Cystic duct dysplasia after cholecystectomy: a systematic review of the literature

Cystic duct dysplasia after cholecystectomy: a systematic review of the literature | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Cystic duct dysplasia after cholecystectomy: a systematic review of the literature Francesco Mongelli, Agnese Cianfarani, Matteo Di Giuseppe, Antonjacopo Ferrario Di Tor Vajana, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.11161/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Oct, 2019 Read the published version in International Surgery Journal → Version 1 posted You are reading this latest preprint version Abstract Purpose Approximately 1 to 3.5% of cholecystectomies are found to have incidental dysplasia on histological examination. Cases of positive resection margins on the cystic stump are rare and evidence lack. The aim of this article was to systematically review the literature and to suggest a possible management algorithm. Methods We searched PubMed, Cochrane Library and Google Scholar databases by combining “cholecystectomy” AND “dysplasia” AND “cystic” according to PRISMA guidelines. Studies providing information about cystic duct dysplasia with positive resection margin after cholecystectomy were included. Results The searches identified 109 articles from PubMed and 4 articles from Cochrane Library and Google Scholar, of which three were eligible. Five were found to have post-operative high-grade dysplasia, one patient had a carcinoma and one had a low-grade dysplasia. Median follow-up was of 10.5 months (range: 0.5 – 26.6 months), no evidence of recurrence was found in patients with dysplasia, while the patient with diagnosis of cholangiocarcinoma died during follow-up. Conclusions Patients with positive resection margins for dysplasia after cholecystectomy should be considered for a surgical treatment. The latter depends on several factors related to the patient and the grade of dysplasia itself. Simple cystic duct stump excision has been suggested and it seems to be safe and effective with no evidence of recurrence during follow-up when a R0 resection is achieved. A multidisciplinary approach and a surveillance program should be always taken into account. Hepatobiliary & Transplant Surgery gallstone cystic duct cystic stump dysplasia cholecystectomy Figures Figure 1 Figure 2 Figure 3 Background Gallstone disease is an extremely widespread disease, being the estimated prevalence around 10-15% in adult population. Symptoms leading to cholecystectomy can be identified in up to 35% of patients with cholecystolithiasis [1], making the laparoscopic cholecystectomy one of the most commonly performed surgical operations in developed countries [2]. Approximately 1 to 3.5% of cholecystectomies are found to have incidental dysplasia on histological examination [3-5]. Biliary dysplasia is considered a risk factor for the development of an invasive carcinoma [6]. Usually, dysplasia does not reach the resection margin, so that no further treatment is needed after cholecystectomy [7]. The clinical implications and management of the resection margin involvement by dysplastic changes are unknown. In this article, we discuss this matter and suggest a possible management algorithm. Methods Search strategy Two researchers independently searched the PubMed, Cochrane Library and Google Scholar databases by combining “cholecystectomy” AND “dysplasia” AND “cystic” (last update: June 1 2019) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [8]. Inclusion and exclusion criteria Were included studies providing adequate information about the cystic duct or stump dysplasia after cholecystectomy on the histopathological examination. Studies were excluded in case of a proved diagnosis of gallbladder or cystic duct cancer. Study selection and quality assessment Two reviewers independently evaluated titles and abstracts to choose potential studies. If data were duplicated or overlapping, only the most recent data were included. Studies not matching inclusion and exclusion criteria were discarded. Studies potentially suitable for inclusion were evaluated in full-text. Disagreements were resolved by discussion. The evidence quality of was assessed with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE approach) [9]. In particular, it was rated from 4 to 1, corresponding 4 to a high level of evidence, 3 to moderate, 2 to low and 1 to very low. With this methodology, the risk of bias, inconsistency, indirectness, imprecision and publication bias were considered to possibly reduce the quality of evidence by 1 or 2 points according to the importance of the factor itself. Results The searches identified 109 articles from PubMed and 4 articles from Cochrane Library and Google Scholar. After removing duplicates, 110 studies remained. Abstracts and titles were screened and 12 articles were considered potentially eligible. Full texts of these studies were retrieved and analysed. Nine studies were excluded because did not match inclusion and exclusion criteria. Finally, three studies were found eligible and considered in this systematic review [10-12] (Figure 1). The characteristics of the included studies are given in Table 1. Seven patients were found in the medical literature. Median age at the moment of the diagnosis was 61 years old (range: 36 – 77). Pre-operative radiographic abnormalities were detected only in 2 out of 7 patients. Four patients had simple cystic duct resection with one 1 case of bile duct exploration for gallstone, 1 patient had cystic duct resection with lymphadenectomy and IV and V segments hepatectomy, 2 patients had bile duct resection with lymphadenectomy , in 1 case with associated IV and V segments hepatectomy. Five patients were found to have post-operative high-grade dysplasia, one patient had a carcinoma and one had a low-grade dysplasia. Median follow-up was of 10.5 months (range: 0.5 – 26.6 months), no evidence of recurrence was found in patients with dysplasia. The patient with pathological diagnosis of cholangiocarcinoma died during follow-up after 15.3 months after surgery. Based on these considerations the proposal for a therapeutic algorithm is presented in figure 2. According to the GRADE approach, due to sparse data and other limitations in the quality of selected studies, the overall quality of evidence of this systematic review was judged “very low” (level of evidence 5). Discussion Cancers of the biliary tract could involve the intra- and extrahepatic ducts, gallbladder and ampulla [13]. The involved biliary segment has been described to vary among different countries, being the intrahepatic carcinoma more common in Asia and the gallbladder cancer in South America. Gallstones are the most important risk factor for the development of a gallbladder cancer and in 70-90% of cases of gallbladder cancer gallstones can be identified [14]. Chronic inflammation, Caroli’s disease, choledochal cysts, infectious diseases as well as a variety of biological and chemical toxins are further factors associated with biliary cancer development [14]. The carcinogenesis of biliary neoplasm is thought to be a multi-step process from metaplasia to malignant degeneration. Antral metaplasia, hyperplasia, non-neoplastic polyps represent non-neoplastic lesions and can be found in around 9 - 59.5% of cases after cholecystectomy [15,16]. The bile-type epithelium with columnar cells and round to oval uniform nuclei differ from the dysplastic changes that are characterized by the loss of epithelium architecture, increased height of cells and nuclear crowding with presence of mitotic figures (figure 3). While reactive changes blend gradually with the normal cells’ architecture, real dysplasia has sharp demarcated areas adjacent to the normal biliary epithelium [6]. Depending on the severity of atypia, dysplasia can be defined as either low- or high-grade. Terms like “moderate” or “severe” dysplasia, as well as “carcinoma in situ” are used to describe histological changes of biliary epithelium. Zen et al. [17] described two main types of premalignant dysplastic lesions: the biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasms (IPN-B). The latter is considered less common, it is associated with ectasia of extrahepatic biliary ducts and cysts formation with an exophytic proliferation of biliary epithelium. Moreover, it can be associated with abdominal pain and jaundice. Zen et al. [17] originally described BilIN as microscopic alterations, asymptomatic and not appreciable with imaging studies. BilIN is frequently detectable in specimens with invasive carcinoma and is an incidental finding in 1% to 3.5% of cholecystectomies. BilIN was recently classified by the World Hospital Organization according to the degree of atypia in BilIN1, BilIN2 and BilIN3 [18]. Therefore, BilIN1 corresponds to low-grade, BilIN2 to intermediate grade and BilIN3 to a high-grade of dysplasia. Although this grading-system may be useful, in daily practice it is easier to apply a two-tiered system (low-grade and high-grade dysplasia). The 5-year survival rate of patients with cholangiocarcinoma is thought to be around 5%-10%. An improved overall survival can only be achieved through a complete surgical resection with tumour-free margins [19] but, unfortunately, these surgical results are difficult to achieve as frequently an advanced disease is diagnosed [20]. Mizumoto et al. [21] reported a 5-year survival rate for early bile duct cancer of 100%. Kurosaki et al. [22] reported a 5-year survival rate for 7 patients with pT1 bile duct cancer of 86%. Therefore, in case of biliary dysplasia, strategies involving prophylactic surgical resections or detection of cancers at early stage could have a dramatic impact on patient’s prognosis. Bickenbach et al. [10] reported a series of five patients with high-grade dysplasia at the cystic duct margin after cholecystectomy without preoperative evidence of malignancy. One of the five patients was found to have a carcinoma and deceased after 15 months despite proper surgery and adjuvant chemotherapy. From this small series, the authors concluded that the risk of underlying bile duct cancer in case of high-grade dysplasia at the cystic stump is not neglectable, as about 10% of biliary carcinomas are multifocal. So, high-grade dysplasia of the cystic stump could represent multifocal neoplastic changes of biliary ducts or express a wide extension of an underlying malignancy. In a recent case report, Moslim et al. [11] suggested the surgical intervention with excision and reconstruction of the main duct in case of positive cystic duct resection margins. More recently, Cianfarani et al. [12] reported a case of positive resection margins for low-grade dysplasia on the cystic duct that was successfully surgical treated with a cystic stump resection. The lack of literature about the surveillance of cystic duct dysplasia makes difficult to draw conclusions. A possible management algorithm is shown in figure 2. Due to the known progression to carcinoma and the multifocality, a multidisciplinary board evaluation in case of dysplasia of the cystic duct is strongly advisable. The surgical treatment of positive resection margins after cholecystectomy with high-grade dysplasia should be considered mandatory. The treatment of cases with low-grade dysplasia should be tailored on patient’s age and general conditions, but a surgical resection can be a reasonable option. Due to the high rate of dysplasia multifocality, an optimal surveillance program should be considered in patient with low- and high-grade dysplasia. There is no evidence that supports one or the other method, so that its choice should be based on the local experience and resources. MRCP, ERCP with SpyGlass cholangioscopy, echoendoscopy and regular liver function tests can play a role in surveillance programs. The main limitation of our study is the sparse data available in literature on positive resection margins for dysplasia after cholecystectomy. A case series and two case reports make difficult to draw proper conclusions. Nevertheless, literature on the gallbladder and the biliary tree dysplasia provides sufficient data to propose a possible treatment algorithm for this uncommon condition. Conclusions Patients with positive resection margins for dysplasia after cholecystectomy should be considered for a surgical treatment. The latter depends on several factors related to the patient and the grade of dysplasia itself. Simple cystic duct stump excision has been suggested and it seems to be safe and effective with no evidence of recurrence during follow-up when a R0 resection is achieved. A multidisciplinary approach and a surveillance program should be always taken into account. Our possible management algorithm of this uncommon disease needs to be validated and should be the matter of future studies. Abbreviations PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses. MRCP: Magnetic Resonance Cholangiopancreatography. ERCP: Endoscopic Retrograde Cholangiopancreatography. BilIN: Biliary intraepithelial neoplasia. IPN-B: intraductal papillary neoplasms. GRADE: Grading of Recommendations, Assessment, Development and Evaluations. Declarations Ethics approval and consent to participate: this study was cleared with the institution review board (IRB) with positive result. Documentation is available on request to the corresponding author. Consent for publication: not applicable. Availability of data and materials: The dataset used and/or analysed during the current study is available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: The authors report no grant or financial support. Authors' contributions: Protocol/project development: FM, AC, MDG, AFTV. Data acquisition and interpretation of data: FM, DLR, AS, FG, MDG. Statistics analysis of data: AC, AS. Manuscript drafting: DLR, FM, AS, AC, FG. Manuscript Revision and accountable for all aspects of the work: FM, AC, MDG, AFTV AS, FG, DLR. All authors read and approved the final manuscript. Acknowledgements: References Schirmer BD, Winters KL, Edlich RF. Cholelithiasis and cholecystitis. J Long Term Eff Med Implants. 2005;15:329-38. Gurusamy KS, Davidson BR. Gallstones. BMJ 2014; 348:g2669. Talreja V, Ali A, Khawaja R, Rani K, Samnani SS, Farid FN. Surgically Resected Gall Bladder: Is Histopathology Needed for All? Surg Res Pract. 2016;2016:9319147. Roa I, Ibacache G, Muñoz S, de Aretxabala X. Gallbladder cancer in Chile: Pathologic characteristics of survival and prognostic factors: analysis of 1,366 cases. Am J Clin Pathol. 2014;141:675-82. Wrenn SM, Callas PW, Abu-Jaish W. Histopathological examination of specimen following cholecystectomy: Are we accepting resect and discard? Surg Endosc. 2017;31:586-93. Katabi N. Neoplasia of gallbladder and biliary epithelium. Arch Pathol Lab Med. 2010;134:1621–7. Rais R, González I, Chatterjee D. Dysplasia in Gallbladder: What Should We Do? J Gastrointest Surg. 2019;23:686-9. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62:1006-12. Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64:401-6. Bickenbach KA, Shia J, Klimstra DS, DeMatteo RP, Fong Y, Kingham TP et al. High-grade dysplasia of the cystic duct margin in the absence of malignancy after cholecystectomy. HPB (Oxford). 2011;13:865-8. Moslim MA, Tang A, Morris-Stiff G. Management of high-grade dysplasia of the cystic duct after cholecystectomy. BMJ Case Rep. 2017;2017. Cianfarani A, Mongelli F, Di Giuseppe M, La Regina D. Dysplasia of Cystic Duct and Positive Resection Margins after Cholecystectomy: A Challenging Decision Making Process. J Surg 2019;4:1195. Klöppel G, Adsay V, Konukiewitz B, Kleeff J, Schlitter AM, Esposito I. Precancerous lesions of the biliary tree. Best Pract Res Clin Gastroenterol. 2013;27:285-97. Marcano-Bonilla L, Mohamed EA, Mounajjed T, Roberts LR. Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations. Chin Clin Oncol. 2016;5:61. Esendağlı G, Akarca FG, Balcı S, Argon A, Erhan SŞ, Turhan N et al. A Retrospective Evaluation of the Epithelial Changes/Lesions and Neoplasms of the Gallbladder in Turkey and a Review of the Existing Sampling Methods: A Multicentre Study. Turk Patoloji Derg. 2018;34:41-8. Mukhopadhyay S, Landas SK. Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens. Arch Pathol Lab Med. 2005;129:386–90. Zen Y, Aishima S, Ajioka Y, Haratake J, Kage M, Kondo F et al. Proposal of histological criteria for intraepithelial atypical/proliferative biliary epithelial lesions of the bile duct in hepatolithiasis with respect to cholangiocarcinoma: preliminary report based on interobserver agreement. Pathol Int. 2005;55:180-8. Akiba J, Nakashima O, Hattori S, Tanikawa K, Takenaka M, Nakayama M et al. Clinicopathologic analysis of combined hepatocellular-cholangiocarcinoma according to the latest WHO classification. Am J Surg Pathol. 2013;37:496-505. Cillo U, Fondevila C, Donadon M, Gringeri E, Mocchegiani F, Schlitt HJ et al. Surgery For Cholangiocarcinoma. Liver Int. 2019. Epub ahead of print. Cha JM, Kim MH, Jang SJ. Early bile duct cancer. World J Gastroenterol. 2007;13:3409-16. Mizumoto R, Ogura Y, Kusuda T. Definition and diagnosis of early cancer of the biliary tract. Hepatogastroenterology. 1993 Feb;40:69-77. Kurosaki I, Tsukada K, Watanabe H, Hatakeyama K. Prognostic determinants in extrahepatic bile duct cancer. Hepatogastroenterology. 1998;45:905-9. Tables Table 1: Patient characteristics of included studies Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Sex Male Female Male Male Female Female Female Age (years) 66 77 61 65 57 36 44 Preoperative imaging MRCP PET/CT MRCP CT MARCP MRCP ERCP CT MRCP ERCP No preoperative images Preoperative pathology High-grade dysplasia High-grade dysplasia High-grade dysplasia High-grade dysplasia High-grade dysplasia High-grade dysplasia Low-grade dysplasia Radiographic abnormality Mildly dilated cystic duct stump Borderline enlarged lymph node No suspicious findings No suspicious findings Minimal thickening of cystic stump Small lesions in segments III and IV of the liver No suspicious findings No suspicious findings - Operation Bile duct resection, portal lymphadenectomy, partial hepatectomy segments IV and V Cystic duct excision, portal Lymphadenectomy, partial hepatectomy segments IV and V Cystic duct excision, common bile duct exploration with removal of stone Bile duct resection and portal lymphadenectomy Cystic duct resection Cystic duct resection Cystic duct resection Operative findings Palpable mass at cystic duct remnant, enlarged portal lymph nodes None Common bile duct stones Palpable mass at cystic duct remnant No liver lesions identified None None None Pathology Cholangiocarcinoma (T2N1) 4/6 nodes positive No evidence of malignancy or dysplasia No evidence of malignancy or dysplasia No evidence of malignancy or dysplasia No evidence of malignancy or dysplasia No evidence of malignancy or dysplasia No evidence of malignancy or dysplasia Status Deceased during follow-up after 15.3 months No evidence of disease after 0.9 months No evidence of disease after 16.0 months No evidence of disease after 25.6 months No evidence of disease after 2.1 months No evidence of disease after 0.5 months Not reported MRCP, magnetic resonance cholangiopancreatography; PET, positron emission tomography; CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; CBD, common bile duct. Supplementary Files PRISMANMAchecklist.docx Cite Share Download PDF Status: Published Journal Publication published 24 Oct, 2019 Read the published version in International Surgery Journal → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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2","display":"","copyAsset":false,"role":"figure","size":804969,"visible":true,"origin":"","legend":"Flow chart of the literature search according to PRISMA Guidelines.","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2071/v1/Figure 2.jpg"},{"id":606490,"identity":"610f1222-49d4-4cd4-b9d5-905a11cd35bc","added_by":"auto","created_at":"2020-03-06 14:30:03","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2178340,"visible":true,"origin":"","legend":"Histologic exam showing a low-grade dysplasia on the cystic duct stump.","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-2071/v1/Figure 3.jpg"},{"id":13468308,"identity":"0fa036e7-ea45-46ba-bc4d-f2040792b276","added_by":"auto","created_at":"2021-09-16 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in adult population. Symptoms leading to cholecystectomy can be identified in up to 35% of patients with cholecystolithiasis [1], making the laparoscopic cholecystectomy one of the most commonly performed surgical operations in developed countries [2].\u003c/p\u003e\n\u003cp\u003eApproximately 1 to 3.5% of cholecystectomies are found to have incidental dysplasia on histological examination [3-5]. Biliary dysplasia is considered a risk factor for the development of an invasive carcinoma [6]. Usually, dysplasia does not reach the resection margin, so that no further treatment is needed after cholecystectomy [7]. The clinical implications and management of the resection margin involvement by dysplastic changes are unknown.\u003c/p\u003e\n\u003cp\u003eIn this article, we discuss this matter and suggest a possible management algorithm.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eSearch strategy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo researchers independently searched the PubMed, Cochrane Library and Google Scholar databases by combining \u0026ldquo;cholecystectomy\u0026rdquo; AND \u0026ldquo;dysplasia\u0026rdquo; AND \u0026ldquo;cystic\u0026rdquo; (last update: June 1 2019) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [8].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion and exclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWere included studies providing adequate information about the cystic duct or stump dysplasia after cholecystectomy on the histopathological examination. Studies were excluded in case of a proved diagnosis of gallbladder or cystic duct cancer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy selection and quality assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo reviewers independently evaluated titles and abstracts to choose potential studies. If data were duplicated or overlapping, only the most recent data were included. Studies not matching inclusion and exclusion criteria were discarded. Studies potentially suitable for inclusion were evaluated in full-text. Disagreements were resolved by discussion. The evidence quality of was assessed with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE approach) [9]. In particular, it was rated from 4 to 1, corresponding 4 to a high level of evidence, 3 to moderate, 2 to low and 1 to very low.\u0026nbsp; With this methodology, the risk of bias, inconsistency, indirectness, imprecision and publication bias were considered to possibly reduce the quality of evidence by 1 or 2 points according to the importance of the factor itself.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe searches identified 109 articles from PubMed and 4 articles from Cochrane Library and Google Scholar. After removing duplicates, 110 studies remained. Abstracts and titles were screened and 12 articles were considered potentially eligible. Full texts of these studies were retrieved and analysed. Nine studies were excluded because did not match inclusion and exclusion criteria. Finally, three studies were found eligible and considered in this systematic review [10-12] (Figure 1). The characteristics of the included studies are given in Table 1.\u003c/p\u003e\n\u003cp\u003eSeven patients were found in the medical literature. Median age at the moment of the diagnosis was 61 years old (range: 36 \u0026ndash; 77). Pre-operative radiographic abnormalities were detected only in 2 out of 7 patients. Four patients had simple cystic duct resection with one 1 case of bile duct exploration for gallstone, 1 patient had cystic duct resection with lymphadenectomy and IV and V segments hepatectomy, 2 patients had bile duct resection with lymphadenectomy , in 1 case with associated IV and V segments hepatectomy. Five patients were found to have post-operative high-grade dysplasia, one patient had a carcinoma and one had a low-grade dysplasia. Median follow-up was of 10.5 months (range: 0.5 \u0026ndash; 26.6 months), no evidence of recurrence was found in patients with dysplasia. The patient with pathological diagnosis of cholangiocarcinoma died during follow-up after 15.3 months after surgery.\u0026nbsp; Based on these considerations the proposal for a therapeutic algorithm is presented in figure 2.\u003c/p\u003e\n\u003cp\u003eAccording to the GRADE approach, due to sparse data and other limitations in the quality of selected studies, the overall quality of evidence of this systematic review was judged \u0026ldquo;very low\u0026rdquo; (level of evidence 5).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCancers of the biliary tract could involve the intra- and extrahepatic ducts, gallbladder and ampulla [13]. The involved biliary segment has been described to vary among different countries, being the intrahepatic carcinoma more common in Asia and the gallbladder cancer in South America. Gallstones are the most important risk factor for the development of a gallbladder cancer and in 70-90% of cases of gallbladder cancer gallstones can be identified [14]. Chronic inflammation, Caroli\u0026rsquo;s disease, choledochal cysts, infectious diseases as well as a variety of biological and chemical toxins are further factors associated with biliary cancer development [14]. The carcinogenesis of biliary neoplasm is thought to be a multi-step process from metaplasia to malignant degeneration. Antral metaplasia, hyperplasia, non-neoplastic polyps represent non-neoplastic lesions and can be found in around 9 - 59.5% of cases after cholecystectomy [15,16]. The bile-type epithelium with columnar cells and round to oval uniform nuclei differ from the dysplastic changes that are characterized by the loss of epithelium architecture, increased height of cells and nuclear crowding with presence of mitotic figures (figure 3). While reactive changes blend gradually with the normal cells\u0026rsquo; architecture, real dysplasia has sharp demarcated areas adjacent to the normal biliary epithelium [6].\u003c/p\u003e\n\u003cp\u003eDepending on the severity of atypia, dysplasia can be defined as either low- or high-grade. Terms like \u0026ldquo;moderate\u0026rdquo; or \u0026ldquo;severe\u0026rdquo; dysplasia, as well as \u0026ldquo;carcinoma in situ\u0026rdquo; are used to describe histological changes of biliary epithelium. Zen et al. [17] described two main types of premalignant dysplastic lesions: the biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasms (IPN-B). The latter is considered less common, it is associated with ectasia of extrahepatic biliary ducts and cysts formation with an exophytic proliferation of biliary epithelium. Moreover, it can be associated with abdominal pain and jaundice.\u003c/p\u003e\n\u003cp\u003eZen et al. [17] originally described BilIN as microscopic alterations, asymptomatic and not appreciable with imaging studies. BilIN is frequently detectable in specimens with invasive carcinoma and is an incidental finding in 1% to 3.5% of cholecystectomies. BilIN was recently classified by the World Hospital Organization according to the degree of atypia in BilIN1, BilIN2 and BilIN3 [18]. Therefore, BilIN1 corresponds to low-grade, BilIN2 to intermediate grade and BilIN3 to a high-grade of dysplasia. Although this grading-system may be useful, in daily practice it is easier to apply a two-tiered system (low-grade and high-grade dysplasia).\u003c/p\u003e\n\u003cp\u003eThe 5-year survival rate of patients with cholangiocarcinoma is thought to be around 5%-10%. An improved overall survival can only be achieved through a complete surgical resection with tumour-free margins [19] but, unfortunately, these surgical results are difficult to achieve as frequently an advanced disease is diagnosed [20]. Mizumoto et al. [21] reported a 5-year survival rate for early bile duct cancer of 100%. Kurosaki et al. [22] reported a 5-year survival rate for 7 patients with pT1 bile duct cancer of 86%. Therefore, in case of biliary dysplasia, strategies involving prophylactic surgical resections or detection of cancers at early stage could have a dramatic impact on patient\u0026rsquo;s prognosis.\u003c/p\u003e\n\u003cp\u003eBickenbach et al. [10] reported a series of five patients with high-grade dysplasia at the cystic duct margin after cholecystectomy without preoperative evidence of malignancy. One of the five patients was found to have a carcinoma and deceased after 15 months despite proper surgery and adjuvant chemotherapy. From this small series, the authors concluded that the risk of underlying bile duct cancer in case of high-grade dysplasia at the cystic stump is not neglectable, as about 10% of biliary carcinomas are multifocal. So, high-grade dysplasia of the cystic stump could represent multifocal neoplastic changes of biliary ducts or express a wide extension of an underlying malignancy. In a recent case report, Moslim et al. [11] suggested the surgical intervention with excision and reconstruction of the main duct in case of positive cystic duct resection margins. More recently, Cianfarani et al. [12] reported a case of positive resection margins for low-grade dysplasia on the cystic duct that was successfully surgical treated with a cystic stump resection.\u003c/p\u003e\n\u003cp\u003eThe lack of literature about the surveillance of cystic duct dysplasia makes difficult to draw conclusions. A possible management algorithm is shown in figure 2. Due to the known progression to carcinoma and the multifocality, a multidisciplinary board evaluation in case of dysplasia of the cystic duct is strongly advisable. The surgical treatment of positive resection margins after cholecystectomy with high-grade dysplasia should be considered mandatory. The treatment of cases with low-grade dysplasia should be tailored on patient\u0026rsquo;s age and general conditions, but a surgical resection can be a reasonable option. Due to the high rate of dysplasia multifocality, an optimal surveillance program should be considered in patient with low- and high-grade dysplasia. There is no evidence that supports one or the other method, so that its choice should be based on the local experience and resources. MRCP, ERCP with SpyGlass cholangioscopy, echoendoscopy and regular liver function tests can play a role in surveillance programs. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; The main limitation of our study is the sparse data available in literature on positive resection margins for dysplasia after cholecystectomy. A case series and two case reports make difficult to draw proper conclusions. Nevertheless, literature on the gallbladder and the biliary tree dysplasia provides sufficient data to propose a possible treatment algorithm for this uncommon condition.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003ePatients with positive resection margins for dysplasia after cholecystectomy should be considered for a surgical treatment. The latter depends on several factors related to the patient and the grade of dysplasia itself. Simple cystic duct stump excision has been suggested and it seems to be safe and effective with no evidence of recurrence during follow-up when a R0 resection is achieved. A multidisciplinary approach and a surveillance program should be always taken into account. Our possible management algorithm of this uncommon disease needs to be validated and should be the matter of future studies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses. MRCP: Magnetic Resonance Cholangiopancreatography. ERCP: Endoscopic Retrograde Cholangiopancreatography. BilIN: Biliary intraepithelial neoplasia. IPN-B: intraductal papillary neoplasms. GRADE: Grading of Recommendations, Assessment, Development and Evaluations.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul\u003e\n\u003cli\u003e\u003cstrong\u003eEthics approval and consent to participate: \u003c/strong\u003ethis study was cleared with the institution review board (IRB) with positive result. Documentation is available on request to the corresponding author.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eConsent for publication: \u003c/strong\u003enot applicable.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eAvailability of data and materials: \u003c/strong\u003eThe dataset used and/or analysed during the current study is available from the corresponding author on reasonable request.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eCompeting interests: \u003c/strong\u003eThe authors declare that they have no competing interests.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eFunding: \u003c/strong\u003eThe authors report no grant or financial support.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eAuthors' contributions: \u003c/strong\u003eProtocol/project development: FM, AC, MDG, AFTV. Data acquisition and interpretation of data: FM, DLR, AS, FG, MDG. Statistics analysis of data: AC, AS. Manuscript drafting: DLR, FM, AS, AC, FG. Manuscript Revision and accountable for all aspects of the work: FM, AC, MDG, AFTV AS, FG, DLR. All authors read and approved the final manuscript.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eAcknowledgements: \u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSchirmer BD, Winters KL, Edlich RF. Cholelithiasis and cholecystitis. J Long Term Eff Med Implants. 2005;15:329-38.\u003c/li\u003e\n\u003cli\u003eGurusamy KS, Davidson BR. Gallstones. BMJ 2014; 348:g2669.\u003c/li\u003e\n\u003cli\u003eTalreja V, Ali A, Khawaja R, Rani K, Samnani SS, Farid FN. Surgically Resected Gall Bladder: Is Histopathology Needed for All? Surg Res Pract. 2016;2016:9319147.\u003c/li\u003e\n\u003cli\u003eRoa I, Ibacache G, Mu\u0026ntilde;oz S, de Aretxabala X. Gallbladder cancer in Chile: Pathologic characteristics of survival and prognostic factors: analysis of 1,366 cases. Am J Clin Pathol. 2014;141:675-82.\u003c/li\u003e\n\u003cli\u003eWrenn SM, Callas PW, Abu-Jaish W. Histopathological examination of specimen following cholecystectomy: Are we accepting resect and discard? Surg Endosc. 2017;31:586-93.\u003c/li\u003e\n\u003cli\u003eKatabi N. Neoplasia of gallbladder and biliary epithelium. Arch Pathol Lab Med. 2010;134:1621\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eRais R, Gonz\u0026aacute;lez I, Chatterjee D. Dysplasia in Gallbladder: What Should We Do? J Gastrointest Surg. 2019;23:686-9.\u003c/li\u003e\n\u003cli\u003eMoher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62:1006-12.\u003c/li\u003e\n\u003cli\u003eBalshem H, Helfand M, Sch\u0026uuml;nemann HJ, Oxman AD, Kunz R, Brozek J et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64:401-6.\u003c/li\u003e\n\u003cli\u003eBickenbach KA, Shia J, Klimstra DS, DeMatteo RP, Fong Y, Kingham TP et al. High-grade dysplasia of the cystic duct margin in the absence of malignancy after cholecystectomy. HPB (Oxford). 2011;13:865-8.\u003c/li\u003e\n\u003cli\u003eMoslim MA, Tang A, Morris-Stiff G. Management of high-grade dysplasia of the cystic duct after cholecystectomy. BMJ Case Rep. 2017;2017.\u003c/li\u003e\n\u003cli\u003eCianfarani A, Mongelli F, Di Giuseppe M, La Regina D. Dysplasia of Cystic Duct and Positive Resection Margins after Cholecystectomy: A Challenging Decision Making Process. J Surg 2019;4:1195.\u003c/li\u003e\n\u003cli\u003eKl\u0026ouml;ppel G, Adsay V, Konukiewitz B, Kleeff J, Schlitter AM, Esposito I. Precancerous lesions of the biliary tree. Best Pract Res Clin Gastroenterol. 2013;27:285-97.\u003c/li\u003e\n\u003cli\u003eMarcano-Bonilla L, Mohamed EA, Mounajjed T, Roberts LR. Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations. Chin Clin Oncol. 2016;5:61.\u003c/li\u003e\n\u003cli\u003eEsendağlı G, Akarca FG, Balcı S, Argon A, Erhan SŞ, Turhan N et al. A Retrospective Evaluation of the Epithelial Changes/Lesions and Neoplasms of the Gallbladder in Turkey and a Review of the Existing Sampling Methods: A Multicentre Study. Turk Patoloji Derg. 2018;34:41-8.\u003c/li\u003e\n\u003cli\u003eMukhopadhyay S, Landas SK. Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens. Arch Pathol Lab Med. 2005;129:386\u0026ndash;90.\u003c/li\u003e\n\u003cli\u003eZen Y, Aishima S, Ajioka Y, Haratake J, Kage M, Kondo F et al. Proposal of histological criteria for intraepithelial atypical/proliferative biliary epithelial lesions of the bile duct in hepatolithiasis with respect to cholangiocarcinoma: preliminary report based on interobserver agreement. Pathol Int. 2005;55:180-8.\u003c/li\u003e\n\u003cli\u003eAkiba J, Nakashima O, Hattori S, Tanikawa K, Takenaka M, Nakayama M et al. Clinicopathologic analysis of combined hepatocellular-cholangiocarcinoma according to the latest WHO classification. Am J Surg Pathol. 2013;37:496-505.\u003c/li\u003e\n\u003cli\u003eCillo U, Fondevila C, Donadon M, Gringeri E, Mocchegiani F, Schlitt HJ et al. Surgery For Cholangiocarcinoma. Liver Int. 2019. Epub ahead of print.\u003c/li\u003e\n\u003cli\u003eCha JM, Kim MH, Jang SJ. Early bile duct cancer. World J Gastroenterol. 2007;13:3409-16.\u003c/li\u003e\n\u003cli\u003eMizumoto R, Ogura Y, Kusuda T. Definition and diagnosis of early cancer of the biliary tract. Hepatogastroenterology. 1993 Feb;40:69-77.\u003c/li\u003e\n\u003cli\u003eKurosaki I, Tsukada K, Watanabe H, Hatakeyama K. Prognostic determinants in extrahepatic bile duct cancer. Hepatogastroenterology. 1998;45:905-9.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Tables","content":"\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eTable 1: Patient characteristics of included studies\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse: collapse; border: none;\" width=\"699\"\u003e\n\u003ctbody\u003e\n\u003ctr style=\"height: 25.35pt;\"\u003e\n\u003ctd style=\"width: 58.0pt; border: none; border-bottom: solid #666666 1.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.35pt;\" width=\"77\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.6pt; border: none; border-bottom: solid #666666 1.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.35pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003ePatient 1\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.35pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003ePatient 2\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.35pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003ePatient 3\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.35pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003ePatient 4\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.35pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003ePatient 5\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.35pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003ePatient 6\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.35pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003ePatient 7\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 7.25pt;\"\u003e\n\u003ctd style=\"width: 58.0pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"77\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eSex \u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.6pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eFemale\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eMale\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eFemale\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eFemale\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 7.25pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eFemale\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 3.4pt;\"\u003e\n\u003ctd style=\"width: 58.0pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 3.4pt;\" width=\"77\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eAge (years)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.6pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 3.4pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e66\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 3.4pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e77\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 3.4pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e61\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 3.4pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e65\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 3.4pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003e57\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 3.4pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e36\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 3.4pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e44\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 31.9pt;\"\u003e\n\u003ctd style=\"width: 58.0pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"77\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003ePreoperative imaging \u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.6pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eMRCP\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003ePET/CT \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eMRCP\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eCT \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eMARCP\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eMRCP\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eERCP\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eCT\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eMRCP\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eERCP\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eNo preoperative images\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 31.9pt;\"\u003e\n\u003ctd style=\"width: 58.0pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"77\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003ePreoperative pathology\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.6pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eHigh-grade dysplasia\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eHigh-grade dysplasia\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eHigh-grade dysplasia\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eHigh-grade dysplasia\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eHigh-grade dysplasia\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eHigh-grade dysplasia\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 31.9pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eLow-grade dysplasia\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 80.05pt;\"\u003e\n\u003ctd style=\"width: 58.0pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 80.05pt;\" width=\"77\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eRadiographic abnormality \u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.6pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 80.05pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eMildly dilated cystic duct stump \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eBorderline enlarged lymph node \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 80.05pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo suspicious findings \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 80.05pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo suspicious findings \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 80.05pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eMinimal thickening of cystic stump \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eSmall lesions in segments III and IV of the liver\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 80.05pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo suspicious findings \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 80.05pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo suspicious findings \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 80.05pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e-\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 25.8pt;\"\u003e\n\u003ctd style=\"width: 58.0pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"77\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eOperation \u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.6pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eBile duct resection, portal \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003elymphadenectomy, partial hepatectomy \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003esegments IV and V \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eCystic duct excision, portal \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eLymphadenectomy, partial hepatectomy \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003esegments IV and V \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eCystic duct excision, common bile duct exploration with removal of stone \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eBile duct resection and portal \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003elymphadenectomy \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eCystic duct resection \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eCystic duct resection \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eCystic duct resection \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 25.8pt;\"\u003e\n\u003ctd style=\"width: 58.0pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"77\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eOperative findings \u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.6pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003ePalpable mass at cystic duct remnant, enlarged portal lymph nodes \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eNone\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eCommon bile duct stones\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003ePalpable mass at cystic duct remnant \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo liver lesions identified \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eNone\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eNone\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eNone\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 26.25pt;\"\u003e\n\u003ctd style=\"width: 58.0pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 26.25pt;\" width=\"77\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003ePathology \u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.6pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 26.25pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eCholangiocarcinoma (T2N1) \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003e4/6 nodes positive \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 26.25pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo evidence of malignancy or dysplasia\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 26.25pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo evidence of malignancy or dysplasia \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 26.25pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo evidence of malignancy or dysplasia \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 26.25pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo evidence of malignancy or dysplasia \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 26.25pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo evidence of malignancy or dysplasia \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 26.25pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo evidence of malignancy or dysplasia \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 25.8pt;\"\u003e\n\u003ctd style=\"width: 58.0pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"77\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003eStatus \u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003cstrong\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.6pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eDeceased during follow-up after 15.3 months \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo evidence of disease after 0.9 months \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo evidence of disease after 16.0 months \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo evidence of disease after 25.6 months \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo evidence of disease after 2.1 months \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; color: #000000; font-family: verdana, geneva;\"\u003eNo evidence of disease after 0.5 months \u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 66.65pt; border: none; border-bottom: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 25.8pt;\" width=\"89\"\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003eNot reported\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin: 0in; margin-bottom: .0001pt; line-height: 150%;\"\u003e\u003cspan style=\"color: #000000; font-size: 10pt; font-family: verdana, geneva;\"\u003e\u003csup\u003e\u003cspan style=\"line-height: 150%;\"\u003eMRCP, magnetic resonance \u003c/span\u003e\u003c/sup\u003e\u003csup\u003e\u003cspan style=\"line-height: 150%;\"\u003echolangiopancreatography; PET, positron emission tomography; CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; CBD, common bile duct.\u003c/span\u003e\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"line-height: 150%;\"\u003e\u003cspan style=\"font-size: 10pt; line-height: 150%; font-family: verdana, geneva; color: #000000;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"gallstone, cystic duct, cystic stump, dysplasia, cholecystectomy","lastPublishedDoi":"10.21203/rs.2.11161/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.11161/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Purpose\n\nApproximately 1 to 3.5% of cholecystectomies are found to have incidental dysplasia on histological examination. Cases of positive resection margins on the cystic stump are rare and evidence lack. The aim of this article was to systematically review the literature and to suggest a possible management algorithm.\n\nMethods\n\nWe searched PubMed, Cochrane Library and Google Scholar databases by combining “cholecystectomy” AND “dysplasia” AND “cystic” according to PRISMA guidelines. Studies providing information about cystic duct dysplasia with positive resection margin after cholecystectomy were included.\n\nResults\n\nThe searches identified 109 articles from PubMed and 4 articles from Cochrane Library and Google Scholar, of which three were eligible. Five were found to have post-operative high-grade dysplasia, one patient had a carcinoma and one had a low-grade dysplasia. Median follow-up was of 10.5 months (range: 0.5 – 26.6 months), no evidence of recurrence was found in patients with dysplasia, while the patient with diagnosis of cholangiocarcinoma died during follow-up.\n\nConclusions\n\nPatients with positive resection margins for dysplasia after cholecystectomy should be considered for a surgical treatment. The latter depends on several factors related to the patient and the grade of dysplasia itself. Simple cystic duct stump excision has been suggested and it seems to be safe and effective with no evidence of recurrence during follow-up when a R0 resection is achieved. A multidisciplinary approach and a surveillance program should be always taken into account.","manuscriptTitle":"Cystic duct dysplasia after cholecystectomy: a systematic review of the literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2019-07-09 20:36:56","doi":"10.21203/rs.2.11161/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e94a8c8a-69ea-4a21-9e3b-7c27a79c5d60","owner":[],"postedDate":"July 9th, 2019","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":15958,"name":"Hepatobiliary \u0026 Transplant Surgery"}],"tags":[],"updatedAt":"2021-07-22T21:13:25+00:00","versionOfRecord":{"articleIdentity":"rs-2071","link":"https://doi.org/10.18203/2349-2902.isj20195155","journal":{"identity":"international-surgery-journal","isVorOnly":true,"title":"International Surgery Journal"},"publishedOn":"2019-10-24 21:13:25","publishedOnDateReadable":"October 24th, 2019"},"versionCreatedAt":"2019-07-09 20:36:56","video":"","vorDoi":"10.18203/2349-2902.isj20195155","vorDoiUrl":"https://doi.org/10.18203/2349-2902.isj20195155","workflowStages":[]},"version":"v1","identity":"rs-2071","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-2071","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}