Pancreatic cancer is a malignant tumor of the pancreas. 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]
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].
[edit] Predisposing factors
Risk factors for pancreatic cancer include:[3]
Age
Male gender
African ethnicity[4]
Smoking. Cigarette smoking causes a 75% risk increase, and the risk persists for at least a decade after quitting. [5]
Diets high in red meat[6]
Obesity[7]
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[citation needed]
Family history, 5-10% of pancreatic cancer patients have a family history of pancreatic cancer. The genes responsible for most of this clustering in families have yet to be identified. 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.[8][1]
Gingivitis or periodontal disease.[9]
Diagnosis
History — Most patients with pancreatic cancer experience pain, weight loss, or jaundice.[10]
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 may 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, 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 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.
Treatment
Surgery
Treatment of pancreatic cancer depends on the stage of the cancer.[11] 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.[citation needed]
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 not recommended.[12]
Surgery may be performed for palliation, if the tumor is invading or compressing the duodenum or colon. In that case, bypass surgery may 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.[13] Fluorouracil (5FU) may also be included.
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 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.[14] 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.
Ukrain is a semisynthetic combination of the herb greater celandine and the classic cancer drug ThioTepa. It was recently licensed as an orphan drug for the treatment of pancreatic cancer in the US and Australia after positive results in two small studies.[15][16]
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 much less than 5%[17] With 37,170 cases diagnosed in the United States in 2007, and 33,700 deaths, pancreatic cancer has the highest fatality rate of all cancers and is the fourth highest cancer killer in the United States among both men and women.[18] Although it accounts for only 2.5% of new cases , pancreatic cancer is responsible for 6% of cancer deaths each year.[19]
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 and vice versa.[20]
Prevention
Prevention of pancreatic cancer consists of avoiding risk factors when possible.[21] 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.[22][23] In 2006 a large prospective cohort study of over 80,000 subjects failed to prove a definite association.[24] 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%.[25][26][27] More studies of this have been called for.