Duct Margin Research Articles

The impact of positive resection margin in perihilar cholangiocarcinoma, ductal margin vs radial margin.

Resection margin status is the important prognostic factor in resected perihilar cholangiocarcinoma (pCCA). Although the impact of ductal margin (DM) was reported in many studies, the influence of radial margin (RM) is unclear. This study aims to investigate the effect of positive RM on survival. Patients with pCCA underwent curative resection between 2013 and 2018 were retrospectively reviewed. Resection margin status was divided into negative resection margin (R0) and positive resection margin (R1); positive RM alone (RM+) and positive DM with or without positive RM (DM+). Of the 167 pCCA patients, 62 (37.1%) had R1 margin. Among 62 R1 patients; 17 (27.4%) had positive DM alone, 20 (32.3%) had positive RM alone and 25 (40.3%) had both positive DM and RM. The R1 patients had a significantly greater number of lymph node metastasis (LNM) and advanced tumor staging than R0 patients, however there was no difference between the RM + and DM + patients. The median survival time of patients with RM + was significantly poorer than R0 patients (13.8 vs. 24.5 months; p < 0.001, respectively) and similar to the DM + patients (9.1 months, p = 0.556). However, in patients with LNM, those who underwent R0 resection had no statistically significant difference in survival outcomes compared to those with R1 resection. Positive resection margin remains the important prognostic factor, and positive RM is common in these patients. Positive RM also had a comparable effect on survival as positive DM. As a result, in pCCA, surgical resection should target both RM and DM.

The Status of Liver Margin in Perihilar Cholangiocarcinoma: A Multicenter Study.

This study aimed to investigate the prevalence and distribution of carcinoma in the liver margin (LM) of resected perihilar cholangiocarcinoma (pCCA) and establish a method for LM examination. LM is the largest margin in resected pCCA with undefined status and assessment method. 227 pCCA cases underwent major hepatectomy were divided into a discovery cohort (n=101) assessed using serial whole-mount digital large sections (WDLS) combined with small sections, and a control cohort (n=126) assessed using only small sections. The LM R1 resection rate was 38.6% (39/101) in the discovery cohort and 5.6% (7/126) in the control cohort. WDLS identified more LM R1 cases compared to the small section in the discovery cohort (38.6% vs. 5.9%, P<0.001). R0 patients in the discovery cohort had better overall survival and recurrence-free survival than those in the control cohort (both P<0.05). Additionally, 95% of carcinoma was found within 20mm of the proximal ductal margin (DM). A proximal DM distance of<5mm was an independent risk factor for LM R1 resection. Patients with which are more likely to experience R1 compared to those with ≥ 5mm (P<0.001). Positive LM was the significant cause for R1 resection of pCCA and the utilization of WDLS improved the diagnostic accuracy of LM. An examination methodology was established, highlighting the necessity of examining LM within a 20mm radius around the proximal DM, especially in patients with a proximal DM of<5mm.

A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas. These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010. In 2018, Japanese and Korean pathologists reached a consensus, classifying IPNBs into type l and type 2 IPNBs. IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis. From a molecular genetic perspective, IPNBs exhibit early genetic variations, and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs. The histological subtypes of IPNBs include gastric, intestinal, pancreaticobiliary, or oncocytic subtypes, but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin. Due to the rarity of these lesions and the absence of specific clinical and laboratory features, imaging is crucial for the preoperative diagnosis of IPNB, with local bile duct dilation and growth along the bile ducts being the main imaging features. Surgical resection remains the optimal treatment for IPNBs, but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

Impact of Surgical Margin Status on Survival and Recurrence After Pancreaticoduodenectomy for Distal Cholangiocarcinoma: Is Microscopic Residual Tumor (R1) Associated with Higher Rates of Local Recurrence?

Patients undergoing macroscopically curative resection for distal cholangiocarcinoma (DCC) have high recurrence rates and poor prognoses. This study aimed to investigate the impact of surgical margin status on survival and recurrence after resection of DCC, specifically focusing on microscopic residual tumor (R1) and its relationship to local recurrence. This was a retrospective analysis of patients who had undergone pancreaticoduodenectomy (PD) for DCC between 2005 and 2021. Surgical margin was classified as R0, R1cis (positive bile duct margin with carcinoma in situ), and R1inv (positive bile duct margin with an invasive subepithelial component and/or positive radial margin). In total, 29 of 133 patients (21.8%) had R1cis and 23 (17.3%) R1inv. The 5-year overall survival (OS) for R0 (55.7%) did not differ significantly from that for R1cis/R1inv (47.4%/33.6%, respectively). The 5-year recurrence-free survival (RFS) for R0 was significantly longer than that for R1inv (50.1% vs. 17.4%, p = 0.003), whereas RFS did not differ significantly between those with R0 and R1cis. R1cis/R1inv status was not an independent predictor of OS and RFS in multivariate analysis. Cumulative incidence of isolated distant recurrence was significantly higher for R1cis/R1inv than for R0 (p = 0.0343/p = 0.0226, respectively), whereas surgical margin status was not significantly associated with rates of local or local plus distant recurrence. Surgical margin status does not significantly impact OS and RFS in patients undergoing PD for DCC following precise preoperative imaging evaluation. Additionally, R1 status is significantly linked to higher isolated distant recurrence rather than local recurrence, highlighting the importance of multidisciplinary therapy.

Clonal analysis of metachronous double biliary tract cancers.

The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC-related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and β-catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled. Among the 12 metachronous tumors, six exhibited anterograde growth in the lower portion and six exhibited retrograde growth in the upper portion of the biliary tree. Surgical resection of metachronous BTCs resulted in recurrence-free survival in seven, local recurrence in five, and death in two patients. Nine achieved 5-year overall survival after primary surgery. Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3. Each of these was altered in at least three cases. A comparison of the molecular features between 12 paired primary and metachronous BTCs indicated that 10 (83%) metachronous tumors developed in clonal association with corresponding primary tumors either successionally or phylogenically. The remaining two (17%) developed distinctly. The successional tumors consisted of direct or evolved primary tumor clones that spread along the bile duct. The phylogenic tumors consisted of genetically unstable clones and conferred a poor prognosis. Metachronous tumors distinct from their primaries harbored fewer mutations than successional and phylogenic tumors. In conclusion, over 80% of metachronous BTCs that develop following primary BTC resection are probably molecularly associated with their primaries in either a successional or a phylogenetic manner. Comparison between the molecular features of a metachronous tumor and those of a preceding tumor may provide effective therapeutic clues for the treatment of metachronous BTC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Role of Intraoperative Frozen Section Assessment of Proximal Bile Duct Margins and the Impact of Additional Re-Resection in Perihilar Cholangiocarcinomas.

Intraoperative frozen section (FS) analysis to assess the bile duct margin status is commonly used to assess the completeness of resection during surgery for perihilar cholangiocarcinoma (pCCA) resection. However, the impact of additional re-section on the long-term outcome after obtaining an initial positive margin remains unclear. Patients diagnosed as pCCA on preoperative imaging and subjected to curative intent surgery from May 2013 to June 2021 with a minimum follow-up of 2years were included. Intraoperative FS analysis of the proximal bile duct margin was performed in all patients. A positive margin was defined by the presence of invasive cancer. Out of the 62 patients with a preoperative diagnosis of pCCA on imaging, 35 patients were included for final analyses after excluding patients with inoperable disease (on staging laparoscopy or local exploration) and other/benign pathology on the final histopathology report. Out of the 35 patients, patients with postoperative 90-day mortality were excluded from the final survival analysis. FS analysis revealed an initial positive margin in 10 (28.5%) patients. Among 10 patients who underwent re-resection to achieve negative proximal margins, only 5 patients achieved a negative margin (secondary R0). An initial positive margin was associated with poor long-term outcomes. Median disease-free survival (DFS) and overall survival (OS) were 16 and 19.6months for patients with an initial positive margin, but 36 and 58.2months for patients with an initial negative margin, respectively (p = 0.012). The median DFS and OS were significantly lower for those with secondary R0 as compared to primary R0 (16 vs. 36months for DFS, p = 0.117 and 19.6 vs. 58.2months for OS, p = 0.027, respectively). An intraoperative FS positive proximal hepatic duct margin dictates poor long-term outcomes for patients with resectable pCCA. Additional resection has a questionable benefit on survival, when a secondary negative margin is achieved.

Impact of running course of segment 4 hepatic artery on proximal ductal margins status in right hepatectomy for perihilar cholangiocarcinoma

Impact of running course of segment 4 hepatic artery on proximal ductal margins status in right hepatectomy for perihilar cholangiocarcinoma

Positive bile duct margin by perineural invasion may not be a true R1 in pancreaticoduodenectomy

Positive bile duct margin by perineural invasion may not be a true R1 in pancreaticoduodenectomy

Role of routine frozen biopsy of cystic duct margin in resectable gallbladder cancer without jaundice

Role of routine frozen biopsy of cystic duct margin in resectable gallbladder cancer without jaundice

Effects of Cystic Duct Margin Involvement on the Survival Rates of Patients With Gallbladder Cancer: A Propensity Score-Matched Case-Control Study.

Background In gallbladder cancer (GBC), extrahepatic bile duct (EHBD) resection is selectively performed if gross direct extension or microscopic involvement of the cystic duct margin (CDM) is detected. Although CDMis usually sent for frozen biopsy intraoperatively in most centers, there are no studies regarding the routine use of CDM frozen biopsy irrespective of the tumor location and paucity of literature regarding the impact ofCDM status on recurrence-free and overall survival inGBC. The presence of obstructive jaundice in GBC usually indicates the involvement of EHBD or cystic duct-bile duct junction. The present study aimed to analyze the necessity of routineCDM frozen biopsy inpatients with resectable GBC withoutjaundice, regardless of the tumor location. The impact of positive CDM on survival was also evaluated. Methods This retrospective observational case-control study was conducted from May 2009 to March 2021 and included 105 patients with resectable GBC without macroscopic EHBD infiltration andjaundice. Patients were divided into CDM-negative (n=91) and CDM-positive (n=14) groups. Propensity score matchingwas performed for variables such asperformance status, tumor size, tumor-node-metastasis (TNM) stage, and adjuvant chemotherapy. After propensity score matching, 27 patients (CDM-negative=13, CDM-positive=14) were included. The primary outcome was to analyze the role of routine CDM frozen biopsy regardless of tumor location, and secondary outcomes were to study the impact of positive CDM status on survival andevaluate predictive factors for CDM positivity. A subgroup analysis was conducted to assess clinicopathologic characteristics and outcomes of the anatomical location of the tumor. Results Of 105 patients, 91 had negative CDM, and 14 had positive CDM. Among 14 patients with positive CDM, only one patient had a tumor in the fundus/body, and the remaining had a tumor involving the neck. All CDM-positive patients underwent bile duct excision with hepaticojejunostomy. Common bile duct (CBD) involvement was present in 50% of patients with positive CDM in the final histopathological examination. In the matched population, patients with positive CDM had a significantly higher rate of neck tumors (p=0.001). Recurrence-free survival (24 vs. 12 months, p=0.30) and overall survival (24.5 vs. 20 months, p=0.417) were comparable between CDM-negative and CDM-positive groups, respectively. On multivariate analysis, preoperative and intraoperative tumor location were independent predictive factors for CDM positivity. On subgroup analysis, 30 patients had tumor involving the neck of the gallbladder, and the remaining 75 had at the fundus and body of the gallbladder. Neck tumors had inferior recurrence-free survival (17 vs. 30 months, p=0.012) and overall survival (24 vs. 36 months, p=0.048) compared to non-neck tumors. Conclusions Routine use of CDM frozen analysis in patients with resectable GBC without jaundice, regardless of tumor location, can be avoided. Itcan be selectively preferred in patients with GBC involving the neck since tumor location is found to be an independent predictive factorfor CDM positivity. Positive CDM has comparable survival outcomes to negative CDM, providing a similarR0 resection rate and tumor stage.However, neck tumors have aworse prognosis than non-neck tumors.

Proposal of a modified classification for hilar cholangiocarcinoma

Abstract Hilar cholangiocarcinoma is a malignant tumor that originates from the left and right hepatic ducts and their confluence. It is highly malignant and associated with a poor prognosis. Surgical resection is the only available curative treatment option. A scientific classification system can aid in the preoperative assessment of resectability and guide the development of appropriate surgical strategies. Several classification systems are available, with the Bismuth-Corlette (BC) classification being the earliest and most widely used. Similar to many other classifications, the BC classification relies on the secondary branching of the bile ducts as an important anatomical landmark, making it unsuitable for cases with variations in the bile duct anatomy. With advances in understanding the hepatic plate and anatomical structures at the hilum, the secondary bile ducts are no longer considered important anatomical landmarks. Therefore, modifications to the BC classification are needed to align with modern anatomical improvements and advancements in surgical techniques. Herein, we propose a modification to the BC classification. In this new system, the boundary of the hilar plate is considered as limit of the proximal ductal margin and used as an anatomical landmark, rather than the concept of “secondary bile ducts” in the BC classification.

Utility and diagnostic accuracy of intraoperative frozen sections in hepato-pancreato-biliary surgical pathology.

Hepato-pancreato-biliary (HPB) surgeries are one of the most challenging and complex procedures. Intraoperative frozen section (IFS) diagnosis plays a pivotal role in management decisions. Comprehensive large cohort studies evaluating utility of IFS in HPB malignancies are lacking. This study aimed to evaluate the accuracy of frozen section analysis and to analyse discrepancies and impact of IFS on the surgical decisions. This was a retrospective study of IFS received for the HPB specimens between years 2009 and 2021. The results were compared to the permanent sections to evaluate diagnostic accuracy, sensitivity and specificity. Indications, disagreements and impact on the surgical management were analysed. A total of 1008 specimens were evaluated: bile duct margin (279; 27.7%), gallbladder (203; 20.1%), liver lesions (125 cases; 12.4%), lymph nodes (147; 14.6%), pancreatic margin (120; 11.9%) and deposits (134; 13.3%). IFS were diagnosed as negative for malignancy (805; 79.9%), positive for dysplasia (8; 0.8%), suspicious for malignancy (6; 0.6%) and positive for malignancy (189; 18.8%). The overall diagnostic accuracy was 98.4%, and the discordant rate was 1.6%. The sensitivity, specificity, positive predictive value and negative predictive value were 94.7%, 99.4%, 97.5% and 98.6% respectively. The most important reason of discordant results was technical, followed by interpretational and sampling errors. The study demonstrates high diagnostic accuracy (98.4%) of IFS in a large dataset of HPB specimens. This comprehensive analysis apprises of the indications, errors and the impact of IFS diagnosis on subsequent HPB surgical management.

Metastatic lymph node ratio as an important prognostic factor in advanced gallbladder carcinoma with at least 6 lymph nodes retrieved

BackgroundThe metastatic lymph node (LN) ratio (LNR) has shown to be an important prognostic factor in various gastrointestinal malignancies. Nevertheless, the prognostic significance of LNR in gallbladder carcinoma (GBC) remains to be determined.MethodsFrom January 2007 to January 2018, 144 advanced GBC patients (T2–4 stages) who underwent curative surgery with at least 6 LNs retrieved were enrolled. Receiver operating characteristic (ROC) curve was performed to identify the optimal cut-off value for LNR. The clinicopathological features stratified by LNR level were analyzed. Meanwhile, univariate and multivariate Cox regression proportional hazard models were performed to identify risk factors for overall survival (OS).ResultsThe optimal cut-off point for LNR was 0.28 according to the ROC curve. LNR>0.28 was associated with higher rate of D2 LN dissection (P=0.004) and higher tumor stages (P<0.001). Extent of liver resection, extrahepatic bile duct resection, tumor stage, LNR, margin status, tumor differentiation, and perineural invasion were associated with OS in univariate analysis (all P<0.05). GBC patients with LNR≤0.28 had a significantly longer median OS compared to those with LNR>0.28 (27.5 vs 18 months, P=0.004). Multivariate analysis indicated that tumor stage (T2 vs T3/T4; hazard ratio (HR) 1.596; 95% confidence interval (CI) 1.195–2.132), LNR (≤0.28 vs >0.28; HR 0.666; 95% CI 0.463–0.958), margin status (R0 vs R1; HR 1.828; 95% CI 1.148–2.910), and tumor differentiation (poorly vs well/moderately; HR 0.670; 95% CI 0.589–0.892) were independent prognostic factors for GBC (all P<0.05).ConclusionsLNR is correlated to advanced GBC prognosis and is a potential prognostic factor for advanced GBC with at least 6 LNs retrieved.

Can the sampling method affect the detection of incidental gallbladder carcinoma? Comparative analysis of two sampling methods

Gallbladder cancer (GBC) is the most common biliary tract carcinoma and is commonly diagnosed incidentally in cholecystectomies performed for gallstones. GBC are mostly unrecognizable macroscopically, and sampling is therefore import. This single center study aimed to find out the effect of sampling method on the identification rate of incidental GBC by comparing random sampling and longitudinal full-thickness slice sampling, which was developed in high-incidence areas. A hospital electronic database was searched for cholecystectomy specimens submitted to the pathology department between 01/2000 and 03/2016. Cases with a preoperative clinical and/or radiological suspicion of neoplasia and cases with a macroscopically identified mass were excluded from the study. Two groups were formed according to the sampling method: “random sampling” group (Group 1, n = 10,954) and “full-thickness slice sampling” group (Group 2, n = 5254). In the first group, random samples from the fundus, body and neck were submitted in gallbladders without grossly visible pathology. In the second group, a full-thickness slice sampling protocol was performed, wherein a longitudinal full-thickness slice, including fundus, corpus-neck and the cystic duct margin was submitted for each gallbladder. Statistical comparisons of GBC incidence and clinicopathologic features was performed. In group 1, GBC prevalence was 0.6 % and low grade dysplasia (LGD) was detected in 199 cases (1.8 %). In group 2, GBC prevalence was 1.5 %, LGD was detected in 166 cases (3.2 %). The GBC rate in Group 2 was significantly (p < 0.05) higher than Group 1. The two groups did not show any statistically significant differences in age, sex and presence of gallstones (p > 0.05). In conclusion, this is the largest study comparing two grossing methods in gallbladders without preoperative clinical and/or radiological suspicion of malignancy and macroscopically identified mass. This study demonstrates the importance of systematic and algorithmic sampling in the detection of GBC.

Application of mesohepatectomy with caudate lobectomy for the treatment of type III–IV hilar cholangiocarcinoma: a single-center retrospective study

BackgroundThe main surgical procedure for Bismuth‒Corlette III–IV hilar cholangiocarcinoma (HCCA) is hemihepatectomy/extended hemihepatectomy. However, many patients have no opportunity for surgery due to having an insufficient remnant liver volume. Preservation of more liver volume on the premise of ensuring R0 resection is the goal. Mesohepatectomy with caudate lobectomy may be a new method to meet these requirements.MethodsThe clinical data of 41 patients with Bismuth‒Corlette III–IV HCCA, including 18 patients who underwent mesohepatectomy with caudate lobectomy (the mesohepatectomy group) and 23 patients who underwent hemihepatectomy or extended hemihepatectomy (the hemihepatectomy group), were analyzed retrospectively. The perioperative indicators and prognostic survival time between the two groups were analyzed.ResultsThe mesohepatectomy group was compared with the hemihepatectomy group, and the operation time was 7.95 ± 1.2 vs. 7.15 ± 1.5 h (P > 0.05); the intraoperative blood loss was 600.0 ± 153.4 vs. 846.1 ± 366.8 mL (P < 0.05); the postoperative hospital stay was 9.9 ± 2.2 vs. 13.8 ± 3.0 days (P < 0.05); and the R0 resection rate was 100% vs. 87.0% (P > 0.05). The postoperative complications of the two groups included bile leakage (22.2% vs. 21.7%), pleural effusion (11.1% vs. 8.7%), and fever (16.7% vs. 8.7%), with no significant differences in the incidences (P > 0.05). The 1-, 3-, and 5-year survival rates of the two groups were 87.5%, 55.7%, 27.8% and 83.5%, 56.1%, 24.5%, respectively, with no significant differences (P > 0.05).ConclusionsMesohepatectomy with caudate lobectomy can preserve more functional liver volume while ensuring the bile duct margin. It can be applied as the surgical treatment of Bismuth‒Corlette III–IV HCCA.

Multifocal biliary carcinoma; whether synchronous or metastatic: A need to conquer

Multiple synchronous primary carcinoma involving gall bladder, liver and common bile duct are rare and difficult to differentiate with hepatic and extrahepatic bile duct metastasis from single primary. Radiological features, molecular landscape, and even integrated mutational profiling are not of much help. We describe a case of 48-year-old male who presented with jaundice and follow up CT scan raised the suspicion of gall bladder carcinoma with hepatic metastasis. Peroperative frozen section examination revealed adenocarcinoma with involvement of cystic duct margin; however revised common duct margin was free from tumor invasion. Final histopathology on resected gall bladder revealed multifocal adenocarcinoma, while histomorphology of hepatic nodule was consistent with cholangiocarcinoma. Common bile duct a one focus had also revealed adenocarcinoma while cut margins were negative form malignancy. In view of different morphology of gall bladder and hepatic tumor, no continuity of three tumors and single large, firm, non umblicated hepatic nodule, diagnosis of multiple synchronous carcinoma was suggested.

How to interpret the high-grade dysplasia in bile duct margin of biliary tract cancer

How to interpret the high-grade dysplasia in bile duct margin of biliary tract cancer

Prognostic impact of proximal ductal margin status in perihilar cholangiocarcinoma according to the presence or absence of lymph node metastasis

BackgroundAlthough both proximal ductal margin status and lymph node metastasis status influence the survival of patients with perihilar cholangiocarcinoma, the effect of proximal ductal margin status on survival according to lymph node metastasis status is unclear. The aim of this study was, thus, to evaluate the prognostic impact of proximal ductal margin status in perihilar cholangiocarcinoma according to the presence or absence of lymph node metastasis. MethodsConsecutive patients with perihilar cholangiocarcinoma who underwent major hepatectomy between June 2000 and August 2021 were retrospectively reviewed. Patients with Clavien-Dindo grade V complications were excluded from the analysis. Overall survival was assessed according to the combination of lymph node metastasis and proximal ductal margin status. ResultsOf the 230 eligible patients, 128 (56%) were lymph node metastasis negative, and 102 (44%) were lymph node metastasis positive. Overall survival was significantly better in lymph node metastasis negative than lymph node metastasis positive patients (P < .0001). Of the 128 lymph node metastasis–negative patients, 104 (81%) were proximal ductal margin negative, and 24 (19%) were proximal ductal margin positive. In lymph node metastasis–negative patients, overall survival was worse in the proximal ductal margin positive than the proximal ductal margin negative group (P = .01). Of the 102 lymph node metastasis–positive patients, 72 (71%) were proximal ductal margin negative and 30 (29%) were proximal ductal margin positive. In these patients, overall survival was similar between the 2 groups (P = .10). ConclusionIn patients with perihilar cholangiocarcinoma, the prognostic impact of proximal ductal margin positivity on survival might differ according to the presence or absence of lymph node metastasis.

ASO Visual Abstract: Role of Intraoperative Assessment of Proximal Bile Duct Margin Status and Additional Resection of Perihilar Cholangiocarcinoma-Can Local Clearance Trump Tumor Biology? A Retrospective Cohort Study.

ASO Visual Abstract: Role of Intraoperative Assessment of Proximal Bile Duct Margin Status and Additional Resection of Perihilar Cholangiocarcinoma-Can Local Clearance Trump Tumor Biology? A Retrospective Cohort Study.

Role of Intraoperative Assessment of Proximal Bile Duct Margin Status and Additional Resection of Perihilar Cholangiocarcinoma: Can Local Clearance Trump Tumor Biology? A Retrospective Cohort Study.

The aim of this study was to evaluate the clinical implications of the proximal bile duct margin status in resection of perihilar cholangiocarcinoma (PHCC). Intraoperative frozen section (IFS) analysis to assess the bile duct margin status is commonly used during PHCC resection. However, the impact of additional resection after obtaining a positive margin on the long-term outcome remains unclear. Among the 257 patients who underwent PHCC resection, 190 patients with a negative distal margin were included and analyzed. IFS analysis of the proximal bile duct margin was performed in all patients. A positive margin was defined by the presence of either invasive cancer, or carcinoma, insitu. IFS analysis revealed an initial positive margin in 69 (36%) patients. Among 20 patients who underwent re-resection, only 11 patients achieved a negative margin (secondary R0). An initial positive margin was associated with poor long-term outcomes: recurrence-free survival (RFS) and overall survival (OS) were 16 and 25 months for patients with an initial positive margin, but 47 and 63 months for patients with an initial negative margin, respectively (p<0.0001). In contrast, there was no difference in RFS or OS between patients with a secondary R0 margin, and those with a final R1 margin (14 vs. 16 months for RFS, p=0.98, and 23 versus 25 months for OS, p=0.63, respectively). An IFS-positive proximal hepatic duct margin dictates poor long-term outcomes for patients with resectable PHCC. Additional resection has minimal impact on survival, even when negative margin is achieved.