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Keywords = Intrahepatic cholangiocarcinoma

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11 pages, 517 KB  
Article
Understanding the Will Rogers Phenomenon in Cholangiocarcinoma Research and Beyond
by Ruslan Akhmedullin, Zhandos Burkitbayev, Tair Koishibayev, Zhanat Spatayev, Abylaikhan Sharmenov, Oxana Shatkovskaya, Dinara Zharlyganova, Almira Manatova, Zhuldyz Kuanysh, Sanzhar Shalekenov and Abduzhappar Gaipov
Cancers 2025, 17(19), 3263; https://doi.org/10.3390/cancers17193263 - 8 Oct 2025
Viewed by 205
Abstract
Background. The existing literature highlights a lack of comparative studies between subtypes of cholangiocarcinoma (CC) and the impact of misclassification on the epidemiological parameters. Methods. A retrospective study was conducted to evaluate the surgical outcomes. The authors used Poisson regression with modified errors [...] Read more.
Background. The existing literature highlights a lack of comparative studies between subtypes of cholangiocarcinoma (CC) and the impact of misclassification on the epidemiological parameters. Methods. A retrospective study was conducted to evaluate the surgical outcomes. The authors used Poisson regression with modified errors to calculate the risk ratios (RR) and reported post-estimation marginal effects. Coefficient estimates, variance inflation factors, and Pearson’s goodness-of-fit test statistics were used to check for multicollinearity and model fit, respectively. We also performed a reclassification analysis by modeling Klatskin tumors (PCC) as extrahepatic (ECC), reclassifying them as intrahepatic (ICC), and comparing the corresponding changes in estimates. Results. Regression analysis revealed an increased risk of death in patients with ICC (RR = 2.05, 95% CI 1.11–3.78) and PCC (RR = 2.03, 95% CI 0.97–4.24) compared to those with DCC. When PCC was analyzed as an ECC, the ICC revealed an RR of 1.52 (95% CI 0.84–2.73). Further reclassification of PCC showed an RR of 2.04 for ICC (95% CI: 1.53–3.53). The adjusted marginal effects saw a reduction in the death probability for both ICC and ECC. However, post hoc analyses revealed insufficient evidence for differences between the reclassified models. Conclusions. Patients with DCC had slightly better prognosis compared to ICC and PCC. We found no differences in survival between ICC and ECC (combining DCC and PCC). The decrease in mortality risk due to reclassification in both groups was not confirmed statistically. Future studies should focus on statistical evidence when referring to the Will Rogers phenomenon, instead of inferring from raw comparisons. Full article
(This article belongs to the Section Methods and Technologies Development)
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37 pages, 437 KB  
Review
Role of Radiation Therapy for Biliary Tract Cancers
by Molly A. Chakraborty, Ritesh Kumar, Brett L. Ecker, Haejin In, Russell C. Langan, Mariam Eskander and Salma K. Jabbour
Curr. Oncol. 2025, 32(10), 545; https://doi.org/10.3390/curroncol32100545 - 28 Sep 2025
Viewed by 305
Abstract
Biliary tract cancers include cholangiocarcinoma, gallbladder cancer, and ampullary cancer. Although overall rare, the incidence is increasing globally, particularly the subset of intrahepatic cholangiocarcinoma. Surgery is currently considered to be the only curative treatment approach; however, survival outcomes after surgery remain poor. Moreover, [...] Read more.
Biliary tract cancers include cholangiocarcinoma, gallbladder cancer, and ampullary cancer. Although overall rare, the incidence is increasing globally, particularly the subset of intrahepatic cholangiocarcinoma. Surgery is currently considered to be the only curative treatment approach; however, survival outcomes after surgery remain poor. Moreover, many patients already have advanced-stage, unresectable disease at the time of diagnosis. Herein, we will review the role of adjuvant radiotherapy to improve local control after surgery, the role of neoadjuvant radiotherapy to increase the proportion of patients able to undergo surgery, and the use of definitive/palliative radiotherapy to provide local control/symptom relief for patients who have inoperable disease. Most studies observed a survival benefit associated with radiotherapy, with the strongest evidence for those with high-risk disease features (e.g., positive surgical margins, lymph node involvement). However, due to the low incidence of biliary tract cancers, most existing studies are retrospective; there is very limited randomized data and prospective studies tend to have small sample sizes, underscoring the need for more high-quality research on radiotherapy for biliary tract cancers. As some studies show evidence of a dose-dependent response, further investigation into the delivery of dose-escalated radiotherapy with modern techniques such as proton therapy is warranted. Full article
(This article belongs to the Special Issue Biliary Tract Cancer Updates: Advancements and Insights)
18 pages, 708 KB  
Review
Hot Topics in the Surgical Treatment of Intrahepatic Cholangiocarcinoma: A Narrative Review of Current Managements
by Silvio Caringi, Antonella Delvecchio, Annachiara Casella, Valentina Ferraro, Michele Dezio, Stefania Marini, Roberto Calbi, Francesco Cortese, Rosalinda Filippo, Matteo Stasi, Tommaso Maria Manzia, Michele Tedeschi, Riccardo Inchingolo and Riccardo Memeo
Cancers 2025, 17(19), 3127; https://doi.org/10.3390/cancers17193127 - 26 Sep 2025
Viewed by 556
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with a poor prognosis. Negative-margin resection is presently the only potentially curative treatment option. Emerging trends with direct applicability to surgical strategy include margin thickness, lymphadenectomy, optimization of future liver remnant (FLR), [...] Read more.
Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with a poor prognosis. Negative-margin resection is presently the only potentially curative treatment option. Emerging trends with direct applicability to surgical strategy include margin thickness, lymphadenectomy, optimization of future liver remnant (FLR), minimally invasive techniques, incorporation of systemic therapy, and reconsideration of liver transplantation. This review emphasizes areas of consensus and ongoing debate. Margins ≥5–10 mm are associated with improved results, but biology generally takes precedence over prognosis. Regional lymphadenectomy enhances staging accuracy, although its therapeutic benefit remains unsettled. PVE is standard for FLR enlargement, LVD provides faster hypertrophy, and ALPPS remains reserved for highly selective cases. Minimally invasive and robotic hepatectomy share oncologic results in skilled institutions. Systemic therapies, including immunotherapy and biomarker-directed targeted therapy, are increasingly being incorporated perioperatively. Liver transplant may be of potential value in early-stage disease or on strict indications after neoadjuvant treatment. The modern surgical management of iCCA encompasses a blend of oncologic considerations, FLR optimization, minimally invasive surgery, and systemic therapy according to tumor biology. Multidisciplinary planning and participation in clinical trials are necessary to align surgical innovation with advancements in molecular and systemic treatments, ultimately leading to improved long-term outcomes. Full article
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22 pages, 5289 KB  
Article
The DNA Minor Groove Binders Trabectedin and Lurbinectedin Are Potent Antitumor Agents in Human Intrahepatic Cholangiocarcinoma
by Erwin Gäbele, Isabella Gigante, Mirella Pastore, Antonio Cigliano, Grazia Galleri, Thea Bauer, Elena Pizzuto, Serena Mancarella, Martina Müller, Fabio Marra, Heiko Siegmund, Gianluigi Giannelli, Matthias Evert, Chiara Raggi, Diego F. Calvisi and Sara M. Steinmann
Int. J. Mol. Sci. 2025, 26(18), 9085; https://doi.org/10.3390/ijms26189085 - 18 Sep 2025
Viewed by 1112
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver tumor. Due to its aggressive nature and resistance to conventional treatments, there is a pressing need to develop novel and more effective therapies for this deadly malignancy. Here, we explored the therapeutic potential [...] Read more.
Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver tumor. Due to its aggressive nature and resistance to conventional treatments, there is a pressing need to develop novel and more effective therapies for this deadly malignancy. Here, we explored the therapeutic potential of the DNA minor groove binders trabectedin (TRB) and lurbinectedin (LUR) for the treatment of iCCA using cell lines, spheroids, cancer-associated fibroblasts (CAFs), patient-derived tumor organoids (PDOs), and the chicken chorioallantoic membrane (CAM) in vivo model. TRB and, more substantially, LUR, significantly inhibited cell growth in iCCA cell lines, spheroids, CAFs, and PDOs at very low nanomolar concentrations. Specifically, the two drugs significantly reduced proliferation, triggered apoptosis, and caused DNA damage in iCCA cells. At the metabolic level, TRB and LUR decreased mitochondrial respiration and glycolysis. At the molecular level, the two compounds effectively downregulated the mammalian target of rapamycin complex 1 (mTORC1) and Hippo/YAP pathways and suppressed the expression of yes-associated protein 1 (YAP1), cellular myelocytomatosis oncogene (c-Myc), E2F transcription factor 1 (E2F1), Bromodomain-containing protein 4 (BRD4), TEA domain transcription factor 4 (TEAD4), and cluster of differentiation 7 (CD7) proto-oncogenes. Furthermore, LUR significantly restrained the in vivo growth of iCCA cells in the CAM model. Our data indicate that TRB and LUR possess strong anti-proliferative and pro-apoptotic activities and could represent promising therapeutic agents for the treatment of iCCA. Full article
(This article belongs to the Special Issue Advanced Research on Cholangiocarcinoma: From Bench to Bedside)
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30 pages, 728 KB  
Review
Immune Landscape of Intrahepatic Cholangiocarcinoma: Evasion and Therapeutic Insights
by Nunzia Porro, Elena Spínola-Lasso, Fabio Marra and Alessandra Gentilini
Immuno 2025, 5(3), 40; https://doi.org/10.3390/immuno5030040 - 17 Sep 2025
Viewed by 621
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive and heterogeneous malignancy characterized by marked resistance to standard chemotherapy and poor prognosis. While the advent of immunotherapy has revolutionized the management of several solid tumors, including melanoma, breast cancer, and non-small cell lung cancer, its [...] Read more.
Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive and heterogeneous malignancy characterized by marked resistance to standard chemotherapy and poor prognosis. While the advent of immunotherapy has revolutionized the management of several solid tumors, including melanoma, breast cancer, and non-small cell lung cancer, its efficacy in iCCA remains limited. Recent clinical trials have demonstrated the efficacy of durvalumab in combination with chemotherapy for iCCA, leading to its approval as a first-line treatment. However, overall response rates remain low, largely due to its immunosuppressive tumor immune microenvironment (TIME). The immune-cold nature of iCCA is typified by a dominant presence of immunosuppressive cell populations, including M2-polarized tumor-associated macrophages, myeloid-derived suppressor cells, and T regulatory cells. In addition, traditional biomarkers such as PD-L1 expression, tumor mutational burden, and microsatellite instability have shown limited predictive value in iCCA, highlighting the need for novel biomarkers and immunotherapeutic strategies. Emerging approaches aimed at reprogramming the TIME, including combination therapies targeting suppressive cells, stromal remodeling, and novel immune effectors like CAR-T and cancer vaccines, hold significant promise for enhancing therapeutic efficacy. This review summarizes the distinct features of iCCA TIME, key mechanisms of immune evasion, current challenges, and future directions to overcome immune resistance, with the aim of developing personalized immunotherapies to improve patient outcomes. Full article
(This article belongs to the Special Issue New Insights of Anti-cancer Immunity and Cancer Immune Evasion)
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7 pages, 294 KB  
Brief Report
Rural–Urban Disparities in Treatment and Disease-Specific Survival for Patients with Intrahepatic Cholangiocarcinoma: A Retrospective Cohort Analysis of the 2000 to 2021 SEER Database
by Odelia H. Moon, Mitchell A. Taylor, Omar Hamadi, Aditya Sharma and Peter Silberstein
Med. Sci. 2025, 13(3), 158; https://doi.org/10.3390/medsci13030158 - 1 Sep 2025
Viewed by 499
Abstract
Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with very poor survival. Prior research suggests rural–urban disparities on a regional scale. We aimed to elucidate these disparities in treatment and disease-specific survival (DSS) for ICC patients on a national scale using the SEER [...] Read more.
Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with very poor survival. Prior research suggests rural–urban disparities on a regional scale. We aimed to elucidate these disparities in treatment and disease-specific survival (DSS) for ICC patients on a national scale using the SEER database. Methods: The SEER database was queried to identify biopsy-confirmed cases of ICC from 2000 to 2021. Differences in clinicopathologic features and treatment between rural and urban patients were assessed using Chi-square and Fischer’s exact tests. Disease-specific survival was compared using Kaplan–Meier and log-rank tests as well as multivariable Cox regressions. Results: A total of 14,940 ICC patients were identified. Rural patients were less likely than urban patients to receive chemotherapy (789 of 1588 [49.7%] vs. 7112 of 13,352 [53.3%], p = 0.006) and surgical treatment (305 of 1588 [19.2%] vs. 2922 of 13,352 [21.9%], p = 0.013). Rural patients experienced reduced 5- and 10-year DSS rates (7.0% and 4.0%) compared to urban patients (9.0% and 6.0%, p < 0.001). In multivariable analysis, rural residence independently demonstrated a 17% increased risk of disease-specific mortality compared to their urban counterparts (aHR 1.17, 95% CI 1.03–1.32). Conclusions: This study demonstrates significant rural–urban disparities in ICC treatment and survival throughout the US, independent of other prognostic factors. Further investigation into factors driving these disparities is warranted to improve outcomes for rural ICC patients. Full article
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19 pages, 333 KB  
Review
Advances in Endoscopic Diagnosis and Management of Cholangiocarcinoma
by Usamah Chaudhary and Shawn L. Shah
J. Clin. Med. 2025, 14(17), 6028; https://doi.org/10.3390/jcm14176028 - 26 Aug 2025
Viewed by 933
Abstract
Cholangiocarcinoma (CCA) is an aggressive malignancy originating from the epithelial lining of the intrahepatic or extrahepatic bile ducts. Although rare globally, its mortality closely mirrors incidence due to late-stage presentation of the disease and limited curative options. While surgical resection and liver transplantation [...] Read more.
Cholangiocarcinoma (CCA) is an aggressive malignancy originating from the epithelial lining of the intrahepatic or extrahepatic bile ducts. Although rare globally, its mortality closely mirrors incidence due to late-stage presentation of the disease and limited curative options. While surgical resection and liver transplantation remain the cornerstone treatments for those with resectable disease, endoscopic techniques have emerged as versatile tools for diagnosis, therapy, and palliation. In recent years, there have been major advancements in endoscopic therapies, including radiofrequency ablation (RFA), intraluminal brachytherapy (ILBT), and photodynamic therapy (PDT). The current narrative review serves to provide an overview of current and emerging endoscopic strategies for CCA, emphasizing diagnostic capabilities, therapeutic approaches, palliative interventions, and future directions. Full article
(This article belongs to the Special Issue Diagnosis, Treatment, and Management of Gastrointestinal Oncology)
23 pages, 933 KB  
Review
Leveraging Multimodal Foundation Models in Biliary Tract Cancer Research
by Yashbir Singh, Jesper B. Andersen, Quincy A. Hathaway, Diana V. Vera-Garcia, Varekan Keishing, Sudhakar K. Venkatesh, Sara Salehi, Davide Povero, Michael B. Wallace, Gregory J. Gores, Yujia Wei, Natally Horvat, Bradley J. Erickson and Emilio Quaia
Tomography 2025, 11(9), 96; https://doi.org/10.3390/tomography11090096 - 25 Aug 2025
Viewed by 931
Abstract
This review explores how multimodal foundation models (MFMs) are transforming biliary tract cancer (BTC) research. BTCs are aggressive malignancies with poor prognosis, presenting unique challenges due to difficult diagnostic methods, molecular complexity, and rarity. Importantly, intrahepatic cholangiocarcinoma (iCCA), perihilar cholangiocarcinoma (pCCA), and distal [...] Read more.
This review explores how multimodal foundation models (MFMs) are transforming biliary tract cancer (BTC) research. BTCs are aggressive malignancies with poor prognosis, presenting unique challenges due to difficult diagnostic methods, molecular complexity, and rarity. Importantly, intrahepatic cholangiocarcinoma (iCCA), perihilar cholangiocarcinoma (pCCA), and distal bile duct cholangiocarcinoma (dCCA) represent fundamentally distinct clinical entities, with iCCA presenting as mass-forming lesions amenable to biopsy and targeted therapies, while pCCA manifests as infiltrative bile duct lesions with challenging diagnosis and primarily palliative management approaches. MFMs offer potential to advance research by integrating radiological images, histopathology, multi-omics profiles, and clinical data into unified computational frameworks, with applications tailored to these distinct BTC subtypes. Key applications include enhanced biomarker discovery that identifies previously unrecognizable cross-modal patterns, potential for improving currently limited diagnostic accuracy—though validation in BTC-specific cohorts remains essential—accelerated drug repurposing, and advanced patient stratification for personalized treatment. Despite promising results, challenges such as data scarcity, high computational demands, and clinical workflow integration remain to be addressed. Future research should focus on standardized data protocols, architectural innovations, and prospective validation studies. The integration of artificial intelligence (AI)-based methodologies offers new solutions for these historically challenging malignancies. However, current evidence for BTC-specific applications remains largely theoretical, with most studies limited to proof-of-concept designs or related cancer types. Comprehensive clinical validation studies and prospective trials demonstrating patient benefit are essential prerequisites for clinical implementation. The timeline for evidence-based clinical adoption likely extends 7–10 years, contingent on successful completion of validation studies addressing current evidence gaps. Full article
(This article belongs to the Section Cancer Imaging)
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12 pages, 6157 KB  
Case Report
Primary Hepatic Mucosa-Associated B-Cell Lymphoma in a Patient with Primary Sclerosing Cholangitis—A Case Ultimately Requiring Liver Transplantation
by Jerica Novak, Mihajlo Đokić, Miha Petrič, Diana Vozlič, Milanka Živanović, Branislava Ranković and Blaž Trotovšek
Diagnostics 2025, 15(16), 2082; https://doi.org/10.3390/diagnostics15162082 - 19 Aug 2025
Viewed by 513
Abstract
Background: Primary hepatic extranodal marginal zone lymphoma of mucosa-associated type (MALT) is an extremely rare liver neoplasm. The lesions are often misdiagnosed for the most common primary hepatic malignancy, such as hepatocellular carcinoma and cholangiocarcinoma. As the diagnosis is most often made after [...] Read more.
Background: Primary hepatic extranodal marginal zone lymphoma of mucosa-associated type (MALT) is an extremely rare liver neoplasm. The lesions are often misdiagnosed for the most common primary hepatic malignancy, such as hepatocellular carcinoma and cholangiocarcinoma. As the diagnosis is most often made after the resection, there are still no clear guidelines for the optimal treatment of these patients. Case Presentation: A 30-year-old male patient with known primary sclerosing cholangitis (PSC) was treated at the Department of Abdominal Surgery Ljubljana due to a mass in the right liver, believed to be an intrahepatic cholangiocarcinoma. Due to the extent of the disease, extended right hepatectomy with the resection of the hepatocholedochus, lymphadenectomy, and hepaticojejunal anastomosis were performed. After the surgery, the patient developed a small-for-size syndrome and therefore necessitated a liver transplantation (LT) that was afterwards successfully performed. Discussion: This case highlights the diagnostic challenges of differentiating primary hepatic MALT lymphoma from cholangiocarcinoma on imaging, especially in patients with underlying liver disease. Preoperative confirmation of the malignant disease could potentially change treatment course in our patient. Therefore, a serious surgical complication with development of small-for-size syndrome after major hepatectomy could potentially be prevented. Regarding the underlying liver disease, the patient could probably be a candidate for LT with the bridging chemotherapy. Conclusions: Primary hepatic MALT lymphoma is an extremely rare liver lesion but remains a valid option in a differential diagnosis of liver lesions in patients with chronic viral infection or autoimmune disease, especially in settings of cirrhosis. Moreover, a high level of suspicion must be raised in young patients with solitary liver mass and autoimmune liver disease. Surgical resection is the best way to achieve elimination of the disease. Full article
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17 pages, 11304 KB  
Case Report
Radiologic and Pathologic Insights in Combined Hepatocellular–Cholangiocarcinoma: A Report of Three Cases
by Katrīna Marija Konošenoka, Nauris Zdanovskis, Aina Kratovska, Artūrs Šilovs and Veronika Zaiceva
Reports 2025, 8(3), 142; https://doi.org/10.3390/reports8030142 - 8 Aug 2025
Viewed by 584
Abstract
Background and Clinical Significance: Combined hepatocellular–cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy exhibiting both hepatocellular and cholangiocellular features. Due to overlapping clinical, imaging, and pathological characteristics with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCC), diagnosis remains challenging. Early and accurate differentiation [...] Read more.
Background and Clinical Significance: Combined hepatocellular–cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy exhibiting both hepatocellular and cholangiocellular features. Due to overlapping clinical, imaging, and pathological characteristics with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCC), diagnosis remains challenging. Early and accurate differentiation is critical for optimal treatment planning. Case Presentation: We report three histologically confirmed cases of cHCC-CC with different imaging features, biomarker profiles, treatment strategies, and clinical outcomes. Patient 1, a 69-year-old female, presented with a large centrally located liver mass exhibiting iCC-like imaging features and mildly elevated AFP and CA 19-9 levels. Biopsy confirmed poorly differentiated cHCC-CC. Treatment involved palliative chemotherapy, with a survival of 16 months following diagnosis. Patient 2, an 80-year-old female with a small lesion in a cirrhotic liver, demonstrated an HCC-like enhancement pattern but normal AFP levels. Surgical resection was performed, and histology confirmed cHCC-CC with a dual phenotype. Despite initial remission, intrahepatic recurrence developed, treated with TACE and systemic therapy. The patient later transitioned to palliative care due to progression and survived 36 months. Patient 3, a 67-year-old male with chronic hepatitis C, presented with an HCC-like lesion and elevated AFP. Due to comorbidities, surgical resection was not feasible, and the patient was treated with percutaneous microwave ablation as a safer alternative. Biopsy during ablation confirmed cHCC-CC; follow-up was ongoing at submission. Conclusions: These cases highlight the diagnostic complexity and clinical variability of cHCC-CC. Imaging may be misleading, and tumor markers do not reliably predict subtype or prognosis. Histological confirmation is essential, particularly in patients with atypical imaging or discordant biomarker profiles. Individualized management, informed by tumor biology and patient condition, remains critical. Further research is needed to refine diagnostic criteria and develop tailored therapeutic strategies for this challenging tumor entity. Full article
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12 pages, 693 KB  
Article
Efficacy and Safety of the Combination of Durvalumab Plus Gemcitabine and Cisplatin in Patients with Advanced Biliary Tract Cancer: A Real-World Retrospective Cohort Study
by Eishin Kurihara, Satoru Kakizaki, Masashi Ijima, Takeshi Hatanaka, Norio Kubo, Yuhei Suzuki, Hidetoshi Yasuoka, Takashi Hoshino, Atsushi Naganuma, Noriyuki Tani, Yuichi Yamazaki and Toshio Uraoka
Biomedicines 2025, 13(8), 1915; https://doi.org/10.3390/biomedicines13081915 - 6 Aug 2025
Viewed by 1002
Abstract
Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and [...] Read more.
Background/Objectives: The TOPAZ-1 phase III trial reported a survival benefit of using durvalumab, an anti-programmed death ligand 1 (anti-PD-L1) antibody, in combination with gemcitabine and cisplatin (GCD) treatment in patients with advanced biliary tract cancer. This retrospective study investigated the efficacy and safety of GCD treatment for advanced biliary tract cancer in real-world conditions. Methods: The study subjects were 52 patients with biliary tract cancer who received GCD therapy between January 2023 and May 2024. The observation parameters included the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), tumor markers (CEA, CA19-9), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: The cohort included 36 men and 16 women, with a median age of 73.0 years. There were 36 cases of cholangiocarcinoma (distal: 10, perihilar: 19, intrahepatic: 7), 13 cases of gallbladder cancer, and 3 cases of ampullary carcinoma. The stages were locally advanced in 30 cases and metastatic in 22 cases. Biliary drainage was performed in 30 cases. There were 38 cases receiving first-line therapy and 14 cases receiving second-line or later treatments. The median values at the start of GCD therapy were ALB 3.7 g/dL, CRP 0.39 mg/dL, NLR 2.4, PLR 162.5, CEA 4.8 ng/mL, and CA19-9 255.9 U/mL. The mGPS distribution was 0:23 cases, 1:18 cases, and 2:11 cases. The treatment outcomes were ORR 25.0% (CR 2 cases, PR 11 cases), DCR 78.8% (SD 28 cases, PD 10 cases, NE 1 case), median PFS 8.6 months, and median OS 13.9 months. The PLR was suggested to be useful for predicting PFS. A decrease in CEA at six weeks after the start of treatment was a significant predictor of PFS and OS. Gallbladder cancer had a significantly poorer prognosis compared to other cancers. The immune-related adverse events included hypothyroidism in two cases, cholangitis in one case, and colitis in one case. Conclusions: The ORR, DCR, and PFS were comparable to those in the TOPAZ-1 trial. Although limited by its retrospective design and small sample size, this study suggests that GCD therapy is an effective treatment regimen for unresectable biliary tract cancer in real-world clinical practice. Full article
(This article belongs to the Special Issue Advanced Research in Anticancer Inhibitors and Targeted Therapy)
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22 pages, 1013 KB  
Review
Genomic Alterations and Microbiota Crosstalk in Hepatic Cancers: The Gut–Liver Axis in Tumorigenesis and Therapy
by Yuanji Fu, Jenny Bonifacio-Mundaca, Christophe Desterke, Íñigo Casafont and Jorge Mata-Garrido
Genes 2025, 16(8), 920; https://doi.org/10.3390/genes16080920 - 30 Jul 2025
Viewed by 943
Abstract
Background/Objectives: Hepatic cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are major global health concerns due to rising incidence and limited therapeutic success. While traditional risk factors include chronic liver disease and environmental exposures, recent evidence underscores the significance of genetic alterations and [...] Read more.
Background/Objectives: Hepatic cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are major global health concerns due to rising incidence and limited therapeutic success. While traditional risk factors include chronic liver disease and environmental exposures, recent evidence underscores the significance of genetic alterations and gut microbiota in liver cancer development and progression. This review aims to integrate emerging knowledge on the interplay between host genomic changes and gut microbial dynamics in the pathogenesis and treatment of hepatic cancers. Methods: We conducted a comprehensive review of current literature on genetic and epigenetic drivers of HCC and CCA, focusing on commonly mutated genes such as TP53, CTNNB1, TERT, IDH1/2, and FGFR2. In parallel, we evaluated studies addressing the gut–liver axis, including the roles of dysbiosis, microbial metabolites, and immune modulation. Key clinical and preclinical findings were synthesized to explore how host–microbe interactions influence tumorigenesis and therapeutic response. Results: HCC and CCA exhibit distinct but overlapping genomic landscapes marked by recurrent mutations and epigenetic reprogramming. Alterations in the gut microbiota contribute to hepatic inflammation, genomic instability, and immune evasion, potentially enhancing oncogenic signaling pathways. Furthermore, microbiota composition appears to affect responses to immune checkpoint inhibitors. Emerging therapeutic strategies such as probiotics, fecal microbiota transplantation, and precision oncology based on mutational profiling demonstrate potential for personalized interventions. Conclusions: The integration of host genomics with microbial ecology provides a promising paradigm for advancing diagnostics and therapies in liver cancer. Targeting the gut–liver axis may complement genome-informed strategies to improve outcomes for patients with HCC and CCA. Full article
(This article belongs to the Special Issue Feature Papers in Microbial Genetics and Genomics)
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17 pages, 331 KB  
Review
Liver Transplantation for Cancer—Current Challenges and Emerging Solutions
by Steven M. Elzein, Elizabeth W. Brombosz and Sudha Kodali
J. Clin. Med. 2025, 14(15), 5365; https://doi.org/10.3390/jcm14155365 - 29 Jul 2025
Viewed by 1127
Abstract
Liver transplantation (LT) for hepatic malignancies is becoming increasingly common, largely because it offers superior survival relative to other treatment approaches. LT is well-accepted for primary liver cancers such as hepatocellular carcinoma and perihilar cholangiocarcinoma and is being increasingly accepted for intrahepatic cholangiocarcinoma [...] Read more.
Liver transplantation (LT) for hepatic malignancies is becoming increasingly common, largely because it offers superior survival relative to other treatment approaches. LT is well-accepted for primary liver cancers such as hepatocellular carcinoma and perihilar cholangiocarcinoma and is being increasingly accepted for intrahepatic cholangiocarcinoma and metastases of colorectal cancer or neuroendocrine tumors to the liver. Over time, indications for transplant oncology have broadened, as has the acceptable disease burden for transplantation, particularly with the advent of new neoadjuvant therapies. Other current frontiers in the field include expanding the donor pool through living donors, extended criteria donors, machine perfusion and increasing access to LT for people from disadvantaged socioeconomic backgrounds. Expanding access to LT can offer renewed hope for long-term survival to patients with primary and secondary liver cancer. Full article
(This article belongs to the Special Issue Developments and Challenges in Liver Transplantation)
8 pages, 863 KB  
Case Report
Anesthetic Management of Acute Airway Decompensation in Bronchobiliary Fistula Due to Intrahepatic Cholangiocarcinoma: A Case Report
by Andrew J. Warburton, Randal A. Serafini and Adam Von Samek
Anesth. Res. 2025, 2(3), 17; https://doi.org/10.3390/anesthres2030017 - 29 Jul 2025
Cited by 1 | Viewed by 438
Abstract
This case report describes the acute and multidisciplinary management anesthesiologists performed for an intra-operative bronchobiliary fistula during a routine endoscopic retrograde cholangiopancreatography for a patient with intrahepatic cholangiocarcinoma. During the procedure, an unexpected rapid airway deterioration was encountered due to bile infiltration of [...] Read more.
This case report describes the acute and multidisciplinary management anesthesiologists performed for an intra-operative bronchobiliary fistula during a routine endoscopic retrograde cholangiopancreatography for a patient with intrahepatic cholangiocarcinoma. During the procedure, an unexpected rapid airway deterioration was encountered due to bile infiltration of the right bronchus and anesthesia circuit, necessitating (1) emergent extubation and reintubation with bronchoscopy, (2) extubation and reintubation with double-lumen endotracheal tube with right-bronchial blocker, and (3) transportation of the patient from endoscopy to interventional radiology for biliary drain placement. Overall, this case highlights a rare but serious consideration for patients with intrahepatic cholangiocarcinoma who may present with a bronchobiliary fistula and the steps taken to prevent total airway compromise and ensure rapid patient stabilization through coordination with advanced gastroenterology, interventional pulmonology, and interventional radiology. Full article
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15 pages, 3635 KB  
Article
Comparison of Apparent Diffusion Coefficient Values on Diffusion-Weighted MRI for Differentiating Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma
by Katrīna Marija Konošenoka, Nauris Zdanovskis, Aina Kratovska, Artūrs Šilovs and Veronika Zaiceva
Diagnostics 2025, 15(15), 1861; https://doi.org/10.3390/diagnostics15151861 - 24 Jul 2025
Viewed by 810
Abstract
Background and Objectives: Accurate noninvasive differentiation between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) remains a clinical challenge. This study aimed to assess the dignostic performance of apparent diffusion coefficient (ADC) values from diffusion-weighted MRI in distinguishing between HCC and ICC, with [...] Read more.
Background and Objectives: Accurate noninvasive differentiation between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) remains a clinical challenge. This study aimed to assess the dignostic performance of apparent diffusion coefficient (ADC) values from diffusion-weighted MRI in distinguishing between HCC and ICC, with histological confirmation as the gold standard. Materials and Methods: A retrospective analysis was performed on 61 patients (41 HCC, 20 ICC) who underwent liver MRI and percutaneous biopsy between 2019 and 2024. ADC values were measured from diffusion-weighted sequences (b-values of 0, 500, and 1000 s/mm2), and regions of interest were placed over solid tumor areas. Statistical analyses included t-tests, one-way ANOVA, and ROC curve analysis. Results: Mean ADC values did not differ significantly between HCC (1.09 ± 0.19 × 10−3 mm2/s) and ICC (1.08 ± 0.11 × 10−3 mm2/s). ROC analysis showed poor discriminative ability (AUC = 0.520; p = 0.806). In HCC, ADC values decreased with lower differentiation grades (p = 0.008, η2 = 0.224). No significant trend was observed in ICC (p = 0.410, η2 = 0.100). Immunohistochemical markers such as CK-7, Glypican 3, and TTF-1 showed significant diagnostic value between tumor subtypes. Conclusions: ADC values have limited utility for distinguishing HCC from ICC but may aid in HCC grading. Immunohistochemistry remains essential for accurate diagnosis, especially in poorly differentiated tumors. Further studies with larger cohorts are recommended to improve noninvasive diagnostic protocols. Full article
(This article belongs to the Special Issue Diagnostic Imaging in Gastrointestinal and Liver Diseases)
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