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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epidemiological patterns for pancreatic and biliary cancers reveal more differences than similarities. Pancreatic carcinoma is common in western countries, although 2 Polynesian groups (New Zealand Maoris and native Hawaiians) have the highest rates internationally. In the United States the disease is rising in frequency, predominating in males and in blacks. The rates are elevated in urban areas, but geographic analysis uncovered no clustering of contiguous counties except in southern Louisiana. The origin of pancreatic cancer is obsure, but a twofold increased risk has been documented for cigarette smokers and diabetic patients. Alcohol, occupational agents, and dietary fat have been suspected, but not proven to be risk factors. Except for the rare hereditary form of pancreatitis, there are few clues to genetic predisposition. In contrast, the reported incidence of biliary tract cancer is highest in Latin American populations and American Indians. The tumor predominates in females around the world, except for Chinese and Japanese who show a male excess. In the United States the rates are higher in whites than blacks, and clusters of high-risk counties have been found in the north central region, the southwest, and Appalachia. The distribution of biliary tumors parallels that of cholesterol gallstones, the major risk factor for biliary cancer. Insights into biliary carcinogenesis depend upon clarification of lithogenic influences, such as pregnancy, obesity, and hyperlipoproteinemia, exogenous estrogens, familial tendencies, and ethnic-geographic factors that may reflect dietary habits. Noncalculous risk factors for biliary cancer include ulcerative colitis, clonorchiasis, Gardner's syndrome, and probably certain industrial exposures. Within the biliary tract, tumors of the gallbladder and bile duct show epidemiological distinctions. In contrast to gallbladder cancer, bile duct neoplasms predominate in males; they are less often associated with stones and more often with other risk factors. In some respects, bile duct and pancreatic tumors are alike. The male predominance of both tumors, an association between cholecystectomy and pancreatic cancer, and other considerations have prompted the notion that the same biliary carcinogens may affect the bile duct, ampulla of Vater, or, by reflux, the pancreatic duct. Various epidemiological and interdisciplinary approaches are needed to further clarify the origins of biliary tract and pancreatic cancers, but nutritional studies hold special promise in laying the groundwork for prevention of these tumors.
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PMID:Cancers of the pancreas and biliary tract: epidemiological considerations. 110 53

It is well known that the patients with anomalous arrangement of pancreatobiliary duct (AAPBD) are combined with biliary tract cancer. To clarify possible carcinogenesis of the gallbladder with AAPBD, DNA analysis of the gallbladder epithelium was performed in control (9 cases), AAPBD (26), gallbladder cancer confined in mucosa (10) and noncancerous epithelium around the gallbladder cancer (21). The mean values of DNA score, as already reported by us as an indicator of cell kinetics, were 12.1 (control), 27.2 (AAPBD, Type a), 13.3 (AAPBD, Type b), 14.8 (noncancerous epithelium around cancer) and 77.2 (gallbladder cancer confined in mucosa). The values of DNA score in the epithelium of AAPBD (Type a) showed significantly high level, which was next to that of cancer. Type a AAPBD may be supposed to have potential malignancy because of its accelerated cell cycle. But as Type b AAPBD without accelerated cell cycle combines cancer at least as often as Type a, further studies should be performed to reveal the relationship between cell cycle and malignancy.
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PMID:[Cell kinetic studies on the gallbladder epithelium in patient with anomalous arrangement of pancreatobiliary duct]. 185 2

The relation between gallstone size and gallbladder cancer was investigated in a matched hospital-based case-control study of surgical patients in a predominantly white population. Stone size was considered to be an indicator of the damaging effects of gallstones on gallbladder mucosa, which may enhance carcinogenesis. A radiologist determined the size of the largest gallstone within the gallbladder by reviewing hard copies of the ultrasonographic examinations of cases and controls. Between 1983 and 1989, 83 surgical patients with gallbladder cancer were identified in 18 participating hospitals. Hard copies were available for 72 patients and 208 matched controls. For 43 cancer patients and 98 matched controls stone size could be determined. In contrast to two other studies, no relation was found between stone size and gallbladder cancer. The reasons for this discrepancy are discussed.
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PMID:Gallstone size and the risk of gallbladder cancer. 832 23

Mismatch repair genes are the responsible genes for hereditary non-polyposis colon cancer, and mutation of these genes causes replication error (RER). In several RER-positive colon cancer cell lines, mutations of repetitive sequences of transforming growth factor beta (TGF-beta) type II receptor (RII) gene have been reported. Since TGF-beta inhibits cell proliferation, loss of response to TGF-beta is an important tumor progression step. In this study, the relationship between RER status and mutation of the RII gene was analyzed in 112 cases of various types of sporadic gastrointestinal and hepatobiliary cancer (41 with gastric, 49 with colorectal, 5 with gallbladder, and 17 with hepatic cancers). RER was found in 17 cases (4 with gastric, 12 with colorectal, and 1 with gallbladder cancer), and 10 of those (3 with gastric and 7 with colorectal cancer) showed mutations of the RII gene. Of interest was that in all seven cases with colorectal cancer, tumors were located at the cecum. These data indicate that mutation of the RII gene, presumably caused by abnormality of repair gene, play an important role in carcinogenesis of sporadic gastrointestinal cancer, especially at the cecum.
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PMID:A transforming growth factor beta type II receptor gene mutation common in sporadic cecum cancer with microsatellite instability. 897 Nov 66

It is well known that the frequency of an associated gallbladder cancer in patients with pancreaticobiliary maljunction (PBM) without congenital choledochal dilation (CCD) is very high, while that of bile duct cancer with CCD is remarkably high, and that of bile duct malignancy without CCD is low. However, recent statistical evaluations have demonstrated that the coincidence rates of gallbladder and bile duct cancer with CCD are 11.5% and 4.6%, respectively, whereas without CCD the rates are 57.1% and 4.1%, respectively. Rates of bile duct cancer with CCD are comparable to those without CCD. We have performed biliary reconstruction after resection of extrahepatic bile ducts along with the gallbladder for PBM patients who had neither CCD nor cancer. Our surgical strategy for these patients without CCD with PBM was assessed from K-ras point mutations and overexpression of p53 protein in the epithelia of the cancerous portions and non-neoplastic portions of the gallbladder and bile duct affected by PBM regardless of choledochal dilatation. The mutation rate in the non-neoplastic gallbladder epithelium without CCD was 80%, that of the bile duct without CCD 57%, not significantly different from the 50% and 40%, respectively, with CCD. The frequency of p53 overexpression in the non-neoplastic bile duct epithelium without CCD was 14%, comparable to the 11% in gallbladder epithelium with CCD. Judging from the statistical data and the molecular biological data, resection of an extrahepatic bile duct with the gallbladder should be the treatment of choice for carcinogenesis prevention.
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PMID:Surgical strategy for patients with pancreaticobiliary maljunction without choledocal dilatation. 944 27

We report a case of anomalous junction of the pancreaticobiliary duct (AJPBD) associated with gallbladder cancer and obstructive jaundice in a patient with high serum and bile cytokine levels. The patient was a 63-year-old woman who complained of right hypochondralgia. Ultrasound, computed tomography, percutaneous transhepatic cholangiography, and endoscopic retrograde cholangio-pancreatatography revealed dilation of the bile ducts, an elevated lesion of the gallbladder, and AJPBD. She underwent percutaneous transhepatic cholangio-drainage (PTCD) for obstructive jaundice. However, the total bilirubin concentration remained high 7 days after PTCD. Her serum interleukin 6 level was 57,359 pg/ml before PTCD, and gradually decreased to 10 pg/ml after PTCD. Bile interleukin 6 level was 10 pg/ml before PTCD, 8997 pg/ ml 3 h after PTCD and gradually decreased there after. Serum and bile levels of tumor necrosis factor alpha and hepatocyte growth factor were high before and after PTCD. The patient underwent an extended cholecystectomy and resection of the extrahepatic bile duct. The resected specimen showed two elevated lesions of the gallbladder which, microscopically, revealed moderately differentiated tubular adenocarcinoma. These findings suggest that pre-existing inconspicuous inflammation of the biliary tract due to reflux of pancreatic juice is involved in elevation of serum and bile cytokines, and that cytokines may participate in gallbladder carcinogenesis associated with AJPBD.
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PMID:Anomalous junction of the pancreaticobiliary duct accompanied by gallbladder cancer and obstructive jaundice in a patient with high serum and bile cytokine levels. 971 51

A 25 year-old woman experienced a sudden onset of epigastralgia with nausea, and consulted our hospital. Because the abdominal pain did not subside with medication, she was hospitalized. On physical examination she had a slight tenderness of the right upper abdominal quadrant. Laboratory studies disclosed increases in the serum alkaline phosphatase, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and serum amylase levels. Abdominal ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography revealed choledocholithiasis and a pancreatic duct which originated from the common bile duct. A common bile duct stone was removed with a basket catheter after an endoscopic sphincterotomy was performed. Since an anomalous union of a pancreatobiliary duct is a high risk factor of gallbladder cancer, laparoscopic cholecystectomy was perfomed. The post-operative course was uneventful and she was discharged on the twentieth post-operative day. In a microscopical examination of the resected specimen, a pyloric type gastric mucosa was clearly evident in the submucosa, while the remaining gallbladder demonstrated chronic cholecystitis. Some cases of heterotopic gastric mucosa in the gallbladder come from metaplasia, and metaplasia is also one of the most important factors in the carcinogenesis of gallbladder cancer. In conclusion, the present case is the first report of gastric mucosa with an anomalous union of the pancreatobiliary duct. Heterotopic gastric mucosa in the gallbladder may be one of the causes of gallbladder cancer, and close attention should, therefore, be paid to any occurrence of heterotopic gastric mucosa in this region.
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PMID:Heterotopic gastric mucosa in a gallbladder with an anomalous union of the pancreatobiliary duct: a case report. 984 91

The significant association between pancreaticobiliary malunion (PBM), especially undilated-type PBM, and a high risk of gallbladder cancer is known. Reflux and stasis of pancreatic juice induce various epithelial changes in the gallbladder. Recently, epithelial hyperplasia of the gallbladder was shown to be significantly and frequently associated with undilated-type PBM, and it is suggested that the majority of epithelial hyperplasia may exist at birth or be acquired in early childhood, and thereafter present throughout the lives of PBM patients. Cell kinetic studies demonstrated a significant stepwise increase in cellular proliferative activity from normal gallbladder mucosa, through epithelial hyperplasia to cancer. Epithelial hyperplasia with increased proliferative activity may predispose the mucosa to mutational events, thereby increasing cancer risk in PBM patients. K-ras mutations were frequently detected in gallbladder cancer in PBM patients and in epithelial hyperplasia as well. Epithelial hyperplasia is demonstrated to be an important premalignant lesion of gallbladder cancer. A multistep process of carcinogenesis as a consequence of multiple genetic alterations of oncogenes and tumor suppressor genes has been demonstrated in various organs; however, there is limited information on the molecular mechanism in gallbladder carcinogenesis with PBM. Recent findings support the idea that epithelial hyperplasia plays an important role in gallbladder carcinogenesis with PBM and also support the concept that neoplastic development in gallbladder with PBM also evolves through a multistep process associated with hyperproliferation and genetic alterations.
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PMID:Epithelial cell proliferation and gene mutation in the mucosa of gallbladder with pancreaticobiliary malunion and cancer. 1052 57

Chromosome banding analysis of 11 short-term cultured gallbladder carcinomas revealed acquired clonal aberrations in seven tumors (five primary and two metastases). Three of these had one clone, whereas the remaining four were cytogenetically heterogeneous, displaying two to seven aberrant clones. Of a total of 21 abnormal clones, 18 had highly complex karyotypes and three exhibited simple numerical deviations. Double minutes and homogeneously staining regions were observed in one and two carcinomas, respectively. To characterize the karyotypic profile of gallbladder cancer more precisely, we have combined the present findings with our three previously reported cases, thereby providing the largest cytogenetic database on this tumor type to date. A total of 287 chromosomal breakpoints were identified, 251 of which were found in the present study. Chromosome 7 was rearranged most frequently, followed by chromosomes 1, 3, 11, 6, 5, and 8. The bands preferentially involved were 1p32, 1p36, 1q32, 3p21, 6p21, 7p13, 7q11, 7q32, 19p13, 19q13, and 22q13. Nine recurrent abnormalities could, for the first time, be identified in gallbladder carcinoma: del(3)(p13), i(5)(p10), del(6)(q13), del(9)(p13), del(16)(q22), del(17)(p11), i(17)(q10), del(19)(p13), and i(21)(q10). The most common partial or whole-arm gains involved 3q, 5p, 7p, 7q, 8q, 11q, 13q, and 17q, and the most frequent partial or whole-arm losses affected 3p, 4q, 5q, 9p, 10p, 10q, 11p, 14p, 14q, 15p, 17p, 19p, 21p, 21q, and Xp. These chromosomal aberrations and imbalances provide some starting points for molecular analyses of genomic regions that may harbor genes of pathogenetic importance in gallbladder carcinogenesis. Genes Chromosomes Cancer 26:312-321, 1999.
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PMID:Nonrandom chromosomal aberrations and cytogenetic heterogeneity in gallbladder carcinomas. 1053 66

Biliopancreatic carcinoma has a poor prognosis since the diagnosis of the tumor occurs late when advanced disease is present. The identification of potential causes and earlier diagnosis are needed to prevent the disease or identify it early enough to improve survival. The main risk factors for pancreatic cancer include advanced age, cigarette smoking, high-fat diet, diabetes mellitus, chronic pancreatitis (especially hereditary pancreatitis) and a positive family history of pancreatic cancer. The most important etiologic factor for the development of gallbladder cancer is gallstone disease. Patients with anatomic abnormalities and chronic inflammatory conditions (primary sclerosing cholangitis, infections with parasites) have an increased incidence of bile duct cancers. Several new and promising imaging techniques have recently become available and our understanding of the mechanisms of carcinogenesis are growing rapidly. However, there is currently no effective screening strategy applicable and it is unknown when to begin screening. For pancreatic cancer, reduction of risk is likely to occur with avoidance of smoking and promotion of healthful diets. Cholecystectomy rates have increased since the introduction of new laparoscopic techniques and will eventually reduce the incidence of gallbladder cancer. Improved imaging techniques, the identification of new genes and a better definition of genetic alterations that characterize preinvasive lesions will hopefully allow to develop sensitive and specific technologies to screen and to detect early biliopancreatic cancer for even premalignant lesions to improve the mostly fatal prognosis if this tumor.
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PMID:[Risk groups for pancreatic and bile duct carcinomas]. 1101 30


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