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Pancreatic Cancer

By Elliot M. Livstone, MD, Emeritus Staff, Sarasota Memorial Hospital, Sarasota, FL

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Pancreatic cancer, primarily ductal adenocarcinoma, accounts for an estimated 53,670 cases and 43,090 deaths in the US annually (1). Symptoms include weight loss, abdominal pain, and jaundice. Diagnosis is by CT, endoscopic ultrasonography, and MRI. Treatment is surgical resection and adjuvant chemotherapy and radiation therapy. Prognosis is poor because disease is often advanced at the time of diagnosis.

Most pancreatic cancers are exocrine tumors that develop from ductal and acinar cells. Pancreatic endocrine tumors are discussed elsewhere.

Adenocarcinomas of the exocrine pancreas arise from duct cells 9 times more often than from acinar cells; 80% occur in the head of the gland. Adenocarcinomas appear at the mean age of 55 yr and occur 1.5 to 2 times more often in men.

Prominent risk factors for pancreatic cancer include smoking, a history of chronic pancreatitis, obesity, being male, and being black. Heredity plays some role. Alcohol and caffeine consumption do not seem to be risk factors.

General reference

Symptoms and Signs

Symptoms of pancreatic cancer such as pain and weight loss are nonspecific, leading to a later diagnosis by which time the disease has spread. By the time of diagnosis, 90% of patients have locally advanced tumors that have involved retroperitoneal structures, spread to regional lymph nodes, or metastasized to the liver or lung.

Most patients have severe upper abdominal pain, which usually radiates to the back. Weight loss is common. Adenocarcinomas of the head of the pancreas cause obstructive jaundice (which can cause pruritus) in 80 to 90% of patients. Cancer in the body and tail may cause splenic vein obstruction, resulting in splenomegaly, gastric and esophageal varices, and GI hemorrhage.

The cancer causes diabetes in 25 to 50% of patients, leading to symptoms of glucose intolerance (eg, polyuria and polydipsia). Pancreatic cancer can also interfere with production of digestive enzymes by the pancreas (pancreatic exocrine insufficiency) in some patients and with the ability to break down food and absorb nutrients (malabsorption). This malabsorption causes bloating and gas and a watery, greasy, and/or foul-smelling diarrhea, leading to weight loss and vitamin deficiencies.

Diagnosis

  • CT, endoscopic ultrasonography, or magnetic resonance cholangiopancreatography (MRCP)

  • CA 19-9 antigen to follow (not for screening)

(See also the U.S. Preventive Services Task Force’s summary of recommendations regarding screening for pancreatic cancer.)

The preferred tests are an abdominal helical CT using pancreatic technique, MRCP, or endoscopic ultrasonography. If these tests show apparent unresectable or metastatic disease, a percutaneous needle aspiration of an accessible lesion might be considered to obtain a tissue diagnosis. If CT shows a potentially resectable tumor or no tumor, MRCP or endoscopic ultrasound may be used to stage disease or detect small tumors not visible with CT. Patients with obstructive jaundice may have ERCP as the first diagnostic procedure.

Routine laboratory tests should be done. Elevation of alkaline phosphatase and bilirubin indicate bile duct obstruction or liver metastases. Pancreas-associated antigen CA 19-9 may be used to monitor patients diagnosed with pancreatic carcinoma and to screen those at high risk. However, this test is not sensitive or specific enough to be used for population screening. Elevated levels should drop with successful treatment; subsequent increases indicate progression. Amylase and lipase levels are usually normal.

Prognosis

Prognosis for pancreatic cancer varies with stage but overall is poor (5-yr survival: < 2%), because many patients have advanced disease at the time of diagnosis.

Treatment

  • Whipple procedure (pancreaticoduodenectomy)

  • Adjuvant chemotherapy and radiation therapy

  • Symptom control

About 80 to 90% of cancers are considered surgically unresectable at time of diagnosis because of metastases or invasion of major blood vessels. Depending on location of the tumor, the procedure of choice for resection of the cancer is most commonly a Whipple procedure (pancreaticoduodenectomy). Adjuvant therapy with gemcitabine plus capecitabine is now recommended (2) and external beam radiation therapy is typically given, resulting in about 40% 2-yr and 25% 5-yr survival. This combination is also used for patients with localized but unresectable tumors and results in median survival of about 1 yr. Gemcitabine and capecitabine and perhaps other newer drugs (eg, irinotecan, paclitaxel, oxaliplatin, carboplatin) may be more effective than 5-FU–based chemotherapy, but no drug, singly or in combination, is clearly superior in prolonging survival. Patients with hepatic or distant metastases may be offered chemotherapy as part of an investigational program, but the outlook is dismal with or without such treatment and some patients may choose to forego it.

If an unresectable tumor is found at operation and gastroduodenal or bile duct obstruction is present or pending, a double gastric and biliary bypass operation is usually done to relieve obstruction. In patients with inoperable lesions and jaundice, endoscopic placement of a bile duct stent relieves jaundice. However, surgical bypass should be considered in patients with unresectable lesions if life expectancy is > 6 to 7 mo because of complications associated with stents.

Symptomatic treatment

  • Analgesics, usually opioids

  • Sometimes procedures to maintain biliary patency

  • Sometimes pancreatic enzyme supplementation

Ultimately, most patients experience pain and die. Thus, symptomatic treatment is as important as controlling disease. Appropriate end-of-life care should be discussed (see also The Dying Patient).

Patients with moderate to severe pain should receive an oral opioid in doses adequate to provide relief. Concern about addiction should not be a barrier to effective pain control. For chronic pain, long-acting preparations (eg, transdermal fentanyl, oxycodone, oxymorphone) are usually best. Percutaneous or operative splanchnic (celiac) block effectively controls pain in some patients. In cases of intolerable pain, opioids given sc or by IV, epidural, or intrathecal infusion provides additional relief.

If palliative surgery or endoscopic placement of a biliary stent fails to relieve pruritus secondary to obstructive jaundice, pruritis can be managed with cholestyramine (4 g po once/day to qid).

Exocrine pancreatic insufficiency is treated with capsules of porcine pancreatic enzymes (pancrelipase). There are a number of commercial products available and the amount of enzyme per capsule varies. The dosage needed varies depending on the patient's symptoms, the degree of steatorrhea, and the fat content of the diet. Typically, patients should take enough enzyme supplement to supply about 25,000 to 40,000 IU of lipase before a typical meal and about 5,000 to 25,000 IU of lipase per snack. If a meal is prolonged (as in a restaurant), some of the tablets should be taken during the meal. Optimal intraluminal pH for the enzymes is 8; thus, some clinicians give a proton pump inhibitor or H2 blocker 2 times/day. Diabetes mellitus should be closely monitored and controlled.

Treatment reference

  • 2. Neoptolemos JP, Palmer DH, Ghaneh P, et al: Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): A multicentre, open-label, randomised, phase 3 trial. Lancet pii: S0140-6736(16)32409-6, 2017. doi: 10.1016/S0140-6736(16)32409-6.

Key Points

  • Pancreatic cancer is highly lethal, typically because it is diagnosed only at a late stage.

  • Prominent risk factors include smoking and a history of chronic pancreatitis; alcohol use does not seem to be an independent risk factor.

  • Diagnosis involves CT, endoscopic ultrasonography, and/or magnetic resonance cholangiopancreatography (MRCP); amylase and lipase levels are usually normal, and the CA 19-9 antigen is not sensitive or specific enough to be used for population screening.

  • About 80 to 90% of cancers are considered surgically unresectable at time of diagnosis because of metastases or invasion of major blood vessels.

  • Do a Whipple procedure when surgery is feasible and also give adjuvant chemotherapy and radiation therapy.

  • Control symptoms with adequate analgesia, gastric and/or biliary bypass to relieve symptoms of obstruction, and sometimes pancreatic enzyme supplements.

More Information

Cystadenocarcinoma

Cystadenocarcinoma is a rare adenomatous pancreatic cancer that arises as a malignant degeneration of a mucous cystadenoma and manifests as upper abdominal pain and a palpable abdominal mass.

Diagnosis of cystadenocarcinoma is made by abdominal CT or MRI, which typically shows a cystic mass containing debris; the mass may be misinterpreted as necrotic adenocarcinoma or pancreatic pseudocyst.

Unlike ductal adenocarcinoma, cystadenocarcinoma has a relatively good prognosis. Only 20% of patients have metastasis at the time of operation; complete excision of the tumor by distal or total pancreatectomy or by a Whipple procedure results in a 65% 5-yr survival.

Intraductal Papillary-Mucinous Tumor

Intraductal papillary-mucinous tumor is a tumor that results in mucus hypersecretion and ductal obstruction. Histology may be benign, borderline, or malignant. Most (80%) tumors occur in women and in the tail of the pancreas (66%).

Symptoms of intraductal papillary-mucinous tumor consist of pain and recurrent bouts of pancreatitis.

Diagnosis of intraductal papillary-mucinous tumor is made by CT, sometimes along with endoscopic ultrasonography, magnetic resonance cholangiopancreatography, or ERCP.

Surgical resection is the treatment of choice for patients with intraductal papillary-mucinous tumor with high-grade dysplasia who have progressed to invasive carcinoma or who have features that suggest a high risk of developing cancer. With surgery, 5-yr survival is > 95% for benign or borderline cases, but 50 to 75% for malignant tumors.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • ACTIQ, DURAGESIC, SUBLIMAZE
  • ELOXATIN
  • CAMPTOSAR
  • PANCREAZE
  • GEMZAR
  • XELODA
  • TAXOL
  • No US brand name
  • OXYCONTIN