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MAP kinase and mammalian target of rapamycin are main pathways of gallbladder carcinogenesis: results from bioinformatic analysis of next generation sequencing data from a hospital-based cohort (NCT05404347). Mol Biol Rep 2022; 49:10153-10163. [PMID: 36018415 DOI: 10.1007/s11033-022-07874-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 08/16/2022] [Indexed: 10/15/2022]
Abstract
BACKGROUND Gallbladder Cancer (GBC) is one of the most common cancers of the biliary tract and the third commonest gastrointestinal (GI) malignancy worldwide. The disease is characterized by the late presentation and poor outcome despite treatment, and hence, newer therapies and targets need to be identified. METHODS The current study investigated various functionally enriched pathways in GBC pathogenesis involving the genes identified through Next Generation Sequencing (NGS) in a hospital-based cohort. The Pathway enrichment analysis and Gene Ontology (GO) were carried out after NGS, followed by the construction of the protein-protein interaction (PPI) network to discover associations among the genes. RESULTS Of the thirty-three patients with GBC who were screened through next-generation sequencing (NGS), 27somatic mutations were identified. These mutations involved a total of 14 genes. The p53 and KRAS were commonly found to be mutated, while mutations in other genes were seen in one case each, the mean number of mutations were 1.2, and maximum mutation in a single case (eight) was seen in one case. The bioinformatics analysis identified MAP kinase, PI3K-AKT, EGF/EGFR, and Focal Adhesion PI3K-AKT-mTOR signaling pathways and cross-talk between these. CONCLUSION The results suggest that the complex crosstalk between the mTOR, MAPK, and multiple interacting cell signaling cascades can promote GBC progression, and hence, mTOR-MAPK targeted treatment will be an attractive option.
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Beltrán MA, Beltrán AA. Common bile duct pressure in patients with and without cholelithiasis: A case-control study. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 28:443-449. [PMID: 33636035 DOI: 10.1002/jhbp.931] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 09/17/2020] [Accepted: 02/21/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The reflux of pancreatic enzymes into the bile duct and the gallbladder is an abnormal phenomenon that plays a role in lithogenesis and carcinogenesis. Because the pressure of the common bile duct depends on the pressures of the sphincter of Oddi, its dysfunction would be reflected in an increase in the pressure of the common bile duct in patients with cholelithiasis. The objective of this study was to measure the pressures of the common bile duct in patients with and without cholelithiasis and to relate them to the presence of pancreatobiliary reflux. METHODS A prospective case-control study was designed. The study universe was constituted by all patients undergoing total gastrectomy for gastric cancer stages I and II over 30 months. The primary outcome measure was to establish differences between common bile duct pressures in patients with and without cholelithiasis. RESULTS Common bile duct pressures in patients with gallstones showed a significant elevation (16.9 mmHg) compared to patients without gallstones (3.3 mm Hg) (p < 0.0001). These pressures correlated with the levels of amylase and lipase in gallbladder bile; higher levels were found in patients with gallstones compared to patients without gallstones (P < 0.0001). CONCLUSIONS Common bile duct pressure in patients with cholelithiasis was significantly higher compared to patients without cholelithiasis leading to pancreatobiliary reflux.
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Affiliation(s)
- Marcelo A Beltrán
- Department of Surgery, Hospital San Juan de Dios de La Serena, Coquimbo, Chile
| | - Andrea A Beltrán
- Medicine School, Universidad de Santiago de Chile, Santiago, Chile
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Kai K, Aishima S, Miyazaki K. Gallbladder cancer: Clinical and pathological approach. World J Clin Cases 2014; 2:515-521. [PMID: 25325061 PMCID: PMC4198403 DOI: 10.12998/wjcc.v2.i10.515] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2014] [Revised: 05/13/2014] [Accepted: 07/18/2014] [Indexed: 02/05/2023] Open
Abstract
Gallbladder cancer (GBC) shows a marked geographical variation in its incidence. Middle-aged and elderly women are more commonly affected. Risk factors for its development include the presence of gallstones, chronic infection and pancreaticobiliary maljunction. Controversy remains in regard to the theory of carcinogenesis from adenomyomatosis, porcelain gallbladder and adenoma of the gallbladder. The surgical strategy and prognosis after surgery for GBC differ strikingly according to T-stage. Discrimination of favorable cases, particularly T2 or T3 lesions, is useful for the selection of surgical strategies for individual patients. Although many candidate factors predicting disease progression, such as depth of subserosal invasion, horizontal tumor spread, tumor budding, dedifferentiation, Ki-67 labeling index, p53 nuclear expression, CD8+ tumor-infiltrating lymphocytes, mitotic counts, Laminin-5-gamma-2 chain, hypoxia-inducible factor-1a, cyclooxygenase-2 and the Hedgehog signaling pathway have been investigated, useful prognostic makers or factors have not been established. As GBC is often discovered incidentally after routine cholecystectomy and accurate preoperative diagnosis is difficult, close mutual cooperation between surgeons and pathologists is essential for developing a rational surgical strategy for GBC.
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Fujita K, Sugiyama A, Otoshi K, Taogoshi T, Kimura Y, Kishikawa N, Kodama M, Kanno K, Kihira K, Tazuma S. Partial characterization of proapoptotic action of biliary deteriorated lipids on biliary epithelial cells in pancreaticobiliary diseases. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2013; 21:212-8. [DOI: 10.1002/jhbp.20] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Affiliation(s)
- Keiko Fujita
- Department of Pharmaceutical Services; Hiroshima University Hospital; Hiroshima Japan
| | - Akiko Sugiyama
- Department of General Internal Medicine; Hiroshima University Hospital; Hiroshima Japan
| | - Kasumi Otoshi
- Department of Pharmaceutical Services; Hiroshima University Hospital; Hiroshima Japan
| | - Takanori Taogoshi
- Department of Pharmaceutical Services; Hiroshima University Hospital; Hiroshima Japan
| | - Yasuhiro Kimura
- Department of Pharmaceutical Services; Hiroshima University Hospital; Hiroshima Japan
| | - Nobusuke Kishikawa
- Department of General Internal Medicine; Hiroshima University Hospital; Hiroshima Japan
| | - Masanobu Kodama
- Department of General Internal Medicine; Hiroshima University Hospital; Hiroshima Japan
| | - Keishi Kanno
- Department of General Internal Medicine; Hiroshima University Hospital; Hiroshima Japan
| | - Kenji Kihira
- Department of Pharmaceutical Services; Hiroshima University Hospital; Hiroshima Japan
| | - Susumu Tazuma
- Department of General Internal Medicine; Hiroshima University Hospital; 1-2-3 Kasumi, Minami-ku Hiroshima 734-8551 Japan
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Siegel AB, Sheynzon V, Samstein B. Uncommon Hepatobiliary Tumors. TEXTBOOK OF UNCOMMON CANCER 2012:423-440. [DOI: 10.1002/9781118464557.ch30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Beltrán MA. Current knowledge on pancreaticobiliary reflux in normal pancreaticobiliary junction. Int J Surg 2012; 10:190-3. [PMID: 22361306 DOI: 10.1016/j.ijsu.2012.02.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2012] [Accepted: 02/13/2012] [Indexed: 02/07/2023]
Abstract
Knowledge on pancreaticobiliary reflux in normal pancreaticobiliary junction and their pathologic implications has experienced tremendous progress during the last few years. This article reviews the current knowledge on this condition and its pathological implications on gallbladder diseases. Many publications with different levels of evidence were found supporting biliary carcinogenesis associated with pancreaticobiliary reflux in normal and abnormal pancreaticobiliary junction. Also, there are many publications supporting the common occurrence of pancreaticobiliary reflux in normal pancreaticobiliary junction, and sphincter of Oddi dysfunction as the most plausible cause of this condition. Although an important body of research has been published regarding pancreaticobiliary reflux in normal pancreaticobiliary junction and their clinical significance, the current evidence does not fully support what has been suggested. The reflux of pancreatic enzymes into the bile tract and gallbladder is a fascinating subject of study which is open to active research. The final demonstration of the pathophysiology and consequences of PBR in NPBL and support by evidence level type I would constitute a major breakthrough in the understanding and eventually in the treatment of gallbladder diseases.
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Affiliation(s)
- Marcelo A Beltrán
- Department of Surgery, Hospital de La Serena, P.O. Box 912, La Serena, IV Región, Chile.
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7
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Beltrán MA. Pancreaticobiliary reflux in patients with a normal pancreaticobiliary junction: Pathologic implications. World J Gastroenterol 2011; 17:953-62. [PMID: 21448346 PMCID: PMC3057156 DOI: 10.3748/wjg.v17.i8.953] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2010] [Revised: 12/03/2010] [Accepted: 12/10/2010] [Indexed: 02/06/2023] Open
Abstract
Knowledge on pancreaticobiliary reflux in normal pancreaticobiliary junction and its pathologic implications has experienced tremendous progress during the last few years. This editorial reviews the current knowledge on this condition and its pathological implications on gallbladder diseases. The following aspects were defined appropriate for discussion: (1) Evidence of carcinogenesis associated with pancreaticobiliary reflux; (2) Evidence of pancreaticobiliary reflux in normal pancreaticobiliary junction; and (3) Evidence of sphincter of Oddi (SO) dysfunction as a cause of pancreaticobiliary reflux in normal pancreaticobiliary junction. The articles reviewed were selected and classified according to five levels of evidence: LevelI, meta-analysis double-blind randomized clinical trials, Level II, cohort non-blinded studies and non-randomized clinical trials, Level III, good quality case-control studies and non-randomized cohort studies, Level IV, case series and poor quality case-control studies, and Level V, case report articles and experts’ opinion. Evidence levels II, III, IV and V were found to support biliary carcinogenesis associated with pancreaticobiliary reflux in normal and abnormal pancreaticobiliary junction. The same levels of evidence were found to support the common occurrence of pancreaticobiliary reflux in normal pancreaticobiliary junction, and SO dysfunction as the most plausible cause of this condition. Although an important body of research has been published regarding pancreaticobiliary reflux in normal pancreaticobiliary junction and its clinical significance, the current evidence does not fully support what has been suggested. Studies with evidence level I have not been undertaken. This is a fascinating subject of study, and if finally supported by evidence level I, the importance of this condition will constitute a major breakthrough in biliary pathology.
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Pancreaticobiliary Reflux in Patients with and without Cholelithiasis: Is It a Normal Phenomenon? World J Surg 2010; 34:2915-21. [DOI: 10.1007/s00268-010-0771-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Domínguez-Comesaña E. [Congenital dilations of the biliary tract]. Cir Esp 2010; 88:285-91. [PMID: 20554272 DOI: 10.1016/j.ciresp.2010.04.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2009] [Accepted: 04/19/2010] [Indexed: 02/07/2023]
Abstract
Congenital dilations of the biliary tract are a group of rare conditions, commonly associated with the presence of an abnormality at the junction of the common bile duct and pancreatic duct, which may lead to the reflux of pancreatic juice within the biliary tree. The main clinical symptoms are, abdominal pain, cholangitis and acute pancreatitis, and the most serious complication is malignant degeneration. The treatment of choice is cholecystectomy and complete excision of the bile duct from its bifurcation to its intra-pancreatic segment.
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Abstract
Gallbladder cancer (GBC) shows a marked geographical variation in its incidence, with the highest figures being seen in India and Chile and relatively low levels in many Western countries. Risk factors for its development include the presence of gallstones, infection and the presence of an anomalous pancreatobiliary ductal junction. It can arise from either a pathway involving metaplasia or dysplasia or one in which there is a pre-existing adenoma. The former is the more common and, because it is often not associated with a macroscopically recognizable lesion, leads to the recommendation that all gallbladders need to be examined microscopically. Accurate staging of invasive cancers is essential to determine prognosis and treatment, and this requires extensive tumour sampling. A number of genetic alterations have been identified in the preinvasive and invasive stages of GBC and they support the morphological evidence of there being two pathways by which tumours develop. Some of these genetic changes are associated with particular risk factors. For example, cases with anomalous pancreatobiliary ductal junction show a higher frequency of K-ras mutations. Some changes are associated with differences in prognosis. For example, cancers without expression of p21 but with expression for p27 have a better prognosis, whereas those that express c-erb-B2 have a worse one. Work has also been done on identifying clinical, imaging and other factors that indicate that patients have a higher risk of having GBC. This is particularly important in high-incidence areas in which GBC is a significant public health problem.
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Affiliation(s)
- Robert David Goldin
- Department of Histopathology, Imperial College Faculty of Medicine at St Mary's, London, UK.
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11
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Pancreaticobiliary maljunction and carcinogenesis to biliary and pancreatic malignancy. Langenbecks Arch Surg 2008; 394:159-69. [PMID: 18500533 DOI: 10.1007/s00423-008-0336-0] [Citation(s) in RCA: 110] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2008] [Accepted: 04/04/2008] [Indexed: 02/07/2023]
Abstract
BACKGROUND It is widely accepted that congenital choledochal cyst is associated with pancreaticobiliary maljunction (PBM). But, PBM is an independent disease entity from choledochal cyst. PBM is synonymous with "abnormal junction of the pancreaticobiliary ductal system", "anomalous arrangement of pancreaticobiliary ducts", "anomalous union of bilio-pancreatic ducts", etc. Cases with PBM not associated with biliary duct dilatation are often found, and these cases are frequently complicated gallbladder cancer. The Japanese Study Group of Pancreaticobiliary Maljunction was started in 1983, and defined diagnostic criteria and nationwide registration system of PBM cases was started. PBM is defined as a union of the pancreatic and biliary ducts which is located outside the duodenal wall. Bile and pancreatic juice reflux and regurgitate mutually. BILIARY CARCINOGENESIS The most bothersome problem is biliary carcinogenesis. Gallbladder cancers arise in 14.8% and bile duct cancers arise in 4.9%. The incidence of the gallbladder carcinoma of PBM without bile duct dilatation is 36.1%. Many investigators have tried to clarify the carcinogenic process, from various aspects. The biliary epithelia are injured by harmful substances, and in the course of repair, multiple alterations of oncogenes and tumor suppressor genes are followed, and they lead to carcinoma through multistage interaction. In the biliary epithelia of PBM, incidence and degree of hyperplasia are characteristic. K-ras gene mutations are observed in the cancerous as well as noncancerous lesions of biliary tract of PBM patients. Mutations of p53 gene and overexpression of p53 protein are also found in the cancerous and noncancerous lesions. These changes are called "hyperplasia-carcinoma sequence". TREATMENT Total excision of the extrahepatic bile duct with gallbladder followed by hepaticojejunostomy, Roux-en-Y, or end-to-side hepaticoduodenostomy are treatment of choice, even for cases with not dilated bile duct, because the incidence of cancer in the nondilated bile duct is not negligible, and genetic changes are seen in a nondilated bile duct.
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Abstract
PURPOSE OF REVIEW Adenocarcinomas of the gallbladder are uncommon, aggressive tumors with poor survival. This review summarizes advances in understanding the biology of gallbladder cancer. RECENT FINDINGS Published response rates of adenocarcinomas of the gallbladder to chemotherapy are less than 30% and no survival benefit has been demonstrated from palliative systemic therapy. New information on the molecular carcinogenic mechanisms of these malignancies, combined with findings from animal models, may lead to improved treatment for patients. SUMMARY Improved understanding of the molecular carcinogenesis of adenocarcinomas of the gallbladder, coupled with the availability of novel molecularly 'targeted' chemotherapeutic agents, may improve outcome for patients.
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Kogure H, Tsujino T, Yagioka H, Sasaki T, Nakai Y, Hirano K, Sasahira N, Isayama H, Tada M, Kawabe T, Omata M. Self-expandable metallic stents for malignant biliary obstruction with an anomalous pancreaticobiliary junction. Surg Endosc 2008; 22:787-91. [PMID: 17704880 DOI: 10.1007/s00464-007-9482-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND Anomalous pancreaticobiliary junction (APBJ) is associated with pancreaticobiliary cancer. Limited data are available on endoscopic biliary drainage for unresectable malignant biliary obstruction with APBJ. This study evaluated the efficacy and safety of self-expandable metallic stents (EMSs) for the management of malignant biliary obstruction with APBJ. METHODS Between 1993 and 2005, 324 patients with unresectable malignant biliary obstruction underwent insertion of an EMS. Six of these patients with concomitant APBJ constituted the subjects of this study. Early (</=30 days after EMS insertion) and late (>30 days after EMS insertion) stent-related complications and stent patency were evaluated in these six patients. RESULTS The cause of biliary obstruction was gallbladder cancer in four patients and pancreatic cancer in two patients. Uncovered EMSs were inserted across the common channel without performance of a biliary sphincterotomy. The diameter of the uncovered EMS used was based on the diameter of the common channel. For all six patients, endoscopic biliary drainage was successful, and their jaundice subsided steadily. None of the six patients experienced early complications, including acute pancreatitis. The mean stent-related complication-free period was 163 days. Stent occlusion caused by tumor ingrowth occurred in two patients. Acute cholangitis and cholecystitis were observed in one patient each. CONCLUSIONS Uncovered EMSs are effective for palliation of unresectable malignant biliary obstruction in patients who have APBJ without increasing the risk of stent-related early complications.
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Affiliation(s)
- H Kogure
- Department of Gastroenterology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
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Kianmanesh R, Scaringi S, Castel B, Flamant Y, Msika S. [Precancerous lesions of the gallbladder]. ACTA ACUST UNITED AC 2008; 144:278-86. [PMID: 17925730 DOI: 10.1016/s0021-7697(07)91953-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
This Mini-review summarizes the epidemiology, predisposing and pre-cancerous conditions related to carcinoma of the gallbladder. In 75% of cases, gallbladder cancer is a cholangiocarcinoma, usually presenting in a late and advanced stage, and it carries one of the worst prognoses of all GI malignancies. Early stage disease is usually discovered incidentally by the pathologist in a gallbladder specimen removed for calculous cholecystitis. It occurs three times more frequently in women than in men and invasive forms usually occur after the age of 60. Incidence varies with geographic location. Besides genetic and geographic factors, the presence of one or more large gallstones is a major risk factor. Gallbladder polyps larger than 1.5 cm. (especially solitary sessile hypoechogenic polyps) are associated with a 50% risk of malignancy. Choledochal cysts and other variations of the biliopancreatic junction are also associated with high risk; cancer may occur at a much younger age in these patients and in the absence of gallstones. Porcelain gallbladder is a risk factor, particularly when there is calcification of the gallbladder mucosa. Chronic gallbladder infection has been implicated as a risk factor for malignant degeneration. Finally, cancer of both the gallbladder and the bile ducts is more frequent in patients suffering from primary biliary cirrhosis.
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Affiliation(s)
- R Kianmanesh
- Service de Chirurgie Générale et Digestive, Hôpital Louis Mourier AP-HP, Université Paris VII - Colombes.
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Noun R, Sayegh R, Tohme-Noun C, Honein K, Smayra T, Aoun N. Extracystic biliary carcinoma associated with anomalous pancreaticobiliary junction and cysts. ACTA ACUST UNITED AC 2006; 13:577-9. [PMID: 17139435 DOI: 10.1007/s00534-006-1115-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2005] [Accepted: 02/14/2006] [Indexed: 02/06/2023]
Abstract
Anomalous pancreaticobiliary junction with cystic dilatation of the biliary tract is usually associated with carcinoma arising from the cyst wall. We report an extracystic location of biliary carcinoma in the presence of anomalous pancreaticobiliary junction and cysts in a patient with obstruction of the origin of the left hepatic duct who underwent hepatobiliary resection. Cholangiocarcinoma was found to have arisen in a noncystic left hepatic duct, in conjunction with cystic dilatation involving both the cystic and common bile ducts. The present case supports a relationship between anomalous pancreaticobiliary junction and biliary carcinogenesis that may affect the extracystic biliary tree.
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Affiliation(s)
- Roger Noun
- Department of Digestive Surgery, Hôtel-Dieu de France Hospital, Bd Alfred Naccache, Achrafieh, B.P: 166830, Beirut, Lebanon
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Mannai S, Kraïem T, Gharbi L, Haoues N, Mestiri H, Khalfallah MT. [Congenital cystic dilatation of bile ducts]. ACTA ACUST UNITED AC 2006; 131:369-74. [PMID: 16630531 DOI: 10.1016/j.anchir.2006.03.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2005] [Accepted: 03/15/2006] [Indexed: 11/29/2022]
Abstract
Congenital cystic dilatation of bile ducts is a rare condition. We report a retrospective study about 18 patients having congenital bile duct cysts. According to Todani's classification, 11 cases were type I and 7 were type V. Six patients from the first group had a pancreatobiliary maljunction. A total resection of the cyst was conducted in the type I cysts. Anatomopathologic examination showed an adenocarcinoma of a common bile duct cyst. In one case, a cancer of the gall bladder associated to a common bile duct cyst in another case. Three patients with segmental dilatation of intrahepatic bile ducts (type V) underwent liver resection. Four patients had a diffuse form, one of them was treated by percutaneous drainage, and in the other cases a hepatojejunostomy was performed. Postoperative course was complicated with acute cholangitis in these four cases. Percutaneous drainage and antibiotics allowed a positive outcome in most of the cases. In one case, secondary biliary cirrhosis occurred as a long-term complication. Congenital cystic dilatation of bile ducts is considered to be a precancer state. Enterocystic anastomosis is proscribed and the resection has to be as complete as possible.
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Affiliation(s)
- S Mannai
- Service de Chirurgie Générale, Hôpital Mongi-Slim, 1004 Tunis, Tunisie.
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Kimura Y, Nishikawa N, Okita K, Furuhata T, Mizuguchi T, Nobuoka T, Nishimori H, Zenbutsu H, Satoh M, Katsuramaki T, Hirata K. Biliary Tract Malignancy and Chronic Inflammation from the Perspective of Pancreaticobiliary Maljunction. Oncology 2005; 69 Suppl 1:41-5. [PMID: 16210877 DOI: 10.1159/000086632] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
This is a brief review of pancreaticobiliary maljunction. The basic treatment for this condition includes either cholecystectomy or extrahepatic bile duct resection. When the condition is accompanied by malignancies, a radical operation should be the first treatment option. Knowledge on molecular pathogenesis is gradually increasing. However, studies should be expanded to include larger patient cohorts, and other types of molecules should be carefully investigated and analyzed.
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Affiliation(s)
- Yasutoshi Kimura
- Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
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Hu B, Gong B, Zhou DY. Association of anomalous pancreaticobiliary ductal junction with gallbladder carcinoma in Chinese patients: an ERCP study. Gastrointest Endosc 2003; 57:541-5. [PMID: 12665766 DOI: 10.1067/mge.2003.136] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Anomalous pancreaticobiliary ductal junction, a rare congenital anomaly, is associated with various biliary and pancreatic diseases. The aim of this study was to determine the frequency of anomalous pancreaticobiliary ductal junction in Chinese patients with gallbladder cancer. METHODS One thousand eight hundred seventy-six patients underwent ERCP between April 2000 and September 2001 with biliary and pancreatic duct opacification in 1082. Among the latter patients, those with proven gallbladder carcinoma were identified. Anomalous pancreaticobiliary ductal junction was defined as a common channel greater than 15 mm in length or a contractile segment totally distal to the union of the biliary and pancreatic ducts. When the common bile duct appeared to join the main pancreatic duct, the anomalous pancreaticobiliary ductal junction was denoted as B-P subtype; if the main pancreatic duct appeared to join the common bile duct, it was denoted P-B subtype. RESULTS Fifty-four patients had gallbladder carcinoma, 7 of whom (3 men, 4 women) had anomalous pancreaticobiliary ductal junction (P-B subtype 6, B-P subtype 1). The mean (SD) length of the common channel was 21.0 mm (11.2 mm) with a range of 12 to 45 mm. One patient had early cystic dilation of bile duct. Three other patients had anomalous pancreaticobiliary ductal junction; 1 had an associated choledochal cyst and 2 a normal biliary tree. The overall frequency of anomalous pancreaticobiliary ductal junction was 0.9% (10/1082 cases). The frequency of anomalous pancreaticobiliary ductal junction was significantly higher in patients with gallbladder carcinoma (p < 0.001; OR, 50.7; 95% CI [12.7, 202.3]). CONCLUSIONS Anomalous pancreaticobiliary ductal junction is strongly associated with gallbladder cancer among Chinese patients.
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Affiliation(s)
- Bing Hu
- Endoscopy Center, Eastern Hepatobiliary Hospital, Shanghai, China
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Otani K, Shimizu S, Chijiiwa K, Yamaguchi K, Noshiro H, Tanaka M. Immunohistochemical detection of 8-hydroxy-2'-deoxyguanosine in gallbladder epithelium of patients with pancreaticobiliary maljunction. Eur J Gastroenterol Hepatol 2001; 13:1363-9. [PMID: 11692064 DOI: 10.1097/00042737-200111000-00016] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Pancreaticobiliary maljunction, an anomalous union of the pancreatic duct with the common bile duct, is a risk factor for biliary carcinoma. We hypothesized that, in patients with pancreaticobiliary maljunction, persistent regurgitation of pancreatic juice into the biliary tract induces oxidative DNA damage. We assessed the expression of an oxidative DNA base-modified product, 8-hydroxy-2'-deoxyguanosine, in gallbladder epithelium. DESIGN Eleven noncancerous gallbladders from patients with pancreaticobiliary maljunction, 12 gallbladder carcinomas from patients without pancreaticobiliary maljunction and 14 noncancerous gallbladders from patients without pancreaticobiliary maljunction (control) were studied. METHODS Immunohistochemistry was performed for 4-hydroxy-2-nonenal-modified protein (as a marker for lipid peroxidation), 8-hydroxy-2'-deoxyguanosine and p53 gene product. RESULTS Stronger cytoplasmic staining of 4-hydroxy-2-nonenal-modified protein was observed in the gallbladder epithelium from patients with pancreaticobiliary maljunction than in epithelium from gallbladder cancer patients or from control subjects with normal gallbladders. Clear, strong nuclear staining of 8-hydroxy-2'-deoxyguanosine was observed in the gallbladder epithelial cells from patients with pancreaticobiliary maljunction. Densitometric quantitation revealed significantly higher expression of 8-hydroxy-2'-deoxyguanosine in gallbladder epithelial cells from patients with pancreaticobiliary maljunction (index 27.3 +/- 3.1) than in cells from patients with gallbladder carcinoma (11.4 +/- 1.5; P < 0.05) or from control subjects with normal gallbladder (6.4 +/- 1.0; P < 0.05). Positivity of p53 was 27% in gallbladder epithelium associated with pancreaticobiliary maljunction, 75% in gallbladder carcinoma epithelium and 0% in control epithelium. CONCLUSIONS These results suggest that reactive oxygen species are produced in the gallbladder of patients with pancreaticobiliary maljunction and that oxidative DNA injury is related to carcinogenesis in these patients.
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Affiliation(s)
- K Otani
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Nambu A, Ichikawa T, Katoh K, Araki T. A case of abnormal pancreaticobiliary junction evidenced by 3D drip infusion cholangiography CT. J Comput Assist Tomogr 2001; 25:653-5. [PMID: 11473200 DOI: 10.1097/00004728-200107000-00023] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
We report a case of abnormal pancreaticobiliary junction (APBJ), in which three-dimensional (3D) drip infusion cholangiography (DIC) computed tomography (CT) was useful to make the diagnosis. The 3D DIC CT clearly demonstrated reflux of the contrast material into the main pancreatic duct as well as a long common channel, dilated biliary tree, and duodenal lumen. Thereby, we could diagnose APBJ. We believe that 3D DIC CT is a valuable method in the evaluation of patients with suspected APBJ.
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Affiliation(s)
- A Nambu
- Department of Radiology, Kofu Municipal Hospital, Kofu City, Yamanashi Prefecture, Japan.
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