Association of gallbladder carcinoma and anomalous pancreaticobiliary ductal union

Kimura, Kazuhiro; Ohto, Masao; Saisho, Hiromitsu; Unozawa, Takao; Tsuchiya, Yukihiro; Murakami, Masahiko; Ebara, Masaaki; Matsutani, Shoichi; Okuda, Kunio

doi:10.1016/0016-5085(85)90641-9

Cited by 287 publications

(184 citation statements)

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“…It is relatively frequent in East Asia and is known to play an important role in the development of GB cancers. (49) K-ras mutations are rare and p53 mutations occur early during the multistage pathogenesis of gallstone-associated GB cancers, whereas AJPBD-associated GB cancers are characterized by K-ras mutations and a relatively late onset of p53 mutations, (4,6) suggesting two pathways involved in the pathogenesis of GB cancers. Although the data regarding the presence of AJPBD are limited, because we do not carry out endoscopic retrograde cholangiopancratography routinely in GB cancer, we assume that pancreatic juice reflux with consequent hyperplasia of the GB epithelium influences hypomethylation of the PGP9.5 gene, as does the K-ras mutation.…”

Section: Discussionmentioning

confidence: 99%

Hypomethylation of the protein gene product 9.5 promoter region in gallbladder cancer and its relationship with clinicopathological features

Lee¹,

Lee²,

Kim³

et al. 2006

Cancer Science

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Protein gene product 9.5 (PGP9.5) is a neurospecific peptide that removes ubiquitin from ubiquitinated proteins and prevents them being targeted for degradation by proteosomes. Its expression is a potential marker of non-small lung cancer, invasive colorectal cancer and esophageal squamous cell carcinoma. Gallbladder (GB) cancer is the most common malignant tumor of the biliary tract and is usually associated with gallstone disease, a late diagnosis, unsatisfactory treatment and a poor prognosis. To understand the role of PGP9.5 in GB cancer, we examined the methylation status of its promoter and its expression in surgical biopsy samples. Formalinfixed, paraffin-embedded tumors and non-neoplastic GB tissues (22 carcinomas, eight adenomas, 26 normal epithelia) were collected from patients who had undergone surgical resection. The methylation status of the promoter region of the PGP9.5 gene was determined by methylation-specific polymerase chain reaction, and the expression of PGP9.5 was examined by immunohistochemistry using tissue microarrays. PGP9.5 promoter was methylated in 84.6% (22/26) of normal GB epithelium, 37.5% ( G allbladder cancer is the most common malignant lesion of the biliary tract and the fifth most common malignant neoplasm of the digestive tract, although it demonstrates pronounced geographic and sex-related variations.(1,2) The etiology of this tumor is complex, but there is a strong association between it and the presence of gallstones related to chronic inflammation.(1) Unfortunately, GB cancer is an aggressive disease with a poor prognosis because of its inherent biology and its often advanced stage at diagnosis. In addition, the symptoms and signs of GB cancer are vague and non-specific, and thus it is difficult to diagnose clinically. Therefore, an understanding of the biological features of GB carcinogenesis is needed to improve its prognosis.Information on the molecular changes involved in GB carcinogenesis is limited.(3) Considerable evidence indicates that mutations of the dominant oncogene (K-ras) and tumor suppressor genes ( p53, p16 and FHIT ) may be involved.(4-7) In addition, genome-wide and specific chromosome arm allelotyping analyses demonstrate that a loss of heterozygosity at multiple sites in the genome is frequent in this neoplasm. (8)(9)(10) Recently, several groups showed that multiple genes, including SHP, 3-OST-2, CDH13, CDH1, CHFR, hMLH, p16, RASSF1A, RUNX3, APC, MGMT, RARβ2, p73 and Reprimo, are hypermethylated in GB tumor tissues, (11)(12)(13)(14) although considerable geographic differences are apparent in methylation patterns of candidate tumor suppressor genes, indicating that gene hypermethylation is a frequent epigenetic event in GB cancer. Moreover, epigenetic transcriptional silencing by promoter hypermethylation is believed to be a common feature in human cancer. (15,16) Hence the delineation of epigenetic alterations that occur in GB cancer may be important for the development of molecular markers of early detection, prognosis and cancer treatment.The ...

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Section: Discussionmentioning

confidence: 99%

Hypomethylation of the protein gene product 9.5 promoter region in gallbladder cancer and its relationship with clinicopathological features

Lee¹,

Lee²,

Kim³

et al. 2006

Cancer Science

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“…High-risk individuals for gallbladder carcinoma have been identified as those with congenital dilation of the common bile duct, abnormal connections between pancreatobiliary ducts, reflux of pancreatic juice into the bile duct, or gallstones, as well as persons belonging to a familial gallbladder cancer kindred (7)(8)(9). Gallstones and abnormal connections between pancreatobiliary ducts and gallstones are two very important risk factors for gallbladder cancer.…”

Section: High Risk For Gallbladder Carcinomamentioning

confidence: 99%

Diagnosis of Gallbladder Tumors

2011

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Gallbladder cancer is among the organs examined in mass screening for cancer using ultrasonography; the reported prevalence of gallbladder cancer in such screening of a general population was 0.011%, while the prevalence of gallbladder polyps was reported as 4.3 to 6.9%. Endoscopic ultrasonography is useful for the differential diagnosis of gallbladder tumors detected by mass screening, as well as for estimating the depth of tumor invasion and detecting abnormal connections between pancreatobiliary ducts. While a systematic approach leading to diagnosis by endoscopic ultrasonography is useful, recent advances of contrast-enhanced ultrasonography are expected to establish it as a new modality for early detection. At our hospital, 7 of 26 patients with abnormal connections between pancreatobiliary ducts developed gallbladder carcinoma (23.1%), and 7 of 48 patients with gallbladder carcinoma had abnormal connections between pancreatobiliary ducts (12.5%). Serial observation in patients with gallstones and prophylactic surgery in patients with abnormal connections between pancreatobiliary ducts are necessary.

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“…Anatomic Anomalies: Congenital bile duct cysts (CBDC), pancreaticobiliary maljunction (PBM) and Caroli's disease have been clearly identified to be precursors of biliary cancer. It has been suggested, that there is an etiological link between congenital bile duct cyst formation and PBM, since several clinical series report coincidence of these two conditions in over 90% of cases [8,18]. In CBDC with PBM chronic exposure of the biliary epithelium to a regurgitated mixture of bile and pancreatic juice is due to an impaired sphincter of Oddi function and induces chronic inflammation.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of biliary carcinogenesis: A pathogenetic multi-stage cascade towards cholangiocarcinoma

1999

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SummaryCarcinomas of the biliary tract are rare cancers developing from the epithelial or blast-like cells lining the bile ducts. A variety of known predisposing factors and recent experimental models of biliary carcinogenesis (e.g., infection with the liver fluke Opisthorchis viverrini, models of chemically induced carcinogenesis and experimental models of pancreaticobiliary maljunction) have elucidated different stages of this complex system of biliary tumorigenesis. Chronic inflammatory processes, generation of active oxygen radicals, altered cellular detoxification mechanisms, activation of oncogenes, functional loss of tumor-suppressor genes and dysregulation of cell proliferation and cell apoptotic mechanisms have been identified as important contributors in the development of cholangiocarcinomas. In this review, the known mechanisms involved in the carcinogenesis of biliary epithelium are addressed. We will divide the topic into four stages: 1) Predisposition and risk factors of biliary cancer. 2) Genotoxic events and alterations leading to specific DNA damage and mutation patterns. 3) Dysregulation of DNA repair mechanisms and apoptosis, permitting survival of mutated cells and 4) Morphological evolution from premalignant biliary lesions to cholangiocarcinoma. Finally, established and hypothetical future therapeutic strategies directed towards specific pathogenetic events during biliary carcinogenesis will be addressed.

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Association of gallbladder carcinoma and anomalous pancreaticobiliary ductal union

Cited by 287 publications

References 5 publications

Hypomethylation of the protein gene product 9.5 promoter region in gallbladder cancer and its relationship with clinicopathological features

Hypomethylation of the protein gene product 9.5 promoter region in gallbladder cancer and its relationship with clinicopathological features

Diagnosis of Gallbladder Tumors

Mechanisms of biliary carcinogenesis: A pathogenetic multi-stage cascade towards cholangiocarcinoma

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