms
• jaundice, weight loss (20 lb), and abdominal pain are the most common symptoms
• vomiting is uncommon early on, but if present suggests duodenal obstruction
• cholangitis occurs in ~ 10%
• new-onset diabetes is diagnosed in ~ 20%
• back pain suggests involvement of the celiac plexus
• duodenal and ampullary tumors may cause intermittent GI bleeding and anemia


2. Signs
• jaundice is the most common finding
• hepatomegaly occurs in 65% and usually represents enlargement secondary to bile obstruction
• a palpable gallbladder (Courvoisier’s sign) suggests malignant obstruction and occurs in 25% of patients
• a palpable abdominal mass and ascites suggest advanced disease
• a Virchow’s node or Blumer’s shelf are evidence of metastatic disease


5. Diagnosis
1. Laboratory Evaluation
• serum bilirubin and alkaline phosphatase are usually markedly elevated
• prothrombin time may be elevated secondary to vitamin k malabsorption
• hypoalbuminemia represents malnutrition
• CA 19-9 is the most reliable tumor marker with a sensitivity and specificity of ~ 80%


2. Imaging
1. CT Scan with Pancreatic Protocol
• accurately determines the level of biliary obstruction, relationship of the tumor to critical vascular structures, and presence of regional or metastatic disease
• tumor is best seen as a hypoattenuated lesion in the portal venous phase
• MRCP may be substituted if the patient has a contrast allergy or renal insufficiency


1. Resectable Tumors
• localized to the pancreas
• no encasement, abutment, distortion or thrombus involving the SMV or portal vein
• preserved fat plane surrounding the SMA, hepatic artery, and celiac branches







2. Borderline Resectable Tumors
• SMV/portal vein distortion or occlusion that is technically reconstructable
• abutment of the SMA or common hepatic arteries ( < 180° contact)
• historically, these lesions were considered unresectable
• now, with vascular reconstruction, many patients can undergo an oncologic resection with reasonable morbidity and mortality
• these patients benefit from neoadjuvant therapy







3. Locally Advanced Tumors
• unreconstructable SMV/PV involvement
• > 180° encasement of the SMA or common hepatic artery
• these patients also benefit from neoadjuvant therapy, and if they have sufficient downstaging, may become surgical candidates







4. Unresectable Tumors
• liver metastases or peritoneal implants
• ascites
• lymph node metastases outside the resection field


2. ERCP
• can be used to obtain brush cytology biopsies, but the yield is low
• preoperative stenting does not decrease operative morbidity and mortality


3. EUS
• FNA provides an accurate tissue diagnosis
• can provide valuable information about the relationship of the tumor to the mesenteric vessels


4. PET-CT
• may be useful in resolving potentially metastatic lesions seen on other imaging


6. Staging
1. Imaging
• preoperative resectability is primarily based on imaging findings
• resected specimens are staged using the TNM system


2. Laparoscopy
• goal is to reduce the number of nontherapeutic laparotomies
• valuable in patients at high risk of occult disease: tumors > 3 cm, CA 19-9 > 1000 U/mL, uncertain findings on CT, or body or tail tumors


7. Surgical Resection
1. Preoperative Preparation
• patients need an assessment of their general medical condition
• some patients will require a period of nutritional repletion
• coagulopathies should be corrected, usually by vitamin K administration
• every patient should have a mechanical and antibiotic bowel prep


2. Determination of Resectability
• initial maneuver is to assess for intra-abdominal metastases: liver metastases, serosal implants and lymph node metastases (hepatic artery, celiac axis nodes) outside the resection area indicate incurable disease
• Kocher maneuver is performed, elevating the duodenum and head of the pancreas off the vena cava and aorta
• superior mesenteric artery is palpated to ensure that it is not encased by the tumor
• neck of the pancreas must be elevated off the superior mesenteric and portal veins
• the tumor should be biopsied only if it is unresectable


3. procedures
1. Pancreaticoduodenectomy
• the classic Whipple resection involves resection of the pancreatic head, duodenum, proximal jejunum, common bile duct and gallbladder
• the pylorus-sparing Whipple resection preserves the gastric antrum, pylorus, and proximal duodenum
• requires 3 anastomoses: pancreaticojejunostomy, hepaticojejunostomy, and gastrojejunostomy (or duodenojejunostomy)
• the pylorus-sparing procedure is associated with less dumping, diarrhea, and bile reflux gastritis than the standard Whipple procedure, but may be associated with a higher incidence of delayed gastric emptying
• 5-year survival rates are equivalent between the two procedures
• most feared complication is a pancreatic leak (5% to 20%), with overall morbidity of 30% to 50%
• perioperative mortality is < 2% in major centers



1. Extent of Lymphadenectomy
• standard Whipple resection removes peripancreatic, portal, and pyloric lymph nodes
• extended lymphadenectomy adds hilar and celiac nodes
• no randomized trial has shown improved survival after the extended procedure


2. Pancreaticoduodenectomy with PV/SMV Resection
• allows for R0 or R1 resection of borderline resectable tumors
• if there is no SMA involvement, PV or SMV invasion does not carry a worse prognosis than tumors with no vein involvement
• limited SMV/PV involvement can be tangentially excised and repaired primarily or with a vein patch
• if segmental venous resection is required, and end-to-end primary repair is often possible
• if a tension-free primary anastomosis cannot be done, then an interposition graft with the internal jugular vein or left renal vein will be necessary
• PTFE should not be used because of the high incidence of postoperative thrombosis







3. Total Pancreatectomy
• procedure reserved for the rare instances when the tumor extends across the pancreatic neck
• also, the potential morbidity of a pancreatic leak is avoided
• however, all patients require exogenous pancreatic enzymes and insulin
• 5-year survival rates are not better than the Whipple procedure


4. Distal Pancreatectomy
• tumors in the body and tail are rarely resectable secondary to locally advanced or metastatic disease
• exploratory laparoscopy should precede any attempt at resection
• involvement of the celiac axis is a contraindication to resection
• resection will require en bloc splenectomy


8. Surgical Complications
1. Delayed Gastric Emptying
• occurs in 5% to 15% of Whipple procedures
• defined as an inability to tolerate a normal diet after one week postop
• must rule out a pancreatic leak or intraabdominal abscess
• anastomotic stricture must be ruled out by imaging or endoscopy
• nutrition is by the feeding jejunostomy or TPN while awaiting stomach function to return


2. Pancreatic Leak
• major source of morbidity after a Whipple procedure
• patients with soft glands and small pancreatic ducts are at higher risk
• defined as drain amylase > 3 times serum on or after POD 3
• method of pancreaticojejunostomy or the use of stents does not influence the incidence of fistulas
• prophylactic use of octreotide does not reduce fistulas
• low volume fistulas do not require any change in the normal postoperative plan
• high volume fistulas may require additional drains, NPO, TPN, and octreotide
• most leaks close spontaneously within 4 weeks
• rarely, repair or revision of the pancreatic anastomosis will be necessary


3. Postoperative Hemorrhage
• bleeding within the first 24 – 48 hours requires a return to the OR
• late bleeding may present as shock, blood from intraabdominal drains, or hematemesis/melena and is frequently associated with a pancreatic leak
• results from a pseudoaneurysm from the GDA stump or mesenteric artery branch
• late bleeding is best evaluated and treated with angiography and embolization


9. Adjuvant and Neoadjuvant Therapy
1. Chemotherapy and Radiation
• 6 months of postoperative gemcitabine or 5-FU is standard
• many centers also add radiation
• 25% of patients will not receive adjuvant therapy because of surgical complications, inability to recover physiologically, or refusal


2. Neoadjuvant Therapy
• potential advantages include higher therapy completion rates, tumor downstaging with higher R0 resection rates, and decreased risk of positive lymph nodes
• for clearly resectable patients, there is no level 1 evidence that neoadjuvant therapy is superior to the surgery first approach
• has become standard for borderline resectable and locally advanced patients


10. Palliation
• 80% to 85% of patients at presentation will not be candidates for surgical resection
• biliary obstruction, gastric outlet obstruction, and pain will require palliation, ideally nonoperatively


1. Biliary Obstruction
• ERCP with metal stent placement is 90% successful
• if ERCP is unsuccessful, PTC with stent internalization will be required
• at laparotomy, if the patient is not resectable, then a hepaticojejunostomy or cholecystojejunostomy will relieve jaundice


2. Duodenal Obstruction
• 20% of locally advanced patients will develop gastric outlet obstruction
• endoscopic stents provide good short-term results, but do not provide long term patency
• at laparotomy, unresectable patients should have a preventive gastrojejunostomy as well as a biliary bypass (double bypass)







3. Pain
• affects most patients with advanced pancreatic cancer
• palliation of pain is mandatory for optimizing the patient’s quality of life
• most patients will require long-acting narcotics
• celiac nerve blocks can be done in the IR suite
• celiac nerve blocks can also be done at the time of laparotomy if the patient is unresectable