Perihilar Cholangiocarcinoma Patients Research Articles

Adjuvant radiotherapy and chemotherapy offer a recurrence and survival benefit in patients with resected perihilar cholangiocarcinoma

The objective of this study was to investigate the benefits of adjuvant treatment for patients with resected perihilar cholangiocarcinoma (PHC). Between 2001 and 2017, 196 patients with PHC adenocarcinoma underwent curative resection. The patients were divided into four groups according to adjuvant treatment type: surgery alone (S; N = 90), surgery with chemotherapy (S+CTx; N = 67), surgery with radiotherapy (S+RTx; N = 18), and surgery with chemoradiotherapy (S+ CRTx; N = 21). The median follow-up duration of the surviving patients was 58months. The 5-year rate of overall survival (OS) was 32%. In multivariate analysis, receiving S+CTx and S+CRTx were significant prognostic factors for OS. In subgroup analyses of the R1 resection patients, the S+CRTx group showed better OS than the S group (p < 0.05). In subgroup analyses of the stage III-IVA patients with a negative resection margin, the S+CTx and S+CRTx groups showed superior OS than the S group (p < 0.05). Our data suggest that adjuvant chemoradiotherapy might be considered for PHC patients with R1 resection. Adjuvant chemotherapy or chemoradiotherapy is suggested for stage III-IVA patients with R0 resection. The results of this study require validation through further prospective studies.

Narrowing of the remnant portal vein diameter and decreased portal vein angle are risk factors for portal vein thrombosis after perihilar cholangiocarcinoma surgery.

To evaluate the incidence, risk factors, management options, and outcomes of portal vein thrombosis following major hepatectomy for perihilar cholangiocarcinoma. A total of 177 perihilar cholangiocarcinoma patients who (1) underwent major hepatectomy and (2) underwent investigating the portal vein morphology, which was measured by rotating the reconstructed three-dimensional images after facilitating bone removal using Aquarius iNtuition workstation between 2002 and 2018, were included. Risk factors were evaluated using the Kaplan-Meier method and Cox proportional hazard models. Six patients developed portal vein thrombosis (3.4%) within a median time of 6.5 (range 0-22) days. Portal vein and hepatic artery resection were performed in 30% and 6% patients, respectively. A significant difference in the probability of the occurrence of portal vein thrombosis (PV) within 30 days was found among patients with portal vein resection, a postoperative portal vein angle < 100°, remnant portal vein diameter < 5.77 mm, main portal vein diameter > 13.4 mm, and blood loss (log-rank test, p = 0.003, p = 0.06, p < 0.0001, p = 0.01, and p = 0.03, respectively). Decreasing the portal vein angle and narrowing of the remnant PV diameter remained significant predictors on multivariate analysis (p = 0.027 and 0.002, respectively). Reoperation with thrombectomy was performed in four patients, and the other two patients were successfully treated with anticoagulants. All six patients subsequently recovered and were discharged between 25 and 70 days postoperatively. Narrowing of the remnant portal vein diameter and a decreased portal vein angle after major hepatectomy for perihilar cholangiocarcinoma are significant independent risk factors for postoperative portal vein thrombosis.

Transhepatic Direct Approach to the “Limit of the Division of the Hepatic Ducts” Leads to a High R0 Resection Rate in Perihilar Cholangiocarcinoma

BackgroundPrevious studies have shown that curative resection (R0 resection) was among the most crucial factors for the long-term survival of patients with PHCC. To achieve R0 resection, we performed the transhepatic direct approach and resection on the limits of division of the hepatic ducts. Although a recent report showed that the resection margin (RM) status impacted PHCC patients’ survival, it is still unclear whether RM is an important clinical factor. ObjectiveTo describe a technique of transhepatic direct approach and resection on the limit of division of hepatic ducts, investigate its short-term surgical outcome, and validate whether the radial margin (RM) would have a clinical impact on long-term survival of perihilar cholangiocarcinoma (PHCC) patients. MethodsConsecutive PHCC patients (n = 211) who had undergone major hepatectomy with extrahepatic bile duct resection, without pancreaticoduodenectomy, in our department were retrospectively evaluated. ResultsR0 resection rate was 92% and 86% for invasive cancer-free and both invasive cancer-free and high-grade dysplasia-free resection, respectively. Overall 5-year survival rate was 46.9%. Univariate analysis showed that preoperative serum carcinoembryonic antigen level (> 7.0 mg/dl), pathological lymph node metastasis, and portal vein invasion were independent risk factors, but R status on both resection margin and bile duct margin was not an independent risk factor for survival. ConclusionThe transhepatic direct approach to the limits of division of the bile ducts leads to the highest R0 resection rate in the horizontal margin of PHCC. Further examination will be needed to determine the adjuvant therapy for PHCC to improve patient survival.

Analysis of Recurrence in Patients who Underwent Curative-intent Resection for Perihilar Cholangiocarcinoma

Introduction: This study aimed to investigate the patterns of recurrence and to evaluate factors associated with the time to recurrence in resected perihilar cholangiocarcinoma patients. Methods: A retrospective analysis was conducted on 138 patients undergoing curative-intent resection of perihilar cholangiocarcinoma. The median follow-up time was 115 months. Results: During the follow-up period, 77 patients (56%) relapsed and the 5-year recurrence rate was 61%. Of 77 patients, 71 (92%) relapsed within 5-years after resection. Distant recurrence was detected in 44 patients (57%), whilst locoregional recurrence in 21 patients (27%), and the both in 12 patients (16%). The sites of distant recurrence were the liver (n = 17), peritoneum (n = 16), distant lymph nodes (n = 14), and lung (n = 9). On multivariate analysis, age (hazard ratio [HR] 1.7, P = 0.039), venous invasion (HR 1.9, P = 0.01), primary tumor status (HR 2.2, P = 0.001), and number of positive nodes (1-3: HR 1.8, P = 0.001, ≥ 4: HR 3.7, P = 0.028) were independent factors associated with time to recurrence. The treatment for the 77 relapsed patients were surgery (n = 8), chemotherapy (n = 41), and best supportive care (n = 28). The 3-year overall survival after recurrence was 38%, 4%, and 0%, respectively (P < 0.001). Conclusions: More than half of patients with perihilar cholangiocarcinoma experience recurrence after curative-intent surgery, and these recurrences occur mostly within 5 years. Adjuvant strategies should be considered, especially for patients with venous invasion, extensive primary tumor, and nodal metastasis.

Infective Complications Following Liver Surgery for Perihilar-cholangiocarcinoma

Purpose: The incidence of infective complications (inf-comp) after liver surgery for perihilar-cholangiocarcinoma (PHCC) has been reported to range between 28 and 61%. The optimal perioperative management of infective complication is still debated. The aim of the present study was to investigate the pre-operative patients’ characteristic associated with the risk of inf-comp following surgery for PHCC. Method: This retrospective single-center study included patients undergone surgery for PHCC from 2010 and 2020. Perioperative microbiological data were collected with rectal swabs, biliary, and blood cultures, and from surgical-site infection (SSI) samples. Results: A total of 98 patients undergone surgery, preoperative biliary drainage (PBD) was performed in 74 (75.6%) patients. A total of 50 (51.0%) patients had post-operative inf-comp. Univariate and multivariate analysis confirmed that patients with a preoperative neutrophil/lymphocyte ratio ≥3.4 (OR, 4.68), an endoscopic sphincterotomy (OR, 3.97), and preoperative acute cholangitis (OR, 3.53) had an increased risk of inf-comp (all p≤0.013). In 74 (75.6%) patients the presence of preoperative multiple drug resistance (MDR) bacteria was confirmed postoperatively (p<0.001). As expected, patients with PBD had a higher incidence of: MDR bacteria, positive intraoperative biliary cultures with ≥3 micro-organisms, SSI, and major complications compared with patients who did not receive PBD (all p≤0.044). Interestingly, patients who developed inf-comp had an increased risk of ICU admission (p=0.03), length of stay ≥20 days (p<0.001), 90-day readmission (p=0.003), major complications (p<0.001) but not 90-day mortality (p=0.52). Conclusions: Several preoperative factors resulted associated with a inf-comp including NLR ≥ 3.4, endoscopic sphincterotomy, and acute cholangitis. Interestingly, the occurrence of preoperative MDR was associated with postoperative MDR inf-comp. These factors should be included in a personalized management of PHCC patients undergoing liver surgery to decrease the incidence of inf-comp.

Occurrence of seeding metastases in resectable perihilar cholangiocarcinoma and the role of low-dose radiotherapy to prevent this.

BACKGROUNDPreoperative biliary drainage in patients with presumed resectable perihilar cholangiocarcinoma (PHC) is hypothesized to promote the occurrence of seeding metastases. Seeding metastases can occur at the surgical scars or at the site of postoperative drains, and in case of percutaneous biliary drainage, at the catheter port-site. To prevent seeding metastases after resection, we routinely treated PHC patients with preoperative radiotherapy (RT) for over 25 years until January 2018.AIMTo investigate the incidence of seeding metastases following resection of PHC.METHODSAll patients who underwent resection for pathology proven PHC between January 2000 and March 2019 were included in this retrospective study. Between 2000-January 2018, patients received preoperative RT (3 × 3.5 Gray). RT was omitted in patients treated after January 2018.RESULTSA total of 171 patients underwent resection for PHC between January 2000 and March 2019. Of 171 patients undergoing resection, 111 patients (65%) were treated with preoperative RT. Intraoperative bile cytology showed no difference in the presence of viable tumor cells in bile of patients undergoing preoperative RT or not. Overall, two patients (1.2%) with seeding metastases were identified, both in the laparotomy scar and both after preoperative RT (one patient with endoscopic and the other with percutaneous and endoscopic biliary drainage).CONCLUSIONThe incidence of seeding metastases in patients with resected PHC in our series was low (1.2%). This low incidence and the inability of providing evidence that preoperative low-dose RT prevents seeding metastases, has led us to discontinue preoperative RT in patients with resectable PHC in our center.

Molecular detection and clinicopathological characteristics of advanced/recurrent biliary tract carcinomas harboring the FGFR2 rearrangements: a prospective observational study (PRELUDE Study)

BackgroundFibroblast growth factor receptor 2 (FGFR2) rearrangement is expected to be a novel therapeutic target in advanced/recurrent biliary tract cancer (BTC). However, efficient detection and the exact frequency of FGFR2 rearrangements among patients with advanced/recurrent BTC have not been determined, and the clinical characteristics of FGFR2 rearrangement-positive patients have not been fully elucidated. We aimed to determine the frequency of FGFR2 rearrangement-positive patients among those with advanced/recurrent BTC and elucidate their clinicopathological characteristics.MethodsParaffin-embedded tumor samples from formalin-fixed surgical or biopsy specimens of patients with advanced/recurrent BTC were analyzed for positivity of FGFR2 rearrangement by fluorescent in situ hybridization (FISH). RNA sequencing was performed on samples from all FISH-positive and part of FISH-negative patients.ResultsA total of 445 patients were enrolled. FISH was performed on 423 patients (272 patients with intrahepatic cholangiocarcinoma (ICC), 83 patients with perihilar cholangiocarcinoma (PCC), and 68 patients with other BTC). Twenty-one patients with ICC and four patients with PCC were diagnosed as FGFR2-FISH positive. Twenty-three of the 25 FISH-positive patients (20 ICC and 3 PCC) were recognized as FGFR2 rearrangement positive by targeted RNA sequencing. Younger age (≤ 65 years; p = 0.018) and HCV Ab- and/or HBs Ag-positivity (p = 0.037) were significantly associated with the presence of FGFR2 rearrangement (logistic regression).ConclusionsFGFR2 rearrangement was identified in ICC and PCC patients, and was associated with younger age and history of hepatitis viral infection.

81TiP Changes in immune function and prognosis in advanced perihilar cholangiocarcinoma patients treated with immunotherapy combined with different topical therapies

81TiP Changes in immune function and prognosis in advanced perihilar cholangiocarcinoma patients treated with immunotherapy combined with different topical therapies

Combining E-PASS model and disease specific risk factors to predict severe morbidity after liver and bile duct resection for perihilar cholangiocarcinoma

BackgroundEstimation of physiologic ability and surgical stress system (E-PASS) has been shown to be effective in predicting morbidity after surgery for perihilar cholangiocarcinoma (PHCC). Nevertheless, E-PASS does not include an assessment of the disease specific risk factors. The aim of the study was to estimate the combined impact of E-PASS and specific preoperative factors on major morbidity for PHCC patients. MethodsA retrospective analysis of a prospectively collected data was performed. Severe morbidity according to complication comprehensive index was defined as ≥40 points. A value of comprehensive risk score (CRS) ≥1 was taken as critical. ResultsMultivariate analysis of perioperative data from 122 patients revealed significant impact of five factors (CRS ≥1, future liver remnant volume <50%, T4 stage, moderate and severe cholangitis, INR) on the risk of severe morbidity after resection. The AUC for the combination of these factors was classified as good predictive value (0.810, 95% CI 0.729–0.891) and poor predictive value (0.673, 95% CI 0.573–0.773) for CRS alone (p = 0.040). ConclusionA combination of E-PASS with disease specific risk factors is a reliable predictive model for major morbidity for patients undergoing radical surgery for PHCC.

High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection

BackgroundTumor budding (TB) is used as an indicator of poor prognosis in various cancers. However, studies on TB in perihilar cholangiocarcinoma are still limited. We examined the significance of TB in resected perihilar cholangiocarcinoma with or without neoadjuvant therapy.MethodsSeventy-eight patients who underwent surgical resection at our institution for perihilar cholangiocarcinoma from 2004 to 2017, (36 with neoadjuvant therapy), were enrolled in this study. TB was defined as an isolated cancer cell or clusters (< 5 cells) at the invasive front and the number of TB was counted using a 20 times objective lens. Patients were classified into two groups according to TB counts: low TB (TB < 5) and high TB (TB ≥5).ResultsIn this 78 patient cohort, high TB was significantly associated with advanced tumor status (pT4: 50.0% vs 22.2%, p = 0.007, pN1/2: 70.8% vs 39.6%, p = 0.011, M1: 20.8% vs 1.9%) and higher histological grade (G3: 25.0% vs 5.7%, p = 0.014). Disease specific survival (DSS) in high TB was significantly inferior compared to that in low TB group (3-y DSS 14.5% vs 67.7%, p < 0.001). Interestingly, DSS in high TB showed similar to survival in unresected patients. In addition, high TB was also associated with advanced tumor status and poor prognosis in patients with neoadjuvant therapy. Multivariate analysis identified high TB as an independent poor prognostic factors for DSS (HR: 5.206, p = 0.001).ConclusionThis study demonstrated that high TB was strongly associated with advanced tumor status and poor prognosis in resected perihilar cholangiocarcinoma patients. High TB can be a novel poor prognostic factor in resected perihilar cholangiocarcinoma regardless of neoadjuvant therapy.

Stage I-laparoscopy partial ALPPS procedure for perihilar cholangiocarcinoma.

The treatment for perihilar cholangiocarcinoma (PHC) is a challenge for the surgeon requiring complex resections with a reported perioperative mortality rate between 15% and 48%. In PHC patients with future liver remnant (FLR) less than 30%, it is advised that hepatectomy can be safely performed after the FLR is modified. Associating Liver Partition and Portal vein ligation for Staged Hepatectomy (ALPPS) procedure is criticized heavily due to its high morbidity and mortality rate in this setting. Hereby, we are reporting a modification of ALPPS procedure for PHC. Clinical presentation, preoperative work-up as well as operation and postoperative course of two cases were described in detail. Both patients were jaundiced preoperatively, stage 1 partial-ALPPS procedures were performed laparoscopically, there was sufficient remnant hypertrophy during the interval stage and there was no posthepatectomy liver failure after the second stage (Supporting Information Video). We have followed patients with a mean follow up of 35 months without any recurrence. Here we describe the key technical aspects of this approach that are discussed in three parts: minimally invasive first stage, biliary drainage of both FLR, and deportalized liver at first stage and biliary reconstruction at the second stage. This technique, in selected patients, can extend the indication of ALPPS procedure for PHC with preoperative jaundice.

Perihilar cholangiocarcinoma: A different concept for radical resection

BackgroundLong-term outcomes depend heavily on the possibility of performing radical resection. PurposeTo evaluate long-term results in perihilar cholangiocarcinoma (PHC) patients from the perspective of a new understanding of radical resection. MethodsConsecutive PHC patients who underwent surgical resection at A.V. Vishnevsky Center of Surgery from 2011 to 2018 were retrospectively reviewed. Fifty eight (87.9%) patients underwent hemihepatectomy (14 extended hemihepatectomies), while 2 (3%) underwent extrahepatic bile duct resection only, 6 (9.1%) underwent S4b, and 5 underwent en bloc resection of the extrahepatic bile duct. The influence of the bile duct wedge R status, nodal status, microvascular invasion, microlymphatic invasion, perineural invasion, liver invasion, and surrounding adipose tissue invasion on survival was tested by Cox's models. Survival rates depending on pathological parameter numbers were compared by log-rank tests. ResultsWedge resection, nodal status, microvascular invasion, microlymphatic invasion, perineural invasion, liver invasion, and surrounding adipose tissue invasion served as extended criteria for curability (R+, 1 to 7 parameters). For R0 resection status and R1 resection status (R+1, R+2), 7 and 5 parameters were negative, respectively. For R1+ resection status (R+3, R+4, R+5, R+6, R+7), 3 to 7 parameters were positive. Patients who underwent R0 and R1 resections had 5-year survival rates of 100%; the 1- 2- 3-year survival rates were 63%, 49%, 33% for patients who underwent R1+ resections, respectively. The expanded criteria for determining radical resection levels correlated with long-term outcomes (р = 0.0001). ConclusionThe new concept for radical resection can accurately reflect surgical treatment results and contribute to selecting appropriate adjuvant therapies in PHC patients. Trial registrationThe study was carried out in accordance with the framework of the “Multimodal treatment of primary and secondary malignant tumors of the liver and pancreas” (state registration № 315030310062).

Eligibility for liver transplantation in patients with perihilar cholangiocarcinoma

Background: Liver transplantation has been performed in a select group of patients presenting with unresectable or primary sclerosing cholangitis (PSC)-associated perihilar cholangiocarcinoma (PHC) in the Mayo Clinic with a reported 5-year survival of 53% on intention-to-treat analysis. The majority of these patients (63%) had PSC-associated PHC. The objective of this study was to estimate eligibility for such a protocol in a cohort of PHC patients in two tertiary referral centers.

The surgeon's contribution to long term survival for peri-hilar cholangiocarcinoma

Background: Surgery for peri-hilar cholangiocarcinoma (PCC) is still demanding and long-term prognosis is still dismal. We sought to investigate the factors related to long term survival. Methods: Data regarding PCC patients who underwent surgical resection with radical intent from January 1990 to December 2017 were analysed from a prospectively maintained database. Clinicopathological characteristics were investigated to identify long-term survival predictors. Patients were staged according to the AJCC/UICC 8th ed. TNM staging system. Results: Among 162 patients submitted to surgical exploration, 123 who underwent radical intent surgery were included in this study. In this group of patients, 102 (82.9%) underwent major liver resections, portal vein resection was conducted in 17.1%, arterial resection in 4.1%, median number of lymph nodes retrieved was 8 [IQR 5-13]. Negative margin resection (R0) was achieved in 69,9% of cases and positive lymph nodes were observed in 45.5% of cases. Overall 3- and 5-year survival (OS) was 54.2% and 26.7% respectively, while 3- and 5-year disease free survival (DFS) were 32.5% and 22.1%, respectively. Multivariable Cox analysis for OS identified that pN stage 8th ed. (HR 1.62; P = 0.006), positive resection margins (HR 1.72; P = 0.027), portal vein resection (HR 1.95; P = 0.016) and number of lymph nodes retrieved ≥ 4 (HR 0.5; P = 0.027) are associated with OS. Interestingly, 5 years OS for R0 and pN0 patients was 40.3% compared to 24.4% for R1 and pN1-2 patients (P = 0.037). Conclusion: The surgeon’s contribution to long term survival in the treatment of PCC is still of great importance by means of oncological radicality and adequate lymph node dissection, which should be the current goal of treatment.

A methodological review of clinical outcomes reported in Liver Transplantation cholangiocarcinoma

Background: In patients undergoing resection for perihilar cholangiocarcinoma(PHC), intraoperative frozen sections are performed to assess completeness of the proximal and distal bile duct resection planes. In case of a positive proximal margin, re-resection of the bile duct stump is usually undertaken to achieve R0-resection. In case of a positive distal margin, additional PPPD (hepato-pancreatoduodenectomy, HPD) is considered. However, the Results of re-resection on R0-status and oncological outcomes in patients with PHC remain inconclusive. Therefore, we aimed to assess survival after re-resection of the bile duct after intra-operative positive frozen section in patients with PHC. Material and Methods: All consecutive patients undergoing resection for PHC at a single tertiary center between 2000-2018 were evaluated. Primary outcome was overall survival(OS), determined in patients with initial R0 resection, R1 resection and R0 resection after re-resection. Secondary outcome was severe morbidity(Clavien-Dindo=3). Results: A total of 162 PHC patients were evaluated(2000-2018), in which 30 positive intra-operative frozen sections were found in 27 patients. Additional resection was performed in 25 patients, representing 27 re-resections(Figure 1). In three cases re-resection was deemed technically not feasible. Re-resection at the distal resection margin(CBD) was performed in 8/27 patients, including 3 HPDs. Although Results of 18/27 re-resections(in 16 patients) were negative, 9 of the 16 patients (56%) still had R1 resection due to other positive, usually circumferential resection margins. Only four patients achieved true R0-resection after re-resection. Median OS for patients with initial R0, R1 and R0 after re-resection were 77, 35 and 33 months, respectively(p=0.334). Severe morbidity was not significantly different (72% after re-resection and 54% without re-resection, p=0.102). Conclusion: In the majority of patients (84%) undergoing re-resection of positive biliary margins in this series, R0-resection was not achieved, often due to additional positive resection margins.

Eligibility for liver transplantation in patients with perihilar cholangiocarcinoma

Background Liver transplantation has been performed in a select group of patients presenting with unresectable or primary sclerosing cholangitis (PSC)-associated perihilar cholangiocarcinoma (PHC) in the Mayo Clinic with a reported 5-year survival of 53% on intention-to-treat analysis. The majority of these patients (63%) had PSC-associated PHC. The objective of this study was to estimate eligibility for such a protocol in a cohort of PHC patients in two tertiary referral centers. Methods: Consecutive patients diagnosed with PHC were included from two high volume hepatobiliary academic centers in the Netherlands. The selection criteria used by the Mayo Clinic were applied to determine the proportion of patients eligible for transplantation. Results: A total of 732 patients with PHC were identified, of whom 24 (4.0%) had PSC-associated PHC. 154 patients were primarily eligible for resection. 335 patients were excluded because of lymph node or distant metastases. After applying the Mayo Clinic inclusion and exclusion criteria, 35 patients were found to be eligible out of a total cohort of 732 patients (4.8%; figure). Median survival from diagnosis for patients eligible for transplantation was 1.1 years (95%CI: 0.4-1.8), and no patient reached 5-year survival. Finally, the strict age limit of 70 years led to the exclusion of 50 patients who would otherwise be eligible based on performance and oncological considerations (figure). Conclusion: At two major tertiary referral centers, 5% of patients with perihilar cholangiocarcinoma were eligible for liver transplantation under the Mayo criteria. Without liver transplantation these patients had a median survival of 1 year.

Preoperative Bilirubin Level Predicts Overall Survival and Tumor Recurrence After Resection for Perihilar Cholangiocarcinoma Patients.

ObjectiveCurrently, the correlation between preoperative bilirubin level and overall survival (OS) remains poorly defined in respectable perihilar cholangiocarcinoma (CC). The objectives of the current study were to evaluate the outcomes of perihilar CC after resection and then to analyze factors influencing curative resection, tumor recurrence and OS.Methods115 patients with perihilar CC underwent surgical resection were retrospectively analyzed based on clinic characteristics, operative details, tumor recurrence and long-term survival data.ResultsThe 1-, 3-, and 5-year OS rates after resection were 75.9%, 36.5%, 21.7%, whereas the corresponding tumor recurrence rates were 29.6%, 70.8%, 85.3%, respectively. Preoperative bilirubin level combined with liver resection, resection margin, vascular invasion and perineural invasion, lymph node metastasis and TNM stage were found to be correlated with OS and tumor recurrence. Multivariate analysis showed that preoperative bilirubin level together with resection margin, perineural invasion, and TNM stage were independent predictors of OS and tumor recurrence. Furthermore, preoperative bilirubin level was related with R0 resection, lymph node metastasis, TNM stage and postoperative liver function recovery.ConclusionPreoperative bilirubin level may effectively reflect the severity of perihilar CC and predict the OS and tumor recurrence after resection for perihilar CC patients.

723P - Frequency and clinicopathological characteristics of biliary tract carcinomas harboring the FGFR2-fusion gene: A prospective observational study (PRELUDE study)

723P - Frequency and clinicopathological characteristics of biliary tract carcinomas harboring the FGFR2-fusion gene: A prospective observational study (PRELUDE study)

Adjuvant Radiotherapy and Chemotherapy Offer a Recurrence and Survival Benefit in Patients with Resected Perihilar Cholangiocarcinoma

The objective of this study was to investigate the benefits of adjuvant treatment for patients with resected perihilar cholangiocarcinoma (PHC). Between 2001 and 2017, 196 patients with PHC adenocarcinoma underwent curative resection. The patients were divided into four groups according to adjuvant treatment type: surgery alone (S; N = 90), surgery with chemotherapy (S+CTx; N = 67), surgery with radiotherapy (S+RTx; N = 18), and surgery with chemoradiotherapy (S+ CRTx; N = 21). The median follow-up duration of the surviving patients was 58 months. The 5-year rate of overall survival (OS) was 32%. In multivariate analysis, receiving S+CTx and S+CRTx were significant prognostic factors for OS. In subgroup analyses of the R1 resection patients, the S+CRTx group showed better OS than the S group (p < 0.05). In subgroup analyses of the stage III–IVA patients with a negative resection margin, the S+CTx and S+CRTx groups showed superior OS than the S group (p < 0.05). Our data suggest that adjuvant chemoradiotherapy might be considered for PHC patients with R1 resection. Adjuvant chemotherapy or chemoradiotherapy is suggested for stage III–IVA patients with R0 resection. The results of this study require validation through further prospective studies.

Impact of tumour budding grade in 310 patients who underwent surgical resection for extrahepatic cholangiocarcinoma.

Tumour budding is a risk factor for poor prognosis in various cancers. Tumour buds may present an epithelial-mesenchymal transition (EMT) morphological phenotype. This study aimed to elucidate the prognostic impact of tumour budding grade and its association with clinicopathological and EMT-related features in perihilar cholangiocarcinoma (PHCC) or distal cholangiocarcinoma (DCC). Subjects included 195 PHCC and 115 DCC patients. The numbers of tumour buds in different patients were stratified for postoperative survival using the recursive partitioning technique. Consequently, the numbers of tumour buds in PHCC patients were classified into three grades; namely, low (0-4 buds); intermediate (5-11 buds); and high (≥12 buds); those of DCC patients were classified into two grades; namely, low (0-4 buds) and high (≥5 buds). In both PHCC and DCC patients, high tumour budding grade was associated with poor histological differentiation, higher pT factor, presence of lymphatic, venous, perineural invasion and regional lymph node metastasis. In PHCC patients, residual invasive tumour in the resected margin was also associated with high tumour budding grade. For both PHCC and DCC patients, high tumour budding grade was an independent adverse prognostic factor in multivariate analysis (P<0001 and P=0.046, respectively). Immunohistochemical examination revealed that the number of tumour buds increased in patients with tumours showing a mesenchymal profile (negative for E-cadherin and positive for vimentin). Higher tumour budding grade is associated with invasive clinicopathological features, adverse postoperative prognosis and EMT status in extrahepatic cholangiocarcinoma.