Pancreatic cancer has recently been the fourth leading cause of cancer deaths in the United States, with an annual incidence and mortality of nearly 40,000 cases per 12 months. Delay in diagnosis, resistance to chemotherapy and radiotherapy, and the internal biological aggressiveness by early metastasis, all lead to the catastrophic prognosis associated with pancreatic cancer manifests.
Cancer pancreatic cancer usually occurs after the 50th Year of life for many years and the increase in incidence with age is diagnosed, most patients 60-80 years. It is slightly more common in men than in women. Autopsy series document that pancreatic cancer to determine the extent of 2% of people in the post-mortem examination.
Several risk factors for adenocarcinoma of the pancreas were determined. Cigarette smoking is the strongest club, and it seems that for a quarter of the cases diagnosed accounts. The association between smoking and cancer, pancreatic cancer is thought to be linked to existing N-nitroso compounds in cigarette smoke.
Exposure to these substances leads to pancreatic ductal hyperplasia, a possible precursor of adenocarcinoma. Other elements with a high risk of pancreatic cancer associated with an increased intake of saturated fatty acids, the exposure to non-chlorinated solvents, pesticides and dichlorodiphenyltrichloroethane (DDT), although the overall proportion of these elements is likely to be small.
Diabetes mellitus has been identified recently as an element of risk for the disease. Chronic pancreatitis increases the risk of developing adenocarcinoma of the pancreas of 10 – to 20-fold. The role of other dietary factors (coffee, higher body fat consumption and consumption of alcohol) is very controversial. The diets of fruit and vegetables are considered protective.
There is a high incidence of malignant tumors of pancreatic cancer in people with hereditary pancreatitis, especially among those who develop calcification of the pancreas. Pancreatic cancer is rare inherited autosomal dominant trait associated with diabetes mellitus and exocrine pancreatic insufficiency.
A genetic predisposition has been identified in many familial cancer syndromes. Carcinomas are much more common in the head (70%) and the whole body (20%) than in the tail (10%) of the pancreas. Although the cell of origin of the malignancy of pancreatic cancer is currently unknown, with the majority of pancreatic ductal adenocarcinomas, one phenotype.
Reports suggest at present that could be the cell of origin or a centro acinar cell to which, when mutated, de-differentiated phenotype in the channel. Pancreatic intraepithelial neoplasia (Panin) and mucin-producing cystic tumors, mucinous cystic tumors and intraductal papillary mucinous tumors are considered precursors of pancreatic ductal adenocarcinoma.
The results of the molecular Analysis (eg, mutations in the proto-oncogene K-ras), a monoclonal cell origin recommend a minimum of 95% of cases. Roughly, the malignancy of pancreatic cancer than low desmoplastic, infiltrating tumor, obstructs the pancreatic duct and therefore often to fibrosis and atrophy of the distal gland.
Carcinoma of the head of the pancreas often inhibit the bile duct to the beginning of their studies, leading to jaundice and, if the cancer is large, the expansion of the duodenal C on the x-ray film contrast or imaging studies. Tumors of the body and tail tend to be later in their existing courses and thus tend to be very large when discovered.
Microscopically, 90% of pancreatic cancers are adenocarcinomas, adenosquamous others, anaplastic carcinoma, and acinar cells. Pancreatic cancer tends to spread into the surrounding tissue, invasion of adjacent organs along the perineural fascia and cause severe discomfort, and the lymphatic system and bloodstream, which metastasized to regional lymph nodes, liver longer with other remote locations.
Like other malignancies, it appears that certain molecular changes in the improvement of pancreatic cancer, such as the overexpression of receptor-ligand binding techniques, activation of oncogenes, inactivation of tumor suppressor genes and mutations incoming tumors of DNA mismatch repair genes in the DNA. For example, activating mutations in the proto-oncogene K-ras codon 12 in more than 90% of pancreatic cancers were determined.
Mutation in the TP53 tumor suppressor gene in cancer is 50-75% of adenocarcinomas of the pancreas are detected. Concomitant loss of TP53 and K-ras function may contribute to aggressive cancer clinic. In addition, approximately 90% of cases the P16 tumor suppressor gene located on chromosome 9p, inactivated.
Mutations in mismatch repair genes may also lead to the malignancy of pancreatic cancer. It appears that multiple mutations must occur to provide for malignancy of pancreatic cancer. Familial pancreatic cancer syndromes malignancy of germline mutations. Examples are mutations in the STK11 Peutz-Jeghers Syndrome and in mismatch repair genes.
The mismatch repair gene BRCA2 is inactivated in approximately 70-10% of pancreatic cancers. If long-term pancreatitis could be a typical way for the development of pancreatic cancer through the long-term inflammatory process, as a strong stromal reaction.
Inflammatory mediators in the stroma of the long term most likely to support a transformation to malignant diseases, although the exact mechanisms remain unknown. Cytokines produced by the activated stroma try to encourage the aggressive behavior of the cell to the pancreatic malignancy.
The clinical symptoms of malignant cancer of the pancreas can sometimes that long-term pancreatitis can be distinguished, in part, only occur because the inflammatory changes in general include both long-term pancreatitis and pancreatic cancer. The clinical manifestations of malignancy of pancreatic cancer vary by location and histological type of tumor growth.
Patients with cancer of the spirit of the pancreas are usually painless, progressive jaundice due to obstruction of the bile ducts. Sometimes the disability caused by cancer in the spirit in the pancreas by the presence of two signals jaundice and distended gall bladder palpable in the upper quadrant correctly (Courvoisier-law).
People with cancer, body or tail of the pancreas with abdominal pain, usually epigastric, deep weight loss, abdominal mass, and anemia. These patients usually no later than on the stage and often have distant metastases, particularly in the liver. Splenic vein thrombosis may occur as a complication of cancer in the body or tail of the gland.
About 70% of patients with malignant pancreatic cancer have glucose intolerance or diabetes Frank. While this may be due to ductal obstruction of proximal and distal atrophy of the gland, some patients turn to the resolution of the glucose tolerance or diabetes with surgical resection have, suggesting that cancers of the pancreas developing a diabetogenic substance not yet identified.
Adenocarcinoma of the pancreas are sometimes associated with superficial thrombophlebitis or DIC, believed to be related to thromboplastins in the secretions of mucinous adenocarcinoma. The rare acinar cell carcinoma can secrete lipase into the bloodstream, making fat necrosis in the subcutaneous tissue (manifested by skin rash) and bone marrow (manifested by lytic bone lesions) in the entire body.
A number of tumor markers such as carcinoembryonic antigen (CEA), CA 19-9, alpha-fetoprotein, pancreatic oncofetal antigen, galactosyltransferase II found in the serum of patients with pancreatic cancer. However, none of these tumor markers has sufficient specificity or predictive value to be useful in screening for the disease.
CA 19-9 may be useful to predict recurrence in men, after a surgical resection or accession, the burden of disease in patients treated with chemotherapy, systemic. To evaluate the patients, with malignant pancreatic cancer is suspected, the first diagnostic test of choice contrast, scan, spiral CT is cut thin.
Among people with equivocal CT scans or inconclusive, endoscopic ultrasound with or without fine-needle aspiration is proposed to assist in the analysis. endoscopic retrograde catheterization of the pancreatic duct (ERCP) with stent placement is useful for relieving obstructive jaundice. In people with diseases of the pancreas head, confirm brushing with biliary tract or pancreas during ERCP, the analysis of pancreatic cancer.
The new imaging technique of positron emission tomography (PET), an increased uptake of the radioactive tracer 2 – [18F] is-fluoro-2-deoxy-D-glucose in about 95% of patients with pancreatic cancer. This adaptation is not observed in humans suffering from pancreatitis, long-term.
In addition to supporting the analysis, spiral CT is useful to delineate the vascular anatomy and regional vascular invasion by the primary tumor, a sign of resectability, or of the presence of metastases found. clinical prognostic factors have been identified.
These include the tumor size, tumor location of cancer, clinical stage, lymph node metastases, type of surgery, anemia requiring blood transfusions, the general performance status, and adjuvant radiotherapy. The prognosis is also influenced by the histological features such as capsular invasion, vascular invasion, tumor multifocality uninvolved epithelial atypia in the areas of the pancreas, and a lymphocytic infiltrate at the edge of cancer growth.
Unfortunately, only 15% of pancreatic cancers are diagnosed at an early stage when cure is possible by surgical resection. Currently, the overall survival rate five years is to stay less than 5% and only 15-20% of patients treated with curative resection of more than five years.
The prognosis is mainly due to an advanced stage of disease at presentation, progression extraordinary local tumor and its spread to systemic onset. People with metastases with a short median survival time (3-6 months), and those with locally advanced, metastatic disease do not live on a little longer than typical (6-10 months).
