Pancreatic Adenocarcinoma

How to Cite This Chapter: Serrano P, Dąbrowski A, Jurkowska G, Wereszczyńska-Siemiątkowska U, Wysocki WM. Pancreatic Adenocarcinoma. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed May 22, 2024.
Last Updated: March 31, 2022
Last Reviewed: March 31, 2022
Chapter Information

Definition and PathogenesisTop

The most common form (80%) is pancreatic ductal adenocarcinoma (PDAC), usually located in the head (65%), less often in the body or tail (25%); the disease is multifocal in ~10% of cases.

Risk factors: Smoking (the risk increases with the number of cigarettes smoked), obesity (increase in body mass index [BMI] by 5 kg/m2 is accompanied by a relative risk increase of ~10%), diabetes, chronic pancreatitis (especially hereditary pancreatitis, which increases risk 50-70 times), infections (Helicobacter pylori, hepatitis B virus [HBV], hepatitis C virus [HCV]), high consumption of butter, saturated fats, processed foods, red meat (high fruit and vegetable intake reduces the risk), exposure to chemicals (including chlorinated bicarbonate solvents, nickel and chromium compounds, silica dust, pesticides), genetic predisposition: familial pancreatic cancer (in families without a confirmed diagnosis of genetic syndromes associated with pancreatic cancer), hereditary syndromes: Peutz-Jeghers syndrome, genetic neoplastic syndromes (hereditary breast or ovarian cancer [related particularly to the BRCA gene mutation], familial atypical multiple mole melanoma [FAMMM] syndrome, Lynch syndrome, familial adenomatous polyposis [FAP], ataxia-telangiectasia syndrome, Li-Fraumeni syndrome, von Hippel-Lindau syndrome, Fanconi anemia).

Clinical Features and Natural HistoryTop

Early in the disease the manifestations are nonspecific: abdominal discomfort, flatulence, anorexia, weight loss (later cachexia), diarrhea, nausea. Late, more specific signs and symptoms may include obstructive jaundice (caused by compression of the common bile duct by pancreatic head cancer or by metastatic lesions in the hepatoduodenal ligament lymph nodes [eg, in advanced cancer of the pancreatic body or tail]), pruritus, epigastric pain or back/shoulder pain, vomiting, Courvoisier sign (enlarged, palpable, nonpainful gallbladder in a patient with jaundice; occurs in 10%-30% of patients), diabetes or impaired glucose tolerance (the development of diabetes, especially in persons aged >50 years, requires differentiation with pancreatic cancer), acute pancreatitis (this precedes the diagnosis of pancreatic cancer in 13% of patients), deep vein thrombosis, migratory thrombophlebitis (Trousseau syndrome), gastrointestinal bleeding, splenomegaly, gastric outlet obstruction, ascites, depressed mood, depression, exhaustion.

Pancreatic cancer is a highly aggressive cancer characterized by rapid local growth and a high tendency for invasion of adjacent organs and vessels. It metastasizes to the peritoneum, lymph nodes, liver, and distant organs.


Diagnostic Tests

1. Laboratory tests: In patients with early pancreatic cancer, laboratory test results are usually normal. In more advanced stages features of cholestasis are found: conjugated hyperbilirubinemia, elevated serum levels of alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) (in ~50% of patients), anemia, hypoalbuminemia; elevated serum carbohydrate antigen (CA) 19-9 levels (this assay has inadequate [particularly in small tumors] and specificity [levels are elevated in patients with cholestasis regardless of the cause; it is important mainly in the diagnostic workup of pancreatic cancer recurrence after resection]).

2. Imaging tests:

1) Ultrasonography allows for detection of only relatively large tumors (solid, hypoechoic in relation to the surrounding pancreatic parenchyma). It is not suitable for screening purposes or for staging, as a normal result does not exclude pancreatic cancer.

2) Multiphase computed tomography (CT) of the abdomen and pelvis with IV contrast medium, performed according to the specific pancreas CT protocol, is the most important diagnostic method; it allows for cancer detection and stage assessment (large vessel infiltration, metastases in regional lymph nodes, and distant metastases).

3) Endoscopic ultrasonography (EUS) is the recommended method in diagnosing focal lesions in the pancreas, especially small tumors (it is more sensitive than CT). EUS is used to perform fine-needle aspiration biopsy (FNAB) without a significant risk of dissemination, for assessment of local and regional tumor staging, particularly vascular invasion, and for prediction of lesion resectability. It is also useful if the CT image is inconclusive.

4) Magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP): The sensitivity and specificity of contrast-enhanced MRI is similar to multiphase CT; however, CT is preferred. MRI/MRCP allows for noninvasive assessment of the bile ducts and the pancreatic duct (including areas outside the obstruction site) and assessment of liver lesions (ie, metastases) when CT is inconclusive.

5) Endoscopic retrograde cholangiopancreatography (ERCP) is not recommended as a diagnostic test, but it is indicated in the case of simultaneous therapeutic intervention (eg, stenting of the obstructed common bile duct in unresectable pancreatic cancer, cholangitis, or in the case of delay of planned resection by >2 weeks).

6) In order to detect possible metastases of cancer to the lungs, chest radiography or CT of the chest is performed.

Screening in Persons at Increased Risk of Pancreatic Cancer

Pancreatic cancer screening by EUS, MRI, or both should be considered in:

1) People with ≥2 relatives with pancreatic cancer, of whom one is a first-degree relative.

2) People with Peutz-Jeghers syndrome.

3) People with a CDKN2A genetic mutation.

4) Carriers of BRCA1, BRCA2, or PALB2 mutations with ≥1 first-degree relative with pancreatic cancer.

5) People with Lynch syndrome with ≥1 first degree relative with pancreatic cancer.

6) People with hereditary pancreatitis.

American Gastroenterological Association (AGA) experts suggest that the screening should start at the age of 50 years or 10 years earlier than the age of earliest pancreatic cancer case in the family. In carriers of the CDKN2A or PRSS1 mutation with hereditary pancreatitis, screening should commence at the age of 40 years, and in the case of Peutz-Jeghers syndrome, 30 to 35 years.

If no pancreatic lesion is found, a repeat examination should be considered in 12 months. If a lesion is found, the decision on the frequency of subsequent examinations or surgical treatment should be made by an interdisciplinary team, depending on the radiographic image of the lesion.

Diagnostic Criteria

Diagnosis and staging is based on imaging (pancreas multiphase CT protocol, EUS, and MRI/MRCP). In the case of a resectable tumor, histologic diagnosis is not required prior to surgery. In patients planned for neoadjuvant therapy and those who are not surgical candidates, cytologic confirmation of the diagnosis is necessary before starting palliative chemotherapy (eg, FNAB of a pancreatic tumor [through the abdominal wall or during EUS]). BAC also allows for the differentiation with acute or chronic pancreatitis.

Differential Diagnosis

Acute and chronic pancreatitis, lymphoma and other pancreatic neoplasms or metastases to the pancreas (including lung cancer, kidney cancer), cholangiocarcinoma, ampullary carcinoma, duodenal carcinoma.


The role of imaging is to distinguish between resectable, borderline resectable, and unresectable pancreatic cancer (ie, locally advanced or systemically disseminated). Therapeutic decisions are based on the assessment of resectability and the general condition of the patient.

1. Surgical treatment: Pancreatic resection is the only curative treatment in pancreatic cancer (possible in 15%-20% of patients); pancreaticoduodenectomy using the Whipple method (removal of the head of the pancreas, gallbladder, common bile duct, duodenum, and pyloric portion of the stomach) or the Traverso method (sparing the pylorus), complete resection of the pancreas (eg, when the tumor is multifocal), or resection of the pancreatic body and tail only and of the spleen (distal pancreatectomy: for left-sided pancreatic tumors).

Adjuvant chemotherapy is recommended following surgery (8-12 weeks after resection). The preferred regimen of chemotherapy is the modified FOLFIRINOX regimen (in patients with good performance status, Eastern Cooperative Oncology Group [ECOG] scale score 0-1; more information on the ECOG scale: or gemcitabine in combination with capecitabine. Alternatively, gemcitabine or 5-fluorouracil with calcium folinate as monotherapy can be considered.

In borderline resectable tumors, systemic preoperative chemotherapy is used following FNAB and confirmation of the diagnosis, to improve the chances of a margin-negative resection. After reassessment (CT or MRI of the abdominal cavity and pelvis and chest radiography or CT), the possibility of resection is considered.

2. Treatment of unresectable tumors:

1) Chemotherapy: The modified FOLFIRINOX regimen or gemcitabine with nab-paclitaxel is used in patients in a good general condition (ECOG 1), and gemcitabine monotherapy, capecitabine, or fluorouracil, in those in a poor general condition.

2) Symptomatic treatment: Pharmacologic pain management (according to the analgesic ladder: see Pain Management: Basic Principles); in some patients, EUS-guided (preferably) or percutaneous celiac plexus neurolysis is useful to control pain.

3) Treatment of obstructive jaundice: Endoscopic biliary stenting.

4) Treatment of exocrine pancreatic insufficiency: see Chronic Pancreatitis.

5) Thromboprophylaxis: see Venous Thromboembolism: Primary Prevention.


The prognosis depends on the cancer stage at diagnosis and on its differentiation. Complete resection is possible only in <20% of patients. After surgery performed in a specialist center, 10% to 25% of patients survive 5 years.

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