Search Results (343)

Background: Although gemcitabine-based palliative chemotherapy remains widely used for advanced biliary tract cancer (BTC), practical pretreatment prognostic factors are needed. This study identified baseline prognostic factors associated with overall survival (OS) and explored a simple risk stratification approach for 12-month survival in advanced BTC patients treated with gemcitabine-based chemotherapy. Methods: This retrospective cohort study included advanced BTC patients treated with gemcitabine-based palliative chemotherapy between 2011 and 2025. Baseline clinical and laboratory variables were collected at treatment initiation. The Kaplan–Meier method estimated OS. Univariable and multivariable Cox proportional hazards regression analyses identified prognostic factors. A post hoc exploratory risk score was developed using routinely available factors independently associated with OS. Results: A total of 154 patients were included, gemcitabine plus cisplatin was administered to 95 patients, whereas 59 received gemcitabine plus carboplatin. Median OS was 9.43 months. Multivariable analysis showed that ECOG performance status ≥ 2 (adjusted HR, 5.68; 95% CI, 2.52–12.81), alkaline phosphatase (ALP) ≥ 2 × ULN (adjusted HR, 1.53; 95% CI, 1.01–2.33), and neutrophil-to-lymphocyte ratio (NLR) ≥ 3 (adjusted HR, 1.51; 95% CI, 1.03–2.20) were associated with worse OS. An exploratory score assigning one point to each factor stratified patients into low-, intermediate-, and high-risk groups. The estimated 12-month OS rates were 59.6%, 40.4%, and 10.8%, respectively. Conclusions: Poor performance status, elevated ALP, and elevated NLR were associated with worse OS in advanced BTC patients receiving gemcitabine-based palliative chemotherapy. However, the associations for ALP and NLR were modest and should be interpreted cautiously. A simple exploratory score based on routinely available factors demonstrated distinct 12-month survival across risk groups and may help inform prognostic discussions in routine practice. This approach should be considered hypothesis-generating, and external validation is warranted. Full article

Background: This study evaluated the association between cumulative chemotherapy exposure and overall survival (OS) in patients with advanced biliary tract cancer (BTC) and explored baseline factors associated with prolonged treatment continuation. Methods: Patients with advanced BTC receiving systemic chemotherapy were stratified by cumulative chemotherapy exposure (<8 vs. ≥8 cycles) and analyzed retrospectively. Logistic regression analysis identified baseline factors associated with receiving ≥8 chemotherapy cycles. OS was evaluated using Kaplan–Meier and landmark-adjusted time-dependent Cox proportional hazards analyses. Results: Among 86 patients analyzed, those receiving ≥8 chemotherapy cycles demonstrated more favorable inflammatory and nutritional profiles and lower metastatic burden. Median OS was longer in patients who received ≥8 chemotherapy cycles (n = 40) than in those who received <8 cycles (n = 46) (19.3 vs. 6.5 months, respectively; log-rank p < 0.001). Multivariable logistic regression identified metastatic disease as an independent factor associated with a lower likelihood of receiving ≥8 cycles (OR 0.34, 95% CI 0.12–0.97, p = 0.044). In landmark-adjusted multivariable analysis (n = 66), receiving ≥8 chemotherapy cycles remained independently associated with longer OS (HR 0.46, 95% CI 0.22–0.96, p = 0.039). Restricted cubic spline analysis demonstrated progressive hazard reduction with increasing chemotherapy exposure, although the magnitude of reduction attenuated beyond approximately 8 cycles. Conclusion: Greater cumulative chemotherapy exposure was associated with prolonged OS in advanced BTC, with attenuation of the survival benefit beyond approximately 8 cycles. Sustained treatment exposure may partly reflect preserved physiological reserve and ability to maintain systemic therapy in real-world clinical practice. Full article

Immune checkpoint inhibitor (ICI)-based combinations have become central systemic treatment options for advanced hepatocellular carcinoma (HCC) and are now being integrated into selected intermediate-stage settings. As tumor responses have improved, some patients who were not initially candidates for curative-intent treatment may later become candidates for resection, ablation, or liver transplantation. However, radiographic response alone does not define curative-intent candidacy, and no shared framework currently guides how post-immunotherapy response should be translated into a treatment decision. Terminology also differs regionally: Asian literature frames a resection-anchored paradigm, whereas Western practice uses transplant-anchored downstaging. This narrative review proposes a multidisciplinary framework for immunotherapy-based conversion to curative-intent treatment in HCC. We first clarify the lexicon of conversion, downstaging, bridging, neoadjuvant therapy, post-ICI transplantation, and drug-free or treatment-free status. We then summarize conversion-relevant evidence across key clinical decision settings, including transarterial chemoembolization (TACE)-unsuitable intermediate-stage disease, portal vein tumor thrombus or macrovascular invasion, borderline-resectable or locally advanced disease, and transplant downstaging or bridging. The central framework defines curative-intent transition through the intersection of three domains: technical suitability, oncologic suitability, and physiologic or liver-reserve suitability. Biomarkers, imaging response, tumor-marker kinetics, liver function, and treatment-related toxicity are discussed as inputs into candidacy rather than as response measures alone. Finally, we propose a multidisciplinary workflow and highlight lessons from pancreatic cancer, biliary tract cancer, and colorectal liver metastases. As an expert-opinion-based framework, this approach should structure multidisciplinary discussion rather than serve as validated selection criteria; harmonized terminology, prospective conversion registries, and conversion-specific endpoints are needed for prospective validation. Full article

Gemcitabine plus cisplatin (GemCis) has been served as an important first-line chemotherapy backbone for unresectable locally advanced or metastatic biliary tract cancer (BTC). However, cisplatin is unsuitable for all patients. Gemcitabine plus carboplatin (GemCarbo) is frequently used as an alternative, but direct comparative data remain limited. We retrospectively review patients with unresectable locally advanced or metastatic BTC who received first-line GemCis or GemCarbo at Songklanagarind Hospital between 2011 and 2025. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and selected laboratory-based safety outcomes. Propensity score matching was applied to reduce baseline treatment selection bias. Among 154 eligible patients, 95 received GemCis and 59 received GemCarbo. In the overall cohort, median OS was 8.44 months with GemCarbo and 9.82 months with GemCis (HR, 1.18; 95% CI, 0.82–1.70; p = 0.382). After propensity score matching, median OS was 8.44 months with GemCarbo and 11.63 months with GemCis (HR, 1.26; 95% CI, 0.84–1.90; p = 0.271). Median PFS was 4.27 and 5.75 months (HR, 0.91; 95% CI, 0.62–1.33; p = 0.617). ORR and DCR were comparable among evaluable patients. Increased serum creatinine was more frequent with GemCis, whereas hematologic toxicities were comparable. GemCarbo showed no statistically significant difference in OS or PFS compared with GemCis, suggesting that it may be considered as an alternative when cisplatin is unsuitable. However, prospective validation is warranted. Full article

Background: Preeclampsia, a condition of high blood pressure during pregnancy, is linked to microangiopathy in various organs and may contribute to cancer development. This study aimed to evaluate cancer risk in women with newly diagnosed preeclampsia. Methods: We conducted a nationwide, population-based retrospective study using data from the Korean National Health Insurance claims database (2008–2020). Women diagnosed with preeclampsia between 2009 and 2013 were compared to a control group who underwent appendectomy but did not have preeclampsia. Participants with a prior cancer diagnosis were excluded. Cancer occurrence was assessed using the International Classification of Diseases, 10th revision codes. Results: Data from 42,380 preeclampsia patients and 105,327 controls were analyzed. Cancer incidence rates were 333.1 per 100,000 person-years in the preeclampsia group and 377.0 in controls. Preeclampsia was associated with significantly higher risks of gallbladder and biliary tract cancers (HR 5.49, 95% CI 1.23–24.50), breast cancer (HR 1.17, 95% CI 1.02–1.34), and thyroid cancer (HR 1.21, 95% CI 1.10–1.34). However, it was linked to lower risks of ovarian cancer (HR 0.44, 95% CI 0.27–0.74) and leukemia (HR 0.36, 95% CI 0.16–0.81). All hazard ratios were adjusted for age, which differed substantially between the two groups; unadjusted incidence rates and age-adjusted hazard ratios therefore differed in direction for some sites. Conclusions: Preeclampsia was associated with an increased risk of certain cancers, including breast and thyroid cancers, and with a decreased risk of ovarian cancer and leukemia. Because the control group was older than the preeclampsia group, crude incidence rates and age-adjusted hazard ratios differed in direction; the age-adjusted estimates should therefore be regarded as the primary findings. Several site-specific associations, particularly those based on small event counts (e.g., gallbladder and biliary tract cancer), should be interpreted as exploratory and warrant replication. Full article

Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder cancers, are characterized by their rarity, poor prognosis, limited treatment options, and significant psychosocial burden among affected individuals. Hope and loneliness are known to play significant roles in shaping cancer-related experiences and outcomes; however, their trajectories in the context of rare cancers remain unexplored. The Canadian Cholangiocarcinoma Collaborative (C3) was founded to enhance access to treatment, research, and support for individuals affected by BTC in Canada. This mixed-methods study aimed to measure hope and loneliness among patients and caregivers over time and to gain a deeper understanding of their experiences. A total of 92 patients and 44 informal caregivers, self-, peer-, or physician-referred, consented to participate in this study. Participants completed electronic self-reported measures of hope (Hope Herth Index (HHI), 12 items) and loneliness (UCLA Loneliness scale, 20 items) upon joining C3 (baseline, T0), following the first informational session with a C3 research navigator (T1), and after two to three months (T2). A subsample (n = 14) also participated in two online focus groups. At baseline, participants reported relatively high levels of hope (patients: M = 39.8, SD = 4.9; caregivers: M = 38.9, SD = 4.68), with the HHI ranging from 12 to 48, where higher scores indicate higher hope. They also reported low-to-moderate levels of loneliness (patients: M = 32.13, SD = 9.63; caregivers: M = 36.69, SD = 12.37), with the scale ranging from 20 to 80, where low loneliness: 20–34; moderate: 35–49; moderately high: 50–64; and high: 65–80. At T1, a significant decrease in hope (mean difference [MD] = −1.38, 95% CI [−2.64, −0.11], p = 0.029) and a significant increase in loneliness (MD = 1.75, 95% CI [0.27, 3.23], p = 0.016) were found among patients, with no further significant changes from T1 to T2. Among caregivers, no significant changes were observed from baseline to T1; however, at T2, there was a significant decrease in hope (MD = −2.01, 95% CI [−3.61, −0.40], p = 0.010) and a significant increase in loneliness (MD = 4.54, 95% CI [1.31, 7.77], p = 0.004). No significant differences in hope or loneliness were found between participants who engaged in C3 activities and those who did not. Dyadic analysis revealed significant correlations between patients’ and caregivers’ hope and loneliness at baseline and at T2. Despite the significant changes, findings indicate consistently high levels of hope and low-to-moderate levels of loneliness over time. Focus group analyses further contextualize quantitative findings by highlighting patients’ and caregivers’ experiences in greater depth. The results serve to inform current and future initiatives aimed at providing timely, personalized psychosocial support to patients and caregivers affected by BTC. Full article

Background: Comprehensive genomic profiling (CGP) is increasingly incorporated into the management of biliary tract tumors (BTTs); however, single-center real-world data integrating clinical utility and site-specific genomic landscape remain limited. Methods: This retrospective single-center observational study included 91 patients with BTTs who underwent CGP. The primary endpoints were the rates of potentially actionable genomic alterations, expert panel-based therapeutic options, and implementation of genomically matched therapy. Secondary endpoints included the distribution of recurrent and clinically relevant genomic alterations according to the primary tumor site. Results: The cohort included 46 patients with intrahepatic cholangiocarcinoma (iCCA), 19 with extrahepatic cholangiocarcinoma (eCCA), 24 with gallbladder cancer (GBC), and 2 with ampullary tumors. CGP was successfully performed in all 91 patients. Reportable genomic alterations were detected in 88 patients (96.7%), whereas no reportable alteration was detected in three patients (3.3%). The most frequently altered genes were TP53 (51/91, 56.0%), KRAS (21/91, 23.1%), CDKN2A (18/91, 19.8%), SMAD4 (14/91, 15.4%), and ARID1A/PBRM1 (12/91, 13.2%). Potentially actionable genomic alterations were identified in 21 patients (23.1%). Expert panel-based therapeutic options were identified in 15 patients (16.5%), and genomically matched therapy was introduced in 7 patients (7.7%). Matched therapy was introduced the most frequently in iCCA (6/46, 13%), followed by GBC (1/24, 4.2%), whereas no patient with eCCA or ampullary tumor received matched therapy. Conclusions: CGP revealed a heterogeneous genomic landscape across BTT subtypes and provided clinically actionable information in a limited but meaningful subset of patients. The practical utility of CGP was the greatest in selected molecular subsets, particularly iCCA. Full article

Biliary tract cancers (BTCs) comprise a heterogeneous group of malignancies arising from the biliary tree, including cholangiocarcinomas and gallbladder carcinomas. Although their incidence is rising globally in Western countries, these cancers are rare and most often diagnosed at advanced stages. Their molecular heterogeneity and frequent resistance to therapy further contribute to their dismal prognosis. In recent years, molecular profiling studies have led to a better understanding of BTC biology and have opened new therapeutic opportunities, particularly for patients with advanced or metastatic disease. Alterations in DNA damage repair (DDR) genes have been identified in a substantial proportion of BTC cases, with some cohorts observing frequencies approaching ~70%. These genetic alterations play a critical role in tumorigenesis and disease progression and may contribute to treatment resistance. In this article, we discuss the current knowledge on: (1) the main DDR signaling pathways; (2) the prevalence of DDR gene alterations across BTC subtypes; (3) the potential of DDR gene alterations as prognostic and/or predictive biomarkers of treatment response; and (4) the latest advances in DDR-based targeted therapies and ongoing clinical trials in BTC. Full article

Background: Biliary tract cancers (BTCs), encompassing cholangiocarcinoma and gallbladder carcinoma, are aggressive malignancies with poor prognosis and increasing incidence in selected regions worldwide. Advances in imaging, biomarker profiling, immunotherapy, and targeted therapies have improved treatment options but have also increased the economic pressure on health systems. Understanding the economic evidence on BTC is therefore important for resource allocation and health technology assessment. Methods: We systematically searched PubMed/MEDLINE, Embase, Scopus, and Web of Science for peer-reviewed economic studies of BTC published from January 2010 to March 2025. Eligible studies included cost-effectiveness, cost–utility, cost–benefit, cost-of-illness, and resource-use analyses. The review followed PRISMA reporting principles. Reporting completeness was assessed using CHEERS 2022, and methodological credibility was appraised using the Drummond framework. Results: Twenty studies were included: 13 cost-effectiveness or cost–utility analyses and seven cost-of-illness or resource-use studies. Conventional chemotherapy strategies, including gemcitabine plus cisplatin in some settings and other cytotoxic combinations in selected jurisdictions, generally produced more favorable economic results than newer systemic therapies, although findings varied by country, threshold, comparator, and price assumptions. First-line immunotherapy combinations and biomarker-directed targeted therapies frequently produced ICERs above jurisdiction-specific willingness-to-pay thresholds at current prices, often requiring substantial price reductions to approach cost-effectiveness. Real-world studies showed high resource use and costs, particularly with hospitalizations and later treatment lines. Evidence on screening and prevention was limited, with one study suggesting that ultrasound surveillance may be cost-effective in a liver fluke-endemic region of Thailand. Discussion: The available economic evidence suggests that affordability and jurisdiction-specific value assessment are central to BTC policy decisions. Current prices for several immunotherapy and targeted agents limit cost-effectiveness in published models, while evidence on prevention, early detection, and care-pathway interventions remains sparse and context-specific. Full article

Cholangiocarcinoma (CCA) is an aggressive and molecularly heterogeneous malignancy characterized by a profoundly immunosuppressive tumor microenvironment (TME) and historically limited therapeutic options. Recent advances have redefined the treatment paradigm, with phase III trials establishing chemoimmunotherapy as a standard of care and multi-omic profiling elucidating the interplay between tumor genomics, stromal architecture, and immune regulation. Despite these gains, durable clinical benefit remains confined to a minority of patients, reflecting convergent mechanisms of primary and acquired resistance—including immune exclusion, myeloid-dominant suppression, and genotype-driven “cold” tumor states. In this review, we synthesize emerging insights into the immune landscape of CCA, integrating data from single-cell, spatial, and translational studies to define the cellular and molecular circuits governing immune evasion. Beyond canonical biomarkers such as mismatch repair and microsatellite status, we highlight how spatial organization of immunity—in particular, tertiary lymphoid structures, dynamic myeloid and stromal interactions, and pathway-level features—shape immunotherapy responsiveness. We also examine how tumor-intrinsic alterations, including IDH1 mutation, FGFR2 fusions, KRAS activation, and MTAP loss, define distinct immunologic phenotypes with direct implications for immunotherapeutic response and biomarker-driven patient selection. We evaluate the expanding clinical trial landscape of immunotherapy in CCA and more broadly in BTC, including adoptive cell therapies and cancer vaccines. Together, these advances position CCA as a paradigm of how tumor genotype and microenvironment co-evolve to define immunotherapy sensitivity and resistance. Full article

Gallbladder cancer (GBC) is an aggressive tumor that, together with the cholangiocarcinomas, constitutes the spectrum of biliary tract cancer (BTC). These tumors are characterized by a frequently late diagnosis, marked genomic heterogeneity, variable response to cytotoxic therapies, and poor overall survival in advanced stages. Nevertheless, the characterization of the tumor microenvironment (TME) and the identification of actionable molecular targets have driven the development of biological therapies. This review summarizes current and emerging evidence on monoclonal antibodies, bispecific antibodies, and antibody–drug conjugates (ADCs) in the management of GBC. The analysis addresses the early exploration of autoantibodies as potential diagnostic biomarkers, mechanistic hypotheses of immune evasion, and the clinical translation of targeted agents in the metastatic setting. Additionally, we critically discuss the extrapolation of data from global BTC trials to the specific GBC setting, the integration of population genetics into epidemiological studies such as the EULAT Eradicate GBC initiative, and the preliminary status of immunotherapy in perioperative scenarios. Full article

Background: Gemcitabine, cisplatin and durvalumab or pembrolizumab are standard first-line treatments for advanced or metastatic biliary tract cancer (BTC). Older patients with BTC may be frail or have contraindications to cisplatin. At our institution, oxaliplatin has been used as an alternative to cisplatin. Methods: In this evaluation, we report the safety and efficacy of gemcitabine with oxaliplatin and durvalumab as a first-line treatment of BTC. The primary objective was overall survival (OS). Secondary objectives included time to progression (TTP), disease control rate (DCR), and the incidence of treatment-related toxicities. Results: Twenty-nine patients were included. The majority were Caucasian (97%) and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1 (97%). Median age was 72 years old. Sixty-six percent had intrahepatic cholangiocarcinoma. Baseline renal insufficiency and/or hearing impairment were the most common reasons for cisplatin contraindication. Median follow-up was 20.6 months. Treatment cycles were every 28 days with durvalumab (1500 mg) given on day 1 and gemcitabine (range 600 mg/m²–1000 mg/m²) plus oxaliplatin (median dose 70 mg/m²) given on days 1 and 15. Median OS was 15.7 months (95% CI: 6.9-NA), median TTP was 6.7 months (95% CI 3.88-NA), and DCR was 76%. Median time on treatment was 3.15 months. Twelve patients (41%) required a dose adjustment, with myelosuppression as the most common toxicity. Conclusions: Oxaliplatin, in combination with durvalumab and gemcitabine, is a suitable platinum substitute for advanced BTC patients when cisplatin is contraindicated. Our analysis showed similar efficacy and no new safety concerns. Given the small sample size, our analysis is hypothesis-generating and calls for a larger prospective analysis. Full article

Background: The biliary and pancreatic tract is increasingly recognized as a microbial ecosystem rather than a sterile environment. Dysbiosis contributes to inflammation, bile acid alterations, and carcinogenesis, with distinct microbiota profiles linked to progression from benign to malignant conditions. Clinical factors, including gut–liver axis disruption and biliary stenting, may further exacerbate microbial imbalance. Objective: The objective of this study is to synthesize current evidence and identify knowledge gaps on the role of biliary microbiota in pancreaticobiliary carcinogenesis and its implications for diagnosis, prognosis, and therapy. Methods: This scoping review was conducted following PRISMA-ScR guidelines. A systematic search of PubMed, Web of Science, and Scopus was performed for studies published between January 2015 and December 2025, guided by the PICo framework. Results: Included studies primarily characterized changes in microbiota composition to identify microbial biomarkers associated with pancreaticobiliary diseases. Predictive bioinformatics analyses suggest that dysbiosis may promote carcinogenesis through metabolic and inflammatory pathways. Machine learning approaches identified microbiota-based signatures with potential diagnostic value for precancerous lesions, although discrimination remains limited. Biliary dysbiosis was also associated with outcomes related to biliary stenting, chemoprophylaxis, postoperative complications, and responses to chemotherapy or surgery. Conclusions: Integration of microbiota profiling with predictive bioinformatics and machine learning may improve understanding of pancreaticobiliary carcinogenesis. Identifying microbial and functional biomarkers could enable personalized diagnostic and therapeutic strategies, ultimately improving patient outcomes. Full article

Focused ultrasound (FUS)-mediated therapies have evolved with the advent of modern ultrasound-guided technology and MRI imaging, moving from their initial use as thermal ablation to a multifunctional platform for thermal and non-thermal ablation, immunomodulation, and targeted drug delivery. This narrative review explores the potential, limitations, and challenges of ablative high-intensity focused ultrasound (HIFU) therapies: HIFU thermal ablation and non-thermal ablation, histotripsy, as well as non-ablative low-intensity focused ultrasound (LIFU) applications in the management of hepatobiliary cancers. HIFU and histotripsy are reviewed as alternative or complementary treatment options in liver tumors, as well as their potential as bridging therapy. Histotripsy is addressed as a theranostic tool, not only by combining ablation with real-time ultrasound imaging guidance, but also by integrating it with sonobiopsy. It facilitates a liquid sonobiopsy of the ablated tumor by releasing intact tumor antigens and damage-associated molecular patterns, leading to potential molecular profiling. LIFU-induced targeted drug delivery (sono-chemotherapy), sonodynamic therapy, radiosensitization, immunomodulation of the immunosuppressive tumor microenvironment (sono-immunotherapy), and the potential to enhance the effect of immune checkpoint inhibitors in these malignancies are discussed. Since FUS-assisted procedures exhibit dual actions through therapeutic functionality associated with intra- and post-procedural ultrasound imaging guidance, they could have value as a theranostic tool in hepatobiliary interventional oncology. Although promising, the available clinical evidence for FUS-mediated therapies in hepatobiliary malignancies consists predominantly of early-stage feasibility studies, retrospective observational cohorts, and non-randomized comparative analyses. Further studies focused on standardized protocols, validation through large-scale, multicenter, prospective randomized clinical trials comparing FUS-based therapies with established treatments, and long-term follow-up of oncological efficacy could define their future role in multimodal oncological strategies. Full article

The undesired prognosis of biliary tract cancer is mainly attributed to the difficulty in detecting cancer lesions, including intraepithelial neoplasia, and other hurdles in procuring sufficient pathological samples by forceps biopsy and brushing, or even their combination. However, the transpapillary approach under endoscopic retrograde cholangiopancreatography (ERCP) is the mainstream approach for the work-up and treatment of biliary tract diseases, especially biliary tract cancers, because the ERCP-guided approach efficiently enables simultaneous biliary drainage for the treatment of cholangitis/jaundice and specimen acquisition for the diagnosis of biliary tract lesions. To improve diagnostic accuracy, several studies have been conducted on the feasibility and efficacy of genomic analysis of endoscopic specimens, namely, brushing samples, forceps biopsy samples, and aspiration samples such as bile with sensitivities ranging from 47 to 100%, with specificities ranging from 69 to 100%. Clinical use of genomic analysis remains heterogeneous due to the panel and next-generation sequencing system. For the efficient and precise treatment of patients with biliary tract cancer, future diagnosis and treatment should be based on molecular and genetic analyses. In this article, we review and summarize the comprehensive gene panel analyses of transpapillary brushing/biopsy/aspiration specimens for biliary tract cancer using next-generation sequencing, promoting effective clinical practice and providing a basis for future studies. Full article