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Pancreatic Cancer

Pancreatic Carcinoma

Overview

Pancreatic cancer arises when cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a tumor. These cancer cells have the ability to invade other parts of the body. There are a number of types of pancreatic cancer. The most common, pancreatic adenocarcinoma, accounts for about 85% of cases, and the term "pancreatic cancer" is sometimes used to refer only to that type. These adenocarcinomas start within the part of the pancreas which make digestive enzymes. Several other types of cancer, which collectively represent the majority of the non-adenocarcinomas, can also arise from these cells. One to two in every hundred cases of pancreatic cancer are neuroendocrine tumors, which arise from the hormone-producing cells of the pancreas. These are generally less aggressive than pancreatic adenocarcinoma.

Pancreatic cancer usually doesn't cause symptoms right away, but can cause yellowing of the skin and eyes, pain in the abdomen and back, weight loss, and fatigue. Some risk factors for developing pancreatic cancer include smoking, long-term diabetes, chronic pancreatitis, and certain hereditary disorders. Because pancreatic cancer is often found late and it spreads quickly, it can be hard to treat. Possible treatments include surgery, radiation, and chemotherapy.

Symptoms - Pancreatic Cancer

Signs and symptoms of pancreatic cancer often don't occur until the disease is advanced. When signs and symptoms do appear, they may include:

  • Upper abdominal pain that may radiate to your back 
  • Yellowing of your skin and the whites of your eyes (jaundice) 
  • Loss of appetite 
  • Weight loss 
  • Depression 
  • Blood clots
  • Bowel obstruction
  • Diabetes

Causes - Pancreatic Cancer

The exact cause of pancreatic cancer is unknown.  

Evidence suggests that pancreatic cancer is linked to inhalation or absorption of the following carcinogens, which are then excreted by the pancreas: cigarettes, food additives, industrial chemicals, such as beta-naphthalene, benzidine, and urea. Possible predisposing factors are chronic pancreatitis, diabetes mellitus, and chronic alcohol abuse (both pancreatitis and diabetes mellitus may be early manifestations of the disease as well). Pancreatic cancer incidence increases with age, peaking between ages 60 and 70. Geographically, the incidence is highest in Israel, the United States, Sweden, and Canada. A small number of cases are related to genetic syndromes that are passed down through families.

Prevention - Pancreatic Cancer

Apart from not smoking, the American Cancer Society recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains, while decreasing consumption of red and processed meat, although there is no consistent evidence this will prevent or reduce pancreatic cancer specifically. A 2014 review of research concluded that there was evidence that consumption of citrus fruits and curcumin reduced risk of pancreatic cancer, while whole grains, folate, selenium, and non-fried fish possibly also had a beneficial effect.

In the general population, screening of large groups is not currently considered effective, although newer techniques, and the screening of tightly targeted groups, are being evaluated. Nevertheless, regular screening with endoscopic ultrasound and MRI/CT imaging is recommended for those at high risk from inherited genetics.

 

Diagnosis - Pancreatic Cancer

The symptoms at diagnosis vary according to the location of the cancer in the pancreas, which anatomists divide (from left to right on most diagrams) into the thick head, the neck, and the tapering body, ending in the tail.

Medical imaging techniques, such as computed tomography (CT scan) and endoscopic ultrasound (EUS) are used both to confirm the diagnosis and to help decide whether the tumor can be surgically removed ( "resectability"). Magnetic resonance imaging (MRI) and positron emission tomography may also be used.  Abdominal ultrasound is less sensitive and will miss small tumors, but can identify cancers that have spread to the liver and build-up of fluid in the peritoneal cavity (ascites). It may be used for a quick and cheap first examination before other techniques.

A biopsy by fine needle aspiration, often guided by endoscopic ultrasound, may be used where there is uncertainty over the diagnosis, but a histologic diagnosis is not usually required for removal of the tumor by surgery.

Liver function tests can show a combination of results indicative of bile duct obstruction (raised conjugated bilirubin, γ-glutamyl transpeptidase and alkaline phosphatase levels). CA19-9 (carbohydrate antigen 19.9) is a tumor marker that is frequently elevated in pancreatic cancer. However, it lacks sensitivity and specificity, not least because 5% of people lack the Lewis (a) antigen and cannot produce CA19-9. It has a sensitivity of 80% and specificity of 73% in for detecting pancreatic adenocarcinoma, and is used for following known cases rather than diagnosis.

Histologic examination of the tissue: The most common form of pancreatic cancer (adenocarcinoma) is typically characterized by moderately to poorly differentiated glandular structures on microscopic examination. There is typically considerable desmoplasia or formation of a dense fibrous stroma or structural tissue consisting of a range of cell types (including myofibroblasts, macrophages, lymphocytes and mast cells) and deposited material (such as type I collagen and hyaluronic acid). 

Prognosis - Pancreatic Cancer

Pancreatic cancer is a difficult disease. Even for surgically resectable (and therefore potentially curable) tumors, the risk of cancer recurrence and subsequent death remains high. Only about 20% of patients undergoing a Whipple procedure for potentially curable pancreatic cancer live five years, with the rest surviving on average less than two years. For patients with incurable (locally advanced unresectable or metastatic) pancreatic cancer, survival is even shorter; typically it is measured in months. 

Treatment - Pancreatic Cancer

Treatment for pancreatic cancer depends on the stage and location of the cancer as well as on your age, overall health and personal preferences. The first goal of pancreatic cancer treatment is to eliminate the cancer, when possible. When that isn't an option, the focus may be on preventing the pancreatic cancer from growing or causing more harm. When pancreatic cancer is advanced and treatments aren't likely to offer a benefit, your doctor will help to relieve symptoms and make you as comfortable as possible.

Surgery may be an option if your pancreatic cancer is confined. Operations include:

  • Surgery for tumors in the pancreatic head. if located in the head of the pancreas, you may consider an operation called a Whipple procedure (pancreatoduodenectomy).

    The Whipple procedure involves removing the head of your pancreas, as well as a portion of your small intestine (duodenum), your gallbladder and part of your bile duct. Part of your stomach may be removed as well. Your surgeon reconnects the remaining parts of your pancreas, stomach and intestines to allow you to digest food.

    Whipple surgery carries a risk of infection and bleeding. After the surgery, some people experience nausea and vomiting that can occur if the stomach has difficulty emptying (delayed gastric emptying).

    Expect a long recovery after a Whipple procedure. You'll spend several days in the hospital and then recover for several weeks at home.

  • Surgery for tumors in the pancreatic tail and body. Surgery to remove the tail of the pancreas or the tail and a small portion of the body is called distal pancreatectomy. Your surgeon may also remove your spleen. Surgery carries a risk of bleeding and infection. 
     

Radiation therapy uses high-energy beams, such as X-rays, to destroy cancer cells. You may receive radiation treatments before or after cancer surgery, often in combination with chemotherapy. Or, your doctor may recommend a combination of radiation and chemotherapy treatments when your cancer can't be treated surgically.

Chemotherapy can also be combined with radiation therapy (chemoradiation). Chemoradiation is typically used to treat cancer that has spread beyond the pancreas, but only to nearby organs and not to distant regions of the body. This combination may also be used after surgery to reduce the risk that pancreatic cancer may recur.

In people with advanced pancreatic cancer, chemotherapy may be used alone or it may be combined with targeted drug therapy.

Targeted therapy:

  • Paclitaxel protein - bound particles (Abraxane) FDA-approved indication: Treatment of metastatic adenocarcinoma of the pancreas as first-line treatment, in combination with gemcitabine.
  • Liposomal irinotecan (Onivyde)  FDA-approved indication: For use in combination with 5-fluorouracil and leucovorin, for the treatment of patients with metastatic adenocarcinoma of the pancreas that has progressed following gemcitabine-based therapy.



Resources - Pancreatic Cancer

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