Pancreatic Cancer

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

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

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

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

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