While postoperative adjuvant chemotherapy (AC) is generally recommended for intrahepatic cholangiocarcinoma (ICC), its benefit remains debated. This study aimed to identify patients that may benefit from AC following liver resection of ICC.

Patients who underwent liver resection for ICC between 2000 and 2023 were identified from an international multi-institutional database. Individual multivariable Cox models were used to evaluate the interaction between each prognostic factor and the effect of AC on survival.

Among 1412 patients, 431 (30.5%) received AC. Both higher tumor burden score (TBS; hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.91-1.00; p = 0.033) and metastatic lymph node status (HR 0.58, 95% CI 0.38-0.89; p = 0.014) demonstrated interactions with the survival benefit from receipt of AC. Interaction plots highlighted how AC was associated with improved survival beyond a TBS of approximately 6. Notably, among 555 (39.3%) patients with TBS <6 and N0 or Nx status, 5-year overall survival (OS) was no different between patients who received AC versus individuals who did not (55.1% [95% CI 48.9-62.1] vs. 58.7% [95% CI 49.8-69.2]; p = 0.900). In contrast, among 857 (60.7%) patients with TBS ≥6 or N1 status, AC was associated with improved 5-year OS (30.7% [95% CI 26.2-36.0] vs. 33.0% [95% CI 26.9-40.5]; p = 0.018).

TBS and lymph node status may be useful in a multidisciplinary setting to inform decisions about AC planning for ICC patients following curative-intent resection.

This study investigated the significance of the Global Leadership Initiative on Malnutrition (GLIM) for patients with resected biliary tract cancers.

The subjects of this retrospective analysis were 114 patients who underwent radical surgery for cholangiocarcinoma between 2018 and 2023. We analyzed both handgrip force and skeletal muscle area and classified patients as having GLIM malnutrition or modified GLIM malcondition. We also evaluated clinicopathological factors, short-term outcomes, and prognoses.

The GLIM criteria identified 47 patients (41.2%) with malnutrition and 13 patients (11.4%) with modified GLIM malcondition. Overall survival (P = 0.009) and recurrence-free survival (P = 0.016) were significantly different between the well-nourished and malnourished patients according to the GLIM criteria. Furthermore, modified GLIM criteria malcondition was a significant prognostic factor for both recurrence-free and overall survival (P = 0.002 and P < 0.001, respectively). Multivariate analysis identified a higher carcinoembryonic antigen level and modified GLIM malcondition as predictors of overall and recurrence-free survival. Pathological stage ≥ III was also a predictor of recurrence-free survival. On comparing the prognoses of modified GLIM malcondition and GLIM malnutrition using the Akaike Information Criteria, the modified GLIM malcondition was identified as a stronger prognostic factor.

A modified GLIM malcondition can be a highly useful prognostic marker for patients with resected biliary tract cancer.

The prognostic value of the preoperative cachexia index for patients with perihilar cholangiocarcinoma remains unclear.

We retrospectively evaluated 236 patients who underwent radical resection for perihilar cholangiocarcinoma from September 2002 to December 2020. The cachexia index was calculated as follows: (skeletal muscle index × albumin level)/neutrophil-to-lymphocyte ratio, with sex-specific cutoff values determined via receiver operating characteristic curves on the basis of 3-year survival data. Clinicopathologic characteristics and survival outcomes were compared between the low-cachexia index (n = 95) and high-cachexia index (n = 141) groups. Multivariable analyses were performed to identify prognostic factors for overall survival and relapse-free survival.

The low-cachexia index group was characterized by greater carbohydrate antigen 19-9 level (56 vs 31 U/mL, P = .024) and greater proportion of preoperative biliary drainage (84% vs 70%, P = .013). The low-cachexia index group underwent vascular resection and reconstruction more frequently (47% vs 29%, P = .006) and had a greater rate of lymph node metastasis (54% vs 35%, P = .005). The median overall survival and relapse-free survival times of the low-cachexia index group were significantly worse than those of the high-cachexia index group (overall survival, 29.0 vs 47.4 months, P < .001; relapse-free survival, 17.2 vs 33.1 months, P < .001). Multivariable analysis revealed that a preoperative cachexia index (hazard ratio for overall survival, 0.95, P = .008; hazard ratio for relapse-free survival, 0.95, P = .017) and high preoperative carbohydrate antigen 19-9 level (hazard ratio for overall survival, 1.01, P = .002; hazard ratio for relapse-free survival, 1.01, P = .012) were prognostic factors.

The cachexia index may be a useful biomarker for the prediction of tumor aggressiveness and prognosis before perihilar cholangiocarcinoma resection.

A 64-year-old man with a history of surgery for rectal cancer and colon cancer was referred for a hepatic mass identified on computed tomography (CT). He was diagnosed with unresectable intrahepatic cholangiocarcinoma (ICC) with perihilar and para-aortic lymph node metastases. After 4 cycles of gemcitabine and cisplatin combination therapy (GC therapy), follow-up CT showed slight enlargement of the primary tumor and a slight increase in carbohydrate antigen (CA) 19-9. Genetic testing was performed during GC therapy based on the strong family history of cancer. Germline pathogenic variant in MLH1 was identified, leading to the diagnosis of Lynch syndrome (LS) with mismatch repair deficiency (dMMR: loss of MLH1/PMS2). Durvalumab was added to GC therapy following regulatory approval in Japan. A significant reduction in tumor size and CA19-9 was observed after only two cycles of GC and durvalumab therapy. Continuous improvement was observed, and conversion surgery involving liver resection, partial inferior vena cava resection, and perihilar and para-aortic lymph nodes dissection was performed with curative intent. No malignant cells were found in any of the resected specimens, consistent with pathological complete response.

Adjuvant therapy with capecitabine is recommended to improve survival for resectable biliary tract cancers (BTC) patients. Considering that the combination of PD-1/PD-L1 inhibitors with chemotherapy has demonstrated a survival benefit over chemotherapy alone in advanced stage BTC, we aim to evaluate the treatment efficacy and safety of tislelizumab, a PD-1 inhibitor, combined with capecitabine vs. capecitabine alone as an adjuvant treatment in patients with resectable BTC.

This multicenter randomized controlled study will include a total of 140 patients who will have undergone curative resection within 4 weeks prior to enrollment and will have been pathologically diagnosed with cholangiocarcinoma (including intrahepatic and extrahepatic cholangiocarcinoma) or muscle-invasive gallbladder carcinoma. Those patients will be randomly assigned 1:1 to tislelizumab combined with capecitabine or capecitabine alone group. The primary endpoint will be recurrence free survival (RFS), the secondary endpoints will be overall survival (OS) and adverse events (AEs). Multi-omics biomarkers will be assessed as exploratory objective.

There remains a major unmet need for more effective adjuvant therapies for resectable BTC. If this study demonstrates that adding tislelizumab enhances the therapeutic efficacy of capecitabine, this combined regimen will potentially improve the prognosis of patients with resectable BTC. In addition, we will analyze the relationship between various gene expression profiles and clinical endpoint events to define the ideal patient population receiving adjuvant immunotherapy.

This study was designed to evaluate the efficacy and safety of hepatopancreatoduodenectomy (HPD) for extrahepatic cholangiocarcinoma, because it remains controversial owing to high morbidity and mortality, as well as uncertain oncological benefits.

Patients who underwent HPD between 2003 and 2020 were reviewed. Short- and long-term outcomes were compared with those of patients who underwent hepatectomy with extrahepatic bile duct resection (HT-B) and pancreatoduodenectomy (PD) for extrahepatic cholangiocarcinoma.

In the study interval, 100 patients underwent HPD, 203 underwent HT-B and 209 underwent PD. The median operating time and blood loss of HPD were 668 min and 1,842 mL, which were significantly longer and greater in comparison to the HT-B (552 min and 1,264 ml) and PD (457 min and 911 ml) groups. The rate of clinically relevant postoperative complications (Clavien-Dindo grade ≥ 3) after HPD was 82%, which was significantly greater in comparison to the HT-B (39%) and PD (68%) groups. However, the mortality rate was 2% and was almost comparable to the HT-B (2.5%) and PD (1.4%) groups. The 3- and 5-year survival rates and median survival times were 59%, 40.7%, and 50 months, respectively, in the HPD group; 61.1%, 41.8%, and 45 months in the HT-B group; and 60.7%, 45.4%, and 48 months in the PD group. No significant differences were observed between the groups.

Although HPD is technically demanding and forces stress on patients, it can be performed with acceptable mortality and survival rate, and is an acceptable option for patients cared for in expert hepatopancreatobiliary centers.

Biliary tract cancer (BTC) is rare. The treatment outcomes in patients with lymph node (LN) metastasis diagnosed by FDG-PET or a biopsy-who are considered to be 'biologically borderline resectable'-are poor. However, perioperative treatment is still under development. Recently, gemcitabine plus cisplatin (GC)-based triplet regimens for unresectable BTC have been developed. We applied GC-based triplet therapy in BTC with LN metastasis.

We administered GC plus S-1 therapy (GCS) or nab-paclitaxel therapy (GCnP) to 30 patients with LN metastasis diagnosed by FDG-PET or a biopsy (GC-based triplet group). A dataset of BTC with FDG-positive LNs, previously used for an analysis of the diagnosis and treatment outcomes according to FDG uptake, was used as a control (upfront surgery group, n = 19).

GCS and GCnP were used by 22 and 8 patients, respectively. The median treatment period was 79 days, the objective response rate was 47 %, the tumor control rate was 87 %, and 22 patients underwent R0 resection (73 %). The groups showed no significant differences with the exception of the FDG uptake by the main tumor. The three-year overall survival (OS) rates in the GC-based triplet and upfront surgery groups were 45.4 % and 15.8 %, respectively (P = 0.0052); there were no significant differences in progression-free or recurrence-free survival. A sub-analysis showed that normalized CA19-9 levels provided better survival than non-normalized CA19-9 levels.

Neoadjuvant GC-based triplet regimens could provide survival benefits in BTC with LN metastasis diagnosed by FGD-PET or a biopsy. CA19-9 normalization may be useful for indicating surgery.

A limited number of randomized controlled trials (RCTs) investigated adjuvant chemotherapy in biliary tract cancers (BTCs). Recurrences and deaths are common in the first 2 years and survival remains poor despite adjuvant treatment.

Phase-III RCTs were included comparing adjuvant chemotherapy and observation in resected BTCs. The primary endpoints were recurrence-free (RFS) and overall survival (OS). Proportional hazard results were used for trial-based analyses. Patient data was curated from published Kaplan-Meier curves to analyze short-term (2-year) hazards. The Parmar and generic inverse variance methods were used.

1308 patients in 4 trials (BILCAP, ASCOT, BCAT, PRODIGE-12) were included. Capecitabine (BILCAP) and S-1 (ASCOT) were grouped as 5-FU-based, gemcitabine (BCAT) and gemcitabine-oxaliplatin (PRODIGE-12) were grouped as gemcitabine-based chemotherapy. Adjuvant 5FU-based chemotherapy improved RFS [HR: 0.80 (95 % CI:0.68-0.95), p = 0.012] and OS [HR: 0.78 (95 % CI:0.65-0.94), p = 0.009]. However, gemcitabine-based chemotherapy did not provide benefit in RFS [HR: 0.90 (95 % CI:0.70-1.15), p = 0.428] and OS [HR: 1.03 (95 % CI:0.78-1.36), p = 0.794]. The benefit of 5-FU-based chemotherapy was more apparent in the short-term (2-year hazards) (RFS: [HR: 0.67 (95 %CI:57-0.79), p < 0.001] and OS: [HR: 0.61 (95 % CI:59-0.64), p < 0.001]). However, gemcitabine-based chemotherapy did not provide RFS benefit in the short term either [HR: 0.80 (95 % CI:0.64-0.1.01), p = 0.067] and seemed to be even detrimental for OS [HR: 1.22 (95 % CI:1.14-1.31), p < 0.001] in the first 2 years.

This study confirms using 5FU-based monotherapy in the adjuvant treatment of resected BTCs. The more prominent benefit in the first 2 years emphasizes that more effective adjuvant treatments with sustained long-term benefits are needed. Two-year proportional hazards OS and RFS are proposed here as an additional secondary end-point to consider in future clinical trials. in this setting. Registration ID (PROSPERO): CRD42024614444.

Biliary tract cancers (BTCs) include intrahepatic, perihilar, distal cholangiocarcinoma, gallbladder cancer, and sometimes papillary Vater cancer. The incidence of BTCs varies worldwide (0.3-85.0/100,000 population). In Japan, the incidence is lowest, but it is increasing (22,000 cases/ year). The 5-year overall survival (OS) in patients with localized BTC is approximately 60%, which is better than that in liver or pancreatic cancer, but is < 5% in patients with metastatic cancers. Surgery requires liver and pancreas surgery with vascular reconstruction, and is associated with a high perioperative mortality rate (> 2%) relative to other cancer surgeries (< 1%). As an adjuvant therapy, fluorouracil prodrugs are effective for improving OS (hazard ratio [HR] 0.69-0.81); however, in patients who receive major hepatectomy, the completion rate is reportedly low (60%). Since 2010, gemcitabine + cisplatin (GC) has become the first-line therapy for unresectable lesions. Subsequently, in 2023-2024 three triplet regimens were reported: GC + S-1(tegafur-gimeracil-oteracil), GC + durvalumab (an anti-PD-L1 antibody), and GC + pembrolizumab (an anti-PD-1 antibody). HRs for OS were 0.79-0.83, objective response rates were 27-42% (GC, 15-29%), and tumor control rates were 75-85% (GC, 62-83%) with small increases in adverse events. In this review, considering the eligibility criteria of currently ongoing neoadjuvant studies, we report two borderline resectable cases with a discussion on resectability. Owing to the high-risk nature of the surgery and to avoid early recurrence due to subclinical metastasis during postoperative recovery, these three triplet regimens for unresectable tumors may change the concept of resectability in BTC.

Hepatopancreatoduodenectomy (HPD) is necessary to achieve a reliable margin-negative resection for widespread perihilar cholangiocarcinoma (PhCC), yet data on long-term outcomes following HPD for PhCC remain limited.

A retrospective cohort study was conducted on 167 patients with PhCC who underwent surgery with curative-intent between 2000 and 2023. Hepatic resection and extrahepatic bile duct resection (Hr-BDR) were performed for cases presumed to have localized tumors, while HPD was conducted for cases with presumed extensive tumor spread. Short- and long-term outcomes, including surgery details, pathological findings, postoperative complications, survival rates, and recurrence patterns, were compared.

Forty-five patients underwent HPD and 122 underwent Hr-BDR. No differences were observed in the T or N factors of the TNM staging between both groups (P = 0.09 and 0.09). Overall postoperative significant complications (38 % vs. 34 %, P = 0.62), 90-day mortality rates (2 % vs. 2 %, P = 0.80), and 5-year cancer-specific survival (45 % vs. 40 %, P = 0.81) were comparable between both groups. However, the 5-year survival rate of the HPD group was significantly higher than that of the Hr-BDR group with positive invasive duodenal-side ductal margins (45 % vs. 0 %, P = 0.03). Local and remnant bile duct recurrence were significantly less frequent in the HPD than in the Hr-BDR group (20 % vs. 37 %, P = 0.04; 11 % vs. 0 %, P = 0.02, respectively).

Although HPD for widespread PhCC requires careful postoperative management, it has the potential to provide excellent long-term outcomes, and it should be considered proactively.

Mass-forming intrahepatic cholangiocarcinoma (MF-ICC) is the second most common primary liver cancer and liver resection offers the best chance of possible cure. This study aimed to assess treatment outcomes and prognostic factors for long-term survival in patients who underwent curative-intent liver resection.

A retrospective analysis was conducted on prospectively collected data from patients with MF-ICC managed at the Royal North Shore/North Shore Private Hospital from January 1998 to October 2023. Baseline, peri-operative and long-term outcomes have been analysed, including an overall survival (OS) and disease-free survival (DFS) analysis.

During the 25-year study period, 47 patients underwent curative-intent liver resection for primary MF-ICC at a median age of 70 years. The median OS was 36 months, with a 5-year OS of 33%. Multiple liver tumours (HR = 2.84; 95% CI = 1.24-6.48; P = 0.013) and a positive resection margin (HR = 2.46; 95% CI = 1.10-5.52; P = 0.029) were identified as independent predictors of poor long-term OS. Recurrence occurred in 62% of patients after a median DFS of 16 months, with poor tumour differentiation (HR = 3.93; 95% CI = 1.62-9.54; P = 0.002) and elevated tumour markers (HR = 3.47; 95% CI = 1.53-7.87; P = 0.003) as independent predictors of poor DFS.

Liver resection can offer a significant chance for prolonged survival in a highly selected population of patients with MF-ICC. However, the surgical challenges inherent in treating this rare disease are evident, emphasizing the need for a multimodal approach and continued exploration of additional therapies to enhance personalized treatment strategies.

Surgery is the only curative therapeutic option for resectable extrahepatic cholangiocarcinoma, but recurrence is common, and prognosis is poor. There is an unmet clinical need for improved decision-making regarding adjuvant chemotherapy (ACT). Herein, we evaluated the usefulness of monitoring longitudinal circulating tumor DNA (ctDNA) for molecular residual disease (MRD) in patients from the STAMP trial, which compared the efficacy of adjuvant capecitabine (CAP) vs. gemcitabine plus cisplatin (GemCis).

Between July 2017 and November 2020, 101 patients were randomized 1:1 to receive GemCis (n = 50) or CAP (n = 51). Efficacy outcomes were analyzed with an extended follow-up of 19 months from the previous report. From a biomarker cohort of 89 patients, longitudinal plasma samples (n = 254) were prospectively collected post-surgery before ACT, and on-ACT at 12 and 24 weeks from cycle 1 day 1 (C1D1). ctDNA was evaluated using a personalized, tumor-informed, 16-plex PCR next-generation sequencing assay and was correlated with clinical outcomes.

In the extended follow-up analysis, median disease-free survival (DFS) and overall survival did not significantly differ between the CAP and GemCis groups. Significantly inferior DFS was associated with ctDNA positivity before ACT (hazard ratio [HR] 1.8; p = 0.029), on-ACT at 12 weeks from C1D1 (HR 7.72; p <0.001), on-ACT at 24 weeks from C1D1 (HR 5.24; p <0.001), and anytime post-surgery (HR 3.81; p <0.001). Analysis of pre-treatment to on-treatment ctDNA dynamics revealed that serially ctDNA-negative patients exhibited a significantly longer DFS compared to those with sustained ctDNA positivity (HR 6.7; p <0.001) or those who turned ctDNA positive (HR 5.8; p <0.001).

In patients with resected extrahepatic cholangiocarcinoma, ctDNA status and dynamics predicted recurrence during adjuvant therapy, and may help optimize clinical decision-making.

The findings from this study highlight the critical role of ctDNA as a prognostic biomarker and monitoring tool for patients with resected extrahepatic cholangiocarcinoma. By demonstrating the superiority of ctDNA to predict disease recurrence compared to conventional biomarkers such as cancer antigen 19-9 and carcinoembryonic antigen, this study underscores its potential in guiding decision-making during adjuvant chemotherapy. These results may be crucial to refine post-surgical treatment strategies and improve patient outcomes. The practical application of ctDNA monitoring could lead to more personalized treatment approaches, enabling timely interventions based on molecular residual disease status.

NCT03079427.

Recent years have witnessed significant advances in the imaging, molecular profiling, and systemic treatment of cholangiocarcinoma (CCA). Despite this progress, the early detection, precise classification, and effective management of CCA remain challenging. Owing to recent developments and the significant differences in CCA subtypes, EASL commissioned a panel of experts to draft evidence-based recommendations on the management of extrahepatic CCA, comprising distal and perihilar CCA. Particular attention is given to the need for accurate classification systems, the integration of emerging molecular insights, and practical strategies for diagnosis and treatment that reflect real-world clinical scenarios.

S-1 adjuvant chemotherapy (AC) is the standard treatment for pancreatic ductal adenocarcinoma (PDAC) after curative surgery in Japan. Our prior research suggested that a lower postoperative geriatric nutritional risk index (GNRI) predicts S-1 discontinuation due to adverse events (AEs). This study aimed to validate the GNRI as a predictor of S-1 non-completion using an independent cohort. Methods: This retrospective study analyzed 180 patients who underwent curative PDAC resection at Dokkyo Medical University from January 2010 to March 2023. Postoperative GNRI values were recorded as part of nutritional screening. Data on S-1 therapy completion and related clinical factors were analyzed statistically. Results: Patients were classified based on S-1 completion (N = 93) and non-completion (N = 48). GNRI values were significantly lower in the non-completion group. A GNRI threshold of 94.4, identified in a prior study, effectively distinguished patients at risk of discontinuation. Univariate analysis confirmed that a GNRI of ≥94.4 was a significant predictor of successful S-1 completion [hazard ratio (HR) for recurrence-free survival (RFS), 1.54; 95% confidence interval (CI) 1.04-2.28 and for overall survival (OS), 1.89; 95% CI 1.20-2.99]. Conclusions: This study validated previous findings, confirming that the postoperative GNRI reliably identifies patients at risk of S-1 non-completion due to AEs after PDAC surgery. The GNRI serves as a practical marker for optimizing patient care and enhancing AC efficacy.

Several randomized controlled trials compared adjuvant systemic chemotherapy with observation in patients with resected biliary tract cancer (BTC) have yielded inconsistent outcomes. In order to assess the efficacy of adjuvant therapy in these patients, we conducted this systematic review and meta-analysis.

We conducted a thorough search in various databases, which included MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ASCO Abstracts, ESMO Abstracts and ClinicalTrials.gov. All relevant randomized controlled trials investigating the adjuvant chemotherapy compared with observation in resected biliary tract cancer were identified. The primary outcome of interest was overall survival (OS), while secondary outcome was relapse-free survival (RFS). Statistical analyses were conducted using Review Manager 5.3. Additionally, publication bias was evaluated using Egger's test in Stata 12.0.

A total of 5 randomized controlled trials, involving 1406 patients, were included in this analysis. Compared with observation, adjuvant chemotherapy improved RFS [HR 0.84 (0.73-0.96), p=0.01] (I2=0%, p=0.89) but not OS [HR 0.89 (0.77-1.03), p=0.12] (I2=51%, p=0.09) in the entire population after BTC resection. Subgroup analyses revealed that adjuvant chemotherapy did improve both OS [HR 0.76 (0.62-0.93), p=0.009] (I2=7%, p=0.37) and RFS [HR 0.74 (0.58-0.95), p=0.02] (I2=0%, p=0.39) in patients with lymph node positivity. Furthermore, patients receiving oral fluoropyrimidine monotherapy showed benefit from the adjuvant therapy, with longer OS [HR 0.78 (0.65-0.94), p=0.009] (I2=2%, p=0.31) and RFS [HR 0.81 (0.68-0.95), p=0.01] (I2=0%, p=0.95).

To conclude, adjuvant chemotherapy have the potential to offer advantages in patients with resected BTC. Specifically, patients demonstrating positive lymph node status have a higher likelihood of benefiting from adjuvant therapy. Our analysis supports the current standard of care of adjuvant fluoropyrimidine. However, the recommendation of oral fluoropyrimidine monotherapy as the preferred option is not definitive, as it is based on limited studies. Further validation of these outcomes is necessary by conducting extensive randomized controlled trials.

Cholangiocarcinoma (CCA) is a serious public health issue due to its insidious onset and dismal prognosis. The past few years have witnessed and highlighted the development of understanding and management of CCA. The combination of gemcitabine and cisplatin (GP) chemotherapy regimen with immunotherapy using immune checkpoint inhibitors has been considered the new standard first-line treatment alternative for advanced CCA. Notably, the proportion of patients with advanced CCA with targetable genetic mutations is approximately 40 %, and these patients may be considered for molecularly targeted therapy in the second-line treatment. In this review, we highlight the advances and progress in targeted therapies for advanced CCA, with special attention to data from Asian populations, including Chinese. In addition, we present in detail the phosphatase tension homolog (PTEN), a novel biomarker for both of first-line chemotherapy and second-line targeted therapy in advanced CCA, and its ability to forecast prognosis in patients with CCA. The mechanisms of rapid resistance to targeted agents warrant further investigation and address in light of the development of new targeted therapies. Precision medicine is gradually playing an increasing role in achieving optimal therapeutic outcomes.

To clarify the short- and long-term validity of pancreatoduodenectomy in octogenarian patients with biliary tract carcinoma.

We compared 23 and 141 patients aged ≥80 and <80 years, who underwent pancreatoduodenectomy for biliary tract carcinoma (distal cholangiocarcinomas and ampullary carcinomas) and evaluated the relationship between age, clinicopathological factors, and surgical and oncological outcomes, especially in terms of recurrence.

Median overall survival time of distal cholangiocarcinoma and ampullary carcinoma was 92 and 109 months (p = 0.13). Postoperative complications, mortality, and adjuvant chemotherapy rates did not differ between the groups. Although the 5-year recurrence-free survival rate was similar, the 5-year disease-specific survival and overall survival rate were significantly shorter in octogenarians (≥80 years: 43.5, 47.1, and 35.3%; <80 years: 54.1, 69.2, and 63.0%; p = 0.41, 0.016, and 0.034, respectively). The median time from recurrence to death for octogenarian patients was significantly shorter than that of younger patients (3.3 vs. 16.1 months, p < 0.001). At recurrence, the serum albumin level, prognostic nutritional index, controlling nutritional status score, and treatment rate for recurrence were lower in octogenarians. The multivariate analysis identified age ≥80 years (hazard ratio: 3.8), low prognostic nutritional index (hazard ratio: 2.9), high serum carbohydrate antigen 19-9 (hazard ratio: 2.6), and failure to implement treatment after recurrence (hazard ratio: 3.0) as independent risk factors for a short time from recurrence to death. Furthermore, age ≥80 years (odds ratio 0.09) was an independent risk factor for treatment implementation after recurrence.

Octogenarians had a shorter survival time after recurrence, resulting from low nutritional indices and a reduced rate of treatment implementation at the time of recurrence.

The role of recurrence-free survival (RFS) as a validated surrogate endpoint for overall survival (OS) among patients undergoing upfront surgery for intrahepatic cholangiocarcinoma (ICC) has not been defined. We sought to evaluate the correlation between RFS and OS after surgical resection for ICC. We hypothesized that RFS was a reliable surrogate endpoint for OS among patients with ICC.

Patients who underwent upfront curative-intent surgery for ICC between 2000 and 2023 were identified from an international, multi-institutional database. The correlation between RFS and OS was assessed using rank correlation. Landmark analysis evaluated concordance between survival at 5 years and recurrence status at 6, 12, 24, 36, 48, and 54 months postoperatively.

Among 1541 patients who underwent curative-intent hepatic resection, the median RFS and OS were 22.6 months and 41.5 months, respectively. A moderately strong correlation between RFS and OS was identified (ρ = 0.79, 95% CI 0.76 to 0.82). In the landmark analysis, the concordance between 5-year OS after surgery and recurrence status at different time points (6, 12, 24, 36, 48, and 54 months) was 60.7%, 72.0%, 81.4%, 83.1%, 83.0%, and 82.5%, respectively. Restricted cubic spline analysis indicated that the prediction of OS based on RFS increased with time and plateaued 3 years after surgery.

Among patients undergoing curative-intent resection of ICC, there was a moderately strong correlation between RFS and OS. Three-year RFS may be a reliable surrogate endpoint to predict 5-year OS and should be considered in future trial design.

Cholangiocarcinoma (CCA) is a unifying title granted to epithelial adenocarcinomas specific to the bile ducts making up 10-25% of all hepatobiliary malignancies. CCA is more appropriately classified based on anatomic site of origin within the biliary tract into intrahepatic cholangiocarcinoma (iCCA), peri-hilar (pCCA) cholangiocarcinoma, and distal cholangiocarcinoma (dCCA). Intrahepatic cholangiocarcinoma makes up 10-20% of CCA and originates within and/or proximal to the second order bile ducts. The incidence of iCCA has been rising overtime with up to 1.26 per 100,000 persons, per year in the United States and up to 3.3 per 100, 000 persons, per year affected globally. Risk factors include chronic hepatic inflammation secondary to viral hepatitis, alcohol/NASH cirrhosis, biliary cystic lesions, and endemic causes, among other less common genetic drivers. Given its rarity, the recognition and diagnosis of cholangiocarcinoma, iCCA specifically, remains challenging resulting in delays in treatment initiation or any treatment at all. Median overall survival (mOS) for iCCA remains low. Early diagnosis, and stage-based treatment approaches have evolved and are associated with improved survival. To this goal, a multi-disciplinary treatment approach has been demonstrated to improve patient outcomes by providing expert evaluation as it pertains to an accurate imaging and histologic diagnosis, staging, radiologic and surgical review for resectability, operative expertise, post operative care, as well as comprehensive knowledge and implementation of systemic/targeted or liver directed therapies. Here, we discuss the central role of imaging in the diagnosis of intrahepatic cholangiocarcinoma to implement a comprehensive treatment plan that frequently involves multiple disciplines to achieve the best outcome for each patient.

In the TOPAZ-1, patients with biliary tract cancers (BTC) and recurrence within 6 months after surgery were excluded, even if this event is frequently observed in clinical practice. Our study aimed to assess if the efficacy of cisplatin-gemcitabine-durvalumab (CGD) in this population is comparable to that reported in the phase 3 trial.

The study cohort included patients with BTC who underwent surgery on the primary tumor, experienced disease recurrence occurring ≤6 months or >6 months after surgery or after the end of adjuvant therapy and started CGD. The primary objectives were overall survival (OS) and progression free survival (PFS).

A total of 178 patients were enrolled. No significant differences were observed between early and late relapse groups in OS (23.4 months vs not reached; HR 1.26; 95% CI, 0.67-2.37; P = .45) and PFS [7.0 months vs 9.8 months; HR 1.3(95% CI, 0.9-2.1) P = .13]. Overall response rate and disease control rate (P = .33 and P = .62) were comparable between the 2 groups, as the overall safety profile. In addition, we compared survival outcomes between the selected population and a historical cohort of patients with BTC treated with cisplatin-gemcitabine (CG) and found that despite the absence of statistical significance, CGD showed an outcome trend compared with CG regardless of the time of recurrence after surgery or adjuvant chemotherapy [(CG ≤ 6 vs CGD ≤ 6 months: HR 0.59, 95%CI, 0.35-1.01, P = .05; HR 0.70; 95%CI, 0.46-1.06, P = .09, OS and PFS, respectively) and (CG > 6 vs. CGD > 6 months: HR 0.50; 95%CI, 0.29-0.88, P = 0.0165; HR 0.54; 95%CI, 0.35-0.84, P = .0068, OS and PFS, respectively)].

Our analysis suggests that CGD retains its efficacy independently of the timing of relapse after surgery or completion of adjuvant treatment in patients with advanced BTC.

Resection outcomes for perihilar cholangiocarcinoma differ between Western and Eastern centres, but reasons behind these disparities remain unclear. This study aimed to compare current outcomes between a Western and an Eastern expert centre to identify prognostic factors.

Patients who underwent hepatobiliary resection for perihilar cholangiocarcinoma between 2010 and 2022 at Karolinska University Hospital (Stockholm, Sweden) and Cancer Institute Hospital (Tokyo, Japan) were retrospectively included. Primary outcome was overall survival. Secondary outcomes were disease-free survival, postoperative complications and 90-day mortality rate.

Two hundred and forty-nine patients were included (Cancer Institute Hospital n = 159, Karolinska n = 90). Median overall survival was 20.4 months at Karolinska and 52.0 months at Cancer Institute Hospital (P < 0.001). Median disease-free survival was 11.9 months at Karolinska and 32.4 months at Cancer Institute Hospital (P < 0.001). Advanced tumours, ASA class ≥III, poor differentiation and radial margin positivity were more common in the Western cohort. Treatment centre, T-status, N1-status, resection side, R1-status, age and carbohydrate antigen 19-9 were prognostic for overall survival. The Eastern cohort had a lower rate of postoperative complications (24.5%) and a lower mortality rate (2.5%) compared with the Western cohort (51.1% and 10.0%).

Advanced tumour stage and radial margin positivity contributed to poor long-term survival in the Western cohort. A higher burden of co-morbidity and a higher rate of extended resections with smaller remnant liver volume influenced the Western postoperative mortality rate.

Due to the limited efficacy of chemotherapy alone in the treatment of unresectable biliary tract cancer, we performed conversion surgery in patients with unresectable biliary tract cancer who responded to down-staging chemotherapy.

Patients with unresectable biliary tract cancer who initiated chemotherapy between 2007 and 2018 were included in this study. We evaluated the short- and long-term outcomes of patients with initially unresectable biliary tract cancer who underwent conversion surgery.

A total of 101 patients with unresectable biliary tract cancers treated with chemotherapy were eligible for the present study. A total of 20 patients eventually underwent conversion surgery; these patients had locally advanced disease in 6 cases, liver metastasis in 6 cases, para-aortic lymph node metastasis in 5 cases, and peritoneal dissemination in 3 cases. The mean operative time was 823 min, and the mean intraoperative blood loss was 1902 mL. Histological R0 resections were performed in 17 patients. Postoperative complications of Clavien-Dindo grade IIIa or higher occurred in 10 patients, with no surgery-associated deaths. The 5-year survival rate was significantly higher in patients who underwent conversion surgery (65.0%) than in those who did not (4.3%, p < 0.001).

Conversion surgery for initially unresectable biliary tract cancer resulted in favorable overall survival and was safely performed despite its high surgical invasiveness. Conversion surgery for an initially unresectable biliary tract cancer is worth considering.

The prognosis of perihilar cholangiocarcinoma (PHC) is poor even after curative resection, highlighting the need for effective adjuvant chemotherapy. The efficacy of adjuvant S-1 chemotherapy following major hepatectomy for PHC is unclear, and thus the aim of this study was to elucidate this.

Consecutive patients with PHC who underwent major hepatectomy (hemihepatectomy or trisectionectomy extending to segment 1 with extrahepatic bile duct resection) at three high-volume centers in Japan from 2007 to 2020 were retrospectively evaluated. Patients with Clavien-Dindo grade V complications, pStage 0, I, or IVB disease, and those who underwent adjuvant radiation therapy were excluded from analysis. Propensity score matching analysis was performed to compare the disease-specific survival (DSS) of patients who underwent adjuvant S-1 chemotherapy with those who underwent observation.

Overall, 373/480 patients were eligible, of whom 81 underwent adjuvant S-1 chemotherapy and 146 underwent observation. In the global cohort, DSS was similar in the S-1 and observation groups (p = 0.18), while in the matched cohort (S-1, n = 44; observation, n = 44), DSS was similar between the S-1 and observation groups (p = 0.09). On multivariate analysis, percutaneous biliary drainage (PTBD), CA19-9 levels of ≥ 300 U/mL at operation, and lymph node (LN) metastasis were independent predictors of poor survival following major hepatectomy for PHC. In subgroup analysis of patients with LN metastasis, DSS was better in the S-1 group than in the observation group (p = 0.001).

Adjuvant S-1 chemotherapy following major hepatectomy might be effective in PHC patients with LN metastasis.

We aimed to define borderline resectable colorectal liver metastases (CRLM) based on the analysis of risk factors for early surgical failure and investigate the efficacy of neoadjuvant chemotherapy in these patients.

This was a retrospective analysis of a multi-institutional cohort of patients diagnosed with technically resectable CRLM. Early surgical failure within 6 months of liver surgery was defined as ESF6. We classified CRLM into three grades (A, B, and C) according to the definition of the Japanese Society for Cancer of the Colon and Rectum.

Among the 249 patients with technically resectable CRLM, 46 (18.5%) developed ESF6. The survival rate of these patients was significantly lower than that of the patients without ESF6. In the multivariate analysis of synchronous CRLM patients, no neoadjuvant chemotherapy, Grade B/C, and Charlson comorbidity index ≥ 3 were independent predictors of ESF6. Among patients with synchronous and Grade B/C CRLM, ESF6 rates, surgical failure-free survival, and overall survival in the neoadjuvant chemotherapy group were significantly better relative to the upfront surgery group.

Patients with synchronous and Grade B/C CRLM are at a high risk of early surgical failure, have a poor long-term prognosis, and can be defined as borderline resectable and good candidates for neoadjuvant chemotherapy.

To evaluate the prognostic impact of diabetes mellitus (DM) in patients who underwent resection for perihilar cholangiocarcinoma (PHCC) and the influence of remnant liver volumes on postoperative glycemic profiles and survival outcomes.

The impact of DM and extended hepatectomy on survival outcomes of patients with PHCC remains unclear.

A total of 184 patients who underwent hepatectomy with extrahepatic bile duct resection for PHCC between 2002 and 2020 were retrospectively analyzed and divided into groups based on DM and future liver remnant (FLR) ≥40% or <40%. Survival outcomes and glycemic profiles were analyzed.

Patients with DM (n = 34) had significantly worse overall survival compared with those without DM (n = 150; median survival time: 23.3 vs 46.7 months; P = 0.003) although cancer-specific survival was comparable (P = 0.894). Patients with DM had a higher incidence of death from infections (P < 0.001). Multivariate analysis identified DM as an independent prognostic factor (hazard ratio, 1.742; P = 0.021). DM with FLR <40% (n = 11) exhibited worse survival (median survival time: 13.7 vs 35.0 months; P = 0.026) and a higher incidence of death from infections (P = 0.016) compared with those with FLR ≥40% (n = 23). The median glucose fluctuation was larger in patients with DM and FLR <40% (80 vs 39 mg/dL; P = 0.023).

DM was an independent prognostic factor in patients with PHCC undergoing hepatectomy. DM and FLR <40% were associated with worse survival and larger glucose fluctuation postoperatively.

Treatment of intrahepatic cholangiocarcinoma (ICC) remains challenging owing to the lack of clear guidelines on surgical resection. The 2021 ICC guidelines have not fully resolved the ongoing debate between surgical and nonsurgical treatment options. This study aimed to identify trends and issues in ICC treatment strategies in the clinical field by surveying the attitudes of hepatobiliary and pancreatic (HBP) surgeons.

A survey was conducted among 235 board-certified HBP surgeons affiliated with the Japanese Society of Hepato-Biliary-Pancreatic Surgery. This survey explored the perspectives on tumor conditions that define resectable, borderline resectable, and unresectable diseases, focusing on tumor size, number, and vascular invasion.

Notable variability was observed in the criteria for oncological resectability. While 42.1% of the respondents considered a maximum tumor diameter of 5 cm as resectable, 37.5% indicated no size limit for resectability. Opinions regarding the resectability of tumors with lymph node involvement and vascular invasion vary widely, highlighting the need for standardized criteria.

This survey revealed diverse approaches for defining resectability in ICC, emphasizing the necessity for more precise guidelines. Further research and expert consensus are required to establish standardized criteria that can guide clinical decision-making and improve patient outcomes.

A histologically involved surgical margin (R1) is often observed after resection for cholangiocarcinoma. Compared with a negative margin (R0), R1 with invasive carcinoma (R1inv) markedly worsens survival, whereas the prognostic effect of R1 with carcinoma in situ (R1cis) remains controversial.

Patients who underwent resection for perihilar cholangiocarcinoma between 2002 and 2019 were retrospectively reviewed. According to the pathological assessment, the duct margin was classified as R0, R1cis, or R1inv; radial margin positivity was treated as R1inv. Recurrence and survival were compared.

Among the 681 patients, 457 had R0, 69 had R1cis, and 155 had R1inv. The overall five-year recurrence rate was 82.8 % with R1inv, 67.8 % with R1cis, and 47.6 % with R0 (P < 0.001); the local recurrence rate also significantly differed among these groups (P < 0.001). The five-year survival rate was significantly worse with R1cis than with R0 (37.3 % vs. 56.7 %, P < 0.001) and better than that with R1inv (20.9 %, P = 0.007). Multivariate analysis revealed that R1cis was an independent predictor of survival (hazard ratio, 1.65; P < 0.001).

Compared with R0, R1cis significantly deteriorated overall survival in the whole resection subset of patients with perihilar cholangiocarcinoma. However, the prognostic impact of R1cis was milder than that of R1inv.

Given the high mortality associated with gallbladder cancer (GBC), the efficacy of adjuvant therapy (AT) remains controversial. We audited our data over an 11-year period to assess the impact of AT.

This study included all patients who underwent curative resection for GBC from 2007 to 2017. Analyses were conducted of clinicopathological characteristics, surgical details, and postoperative therapeutic records. The benefits of adjuvant chemotherapy (CT) or chemoradiotherapy (CTRT) were evaluated against surgery alone using SPSS version 20 for statistical analysis.

The median age of patients (n = 142) was 50 years. The median overall survival (OS) was 93, 34, and 30 months with CT, CTRT, and surgery alone respectively (p = 0.612). Multivariate analysis indicated that only disease stage and microscopically involved margins significantly impacted OS and disease-free survival (DFS). CT showed increased effectiveness across all prognostic subsets, except for stage 4 and margin-positive resections. Following propensity score matching, median DFS and OS were higher in the CT group than in the CTRT group, although the differences were not statistically significant (p > 0.05).

Radically resected GBC patients appear to benefit more from adjuvant CT, while CTRT should be reserved for cases with high-risk features.

Signet ring cell carcinoma (SRC) of the gallbladder is a rare type of gallbladder cancer. We report a case of SRC of the gallbladder that was characterized by the diffuse presence of SRC on the gallbladder mucosa and diagnosed after cholecystectomy.

A 40-year-old man was referred to our department with upper abdominal pain and vomiting. Based on the findings of blood tests, computed tomography, and magnetic resonance imaging, acute cholecystitis was suspected, and emergency laparoscopic cholecystectomy was performed. Intraoperative findings showed mild inflammation. Although the tumor remained within the mucosa, tumor cell infiltration was suspected at the edge of cystic duct pathologically. Although additional endoscopic ultrasound and endoscopic retrograde cholangiography showed that horizontal extension into the residual cholecystic duct was suspected, there was no evidence of invasion into the common bile duct, lymph node metastasis, or distant metastasis. One and a half months after cholecystectomy, the patient underwent extrahepatic bile duct resection, lymph node dissection, and bile duct jejunal anastomosis. The postoperative course was uneventful, and the patient was discharged on the 10th postoperative day. Postoperative pathological analysis showed no obvious residual tumor tissue in the common bile duct or choledochal duct margins, and no metastasis in the submitted lymph nodes. Based on the above, a diagnosis of pT1aN0M0, pStage IA SRC was made. As no lymph node metastasis was observed, it was decided to follow up the patient without initiating postoperative chemotherapy, and the patient has been recurrence-free for 12 months after surgery.

We describe an incidentally discovered case of intramucosal SRC diffusely spreading throughout the gallbladder after cholecystectomy for acute cholecystitis.

Combination of gemcitabine and cisplatin (GemCis) is the current first-line treatment for unresectable biliary tract cancer (UR-BTC), but it confers a median overall survival (OS) of less than one year. This study aimed to evaluate the survival benefit of conversion surgery for initially UR-BTC.

Eligible studies published between January 2000 and May 2024 were identified via an electronic search of PubMed and Web of Science databases. The primary endpoint was OS.

Included in this study were 96 observational studies involving 466 patients with 231 cases (49.6%) of intrahepatic cholangiocarcinoma, 131 cases of (28.1%) extrahepatic cholangiocarcinoma, and 104 cases (22.3%) of gallbladder cancer. The 90-day mortality rate was 4.3%, and the median survival duration was 36.8 (17.9-57.6) months, with a 1-, 3- and 5-year OS rate of 86% (74-95.9%), 59.9% (32.3-78.7%), and 41.1% (24-58.5%) respectively. Meta-analysis showed that survival in patients who underwent conversion surgery was significantly higher than that in those who received non-surgical treatment (hazard ratio [HR] 0.39, P < 0.001) and comparable to that in those who underwent up-front surgery for resectable cancer (HR 1.02, P = 0.43). Pooled analysis of 149 individual participant data showed that male gender (HR 20.649, P = 0.014) and lymph node metastasis (HR 14.671, P = 0.005) were independently associated with reduced OS.

Conversion surgery is justified in initially UR-BTC with favorable long-term survival, and may prove to be a promising option for the multimodality treatment of UR-BTC.

Despite complete resection, the recurrence rate of biliary tract cancer (BTC) remains high, leading to poor prognosis. Postoperative adjuvant chemotherapy (ACT) following radical resection may substantially reduce the recurrence risk by eradicating micrometastatic lesions. However, the benefits of postoperative ACT and the optimal ACT strategy are still unclear for BTC. The objectives of this study are to evaluate the prognostic value of ACT and compare the effectiveness of different ACTs among BTC patients after curative resection.

A comprehensive literature search was conducted across PubMed, Cochrane Library, Web of Science, and EMBASE databases to identify randomized controlled trials (RCTs) comparing the benefits of ACT versus no intervention or other ACTs in BTC patients after curative resection. A random-effects network meta-analysis was performed to compare overall survival (OS) and relapse-free survival (RFS). The quality of evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation framework.

Eight RCTs comprising 1803 patients were included in the meta-analysis. ACT was associated with significant improvements in 5-year all-cause mortality [four RCTs, hazard rate (HR) 0.93; 95% confidence interval (CI), 0.87-1.00, marginally significant; low-certainty evidence], RFS (five RCTs, HR 0.87; 95% CI, 0.78-0.98; moderate-certainty evidence), and OS (7 studies, HR 0.85; 95% CI, 0.75-0.96; low-certainty evidence) compared with observation. ACT had significantly better survival benefits on patients with negative margins (R0), lymph node-positive (N+), and tumor node metastasis classification (TNM) stage I/II ( P < 0.05). Further network meta-analysis demonstrated that fluorouracil-based ACT was significantly inferior to gemcitabine-based ACT (HR 1.20; 95% CI, 1.10-1.25) in improving RFS. However, both were superior to observation ( P < 0.05). No statistical difference in OS was observed between gemcitabine-based and fluorouracil-based chemotherapy (HR 1.00; 95% CI, 0.86-1.20). In subgroup analysis, fluorouracil-based ACT but not gemcitabine-based ACT achieved significantly better OS benefits on patients with N+ (HR 0.67; 95% CI, 0.52-0.86) and R0 (HR 0.69; 95% CI, 0.54-0.88).

Compared with observation, ACT should be routinely recommended to improve survival outcomes in BTC patients after curative resection, especially for those with R0, N+, and TNM stage I/II. Gemcitabine-based ACT performed better than other chemotherapies in improving RFS. This network meta-analysis provides precise information for determining the best adjuvant treatment for resected BTC. Further thorough and high-quality RCTs are needed.