- Anal Cancer
- Benign Esophageal Tumors
- Colorectal Cancer
- Colorectal Cancer Screening
- Esophageal Cancer
- Familial Adenomatous Polyposis
- Gastrointestinal Stromal Tumors (GISTs)
- Lynch Syndrome
- MUTYH Polyposis Syndrome
- Pancreatic Cancer
- Peutz-Jeghers Syndrome
- Polyps of the Colon and Rectum
- Small-Bowel Tumors
- Stomach Cancer
Pancreatic cancer is most commonly caused by ductal adenocarcinoma. Symptoms include weight loss, abdominal pain, and jaundice. Diagnosis is by CT or MRI/magnetic resonance cholangiopancreatography (MRCP), and then endoscopic ultrasound with biopsy. Treatment is a combination of surgical resection and chemotherapy. In some instances, radiation therapy is also used. Prognosis is poor because disease is often advanced at the time of diagnosis.
Pancreatic cancer, primarily ductal adenocarcinoma, accounts for an estimated 66,440 cases and 51,750 deaths in the United States annually (1). 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 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, obesity, 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.
Reference
Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024 [published correction appears in CA Cancer J Clin. 2024 Mar-Apr;74(2):203. doi: 10.3322/caac.21830.]. CA Cancer J Clin. 2024;74(1):12-49. doi:10.3322/caac.21820
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). 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 ultrasound with fine-needle aspiration (EUS/FNA) biopsy
CA 19-9 antigen for monitoring (not for screening)
The preferred tests are an abdominal CT using pancreatic technique (triple-phase protocol, imaging slices ≤ 5 mm) or MRI/MRCP; these are followed by endoscopic ultrasound 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 ultrasound may be used to stage disease or detect small tumors not visible with CT.
Patients with obstructive jaundice may have endoscopic retrograde cholangiopancreatography (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 performed. 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, or BRCA2 or HNPCC mutations) (1). 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.
Screening for cancer of the pancreas should be considered in patients with genetic syndromes associated with an increased risk of pancreatic cancer, including all patients with the following (1):
Hereditary pancreatitis
CDKN2A gene mutation
1 or more first-degree relatives with pancreatic cancer with Lynch syndrome
Mutations in BRCA1, BRCA2, PALB2, and ATM genes
Individuals at average risk of developing pancreatic cancer should not be screened. Screening in this high-risk population begins either at age 50 or 10 years prior to the youngest age of initial family onset (whichever is youngest). Exceptions include CKDN2A and PRSS1 mutation carriers with hereditary pancreatitis (age 40) and Peutz-Jeghers syndrome (age 35). Annual MRI is typically used, with endoscopic ultrasound (EUS) performed for indeterminate or high-risk lesions identified on screening MRI .
Diagnosis reference
1. Aslanian HR, Lee JH, Canto MI. AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review. Gastroenterology. 2020;159(1):358-362. doi:10.1053/j.gastro.2020.03.088
Treatment of Pancreatic Cancer
Surgical resection (pancreaticoduodenectomy)
Neoadjuvant chemotherapy or combination chemotherapy and radiation therapy (chemoradiation)
Symptom control
Approximately 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 performed. Tumors in the head of the pancreas are removed with a Whipple procedure (resection of the pancreatic head, duodenum, proximal jejunum, common bile duct, gallbladder, and a segment of the stomach). Tumors in the neck, body, or tail are generally removed with distal pancreatectomy, wherein the head of the pancreas is left in situ.
For borderline resectable disease, neoadjuvant (preoperative) chemotherapy or chemoradiation has become increasingly utilized owing to the aggressive nature of this disease subset and data supporting improved oncologic outcomes. Data from a randomized trial showed an overall survival benefit in borderline resectable patients who received neoadjuvant chemotherapy compared with those who underwent upfront surgery (1).
The preferred regimens for neoadjuvant or adjuvant therapy are FOLFIRINOX (fluorouracil, oxaliplatin, leucovorin, and irinotecan) or gemcitabine plus nanoparticle albumin-bound paclitaxel (nab) paclitaxel. In a pivotal trial, the FOLFIRINOX regimen yielded a median overall survival of 54 months after surgical resection of ductal adenocarcinoma that was significantly longer when compared with gemcitabine (The preferred regimens for neoadjuvant or adjuvant therapy are FOLFIRINOX (fluorouracil, oxaliplatin, leucovorin, and irinotecan) or gemcitabine plus nanoparticle albumin-bound paclitaxel (nab) paclitaxel. In a pivotal trial, the FOLFIRINOX regimen yielded a median overall survival of 54 months after surgical resection of ductal adenocarcinoma that was significantly longer when compared with gemcitabine (2). Another trial found a similar overall survival when comparing perioperative use of the FOLFIRINOX regimen with nab-paclitaxel (median overall survival of 23.2 months with FOLFIRINOX compared with 23.6 months with ). Another trial found a similar overall survival when comparing perioperative use of the FOLFIRINOX regimen with nab-paclitaxel (median overall survival of 23.2 months with FOLFIRINOX compared with 23.6 months withgemcitabine and nab-paclitaxel) (3).
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 performed. 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.
Symptomatic treatment
Analgesics, usually opioids
Sometimes procedures to maintain biliary patency
Sometimes pancreatic enzyme supplementation
Many patients with pancreatic cancer experience substantial pain. Thus, symptomatic treatment is as important as controlling disease. Appropriate end-of-life care should also be discussed given the high mortality rate associated with the disease (see also The Dying Patient).
Patients with moderate to severe pain should receive an oral opioid in doses adequate to provide relief (4). 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.). 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). 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. 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.
Treatment references
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
4. Coveler AL, Mizrahi J, Eastman B, et al; Precision Promise Consortium. Pancreas Cancer-Associated Pain Management. Oncologist. 2021 Jun;26(6):e971-e982. doi: 10.1002/onco.13796
Prognosis for Pancreatic Cancer
Prognosis for pancreatic cancer varies with stage but is generally poor because many patients have advanced disease at the time of diagnosis. In a population-based study, the 5-year survival was found to be below 5% despite improvement of survival for a subset of patients who underwent surgical resection (1).
Prognosis reference
1. Bengtsson A, Andersson R, Ansari D. The actual 5-year survivors of pancreatic ductal adenocarcinoma based on real-world data. Sci Rep. 2020 Oct 2;10(1):16425. doi: 10.1038/s41598-020-73525-y
Key Points
Pancreatic cancer has a high mortality rate, 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 ultrasound 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.
Approximately 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
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. Degeneration of a pancreatic cystadenoma is rare, approximating 1 to 3% of cases of serous cystic neoplasms (1).
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. Surgical resection is generally recommended for serous cystic neoplasms of the pancreas, which are > 4 cm or have worrisome or high-risk imaging features because of their risk of malignant transformation. Once degenerated to cystadenocarcinoma, disease progression and management is similar to that of ductal adenocarcinoma.
Cystadenocarcinoma reference
1. Van Dyke TJ, Johlin FC, Bellizzi AM, Howe JR. Serous Cystadenocarcinoma of the Pancreas: Clinical Features and Management of a Rare Tumor. Dig Surg. 2016;33(3):240-248. doi:10.1159/000444721
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 3 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. 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 that has progressed to invasive carcinoma or who have features that suggest a high risk of developing cancer. The updated Fukuoka guidelines are commonly used to guide the management of IPMNs (1). In general, "high-risk stigmata," including a main pancreatic duct > 1 cm, an enhancing mural nodule > 5 mm, or obstructive jaundice, warrants consideration of surgical resection. Worrisome imaging features (cyst > 3 cm, enhancing mural nodule < 5 mm, thickened or enhancing cyst wall, main duct size 5 to 9 mm, abrupt main duct cutoff with distal gland atrophy, lymphadenopathy, elevated serum CA19-9, cyst growth > 5 mm/year for 2 years) prompts examination by endoscopic ultrasound with cyst fluid cytology. Surgery is then recommended if cytology confirms cancer, or if endoscopic ultrasound identifies features concerning for malignancy, including definite mural nodules > 5 mm or main duct involvement of the cyst.
For patients with underlying cancer, postoperative systemic therapy is similar to that for pancreatic adenocarcinoma.
Intraductal papillary-mucinous neoplasm reference
1. Tanaka M, Fernández-Del Castillo C, Kamisawa T, J, et al. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology. 2017 Sep-Oct;17(5):738-753. doi: 10.1016/j.pan.2017.07.007
Key Points
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 mass.
Diagnosis of cystadenocarcinoma is made by abdominal CT or MRI.
Unlike pancreatic ductal adenocarcinoma, cystadenocarcinoma has a relatively good prognosis and is typically treated surgically.
Intraductal papillary-mucinous neoplasms (IPMNs) are cystic neoplasms that result in mucus hypersecretion and ductal obstruction.
Histology of IPMN may be benign, borderline, or malignant.
IPMNs are broadly classified into 3 types: main duct, branch duct, and mixed type.
Symptoms of IPMN consist of pain and recurrent bouts of pancreatitis.
Diagnosis of IPMN is made by cross-sectional imaging (CT or MRI).
Surgical resection is usually the treatment of choice for patients with IPMN that has progressed to invasive carcinoma or for patients who have high risk features for malignancy.
