Pancreatic cancer

Pancreatic cancer is a malignant tumor within the pancreatic gland. Each year about 33,000 individuals in the United States are diagnosed with this condition, and more than 60,000 in Europe. Depending on the extent of the tumor at the time of diagnosis, the prognosis is generally regarded as poor, with few victims still alive five years after diagnosis, and complete remission still extremely rare.^[1]

About 95 percent of pancreatic tumors are adenocarcinomas (M8140/3). The remaining 5 percent include other tumors of the exocrine pancreas (e.g., serous cystadenomas), acinar cell cancers, and pancreatic neuroendocrine tumors (such as insulinomas, M8150/1, M8150/3). These tumors have a completely different diagnostic and therapeutic profile, and generally a more favorable prognosis.^[1]

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Signs and symptoms

Presentation

Early diagnosis of pancreatic cancer is difficult because the symptoms are so non-specific and varied. Common symptoms include pain in the upper abdomen that typically radiates to the back and is relieved by leaning forward (seen in carcinoma of the body or tail of the pancreas), loss of appetite, significant weight loss and painless jaundice related to bile duct obstruction (carcinoma of the head of the pancreas). All of these symptoms can have multiple other causes. Therefore, pancreatic cancer is often not diagnosed until it is advanced.

Jaundice occurs when the tumor grows and obstructs the common bile duct, which runs partially through the head of the pancreas. Tumors of the head of the pancreas (approximately 60% of cases) are more likely to cause jaundice by this mechanism.

Trousseau sign, in which blood clots form spontaneously in the portal blood vessels, the deep veins of the extremities, or the superficial veins anywhere on the body, is sometimes associated with pancreatic cancer.

Clinical depression has been reported in association with pancreatic cancer, sometimes presenting before the cancer is diagnosed. However, the mechanism for this association is not known.^[2].

Predisposing factors

Risk factors for pancreatic cancer include:^[3]

• Age
• Male gender
• African ethnicity^[4]
• Smoking
• Diets high in meat
• Obesity
• Diabetes mellitus
• Chronic pancreatitis has been linked, but is not known to be causal
• Helicobacter pylori infection
• Occupational exposure to certain pesticides, dyes, and chemicals related to gasoline
• Family history, including autosomal recessive ataxia-telangiectasia and autosomal dominantly inherited mutations in the BRCA2 gene, Peutz-Jeghers syndrome due to mutations in the STK11 tumor suppressor gene, hereditary non-polyposis colon cancer (Lynch syndrome), familial adenomatous polyposis, and the familial atypical multiple mole melanoma-pancreatic cancer syndrome (FAMMM-PC) due to mutations in the CDKN2A tumor suppressor gene.^[5][1]
• Gingivitis or periodontal disease.^[6]

Diagnosis

Courvoisier sign defines the presence of jaundice and a painlessly distended gallbladder as strongly indicative of pancreatic cancer, and may be used to distinguish pancreatic cancer from gallstones.

Pancreatic cancer is usually discovered during the course of the evaluation of aforementioned symptoms. Liver function tests may 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.

Imaging studies, such as ultrasound or abdominal CT may be used to identify tumors. Endoscopic ultrasound (EUS) is another procedure that can help visualize the tumor and obtain tissue to establish the diagnosis.

Recent research indicates that in pancreatic cancer malignancies, the tumor contains markedly higher levels of certain microRNAs (miRNA) than does the patient's benign pancreatic tissue or that found in other healthy pancreases.^{[citation needed]} This paves the way for two possibilities: 1) a more early but likely expensive genetic and biochemical molecular screening test profile, which would be an innovation in this cancer; and 2) also possible new, creative and more effective therapies based on the various microRNA levels. This opens up a new front in confronting this type of cancer.

Treatment

Treatment of pancreatic cancer depends on the stage of the cancer.^[7] Recent advances have made possible resection (surgical removal) of tumors that were previously unresectable due to blood vessel involvement. The Whipple procedure is the most common surgical treatment for cancers involving the head of the pancreas.

Fluorouracil, gemcitabine, and erlotinib are the chemotherapeutic drug agents of choice. Gemcitabine was approved by the US FDA in 1998 after a clinical trial reported improvements in quality of life in patients with advanced prostate cancer. This marked the first FDA approval of a chemotherapy drug for a non-survival clinical trial endpoint.

On the back of the results of a Canadian led Phase III Randomised Controlled trial involving 569 patients with advanced pancreatic cancer, the US FDA has licensed the use of erlotinib (Tarceva) in combination with gemcitabine as a palliative agent for this tumour. This trial compared the action of gemcitabine/erlotinib vs gemcitabine/placebo and demonstrated improved survival rates, improved tumour response and improved progression free survival rates. The survival improvement with the combination is on the order of less than four weeks, leading some cancer experts to question the incremental value of adding erlotinib to gemcitabine treatment. New trials are now investigating the effect of the above combination in the adjuvant and neoadjuvant setting.^[8]

In September 2006, it was announced that a new vaccine had been developed to fight pancreatic cancer, with testing on human patients showing promising results.^[9][10]

January 20, 2007, researchers reported at the 2007 Gastrointestinal Cancers Symposium that a trial of bevacizumab (Avastin) as an addition to chemotherapy has shown no improvement in survival of patients with advanced pancreatic cancer. It may cause higher rates of high blood pressure, bleeding in the stomach and intestine, and intestinal perforations.

Prognosis

Patients diagnosed with pancreatic cancer typically have a poor prognosis partly because the cancer usually causes no symptoms early on, leading to metastatic disease at time of diagnosis. Median survival from diagnosis is around 3 to 6 months; 5-year survival is much less than 5%^[11] With 37,170 new diagnoses in the United States every year, and 33,700 deaths, pancreatic cancer has the highest fatality rate of all cancers and the fourth highest cancer killer in the United States among both men and women.^[12][13]

Pancreatic cancer occasionally may result in diabetes. Insulin production is hampered and it has been suggested that the cancer can also prompt the onset of diabetes and vice versa.^[14]

Prevention

Prevention of pancreatic cancer consists of avoiding risk factors when possible.^[15] Cigarette smoking is considered to be the most significant and avoidable risk factor for pancreatic cancer. Maintaining a healthy weight and exercising may be helpful.

The American Cancer Society recommends increasing consumption of fruits, vegetables, and whole grains while decreasing red meat intake. This has been questioned by several research groups.^[16][17] In 2006 a large prospective cohort study of over 80,000 subjects failed to prove a definite association.^[18] The evidence in support of this lies mostly in small case-control studies.

In September 2006, a long-term study concluded that taking Vitamin D can substantially cut the risk of pancreatic cancer (as well as other cancers) by up to 50%.^[19][20][21] More studies of this have been called for.

Several studies, including one published June 1, 2007, indicate that B vitamins such as B12, B6, and folate, can reduce the risk of pancreatic cancer when consumed in food, but not when ingested in vitamin tablet form.^[22][23]

Awareness

• November is Pancreatic Cancer Awareness Month
• Purple is the traditional color chosen to represent pancreatic cancer awareness.
• The National Cancer Institute’s cancer research budget was $4.824 billion in 2004, an estimated $52.7 million of which was devoted to pancreatic cancer.^[24]
• Research spending per pancreatic cancer patient is $1145, the lowest of any leading cancer.^[25]
• For a list of celebrities who have succumbed to this disease, see
• The Pancreatic Cancer Action Network (PanCAN) was created as an advocacy group for pancreatic cancer.
• The national charity Pancreatic Cancer UK works to raise awareness in the UK

References