Pancreatic Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Pancreatic Cancer, including details on symptoms, causes, treatment, information. | |||||||
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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 symptomsPresentationEarly 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 factorsRisk factors for pancreatic cancer include:[3]
DiagnosisHistory — 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, acholic stools, 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.
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. TreatmentTreatment of pancreatic cancer depends on the stage of the cancer.[11] 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 pancreatic 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.[12] 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.[13][14] On 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. COMBINATION CHEMOTHERAPY — With few exceptions, multiagent regimens are associated with higher response rates, but no clear survival benefit in patients with advanced pancreatic cancer. Older 5-FU-based combination regimens — Despite higher objective response rates in some studies, randomized trials do not support a survival benefit for 5-FU-based combination regimens compared to 5-FU alone. As examples: In one trial, 385 patients were randomly assigned to single agent 5-FU, 5-FU plus doxorubicin, or 5-FU, doxorubicin plus mitomycin (FAM) . There was no difference in either response rate or median survival among the regimens; the median survival for all patients was 5.5 months.[15] Similar results were noted in a second report, in which 187 patients with advanced pancreatic cancer were randomly assigned to single agent 5-FU, or 5-FU, doxorubicin and cisplatin, or 5-FU, cyclophosphamide, methotrexate, vincristine and mitomycin. Again, neither combination regimen offered a survival advantage over 5-FU alone. PrognosisPatients 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%[16] 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.[17] Although it accounts for only 2.5% of new cases , pancreatic cancer is responsible for 6% of cancer deaths each year.[18] 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.[19] PreventionPrevention of pancreatic cancer consists of avoiding risk factors when possible.[20] 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.[21][22] In 2006 a large prospective cohort study of over 80,000 subjects failed to prove a definite association.[23] 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%.[24][25][26] 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.[27][28] Awareness
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