Pancreatic Cancer

Pancreatic cancer is a malignant tumor of the pancreas. Each year about 37,680 individuals in the United States are diagnosed with this condition, and 34,290 die from the disease. Depending on the extent of the tumor at the time of diagnosis, the prognosis is generally regarded as poor, with less than 5 percent of those diagnosed still alive five years after diagnosis, and complete remission still extremely rare. 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.





Signs and symptoms

Presentation

Pancreatic cancer is sometimes called a "silent disease" because early pancreatic cancer often does not cause symptoms, and the later symptoms are usually 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, or nausea and vomiting;
• significant weight loss;
• painless jaundice (yellow skin/eyes, dark urine) related to bile duct obstruction (carcinoma of the head of the pancreas). This may also cause acholic stool and steatorrhea.

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.

Development

Predisposing factors

Risk factors for pancreatic cancer include:

• Age (particularly over 60)
• Male gender
• Smoking. Cigarette smoking nearly doubles one's risk, and the risk persists for at least a decade after quitting.
• Diets low in vegetables and fruits
• Diets high in red meat
• Obesity
• Diabetes mellitus
• Chronic pancreatitis has been linked, but is not known to be causal
• Helicobacter pylori infection
• Family history, 5-10% of pancreatic cancer patients have a family history of pancreatic cancer. Pancreatic cancer has been associated with the following syndromes; 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.
• Gingivitis or periodontal disease.
• Alcohol might be a risk factor

Diagnosis

Most patients with pancreatic cancer experience pain, weight loss, or jaundice.

Pain is present in 80 to 85 percent of patients with locally advanced or advanced metastic disease. The pain is usually felt in the upper abdomen as a dull ache that radiates straight through to the back. It may be intermittent and made worse by eating. Weight loss can be profound; it can be associated with anorexia, early satiety, diarrhea, or steatorrhea. Jaundice is often accompanied by pruritus and dark urine. Painful jaundice is present in approximately one-half of patients with locally unresectable disease, while painless jaundice is present in approximately one-half of patients with a potentially resectable and curable lesion. The initial presentation varies according to tumor location. Tumors in the pancreatic body or tail usually present with pain and weight loss, while those in the head of the gland typically present with steatorrhea, weight loss, and jaundice. The recent onset of atypical diabetes mellitus, a history of recent but unexplained thrombophlebitis(Trousseau's sign), or a previous attack of pancreatitis are sometimes noted. 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 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. When a cutoff above 37 U/mL is used, this marker has a sensitivity of 77% and specificity of 87% in discerning benign from malignant disease. CA 19-9 might be normal early in the course, and could be elevated due to benign causes of biliary obstruction.

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

Treatment

Surgery

Treatment of pancreatic cancer depends on the stage of the cancer. The Whipple procedure is the most common surgical treatment for cancers involving the head of the pancreas. It can only be performed if the patient is likely to survive major surgery, and if the tumor is localised without invading local structures or metastasizing. It can therefore only be performed in the minority of cases. Recent advances have made possible resection (surgical removal) of tumors that were previously unresectable due to blood vessel involvement.

Tumors of the tail of the pancreas can be resected using a procedure known as a distal pancreatectomy. Recently localized tumors of the pancreas have been resected using minimally invasive (laparoscopic) approaches.

After surgery, adjuvant chemotherapy with gemcitabine may be offered to eliminate whatever tumor tissue may remain in the body. This has been shown to increase 5-year survival rates. Addition of radiation therapy is a hotly debated topic, with groups in the US often favoring the use of adjuvant radiation therapy, while groups in Europe do not.

Surgery can be performed for palliation, if the tumor is invading or compressing the duodenum or colon. In that case, bypass surgery might overcome the obstruction and improve quality of life, but it is not intended as a cure.

Chemotherapy

In patients not suitable for resection with curative intent, palliative chemotherapy may be used to improve quality of life and gain a modest survival benefit. Gemcitabine was approved by the US FDA in 1998 after a clinical trial reported improvements in quality of life in patients with advanced pancreatic cancer. This marked the first FDA approval of a chemotherapy drug for a non-survival clinical trial endpoint. Gemcitabine is administered intravenously on a weekly basis. Addition of oxaliplatin (Gem/Ox) conferred benefit in small trials, but is not yet standard therapy. Fluorouracil (5FU) may also be included.

The US FDA has licensed the use of erlotinib (Tarceva) in combination with gemcitabine as a palliative regimen for pancreatic cancer. This trial compared the action of gemcitabine/erlotinib vs gemcitabine/placebo and demonstrated improved survival rates, improved tumor 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. A trial of anti-angiogenesis agent 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.

Nutritional Supplements

A clinical trial studying the effect of curcumin on pancreatic cancer was completed and the study used 8 grams per day in 21 patients and stopped treatment if the tumor size increased. The conclusion of the study was "Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer."

Prognosis

Patients diagnosed with pancreatic cancer typically have a poor prognosis partly because the cancer usually causes no symptoms early on, leading to locally advanced or metastatic disease at time of diagnosis. Median survival from diagnosis is around 3 to 6 months; 5-year survival is less than 5%. With 37,170 cases diagnosed in the United States in 2007, and 33,700 deaths, pancreatic cancer has one of the highest fatality rates of all cancers and is the fourth highest cancer killer in the United States among both men and women. Although it accounts for only 2.5% of new cases, pancreatic cancer is responsible for 6% of cancer deaths each year.

Pancreatic cancer may occasionally result in diabetes. Insulin production is hampered and it has been suggested that the cancer can also prompt the onset of diabetes. Thus diabetes is both a risk factor for the development of pancreatic cancer and diabetes can be an early sign of the disease in the elderly.

Prevention

According to the American Cancer Society, there are no established guidelines for preventing pancreatic cancer, although cigarette smoking is responsible for 20-30% of pancreatic cancers.

The ACS recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains while decreasing red meat intake, although there is no consistent evidence that this will prevent or reduce pancreatic cancer specifically. In 2006 a large prospective cohort study of over 80,000 subjects failed to prove a definite association. The evidence in support of this lies mostly in small case-control studies.

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%.

Several studies, 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.