Resection Of Cholangiocarcinoma Research Articles

Influence of steatosis and fibrosis on the outcome after major liver resection of perihilar cholangiocarcinoma

Influence of steatosis and fibrosis on the outcome after major liver resection of perihilar cholangiocarcinoma

Cholangiocarcinoma of the Middle Bile Duct: A Narrative Review.

Resectable cholangiocarcinoma (CCA) arising from the middle of the extrahepatic biliary tree has historically been classified as perihilar or distal CCA, depending on the operation contemplated or performed, namely the associated hepatectomy or pancreaticoduodenectomy, respectively. Segmental bile duct resection is a less invasive alternative for select patients harboring true middle extrahepatic CCA (MCC). A small, yet growing body of literature has emerged detailing institutional experiences with bile duct resection versus pancreaticoduodenectomy or concomitant hepatectomy for MCC. Herein, we provide a brief overview of the epidemiology, preoperative evaluation, and emerging systemic therapies for MCC, and narratively review the existing work comparing segmental resection with pancreaticoduodenectomy or less commonly, hepatectomy, for MCC, with emphasis on the surgical management and oncologic implications of the approach used.

Unveiling the prognostic role of blood inflammatory indexes in a retrospective cohort of patients undergoing liver resection for intrahepatic cholangiocarcinoma.

Systemic inflammation is relevant in intrahepatic cholangiocarcinoma (iCCA), but controversial results exist on the prognostic role of inflammatory indexes and their correlation with tumor microenvironment (TME). We aimed to explore the biological and prognostic values of these indexes. A retrospective cohort study involving iCCA patients who underwent hepatic resection between 2010-2021 was conducted. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and clinic-pathological factors were recorded. Immune-cell subpopulations, isolated from surgical specimens, were analyzed by flow cytometry. NLR and LMR cut-offs were calculated by X-Tile software. Linear regression, Kaplan-Meier, and Cox regression analyses were conducted. A total of 101 iCCA patients were considered. NLR ≥3.83 and LMR <2.28 correlated with worse survival. Patients were divided into groups: 67 (66.3%) in the low-risk and 34 (33.7%) in the high-risk (having at least one worse prognostic ratio). The 5-year overall survival was 49.8% and 18.9% for low- and high-risk groups, respectively (P=0.003). An elevated CA19.9 in the high-risk group gives 2.148 HR (95%CI:1.060-4.349) of mortality and 2.182 HR (95%CI:1.206-3.948) of disease recurrence. Flow cytometry analysis of 20 surgical specimens highlighted that NLR was associated with tumor-derived NLR (P=0.026) and LMR with tumor-infiltrating lymphocytes (P=0.002). In a subset of five high-risk vs five low-risk patients, T-cell evaluation showed a higher prevalence of CD4+ compared to CD8+ cells in the high-risk group (78.5% vs. 21.5%, P<0.0001). Conversely, low-risk patients demonstrated a noteworthy infiltration of CD8+ cells compared to the high-risk group (21.5% vs. 48.7%, P=0.037). The combination of blood inflammatory indexes determined two survival-risk profiles. The correlation between the blood scores and the iCCA microenvironment suggests a link between immune-cell infiltration and the risk group. These findings open the possibility of patient stratification with the chance to identify subgroups suitable for dedicated follow-up and targeted immuno-chemotherapy protocols.

A single institution’s experience with robotic resections of biliary tract cancers: an analysis of the short-term outcomes and long-term survival

IntroductionPerihilar cholangiocarcinoma, intrahepatic cholangiocarcinoma (IHCC), and gall bladder cancer are difficult malignancies to treat and are characterized by a tendency for local recurrence and a generally unfavorable prognosis. Surgical resection offers the only potential cure, conventionally performed via the open approach. Although minimally invasive approaches show promise, data remain limited. MethodsWith the institutional review board’s approval, we prospectively followed 100 patients between 2013 and 2023 who underwent robotic surgical resection for perihilar, IHCC, and gallbladder cholangiocarcinoma. Data are presented as median (mean ± SD). Significance was accepted at P ≤ .05. ResultsThe median patient age was 70 years, and the median operative duration was 333 min, with an estimated blood loss of 200 mL. Importantly, no unplanned conversions occurred, and only 1 intraoperative complication occurred within the IHCC cohort. The median length of stay was 4 days. There were a total of 19 postoperative complications and 19 readmissions within 30 days. Additionally, there were 3 in-hospital mortalities and 5 90-day mortalities. R0 resection was achieved in 87% of patients and R1 resection in 13%. At a median follow-up of 36 months, 62% of patients demonstrated disease-free survival, whereas 6% continued to live with the disease, and 32% did not survive. ConclusionOur experience demonstrates the feasibility and safety of robotic resection for these complex malignancies, yielding promising short-term outcomes. Further investigation is required to ascertain the long-term oncologic outcomes.

Robotic Right Hepatectomy with En Bloc Caudatectomy for Bismuth IIIa Hilar Cholangiocarcinoma: A Video Demonstration of Left-Liver-First Anterior Radical Modular Orthotopic Right Hemihepatectomy.

Minimally invasive resection for perihilar cholangiocarcinoma is a complicated and technically demanding surgical procedure. Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma.1,2 Right hepatectomy with caudate lobe resection is necessary as the treatment for bismuth IIIa hilar cholangiocarcinoma.3 The left-liver-first anterior radical modular orthotopic right hemihepatectomy (LARMORH), which can simplify surgical steps and decrease procedural difficulty, may be a better choice for Bismuth IIIa hilar cholangiocarcinoma.4 However, there are no reports of this approach using robotic technique for this operation. We will provide a detailed introduction to this method through this video. A 45-year-old female patient was diagnosed with a hilar cholangiocarcinoma. Following a 7-day percutaneous biliary drainage of the left intrahepatic bile duct and obtaining informed consent, we performed a robotic radical resection of the HCCA using the LARMORH approach. The patient was positioned supine with the entire bed elevated 20° and tilted 15° to the left. Trocars were placed in position (Fig. 1). After entering the abdominal cavity, it was explored for tumor metastasis. The surgery adopted a left approach, initially exploring the left hepatic artery and vein to further assess resectability. After confirming resectability, the right hepatic artery and gastroduodenal artery (GDA) were dissected. The common bile duct was dissected and transected at its distal end, ensuring R0 surgical margins. Lymph nodes were cleared from the foot side to the head side, confirming the metastasis to the lymph node group 13a, so we further cleared the group 16 and 9 lymph nodes.5 Subsequently, we approached the resection of the right half and the entire caudate lobe with the reverse thinking of left hepatic resection mode, preserving only the left branch of the portal vein and left hepatic artery, and dissecting the liver tissue along the resection plane of the left liver. After transection of the left hepatic duct, the activity space of the left liver was larger and the caudate lobe could be better exposed. The Spiegel lobe was lifted to the right in a "turn the page" fashion for in situ resection of the entire caudate lobe and the right half of the liver. Finally, a bilioenteric anastomosis was performed using the Roux-en-Y method. Robotic right hepatectomy with caudate lobectomy was successfully performed in 450 min, with an estimated blood loss of 200ml. The histological grading was determined as T1aN1M0 (stage IIIB) on the basis of postoperative pathological biopsy results. The patient achieved a satisfactory postoperative recovery and was discharged on the 14th postoperative day without any major complications. Following the operation, the patient received capecitabine chemotherapy according to the Chinese Society of Clinical Oncology (CSCO) criteria. Since September 2022, our team has completed three radical resections for Bismuth IIIa HCCA using this technique. All patients achieved a satisfactory postoperative recovery without any further complications. Robotic left-liver-first anterior radical modular orthotopic right hemihepatectomy for Bismuth IIIa HCCA is both safe and feasible. This method may provide a new surgical approach for patients with type IIIA HCCA or liver diseases requiring right hemihepatectomy combined with total caudate lobectomy.

Initial clinical outcomes of robotic resection for perihilar cholangiocarcinoma: Is it safe and effective?

We aimed to describe our outcomes of robotic resection for perihilar cholangiocarcinoma, the largest single institutional series in the Western hemisphere to date. Between 2016 and 2022, we prospectively followed all patients who underwent robotic resection for perihilar cholangiocarcinoma. In total, 23 patients underwent robotic resection for perihilar cholangiocarcinoma, 18 receiving concomitant hepatectomy. The median age was 73 years. Operative time was 470 min with an estimated blood loss of 150 mL. No intraoperative conversions to open or other intraoperative complications occurred. Median length of stay was 5 days. Four postoperative complications occurred. Three readmissions occurred within 30 days with one 90-day mortality. R0 resection was achieved in 87% of patients and R1 in 13% of patients. At a median follow-up of 27 months, 15 patients were alive without evidence of disease, two patients with local recurrence at 1 year, and six were deceased. Utilization of the robotic platform for perihilar cholangiocarcinoma is safe and feasible with excellent perioperative outcomes. Further studies are needed to determine the long-term oncological outcomes.

Robotic-assisted radical resection versus open surgery for cholangiocarcinoma: a systematic review and meta-analysis.

To compare the clinical efficacy and safety of robot-assisted resection and open surgery for cholangiocarcinoma (CCA). We conducted a comprehensive search of PubMed, the Cochrane Library, and Embase databases for studies comparing treatment for CCA, covering the period from database inception to January 30, 2024. Two researchers will independently screen literature and extract data, followed by meta-analysis using Review Manager 5.3 software. A total of 5 articles with 513 patients were finally included. Among them, 231 in the robotic group, and 282 in the open group. The Meta-analysis revealed that the robotic group had a significant advantage in terms of intraoperative blood loss (MD = -101.44, 95% CI -135.73 to -67.15, P < 0.05), lymph node harvest(MD = 1.03, 95% CI 0.30-1.76, P < 0.05) and length of hospital stay(MD = -1.92, 95% CI -2.87 to-0.97, P < 0.05). However, there were no statistically significant differences between the two groups in terms of transfusion rate (OR = 0.62, 95% CI 0.31-1.23, P > 0.05), R0 resection (OR = 1.49, 95% CI 0.89- 2.50, P > 0.05), 30-day mortality (OR = 1.68, 95% CI 0.43-6.65, P > 0.05) and complications (OR = 0.76, 95% CI 0.30- 1.95, P > 0.05). Robotic-assisted radical resection for CCA is feasible and safe, and its long-term efficacy and oncological outcomes need to be confirmed by further studies.

A snapshot on current approaches to lymphadenectomy in liver resection for intrahepatic cholangiocarcinoma: results from an international survey.

The use of lymphadenectomy (LND) during resection of intrahepatic cholangiocarcinoma (ICC) is still debated, leading to differing practices in different centers and countries. The aim of this study was to assess such differences. A survey on LND for ICC was distributed to the members of the International Hepato-PancreatoBiliary Association (IHPBA) and the Italian Chapter of IHPBA (AICEP). Two-hundred thirty-four surgeons completed the survey (88% males; median age 46 years). Preoperative nodal staging was deemed mandatory/very important by 65%. Adequate LND was defined as hepatoduodenal ligament LND by 33%, LND at specific nodal stations by 28% and retrieval of > 5 nodes by 28%. The decision to perform LND was influenced by comorbidities (48%), chronic liver disease (38%) and satellitosis (32%). Most participants modify perioperative management in case of clinically positive nodes, 50% stating they would give neoadjuvant therapy. The role of LND in clinically node negative disease was adequate staging for 88%, survival benefit for 50.5% and clinical trials eligibility for 18.5%. Our survey confirms heterogeneity in the evaluation of role and extent of LND for ICC, how this relates to subjective perception of importance of LND, and need of a systematic approach in this area.

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.

An assessment of risk factors for recurrence and survival for patients undergoing liver resection for intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy with increasing rates of incidence and mortality. Surgical resection is curative for patients who are diagnosed at early stages of iCCA. Limited data exist regarding risk factors for postresection recurrence and overall survival as iCCA is rare, and majority of patients are diagnosed at an advanced stage and thus not candidates for resection. We aimed to analyze clinical and laboratory characteristics, tumor histology, locoregional invasion, recurrence and survival in patients undergoing curative resection for iCCA. All patients who underwent curative resection for iCCA between 2006 and 2023 at our institution were included in the study. Clinical characteristics, laboratory, histological and follow-up data were collected. The 1-, 3-, and, 5-year survival rates were 90.9%, 65.9% and 44.2%, respectively. About 65.6% of patients had recurrence in a median of 1.2 years after liver resection. Positive surgical margins were present in 20.73% of patients. Notably, 80.51% had solitary tumor and the remaining 19.48% had multifocal tumor. A total of 64.51% of patients received adjuvant chemotherapy after resection. A total of 26 (31.3%) patients had died during the follow-up period. Duration from liver resection to last follow-up or death was 1.6 years (0.8-3.2). Overall median survival was 4.6 years. The presence of lymph node metastases, vascular invasion, positive surgical margin and advanced tumor stage at diagnosis were associated with significantly worse overall survival, which remained significant in multivariable model for advanced tumor stage and positive surgical margin. Despite curative resection, recurrence rate is high and overall survival is poor in patients with iCCA. Real-world data regarding patient characteristics and longitudinal follow-up remain important as iCCA is a rare malignancy.

Effects of preoperative biliary drainage on the outcomes of surgical treatment in cholangiocarcinoma: A propensity score matching analysis

BackgroundHyperbilirubinemia is known to increase morbidity and mortality in patients undergoing liver resection for cholangiocarcinoma (CCA). Preoperative biliary drainage (PBD) in patients who have no acute cholangitis or require portal vein embolization is still debatable. The goal of this study is to investigate how PBD affects the surgical results after liver resection. MethodsBetween October 2013 and December 2020, CCA patients presenting with obstructive jaundice who underwent liver resection were retrospectively reviewed. The pre-operative, peri-operative and post-operative characteristics were extracted. To compare the outcomes of the PBD and direct surgery groups, propensity score matching analysis (PSM) and multivariable risk regression analysis were used to analyze. ResultsA total of 355 patients were enrolled, with 99 of them undergoing PBD. At diagnosis, those with PBD showed significantly greater bilirubin levels than those without (20.7 vs 9.6 ​mg/dL, p ​< ​0.001). However, after drainage, the bilirubin level in the PBD group was lower than the direct surgery group (5.5 vs 9.6 ​mg/dL, p ​< ​0.001). Overall postoperative morbidity and mortality were unaffected by PBD in full patient cohort. However, after PSM, PBD was associated with decreased major post-hepatectomy liver failure (PHLF) and 90-day mortality rate, (20.3% vs 39.24%, p ​= ​0.014 and 3.8% vs 22.8%, p ​= ​0.001, respectively). At multivariable analysis of PSM patient cohort, PBD was associated with decreased major post-operative complication (RR 0.64, 95%CI 0.419–0.986), PHLF (RR 0.40, 95%CI 0.227–0.705) and 90-day mortality (RR 0.21, 95%CI 0.086–0.629). ConclusionPBD was associated with decreased post-hepatectomy liver failure and postoperative mortality after liver resection in jaundiced CCA patients.

Sex disparity in clinical characteristics and long-term prognosis after liver resection for patients with intrahepatic cholangiocarcinoma: A propensity score matching analysis

AimTo compare the survival outcomes between male and female patients with intrahepatic cholangiocarcinoma who underwent liver resection. MethodsData from 976 consecutive intrahepatic cholangiocarcinoma patients undergoing liver resection between January 2005 and May 2013 at the Eastern Hepatobiliary Surgery Hospital were prospectively collected and retrospectively reviewed. Patient clinicopathological characteristics, overall survival, and cumulative recurrence rates were compared between male and female patients using propensity score matching. ResultsPropensity score matching generated 313 matched pairs of patients. Among the entire cohort, the 1-, 3-, and 5-year overall survival and recurrence rates of the male and female patients were 60.2 %, 37.3 %, and 27.7 % vs. 65.8 %, 40.4 %, and 31.0 % (P = 0.380) and 50.6 %, 67.4 %, and 74.2 % vs. 44.4 %, 63.5 %, and 69.6 % (P = 0.123), respectively. In the matched cohort, the 1-, 3-, and 5-year overall survival and recurrence rates of the male and female patients were 60.6 %, 35.9 % and 22.4 % vs. 66.4 %, 40.6 % and 31.1 % (P = 0.041) and 51.5 %, 69.3 % and 83.9 % vs. 44.3 %, 63.6 %, and 69.9 % (P = 0.041), respectively. After adjustment for other confounding variables by multivariate Cox regression analysis, male sex was independently associated with worse overall survival (hazard ratio = 1.322, 95 % confidence interval: 1.079–1.621, P = 0.007) and tumor recurrence (hazard ratio = 1.337, 95 % confidence interval: 1.088–1.645, P = 0.006). A subgroup analysis of patients younger than 55 years old after propensity score matching showed that male patients had significantly worse overall survival and higher recurrence rates than female patients after surgery, while no significant difference in long-term overall survival and recurrence was observed between male and female patients older than 55 years old after propensity score matching. ConclusionMale sex was an independent risk factor for overall survival and tumor recurrence in patients after liver resection for intrahepatic cholangiocarcinoma.

Prediction of prognosis of patients with radical resection of intrahepatic cholangiocarcinoma based on single cell omics

Objectives: To analyze the survival benefit of intrahepatic cholangiocarcinoma (ICC) radical resection based on single cell omics. Methods: This is a retrospective case-series study. ICC single-cell sequencing was integrated from four data sets in the Gene Expression Omnibus Database, with a total of 46 patients undergoing radical resection, to explore the characteristics of the microenvironment. Microarray data of 100 ICC cases was analyzed in the EMBI database with survival data. The infiltration abundance of each epithelial cell cluster was calculated in each microarray data sample using the ssGSEA algorithm. The key epithelial cell cluster associated with poor patient outcomes was explored. The clinical value of key marker genes in this subgroup was studied. Prognostic marker genes were selected using the univariate and multivariate Cox proportional hazards(CoxPH) model. The The CoxPH model was constructed by the target genes and a nomogram was drawn. Kaplan-Meier survival analysis was used to verify the relationship between score and prognosis of patients. The predictive power of the model was evaluated by receiver operating characteristic(ROC) curves, calibration curves, and decision curve analysis (DCA). Results: Epithelial cell clusters infiltrated almost exclusively in tumor tissue. The MT2A+ epithelial cell subset was associated with a poorer prognosis for patients with a high invasion abundance and patients characterized by infiltration of this group were defined as antioxidant. After screening marker genes in this cluster using a univariate and multivariate CoxPH model, the following genes were found to be independent prognostic factors: FILPIL, NFKBIA, PEG10, SERPINB5. The CoxPH model was constructed using the four gene expression levels, and the survival rate of patients in the high-risk group was significantly lower than those in the low-risk group (all P<0.05). The constructed nomogram had good discrimination and validity. The ROC curve showed that the predicted area under the curve was 0.779, 0.844 and 0.845 at 1, 3 and 5 years, respectively. Compared to clinical indicators, the model had better predictive power using the calibration curve and the DCA test. Conclusions: The MT2A+ epithelial cell group may be associated with the prognosis of patients with ICC, and the concept of ICC tissue typing of antioxidant and non-antioxidant types is proposed. The type of antioxidant may predict the poor prognosis of the patients, and postoperative adjuvant therapy and other means could be considered to improve the survival of the patients.

Prognostic Impact of Visceral Adipose Tissue Imaging Parameters in Patients with Cholangiocarcinoma after Surgical Resection.

Visceral adiposity is known to be related to poor prognosis in patients with cholangiocarcinoma; however, the prognostic significance of the qualitative features of adipose tissue in cholangiocarcinoma has yet to be well defined. This study investigated the prognostic impact of adipose tissue imaging parameters reflecting the quantity and qualitative characteristics of subcutaneous (SAT) and visceral (VAT) adipose tissue on recurrence-free survival (RFS) and overall survival (OS) in 94 patients undergoing resection of cholangiocarcinoma. The area, mean computed tomography (CT) attenuation, and mean 2-deoxy-2-[18F]fluoro-D-glucose (FDG) uptake of SAT and VAT on positron emission tomography (PET)/CT for staging work-up were measured, and the relationship of these adipose tissue imaging parameters with clinicopathological factors and survival was assessed. TNM stage, histologic grade, lymphovascular invasion, and the size of cholangiocarcinoma showed positive correlations with adipose tissue imaging parameters. Multivariate survival analysis demonstrated that the visceral-to-subcutaneous adipose tissue area ratio (VSR) (p = 0.024; hazard ratio, 1.718) and mean FDG uptake of VAT (p = 0.033; hazard ratio, 9.781) were significant predictors for RFS, but all of the adipose tissue imaging parameters failed to show statistical significance for predicting OS. In addition to visceral adiposity, FDG uptake of VAT might be a promising prognostic parameter for predicting RFS in patients with cholangiocarcinoma.

Outcomes of liver resection in hepatitis C virus-related intrahepatic cholangiocarcinoma: A systematic review and meta-analysis.

Cholangiocarcinoma is the second most common primary liver malignancy. Its incidence and mortality rates have been increasing in recent years. Hepatitis C virus (HCV) infection is a risk factor for development of cirrhosis and cholangiocarcinoma. Currently, surgical resection remains the only curative treatment option for cholangiocarcinoma. We aim to study the impact of HCV infection on outcomes of liver resection (LR) in intrahepatic cholangiocarcinoma (ICC). To study the outcomes of curative resection of ICC in patients with HCV (i.e., HCV+) compared to patients without HCV (i.e., HCV-). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies to assess the outcomes of LR in ICC in HCV+ patients compared to HCV- patients in tertiary care hospitals. PubMed, EMBASE, The Cochrane Library and Scopus were systematically searched from inception till August 2023. Included studies were RCTs and non-RCTs on patients ≥ 18 years old with a diagnosis of ICC who underwent LR, and compared outcomes between patients with HCV+ vs HCV-. The primary outcomes were overall survival (OS) and recurrence-free survival. Secondary outcomes include perioperative mortality, operation duration, blood loss, intrahepatic and extrahepatic recurrence. Seven articles, published between 2004 and 2021, fulfilled the selection criteria. All of the studies were retrospective studies. Age, incidence of male patients, albumin, bilirubin, platelets, tumor size, incidence of multiple tumors, vascular invasion, bile duct invasion, lymph node metastases, and stage 4 disease were comparable between HCV+ and HCV- group. Alanine transaminase [MD 22.20, 95%confidence interval (CI): 13.75, 30.65, P < 0.00001] and aspartate transaminase levels (MD 27.27, 95%CI: 20.20, 34.34, P < 0.00001) were significantly higher in HCV+ group compared to HCV- group. Incidence of cirrhosis was significantly higher in HCV+ group [odds ratio (OR) 5.78, 95%CI: 1.38, 24.14, P = 0.02] compared to HCV- group. Incidence of poorly differentiated disease was significantly higher in HCV+ group (OR 2.55, 95%CI: 1.34, 4.82, P = 0.004) compared to HCV- group. Incidence of simultaneous hepatocellular carcinoma lesions was significantly higher in HCV+ group (OR 8.31, 95%CI: 2.36, 29.26, P = 0.001) compared to HCV- group. OS was significantly worse in the HCV+ group (hazard ratio 2.05, 95%CI: 1.46, 2.88, P < 0.0001) compared to HCV- group. This meta-analysis demonstrated significantly worse OS in HCV+ patients with ICC who underwent curative resection compared to HCV- patients.

Survival outcomes of surgical resection in perihilar cholangiocarcinoma in endemic area of O. Viverrini, Northeast Thailand

BackgroundPerihilar cholangiocarcinoma (pCCA) is an intractable malignancy and remains the most challenge for surgeon. This study aims to investigate survival outcomes and prognostic factors in pCCA patient. MethodsFrom October 2013 to December 2018, 240 consecutive patients with pCCA underwent surgical exploration were retrospectively reviewed. The clinicopathological parameters and surgical outcomes were extracted. Patients were divided into two groups: unresectable and resectable group. The restricted mean survival time between two groups were analyzed. Factors associated with overall survival in resectable group were explored with multivariable Cox regression analysis. ResultsOf the 240 patients, 201 (83.75%) were received surgical resection. The survival outcomes of resectable group were better than unresectable group significantly. The restricted mean survival time difference were 0.5 (95%CI 0.22–0.82) months, 1.8 (95%CI 1.15–2.49) months, 4.7 (95%CI 3.58–5.87) months, and 9.1 (95%CI 7.40–10.78) months at four landmark time points of 3, 6, 12 and 24 months, respectively. The incidence of major complications and 90-day mortality in resectable group were 35.82% and 11.44%, respectively. Multivariable analysis revealed that Bismuth type IV (HR:4.43, 95%CI 1.85–10.59), positive resection margin (HR:4.24, 95%CI 1.74–10.34), and lymph node metastasis (HR:2.29, 95%CI 1.04–4.99) were all independent predictors of long-term survival. For pM0, R0 and pN0 patients, the median survival time was better than pM0, R1 or pN1/2 patients and pM0, R1 and pN1/2 patients (32.4, 10.4 and 4.9 months, respectively; p < 0.001) ConclusionSurgical resection increased survival in pCCA. Bismuth type IV, positive resection margin and lymph node metastasis were independent factors for long-term survival.

Contemporary trends and outcomes after liver transplantation and resection for intrahepatic cholangiocarcinoma

BackgroundLiver transplantation has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma, yet has traditionally been contraindicated for intrahepatic cholangiocarcinoma. Herein, we aimed to examine contemporary trends and outcomes for surgical resection and liver transplantation for intrahepatic cholangiocarcinoma. MethodsThe National Cancer Database was queried for patients presenting with stage I-III intrahepatic cholangiocarcinoma between 2010 and 2018 who underwent resection or liver transplantation. Overall survival was compared with Kaplan-Meier and multivariable Cox proportional hazards methods stratified by management. Secondary analysis of patients undergoing transplant for cholangiocarcinoma was performed with the United Network for Organ Sharing database. ResultsOf 2,565 patients, 2,412 (94.0%) underwent resection and 153 (5.96%) liver transplantation of which 84 (54.9%) received neoadjuvant therapy. Utilization of liver transplantation remained between 3.9-7.8% annually. Unadjusted 5-year overall survival was higher for liver transplantation than resection (59.8% vs 39.9%, p=0.0067). Yet, adjusted analysis revealed no significant difference in mortality (hazard ratio 0.91, 95% confidence interval 0.66-1.27, p=0.58). On secondary analysis including 437 patients with all subtypes of cholangiocarcinoma, unadjusted 5-year overall survival was higher for non-cholangiocarcinoma indications (79% vs 52-54%, p<0.001). ConclusionUtilization of liver transplantation for intrahepatic cholangiocarcinoma remains low and many cases are likely incidental. While partial hepatectomy remains the standard of care for patients with resectable disease, our findings suggest that highly selected patients with unresectable intrahepatic cholangiocarcinoma may achieve favorable outcomes after liver transplantation. Granular, prospective data is needed to identify patients most likely to benefit from transplant and allocate scarce liver grafts.

Nodal recurrence mapping and clinical target volumes after resection of intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma

BackgroundScarce evidence exists for clinical target volume (CTV) definitions of regional lymph nodes (LNs) in intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellular-cholangiocarcinoma (cHCC-CCA). We investigated the mapping pattern of nodal recurrence after surgery for iCCA and cHCC-CCA and provided evidence for the nodal CTV definition. MethodsWe retrospectively reviewed the medical records of patients with iCCA or cHCC-CCA who underwent surgery between 2010 and 2020. Eligibility criteria included patients pathologically diagnosed with iCCA or cHCC-CCA after surgery and a first recurrent event in regional LNs during follow-up. All recurrent LNs were registered onto reference computed tomography images based on the vascular structures to reconstruct the node mapping. Fifty-three patients were eligible. LN regions were classified into four risk groups. ResultsHepatic hilar and portal vein-vena cava were the most common recurrent regions, with recurrence rates of 62.3 % and 39.6 % (high-risk regions), respectively. Recurrence rates in the left gastric, diaphragmatic, common hepatic, superior mesenteric vessels, celiac trunk, and paracardial regions ranged from 15.1 % to 30.2 % (intermediate-risk regions). There were fewer recurrences in the para-aortic (16a1, a2, b1) and splenic artery and hilum regions, with rates <10 % (low-risk regions). No LN recurrence was observed in the para-oesophageal or para-aortic region (16b2) (very low-risk regions). Based on node mapping, the CTV should include high- and intermediate-risk regions for pathologically negative LN patients during postoperative radiotherapy. Low-risk regions should be included for pathologically positive LN patients. ConclusionWe provide evidence for CTV delineation in patients with iCCA and cHCC-CCA based on recurrent LN mapping.

Liver Fibrosis Is Associated with Poorer Overall Survival and Higher Recurrence Rate in Patients with Cholangiocarcinoma

Introduction: Cholangiocarcinoma is the second most common primary liver tumour worldwide with an increasing incidence in recent decades. While the effects of fibrosis on hepatocellular carcinoma have been widely demonstrated, the impact on cholangiocarcinoma remains unclear. The aim of this study was to evaluate the impact of liver fibrosis on overall survival (OS) and disease-free survival (DFS) in patients who have undergone liver resection for cholangiocarcinoma. Methods: Eighty patients with cholangiocarcinoma who underwent curatively intended liver surgery between January 2007 and December 2020 were included in this retrospective single-centre study. Clinical and histopathological features were analysed. The primary endpoint was cause-specific survival. Secondary endpoints were DFS and identification of prognostic factors. Results: The present study shows that the median OS is significantly reduced in patients with fibrosis (p < 0.001). The median OS in patients with fibrosis was three times shorter than in the group without fibrosis. In addition, a significantly shorter DFS was observed in patients with fibrosis (p < 0.002). Multivariate analysis showed that fibrosis is the strongest independent factor with a negative impact on OS and DFS. Conclusion: Liver fibrosis has a significant impact on OS and DFS in patients with cholangiocarcinoma. Patients with known liver fibrosis require thorough perioperative care and postoperative follow-up.

The impact of post-hepatectomy liver failure on long-term survival after liver resection for perihilar cholangiocarcinoma

BackgroundAlthough post-hepatectomy liver failure (PHLF) can accurately predict short-term mortality of liver resection for perihilar cholangiocarcinoma (pCCA), its significance in predicting long-term overall survival (OS) is still uncertain. MethodsRetrospective analysis was performed on patients with pCCA who underwent liver resection between October 2013 and December 2018. The patients were divided into 3 groups; No PHF, PHLF (all grade) and grade B/C PHLF according to The International Study Group of Liver Surgery (ISGLS) criteria. ResultsA total of 177 patients were enrolled, 65 (36.7%) had PHLF; 25 (14.1%) had grade A, and 40 (22.6%) had grade B/C. Prior to surgery, patients with PHLF showed significantly greater bilirubin levels and CA 19-9 level than those without (11.5 vs 6.7 mg/dL, p = 0.002 and 232.4 vs 85.9 U/mL, p = 0.005, respectively). Additionally, pre-operative future liver remnant volume in PHLF group was lower than no PHLF group significantly (39.6% vs 43.5%, p = 0.006). Major complication and 90-day mortality were higher in PHLF group than no PHLF group (69.2% vs 20.5%, p < 0.001 and 29.2% vs 3.6%, p < 0.001, respectively). The OS in both grade A PHLF and grade B/C PHLF was significantly worse compared to no PHLF, with median survival times of 8.4, 3.3, and 19.2 months, respectively (p < 0.001 and p < 0.001, respectively). Multivariable analysis revealed that PHLF was independently prognostic factor for long-term survival. ConclusionTo achieve negative resection margin, the surgical resection in pCCA was aggressive, however this increased the risk of PHLF, which also affects the OS. Consequently, it is necessary for establishing a balance between aggressive surgery and PHLF.