Most pancreatic cancers are exocrine tumors that develop from ductal and acinar cells. Pancreatic endocrine tumors Overview of Pancreatic Endocrine Tumors Pancreatic endocrine tumors arise from islet and gastrin-producing cells and often produce many hormones. Although these tumors develop most often in the pancreas, they may appear in other organs... read more 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 years and occur 1.5 to 2 times more often in men. Acinar cell carcinoma is a rare cause of pancreatic cancer. It has a better prognosis than traditional ductal adenocarcinoma.
Prominent risk factors for pancreatic cancer include smoking, a history of chronic pancreatitis Chronic Pancreatitis Chronic pancreatitis is persistent inflammation of the pancreas that results in permanent structural damage with fibrosis and ductal strictures, followed by a decline in exocrine and endocrine... read more , obesity Obesity Obesity is a chronic, multifactorial, relapsing disorder characterized by excess body weight and defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders... read more , and chemical exposures (eg, beta-naphthylamine, benzidine, asbestos, benzene, chlorinated hydrocarbons). Alcohol and caffeine consumption do not seem to be risk factors.
Heredity plays some role; 10% of pancreatic cancers are associated with an underlying genetic component. Genetic testing is now offered routinely to all patients diagnosed with pancreatic cancer.
Symptoms and Signs of Pancreatic Cancer
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 gastrointestinal hemorrhage.
Pancreatic cancer causes diabetes in up to half 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 Overview of Malabsorption Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport. Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats)... read more ). This malabsorption causes bloating and gas and a watery, greasy, and/or foul-smelling diarrhea, leading to weight loss and vitamin deficiencies.
Diagnosis of Pancreatic Cancer
CT or magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP), followed by endoscopic ultrasonography with fine-needle aspiration (EUS/FNA) biopsy
CA 19-9 antigen to follow (not for screening)
The preferred tests are an abdominal helical CT using pancreatic technique (triple-phase protocol, imaging slices ≤ 5 mm) or MRI/MRCP; these are followed by endoscopic ultrasonography with fine-needle aspiration (EUS/FNA) biopsy for tissue diagnosis and to assess surgical resectability. CT or MRI/MRCP is typically chosen based on local availability and expertise. Even if these imaging tests show apparent unresectable or metastatic disease, EUS/FNA or a percutaneous needle aspiration of an accessible lesion is done to obtain a tissue diagnosis. If CT shows a potentially resectable tumor or no tumor, MRI/MRCP or endoscopic ultrasonography may be used to stage disease or detect small tumors not visible with CT.
Patients with obstructive jaundice may have endoscopic retrograde cholangiopancreatography Endoscopic retrograde cholangiopancreatography (ERCP) Imaging is essential for accurately diagnosing biliary tract disorders and is important for detecting focal liver lesions (eg, abscess, tumor). It is limited in detecting and diagnosing diffuse... read more (ERCP) as the first diagnostic procedure. In ERCP, often a stent is placed to relieve the biliary obstruction and allow administration of any preoperative treatments.
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 (eg, those with hereditary pancreatitis; ≥ 2 first-degree family members with pancreatic cancer, Peutz-Jeghers syndrome Peutz-Jeghers Syndrome Peutz-Jeghers syndrome is an autosomal dominant disease with multiple hamartomatous polyps in the stomach, small bowel, and colon along with distinctive pigmented skin lesions. Most (66 to 94%)... read more , or BRCA2 or HNPCC Lynch Syndrome Lynch syndrome is an autosomal dominant disorder responsible for 2 to 3% of cases of colorectal cancer ( 1). Symptoms, initial diagnosis, and treatment are similar to other forms of colorectal... read more mutations). However, this test is not sensitive or specific enough to be used for population screening, the CA 19-9 level is not always elevated in patients with proven pancreatic cancer (ie, nonproducers). Elevated levels should drop with successful treatment; subsequent increases indicate progression. Amylase and lipase levels are usually normal.
Treatment of Pancreatic Cancer
Whipple procedure (pancreaticoduodenectomy)
Neoadjuvant chemotherapy or combination chemotherapy and radiation therapy (chemoradiation)
About 80 to 90% of cancers are considered surgically unresectable at time of diagnosis because of metastases or invasion of major blood vessels.
For patients undergoing resective surgery, the location of the tumor in the pancreas determines the type of procedure that is done. Tumors in the head of the pancreas are removed with a Whipple procedure. Tumors in the neck, body, or tail are generally removed with distal pancreatectomy, wherein the head of the pancreas is left in situ.
Use of neoadjuvant (preoperative) chemotherapy or chemoradiation has become increasingly popular because of the aggressive nature of this disease and because of patient difficulty tolerating chemotherapy after pancreatic surgery. Data from a recent study suggest that neoadjuvant chemotherapy showed a survival benefit in borderline resectable patients (1 Treatment references Pancreatic cancer, primarily ductal adenocarcinoma, accounts for an estimated 64,050 cases and 50,550 deaths in the United States annually ( 1). Symptoms include weight loss, abdominal pain... read more ). In another study, the FOLFIRINOX regimen (fluorouracil, oxaliplatin, leucovorin, and irinotecan) yielded a median overall survival of 54 months after surgical resection and set the new standard for chemotherapy among highly selected patients with pancreatic cancer (2 Treatment references Pancreatic cancer, primarily ductal adenocarcinoma, accounts for an estimated 64,050 cases and 50,550 deaths in the United States annually ( 1). Symptoms include weight loss, abdominal pain... read more ). A second common regimen is gemcitabine combined with nab-paclitaxel (nanoparticle albumin-bound paclitaxel), which was shown in another study to be similarly effective as the FOLFIRINOX regimen when used perioperatively (median overall survival of 23.2 months with FOLFIRINOX compared with 23.6 months with gemcitabine and nab-paclitaxel) (3 Treatment references Pancreatic cancer, primarily ductal adenocarcinoma, accounts for an estimated 64,050 cases and 50,550 deaths in the United States annually ( 1). Symptoms include weight loss, abdominal pain... read more ).
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. Duodenal stenting is frequently done. However, surgical bypass should be considered in patients with unresectable lesions if life expectancy is > 6 to 7 months because of complications associated with stents.
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 The Dying Patient Dying patients can have needs that differ from those of other patients. So that their needs can be met, dying patients must first be identified. Before death, patients tend to follow 1 of 3... read more ).
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 subcutaneously 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, pruritus can be managed with cholestyramine (4 g orally once a day to 4 times a day).
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. Optimal intraluminal pH for the enzymes is 8; thus, some clinicians give a proton pump inhibitor or H2 blocker twice a day.
Diabetes mellitus should be closely monitored and controlled.
1. Versteijne E, van Dam JL, Suker M, et al: Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin Oncol 40(11):1220-1230, 2022. doi: 10.1200/JCO.21.02233
2. Conroy T, Hammel P, Hebbar M, et al: FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med 379(25):2395-2406, 2018. doi: 10.1056/NEJMoa1809775
3. Sohal DPS, Duong M, Ahmad SA, et al: Efficacy of Perioperative Chemotherapy for Resectable Pancreatic Adenocarcinoma: A Phase 2 Randomized Clinical Trial. JAMA Oncol 7(3):421-427, 2021. doi: 10.1001/jamaoncol.2020.7328. Clarification and additional information. JAMA Oncol 23:e215278, 2021. doi: 10.1001/jamaoncol.2021.5278
Prognosis for Pancreatic Cancer
Prognosis for pancreatic cancer varies with stage but overall is poor (5-year survival: < 2%), because many patients have advanced disease at the time of diagnosis.
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.
Diagnosis involves CT or magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) and endoscopic ultrasonography with biopsy; 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.
Combination surgery and chemotherapy offers the best oncologic outcomes for patients who are candidates for resective surgery.
Control symptoms with adequate analgesia, gastric and/or biliary bypass to relieve symptoms of obstruction, and sometimes pancreatic enzyme supplements.
Cystadenocarcinoma is a rare adenomatous pancreatic cancer that arises as a malignant degeneration of a mucinous 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-year survival.
Intraductal Papillary-Mucinous Neoplasms
Intraductal papillary-mucinous neoplasms (IPMN) are cystic neoplasms that result 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%).
IPMNs are broadly classified into three types: main duct, branch duct, and mixed type.
Main duct IPMN is diagnosed when the tumor involves the main pancreatic duct. This usually results in main duct dilation (often to > 10 mm) as well as extrusion of mucin through the sphincter of Oddi. Main duct IPMN carries a high risk of underlying cancer, and people are routinely offered surgical resection when diagnosed.
Branch duct IPMN is a result of neoplastic involvement of a side duct of the main pancreatic duct. These tumors do not lead to dilation of the main pancreatic duct. Unlike main duct IPMN, branch duct IPMN harbor a variable risk of cancer, and the decision to operate or survey the tumor is based on a series of imaging and endoscopic tests (often with biopsy and cyst fluid analysis). If surveillance is offered, it is usually a combination of imaging and endoscopic ultrasound.
Mixed-type IPMN has characteristics of both main duct and branch duct IPMN, namely resulting in dilation of both the main duct and its associated branch ducts. Mixed-type IPMN harbor the same malignancy risk profile as main duct IPMN and are treated similarly with surgical resection.
Symptoms of IPMN consist of pain and recurrent bouts of pancreatitis Overview of Pancreatitis Pancreatitis is classified as either acute or chronic. Acute pancreatitis is inflammation that resolves both clinically and histologically. Chronic pancreatitis is characterized by histologic... read more . Often, they are seen incidentally on cross-sectional imaging that is done for other reasons.
Diagnosis of IPMN is made by cross-sectional imaging (CT or MRI). Often, endoscopic ultrasound with aspiration and cytology is used adjunctively to clarify the diagnosis. A classic finding on endoscopy that indicates main duct IPMN is a fish-mouth appearance caused by extrusion of mucin from the sphincter of Oddi.
Surgical resection is the treatment of choice for patients with IPMN with high-grade dysplasia who have progressed to invasive carcinoma or who have features that suggest a high risk of developing cancer. For patients with underlying cancer, postoperative systemic therapy is similar to that for pancreatic adenocarcinoma.
With surgery, 5-year survival is > 95% for benign or borderline cases, but 50 to 75% for malignant tumors.
Drugs Mentioned In This Article
|Drug Name||Select Trade|
|Adrucil, Carac, Efudex, Fluoroplex, Tolak|
|No brand name available|
nanoparticle albumin-bound paclitaxel
|ABSTRAL, Actiq, Duragesic, Fentora, IONSYS, Lazanda, Onsolis, Sublimaze, SUBSYS|
|Dazidox , Endocodone , ETH-Oxydose, Oxaydo, OXECTA, OxyContin, Oxydose , OxyFast, OxyIR, Percolone, Roxicodone, Roxybond, XTAMPZA|
|Numorphan, Opana, Opana ER|
|Locholest , Locholest Light, Prevalite , Questran, Questran Light|
|Cotazym S , Creon, Creon 10, Creon 20, Creon 5, Dygase, Kutrase, Ku-Zyme , Ku-Zyme HP, Lapase , Lipram, Lipram-CR, Lipram-PN, Lipram-UL, Palcaps , Pancrease, Pancrease MT, Pancreaze, Pancrecarb MS, Pancron, Pangestyme CN, Pangestyme EC, Pangestyme MT, Pangestyme UL, Panocaps, Panocaps MT, Panokae-16, Panokase , Pertzye, Plaretase, Ultracaps MT, Ultrase, Ultrase MT12, Ultrase MT18, Ultrase MT20, Ultresa, Viokace 10, Viokace 20, Viokase, Viokase 16, Viokase 8, Zenpep|