Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 39-08: Carcinoma of the Pancreas & Ampulla of Vater + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Obstructive jaundice (may be painless) Enlarged gallbladder (may be painful) Upper abdominal pain with radiation to back, weight loss, and thrombophlebitis are usually late manifestations +++ General Considerations ++ Adenocarcinomas Most common pancreatic neoplasm About 75% are in the head and 25% in the body and tail Pancreatic carcinomas comprise 2% of all cancers and 5% of cancer deaths Neuroendocrine tumors account for 1–2% of pancreatic neoplasms Majority of pancreatic cancers originate from pancreatic intraepithelial neoplasias, which measure < 5 mm in diameter and can only be seen with a microscope Cystic neoplasms Only 1% of pancreatic cancers May be mistaken for pseudocysts Should be suspected when a cystic lesion in the pancreas is found in the absence of a history of pancreatitis Serous cystadenomas are benign However, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, solid pseudopapillary tumors, and cystic islet cell tumors may be malignant Mucinous cystic neoplasms and intraductal papillary mucinous neoplasms account for 15–30% of pancreatic cancers Adenocarcinoma staging is by the TNM classification Tis: carcinoma in situ T1a: tumor limited to the pancreas, ≤ 0.5 cm in greatest dimension T1b: tumor > 0.5 cm and < 1 cm T1c: tumor 1–2 cm T2: tumor limited to the pancreas, > 2 cm and ≤ 4 cm in greatest dimension T3: tumor > 4 cm in greatest dimension T4: tumor involves the celiac axis, superior mesenteric artery, or common hepatic artery regardless of size N1: metastasis to one to three regional lymph nodes N2: metastasis to four or more regional lymph nodes M1: distant metastasis +++ Demographics ++ Risk factors for pancreatic carcinoma Age Obesity Tobacco use Heavy alcohol use Chronic pancreatitis Diabetes mellitus Prior abdominal radiation Family history Gastric ulcer (possibly) Exposure to arsenic, cadmium About 7–8% of pancreatic cancer patients have a first-degree relative with pancreatic cancer, compared with 0.6% of control subjects + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Pain Present in over 70% Often vague and diffuse Located in the epigastrium when lesion is in the pancreatic head or body; or located in the left upper quadrant when lesion is in the tail Radiation into the back is common and sometimes predominates Sitting up and leaning forward may afford some relief, which usually indicates extrapancreatic spread and inoperability Diarrhea, perhaps from maldigestion, is an occasional early symptom Weight loss commonly occurs late and may be associated with depression Occasionally, acute pancreatitis or new-onset diabetes mellitus is the presentation Jaundice is usually due to biliary obstruction in the pancreatic head A palpable gallbladder is indicative of obstruction by neoplasm (Courvoisier law), but there are frequent exceptions A hard, fixed, occasionally tender mass may be present In advanced cases, a hard periumbilical (Sister Mary Joseph's) nodule (lymph node) may be palpable Migratory thrombophlebitis is a rare sign Hyperglycemia and decreases in subcutaneous abdominal fat and serum lipid levels have been reported to precede a diagnosis of pancreactic cancer +++ Differential Diagnosis ++ Choledocholithiasis Pancreatic pseudocyst or cystic neoplasm Carcinoma of the biliary tract Biliary stricture Hepatocellular carcinoma Primary sclerosing cholangitis Primary biliary cholangitis + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Mild anemia may be present Glycosuria, hyperglycemia, and impaired glucose tolerance or true diabetes mellitus (10–20% of cases) Serum amylase or lipase level is occasionally elevated Liver chemistries may suggest obstructive jaundice Steatorrhea in the absence of jaundice is uncommon Occult blood in the stool is suggestive of ampulla of Vater carcinoma (the combination of biliary obstruction and bleeding may give the stools a distinctive silver appearance) CA 19-9, with a sensitivity of 70% and a specificity of 87%, is not useful for early detection; increased values are also found in acute and chronic pancreatitis and cholangitis +++ Imaging Studies ++ Ultrasonography is not reliable because of interference by intestinal gas Multiphase thin-cut helical CT Detects a mass in over 80% of cases Can delineate the extent of the tumor and allow for percutaneous fine-needle aspiration for cytologic studies MRI is an alternative to CT Positron emission tomography appears to be a sensitive technique for detecting pancreatic cancer and metastases +++ Diagnostic Procedures ++ Endoscopic ultrasonography More sensitive than CT in diagnosing pancreatic cancer and equivalent to CT for determining nodal involvement and resectability Can guide fine-needle aspiration or biopsy for tissue diagnosis, tumor markers, and DNA analysis Endoscopic retrograde cholangiopancreatography (ERCP) may clarify an ambiguous CT or MRI scan by Delineating the pancreatic duct system Confirming an ampullary or biliary neoplasm Magnetic resonance cholangiopancreatography (MRCP) is as sensitive as ERCP in diagnosing pancreatic cancer Pancreatoscopy or intraductal ultrasonography Can evaluate filling defects in the pancreatic duct Can assess resectability of intraductal papillary mucinous tumors With obstruction of the splenic vein, splenomegaly or gastric varices are present; the latter are detected by endoscopy, endoscopic ultrasonography, or angiography Selective mesenteric arteriography May demonstrate superior mesenteric artery invasion by a tumor, thus its inoperability In general, has been replaced by multiphase helical CT Cystic neoplasms can be distinguished by their appearance on CT, endoscopic ultrasonography, and ERCP and features of the cyst fluid on gross, cytologic, and genetic analysis + Treatment Download Section PDF Listen +++ +++ Medications ++ Combined irradiation and chemotherapy may be used for palliation of unresectable cancer confined to the pancreas Adjuvant chemotherapy with gemcitabine, 5-fluorouracil, or gemcitabine with capecitabine is superior to no adjuvant therapy Gemcitabine with capecitabine and a modified FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) regimen have been found to be superior to gemcitabine alone The role of adjuvant chemoradiation is controversial but often used in the United States Neoadjuvant chemotherapy with or without radiation is increasingly being used to downstage patients and in those with resectable cancer Common chemotherapy regimens for this purpose include FOLFIRINOX and gemcitabine with albumin-bound (nab)-paclitaxel Chemotherapy has been disappointing in metastatic pancreatic cancer, although improved response rates have been reported with FOLFIRINOX and with the combination of gemcitabine and nab-paclitaxel. In patients who have received prior chemotherapy, 5-fluorouracil and leucovorin, in combination with nanoliposomal irinotecan, has resulted in improved survival compared with 5-fluorouracil and leucovorin alone In patients with a BRCA1 or BRCA2 germline mutation, olaparib, a poly(adenosine diphosphate-ribose) polymerase inhibitor, has been reported to improve progression-free survival in metastatic pancreatic cancer +++ Surgery ++ In up to 30% of cases, abdominal exploration is necessary when cytologic diagnosis cannot be made or if resection is attempted If a mass is localized in the head of the pancreas and there is no jaundice, laparoscopy may detect tiny peritoneal or liver metastases and therefore nonresectability in about 4–13% of patients Radical pancreaticoduodenal (Whipple) resection is indicated only for cancers strictly limited to the head of the pancreas, periampullary zone, and duodenum Surgical resection is indicated for all mucinous cystic neoplasms, symptomatic serous cystadenomas, and cystic tumors > 2 cm in diameter that remain undefined after helical CT, endoscopic ultrasound, and diagnostic aspiration +++ Therapeutic Procedures ++ When resection is not feasible, endoscopic stenting of the bile duct, or surgical biliary bypass, is performed to relieve jaundice A surgical duodenal bypass is also done if duodenal obstruction is expected to develop later Alternatively, endoscopic placement of a self-expandable duodenal stent may be feasible Photodynamic therapy is under study + Outcome Download Section PDF Listen +++ +++ Prognosis ++ Lesions that are < 1 cm in diameter and nonfunctioning without evidence of local invasion or metastasis may be followed expectantly Adenocarcinoma of the pancreas, especially in the body or tail, has a poor prognosis 80–85% of patients present with advanced unresectable disease Reported 5-year survival rates range from 2% to 5% Jaundice and lymph node involvement are adverse prognostic factors Lesions of the ampulla have a better prognosis, with reported 5-year survival rates of 20–40% after resection Pancreatic cystic neoplasms have a better prognosis than pancreatic adenocarcinoma In very carefully selected patients, resection of cancer of the pancreatic head (Whipple procedure) is feasible and sometimes results in reasonable survival rates In a person whose disease progresses with treatment, meticulous efforts at palliative care are essential Celiac plexus nerve block or thoracoscopic splanchnicectomy may improve pain control +++ Prevention ++ In persons with a family history of pancreatic cancer in at least two first-degree relatives, or with a genetic syndrome associated with an increased risk of pancreatic cancer, screening with endoscopic ultrasonography and helical CT or MRI/MRCP should be considered beginning at age 40–45 or 10 years before the age at which pancreatic cancer was first diagnosed in a family member +++ When to Refer ++ All patients +++ When to Admit ++ Patients who require surgery and other interventions + References Download Section PDF Listen +++ + +Canto MI et al. Risk of neoplastic progression in individuals at high risk for pancreatic cancer undergoing long-term surveillance. Gastroenterology. 2018 Sep;155(3):740–51. [PubMed: 29803839] + +Conroy T et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018 Dec 20;379(25):2395–406. [PubMed: 30575490] + +Elta GH et al. ACG Clinical Guideline: diagnosis and management of pancreatic cysts. Am J Gastroenterol. 2018 Apr;113(4):464–79. [PubMed: 29485131] + +Goggins M et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020 Jan;69(1):7–17. [PubMed: 31672839] + +Hamada T et al. Prediagnosis use of statins associates with increased survival times of patients with pancreatic cancer. Clin Gastroenterol Hepatol. 2018 Aug;16(8):1300–6. [PubMed: 29474971] + +Jin J. JAMA patient page. Screening for pancreatic cancer. JAMA. 2019 Aug 6;322(5):478. [PubMed: 31386136] + +Khalaf N et al. Regular use of aspirin or non-aspirin nonsteroidal anti-inflammatory drugs is not associated with risk of incident pancreatic cancer in two large cohort studies. Gastroenterology. 2018 Apr;154(5):1380–90. [PubMed: 29229401] + +Lennon AM et al. Screening for pancreatic cancer—is there hope? JAMA Intern Med. 2019;179(10):1313–5. [PubMed: 31386154] + +Neoptolemos JP et al. Therapeutic developments in pancreatic cancer: current and future perspectives. Nat Rev Gastroenterol Hepatol. 2018 Jun;15(6):333–48. [PubMed: 29717230] + +Sah RP et al. Phases of metabolic and soft tissue changes in months preceding a diagnosis of pancreatic ductal adenocarcinoma. Gastroenterology. 2019 May;156(6):1742–52. [PubMed: 30677401] + +US Preventive Services Task Force; Owens DK et al. Screening for pancreatic cancer: US Preventive Services Task Force reaffirmation recommendation statement. JAMA. 2019 Aug 6;322(5):438–44. [PubMed: 31386141]