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Pancreatic Cancer (Adenocarcinoma)

Pathology || Risk Factors || Signs and Symptoms || Diagnosis || Treatment
Overview || Related Articles || References and Resources
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Pathology





In order to understand pancreatic cancer we have to first appreciate the pancreatic tissue itself. The pancreas is composed of different types of cells with different functions. The first functional category of the pancreas is called the "endocrine pancreas". It is arranged in clusters of cells known as the "islets of Langerhans". The cells within the islets secrete insulin, glucagon, and somatostatin into the blood stream. Occasionally, tumors can develop from these cells (ie: insulinomas, glucagonomas, etc.), but they are outside the scope of this discussion.

The second main division of the pancreas is the "exocrine pancreas". Its purpose is to secrete enzymes into the digestive tract to aid in the digestion of food. These enzymes are secreted into empty spaces known as "acini", which then drain down ducts into the intestine. The cells that make up those ducts - columnar epithelium - are the cells that develop into what is commonly called pancreatic cancer, or more appropriately, pancreatic adenocarcinoma (ie: in general, adenocarcinoma refers to cancers that arise from the cells that line ducts).

Pancreas Anatomy

The ductal cells become cancerous because of genetic mutations, either inherited or acquired, in tumor suppressors and/or oncogenes.

Commonly mutated genes in pancreatic adenocarcinoma include the oncogene K-ras, and the tumor suppressors p16 and SMAD4; however, many other mutations are also known to exist, and many cancerous cells have multiple mutations.

Regardless of which genes are involved, the end result is the same - uncontrollable cell division leading to cancerous growth.

Pancreatic cancer is most commonly found in the "head" of the pancreas, which is the part closest to its intestinal drainage site. Approximately 67% of cases occur in the head, with the remaining 33% occurring in either the body or the tail of the pancreas.

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Risk Factors

There are several risk factors for pancreatic cancer. Smoking, diabetes mellitus, alcohol use (chronic and heavy), chronic pancreatitis, diets rich in fats and meats are all risk factors. In addition, African Americans are more likely than whites to get pancreatic adenocarcinomas; and males are more likely than females.

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Signs and Symptoms

Pancreatic adenocarcinoma is commonly known as a "silent killer." This is because when symptoms of pancreatic cancer develop it is often late in the disease.

The classically taught symptom of pancreatic cancer is painless jaundice. Jaundice refers to yellowing of the skin and eyes from increased levels of bilirubin (a breakdown product of red blood cells) in the blood. In pancreatic cancer this is due to compression of the common bile duct by tumor. This results in impaired bile flow from the gallbladder and liver. The backup of bile in the body, of which bilirubin is a component, causes the jaundice. The backup of bile also causes itching (ie: pruritis); this is secondary to bile acids depositing underneath the skin. Finally, if bile is unable to make it into the intestine, fecal matter will often appear a light gray color since bile components give poop its brown coloration.

Many patients also develop a dull abdominal pain that can radiate to the back. The bulk majority of patients lose a significant amount of weight, which is a symptom of many cancers. In addition, about a third of patients develop Courvoisier's sign, which refers to a gallbladder that can be felt through the abdomen on physical exam.

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Diagnosis

Pancreatic Adenocarcinoma CT

If pancreatic adenocarcinoma is suspected many tests are ordered to confirm the diagnosis.

The first test that is usually ordered is a CT scan of the abdomen (see image). This will often show the tumor in the head of the pancreas. Ultrasound of the pancreas is also often performed. An invasive procedure known as endoscopic retrograde cholangiopancreatography (ERCP) can be done to rule out obstruction of the common bile duct; it can also be used to obtain cells for analysis by the pathologists to confirm the diagnosis.

Other blood tests are also commonly ordered. They include bilirubin levels, which are often elevated if compression of the bile duct has occurred. Alkaline phosphatase, which measures bile duct damage can also be elevated. Liver function tests (LFTs) are also commonly ordered. Finally, a tumor marker known as Ca-19-9 (carbohydrate antigen 19-9) is also commonly sent. It is not diagnostic of pancreatic cancer, and is more useful in determining recurrence after treatment.

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Treatment

Treatment of pancreatic cancer is highly dependent on the stage of the disease. Staging pancreatic cancer is based on three important elements: size of the primary tumor, lymph node involvement, and metastatic disease. A highly simplified version for staging pancreatic adenocarcinoma is given below:

Stage 1 and stage 2 cancers are amenable to surgical resection. The procedure that is usually done for cancer in the head of the pancreas is called the "Whipple procedure". It involves removing the gallbladder, a portion of the stomach, head of the pancreas, and a portion of the duodenum.

Stage 3 cancer is treated with chemotherapy and palliative surgery (ie: designed to treat symptoms and not cure the cancer). This includes procedures designed to stent open the bile duct to control jaundice and pruritis. In addition, if the duodenum is blocked by tumor an anastomosis (surgically made connection) between the stomach and jejunum (second part of the small intestine) can be done to allow movement of food through the GI tract.

Treatment for stage 4 cancer is similar to stage 3 cancer. It involves palliative procedures as well as chemotherapy.

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Overview

Pancreatic adenocarcinoma is a cancer of the duct cells that line the exocrine pancreas. It most commonly occurs in the head of the pancreas. It is usually diagnosed late in the disease course after tumor has spread and compressed adjacent anatomical structures like the common bile duct. Symptoms include weight loss, muscle wasting, jaundice, and pruritus (itching). Diagnosis is made by imaging studies and more invasive procedures like ERCP. Treatment is dependent on tumor stage, but includes surgery and/or chemotherapy.

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Related Articles

- Barrett's esophagus

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References and Resources

(1) Galasso D, Carnuccio A, Larghi A. Pancreatic cancer: diagnosis and endoscopic staging. Eur Rev Med Pharmacol Sci. 2010 Apr;14(4):375-85.

(2) Squadroni M, Fazio N. Chemotherapy in pancreatic adenocarcinoma. Eur Rev Med Pharmacol Sci. 2010 Apr;14(4):386-94.

(3) Maisonneuve P, Lowenfels AB. Epidemiology of pancreatic cancer: an update. Dig Dis. 2010;28(4-5):645-56. Epub 2010 Nov 18.

(4) Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. Seventh Edition. Philadelphia: Elsevier Saunders, 2004.

(5) Blackbourne LH. Surgical Recall, Fifth North American Edition (Recall Series). Fifth Edition. Philadelphia: Lippincott Williams and Wilkins, 2009.

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