New Insights in Biliary Tract Cancers Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 26501

Special Issue Editor


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Guest Editor
Division of General and Hepatobiliary Surgery, Department of Surgery, Dentistry, Pediatrics and Gynaecology, University of Verona, 37134 Verona, Italy
Interests: preoperative and intraoperative management; clinical and molecular prognostic factors after resection of biliary tract cancers

Special Issue Information

Dear Colleagues,

Biliary tract cancers (BTCs) are an aggressive and assorted group of malignancies which arise from the epithelium of the biliary ducts and that represent about 3% of all gastrointestinal tumors. Depending on the site of origin, they are classified as intrahepatic cholangiocarcinoma (ICC), perihilar cholangiocarcinoma (PCC), distal cholangiocarcinoma (DCC), and gallbladder cancer (GBC). Regardless of their location, BTCs are characterized by a dismal prognosis, with high rate of local invasion and metastatic spreading. However, the classification guides the management and treatment strategy.

Surgical resection, when applicable, remains the treatment which offers the best chance of long-term survival. However, over the past few years, new chemotherapy regimens, based on molecular profiling, and multimodal strategies have shown encouraging results.

We are pleased to invite you to contribute to this Special Issue of Cancers titled “New Insights in Biliary Tract Cancers Therapy” that aims to highlight the emerging evidence and recent development in the treatment strategy for biliary tract cancers.

This Special issue of Cancers therefore encompasses new research articles and timely reviews regarding the surgical approach, preoperative management, clinical and molecular prognostic factors, and systemic and local therapies.

Dr. Simone Conci
Guest Editor

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Keywords

  • biliary tract cancers
  • BTC
  • cholangiocarcinoma
  • gallbladder cancer
  • surgery for biliary tract cancers
  • chemotherapy
  • preoperative biliary drainage

Published Papers (11 papers)

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Research

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14 pages, 2160 KiB  
Article
Radiomic Analysis of Intrahepatic Cholangiocarcinoma: Non-Invasive Prediction of Pathology Data: A Multicenter Study to Develop a Clinical–Radiomic Model
by Francesco Fiz, Noemi Rossi, Serena Langella, Andrea Ruzzenente, Matteo Serenari, Francesco Ardito, Alessandro Cucchetti, Teresa Gallo, Giulia Zamboni, Cristina Mosconi, Luca Boldrini, Mariateresa Mirarchi, Stefano Cirillo, Mario De Bellis, Ilaria Pecorella, Nadia Russolillo, Martina Borzi, Giulio Vara, Caterina Mele, Giorgio Ercolani, Felice Giuliante, Matteo Ravaioli, Alfredo Guglielmi, Alessandro Ferrero, Martina Sollini, Arturo Chiti, Guido Torzilli, Francesca Ieva and Luca Viganòadd Show full author list remove Hide full author list
Cancers 2023, 15(17), 4204; https://doi.org/10.3390/cancers15174204 - 22 Aug 2023
Cited by 1 | Viewed by 1026
Abstract
Standard imaging cannot assess the pathology details of intrahepatic cholangiocarcinoma (ICC). We investigated whether CT-based radiomics may improve the prediction of tumor characteristics. All consecutive patients undergoing liver resection for ICC (2009-2019) in six high-volume centers were evaluated for inclusion. On the preoperative [...] Read more.
Standard imaging cannot assess the pathology details of intrahepatic cholangiocarcinoma (ICC). We investigated whether CT-based radiomics may improve the prediction of tumor characteristics. All consecutive patients undergoing liver resection for ICC (2009-2019) in six high-volume centers were evaluated for inclusion. On the preoperative CT, we segmented the ICC (Tumor-VOI, i.e., volume-of-interest) and a 5-mm parenchyma rim around the tumor (Margin-VOI). We considered two types of pathology data: tumor grading (G) and microvascular invasion (MVI). The predictive models were internally validated. Overall, 244 patients were analyzed: 82 (34%) had G3 tumors and 139 (57%) had MVI. For G3 prediction, the clinical model had an AUC = 0.69 and an Accuracy = 0.68 at internal cross-validation. The addition of radiomic features extracted from the portal phase of CT improved the model performance (Clinical data+Tumor-VOI: AUC = 0.73/Accuracy = 0.72; +Tumor-/Margin-VOI: AUC = 0.77/Accuracy = 0.77). Also for MVI prediction, the addition of portal phase radiomics improved the model performance (Clinical data: AUC = 0.75/Accuracy = 0.70; +Tumor-VOI: AUC = 0.82/Accuracy = 0.73; +Tumor-/Margin-VOI: AUC = 0.82/Accuracy = 0.75). The permutation tests confirmed that a combined clinical–radiomic model outperforms a purely clinical one (p < 0.05). The addition of the textural features extracted from the arterial phase had no impact. In conclusion, the radiomic features of the tumor and peritumoral tissue extracted from the portal phase of preoperative CT improve the prediction of ICC grading and MVI. Full article
(This article belongs to the Special Issue New Insights in Biliary Tract Cancers Therapy)
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19 pages, 4587 KiB  
Article
Targeting FGFRs Using PD173074 as a Novel Therapeutic Strategy in Cholangiocarcinoma
by Brinda Balasubramanian, Kiren Yacqub-Usman, Simran Venkatraman, Kyaw Zwar Myint, Jitlada Juengsamarn, Poowanai Sarkhampee, Nithi Lertsawatvicha, Jittiyawadee Sripa, Thiti Kuakpaetoon, Chinnawut Suriyonplengsaeng, Kanokpan Wongprasert, Anna M. Grabowska, David O. Bates, Tavan Janvilisri and Rutaiwan Tohtong
Cancers 2023, 15(9), 2528; https://doi.org/10.3390/cancers15092528 - 28 Apr 2023
Viewed by 1989
Abstract
Cholangiocarcinoma (CCA) is an architecturally complex tumour with high heterogeneity. Discovery at later stages makes treatment challenging. However, the lack of early detection methodologies and the asymptomatic nature of CCA make early diagnosis more difficult. Recent studies revealed the fusions in Fibroblast Growth [...] Read more.
Cholangiocarcinoma (CCA) is an architecturally complex tumour with high heterogeneity. Discovery at later stages makes treatment challenging. However, the lack of early detection methodologies and the asymptomatic nature of CCA make early diagnosis more difficult. Recent studies revealed the fusions in Fibroblast Growth Factor Receptors (FGFRs), a sub-family of RTKs, as promising targets for targeted therapy for CCA. Particularly, FGFR2 fusions have been of particular interest, as translocations have been found in approximately 13% of CCA patients. Pursuing this, Pemigatinib, a small-molecule inhibitor of FGFR, became the first targeted therapy drug to be granted accelerated approval by the FDA for treating CCA patients harbouring FGFR2 fusions who have failed first-line chemotherapy. However, despite the availability of Pemigatinib, a very limited group of patients benefit from this treatment. Moreover, as the underlying mechanism of FGFR signalling is poorly elucidated in CCA, therapeutic inhibitors designed to inhibit this pathway are prone to primary and acquired resistance, as witnessed amongst other Tyrosine Kinase Inhibitors (TKIs). While acknowledging the limited cohort that benefits from FGFR inhibitors, and the poorly elucidated mechanism of the FGFR pathway, we sought to characterise the potential of FGFR inhibitors in CCA patients without FGFR2 fusions. Here we demonstrate aberrant FGFR expression in CCA samples using bioinformatics and further confirm phosphorylated-FGFR expression in paraffinised CCA tissues using immunohistochemistry. Our results highlight p-FGFR as a biomarker to guide FGFR-targeted therapies. Furthermore, CCA cell lines with FGFR expression were sensitive to a selective pan-FGFR inhibitor, PD173074, suggesting that this drug can be used to suppress CCA cells irrespective of the FGFR2 fusions. Finally, the correlation analysis utilising publicly available cohorts suggested the possibility of crosstalk amongst the FGFR and EGFR family of receptors as they are significantly co-expressed. Accordingly, dual inhibition of FGFRs and EGFR by PD173074 and EGFR inhibitor erlotinib was synergistic in CCA. Hence, the findings from this study provide support for further clinical investigation of PD173074, as well as other FGFR inhibitors, to benefit a larger cohort of patients. Altogether, this study shows for the first time the potential of FGFRs and the importance of dual inhibition as a novel therapeutic strategy in CCA. Full article
(This article belongs to the Special Issue New Insights in Biliary Tract Cancers Therapy)
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16 pages, 1836 KiB  
Article
Evaluation of Tazemetostat as a Therapeutically Relevant Substance in Biliary Tract Cancer
by Dino Bekric, Daniel Neureiter, Celina Ablinger, Heidemarie Dobias, Marlena Beyreis, Markus Ritter, Martin Jakab, Johannes Bischof, Ulrich Koller, Tobias Kiesslich and Christian Mayr
Cancers 2023, 15(5), 1569; https://doi.org/10.3390/cancers15051569 - 2 Mar 2023
Cited by 6 | Viewed by 3151
Abstract
Biliary tract cancer (BTC) is a gastrointestinal malignancy associated with a poor survival rate. Current therapies encompass palliative and chemotherapeutic treatment as well as radiation therapy, which results in a median survival of only one year due to standard therapeutic ineffectiveness or resistance. [...] Read more.
Biliary tract cancer (BTC) is a gastrointestinal malignancy associated with a poor survival rate. Current therapies encompass palliative and chemotherapeutic treatment as well as radiation therapy, which results in a median survival of only one year due to standard therapeutic ineffectiveness or resistance. Tazemetostat is an FDA-approved inhibitor of enhancer of Zeste homolog 2 (EZH2), a methyltransferase involved in BTC tumorigenesis via trimethylation of histone 3 at lysine 27 (H3K27me3), an epigenetic mark associated with silencing of tumor suppressor genes. Up to now, there are no data available regarding tazemetostat as a possible treatment option against BTC. Therefore, the aim of our study is a first-time investigation of tazemetostat as a potential anti-BTC substance in vitro. In this study, we demonstrate that tazemetostat affects cell viability and the clonogenic growth of BTC cells in a cell line-dependent manner. Furthermore, we found a strong epigenetic effect at low concentrations of tazemetostat, which was independent of the cytotoxic effect. We also observed in one BTC cell line that tazemetostat increases the mRNA levels and protein expression of the tumor suppressor gene Fructose-1,6-bisphosphatase 1 (FBP1). Interestingly, the observed cytotoxic and epigenetic effects were independent of the mutation status of EZH2. To conclude, our study shows that tazemetostat is a potential anti-tumorigenic substance in BTC with a strong epigenetic effect. Full article
(This article belongs to the Special Issue New Insights in Biliary Tract Cancers Therapy)
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13 pages, 1916 KiB  
Article
The Prognostic Role of True Radical Resection in Perihilar Cholangiocarcinoma after Improved Evaluation of Radial Margin Status
by Mario De Bellis, Maria Gaia Mastrosimini, Simone Conci, Sara Pecori, Tommaso Campagnaro, Claudia Castelli, Paola Capelli, Aldo Scarpa, Alfredo Guglielmi and Andrea Ruzzenente
Cancers 2022, 14(24), 6126; https://doi.org/10.3390/cancers14246126 - 12 Dec 2022
Cited by 4 | Viewed by 1601
Abstract
Background: The evaluation of surgical margins in resected perihilar cholangiocarcinoma (PHCC) remains a challenging issue. Both ductal (DM) and radial margin (RM) should be considered to define true radical resections (R0). Although DM status is routinely described in pathological reports, RM status is [...] Read more.
Background: The evaluation of surgical margins in resected perihilar cholangiocarcinoma (PHCC) remains a challenging issue. Both ductal (DM) and radial margin (RM) should be considered to define true radical resections (R0). Although DM status is routinely described in pathological reports, RM status is often overlooked. Therefore, the frequency of true R0 and its impact on survival might be biased. Objective: To improve the evaluation of RM status and investigate the impact of true R0 on survival. Methods: From 2014 to 2020, 90 patients underwent curative surgery for PHCC at Verona University Hospital, Verona, Italy. Both DM (proximal and distal biliary margin) and RM (hepatic, periductal, and vascular margin) status were evaluated by expert hepatobiliary pathologists. Patients with lymph-node metastases or positive surgical margins (R1) were candidates for adjuvant treatment. Clinicopathological and survival data were retrieved from an institutional database. Results: True R0 were 46% (41) and overall R1 were 54% (49). RM positivity resulted in being higher than DM positivity (48% versus 27%). Overall survival was better in patients with true R0 than in patients with R1 (median survival time: 53 vs. 28 months; p = 0.016). Likewise, the best recurrence-free survival was observed in R0 compared with R1 (median survival time: 32 vs. 15 months; p = 0.006). Multivariable analysis identified residual disease status as an independent prognostic factor of both OS (p = 0.009, HR = 2.68, 95% CI = 1.27–5.63) and RFS (p = 0.009, HR = 2.14, 95% CI = 1.20–3.83). Conclusion: Excellent survival was observed in true R0 patients. The improved evaluation of RM status is mandatory to properly stratify prognosis and select patients for adjuvant treatment. Full article
(This article belongs to the Special Issue New Insights in Biliary Tract Cancers Therapy)
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20 pages, 6658 KiB  
Article
Novel Drug Candidate Prediction for Intrahepatic Cholangiocarcinoma via Hub Gene Network Analysis and Connectivity Mapping
by Yao Xiao, Baoluhe Zhang, Jordan M. Cloyd, Laura Alaimo, Gang Xu, Shunda Du, Yilei Mao and Timothy M. Pawlik
Cancers 2022, 14(13), 3284; https://doi.org/10.3390/cancers14133284 - 5 Jul 2022
Cited by 12 | Viewed by 3831
Abstract
Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy, and there is a need for effective systemic therapies. Gene expression profile-based analyses may allow for efficient screening of potential drug candidates to serve as novel therapeutics for patients with ICC. The RNA expression profile of [...] Read more.
Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy, and there is a need for effective systemic therapies. Gene expression profile-based analyses may allow for efficient screening of potential drug candidates to serve as novel therapeutics for patients with ICC. The RNA expression profile of ICC and normal biliary epithelial cells were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Function annotation and enrichment pathway analyses of the differentially expressed genes (DEGs) were finished using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. A weighted gene co-expression network (WGCN) was constructed by WGCN analysis (WGCNA). Key genes from the DEGs and co-expression gene modules were analyzed to generate a protein–protein interaction (PPI) network. The association between the top 10 screened hub genes and the overall and disease-free survival of ICC patients was examined. The Connectivity Map (cMap) analysis was performed to identify possible drugs for ICC using hub genes. A total of 151 key genes were selected from the overlapping genes of 1287 GSE-DEGs, 8183 TCGA-DEGs and 1226 genes in the mixed modules. A total of 10 hub genes of interest (CTNNB1, SPP1, COL1A2, COL3A1, SMAD3, SRC, VCAN, PKLR, GART, MRPS5) were found analyzing protein–protein interaction. Using the cMap, candidate drugs screened with potential efficacy for ICC included three tyrosine kinase inhibitors (dasatinib, NVP-BHG712, tivantinib), two cannabinoid receptor agonists (palmitoylethanolamide, arachidonamide), two antibiotics (moxifloxacin, amoxicillin), one estrogen receptor agonist (levonorgestrel), one serine/threonine protein kinase inhibitor (MK-2206) and other small molecules. Key genes from network and PPI analysis allowed us to identify potential drugs for ICC. The identification of novel gene expression profiles and related drug screening may accelerate the identification of potential novel drug therapies for ICC. Full article
(This article belongs to the Special Issue New Insights in Biliary Tract Cancers Therapy)
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10 pages, 840 KiB  
Article
Preoperative Osteopenia Is Associated with Significantly Shorter Survival in Patients with Perihilar Cholangiocarcinoma
by Jun Watanabe, Atsushi Miki, Yasunaru Sakuma, Kentaro Shimodaira, Yuichi Aoki, Yoshiyuki Meguro, Kazue Morishima, Kazuhiro Endo, Hideki Sasanuma, Alan Kawarai Lefor, Takumi Teratani, Noriyoshi Fukushima, Joji Kitayama and Naohiro Sata
Cancers 2022, 14(9), 2213; https://doi.org/10.3390/cancers14092213 - 28 Apr 2022
Cited by 3 | Viewed by 2232
Abstract
Background: Osteopenia is defined as low bone mineral density (BMD) and has been shown to be associated with outcomes of patients with various cancers. The association between osteopenia and perihilar cholangiocarcinoma is unknown. The aim of this study was to evaluate osteopenia as [...] Read more.
Background: Osteopenia is defined as low bone mineral density (BMD) and has been shown to be associated with outcomes of patients with various cancers. The association between osteopenia and perihilar cholangiocarcinoma is unknown. The aim of this study was to evaluate osteopenia as a prognostic factor in patients with perihilar cholangiocarcinoma. Methods: A total of 58 patients who underwent surgery for perihilar cholangiocarcinoma were retrospectively analyzed. The BMD at the 11th thoracic vertebra was measured using computed tomography scan within one month of surgery. Patients with a BMD < 160 HU were considered to have osteopenia and b BMD ≥ 160 did not have osteopenia. The log-rank test was performed for survival using the Kaplan–Meier method. After adjusting for confounding factors, overall survival was assessed by Cox′s proportional-hazards model. Results: The osteopenia group had 27 (47%) more females than the non-osteopenia group (p = 0.036). Median survival in the osteopenia group was 37 months and in the non-osteopenia group was 61 months (p = 0.034). In multivariable analysis, osteopenia was a significant independent risk factor associated with overall survival in patients with perihilar cholangiocarcinoma (hazard ratio 3.54, 95% confidence interval 1.09–11.54, p = 0.036), along with primary tumor stage. Conclusions: Osteopenia is associated with significantly shorter survival in patients with perihilar cholangiocarcinoma. Full article
(This article belongs to the Special Issue New Insights in Biliary Tract Cancers Therapy)
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Review

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28 pages, 486 KiB  
Review
Locoregional Therapy for Intrahepatic Cholangiocarcinoma
by Mackenzie Owen, Mina S. Makary and Eliza W. Beal
Cancers 2023, 15(8), 2384; https://doi.org/10.3390/cancers15082384 - 20 Apr 2023
Cited by 8 | Viewed by 1831
Abstract
Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, and surgical resection (SR) offers the only potential for cure. Unfortunately, only a small proportion of patients are eligible for resection due to locally advanced or metastatic disease. Locoregional therapies (LRT) are often used in unresectable [...] Read more.
Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, and surgical resection (SR) offers the only potential for cure. Unfortunately, only a small proportion of patients are eligible for resection due to locally advanced or metastatic disease. Locoregional therapies (LRT) are often used in unresectable liver-only or liver-dominant ICC. This review explores the role of these therapies in the treatment of ICC, including radiofrequency ablation (RFA), microwave ablation (MWA), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), external beam radiotherapy (EBRT), stereotactic body radiotherapy (SBRT), hepatic arterial infusion (HAI) of chemotherapy, irreversible electroporation (IE), and brachytherapy. A search of the current literature was performed to examine types of LRT currently used in the treatment of ICC. We examined patient selection, technique, and outcomes of each type. Overall, LRTs are well-tolerated in the treatment of ICC and are effective in improving overall survival (OS) in this patient population. Further studies are needed to reduce bias from heterogenous patient populations and small sample sizes, as well as to determine whether certain LRTs are superior to others and to examine optimal treatment selection. Full article
(This article belongs to the Special Issue New Insights in Biliary Tract Cancers Therapy)
13 pages, 1212 KiB  
Review
Extrahepatic Distal Cholangiocarcinoma vs. Pancreatic Ductal Adenocarcinoma: Histology and Molecular Profiling for Differential Diagnosis and Treatment
by Anastasios Gkountakos, Filippo M. Martelli, Nicola Silvestris, Michele Bevere, Mario De Bellis, Laura Alaimo, Elena Sapuppo, Francesca Masetto, Aldo Mombello, Michele Simbolo, Elena Bariani, Michele Milella, Matteo Fassan, Aldo Scarpa and Claudio Luchini
Cancers 2023, 15(5), 1454; https://doi.org/10.3390/cancers15051454 - 24 Feb 2023
Cited by 3 | Viewed by 2774
Abstract
Pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are very aggressive tumors with a high mortality rate. Pancreas and distal bile ducts share a common embryonic development. Hence, PDAC and dCCA exhibit similar histological features that make a differential diagnosis during routine diagnostic [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) and distal cholangiocarcinoma (dCCA) are very aggressive tumors with a high mortality rate. Pancreas and distal bile ducts share a common embryonic development. Hence, PDAC and dCCA exhibit similar histological features that make a differential diagnosis during routine diagnostic practice challenging. However, there are also significant differences, with potential clinical implications. Even if PDAC and dCCA are generally associated with poor survival, patients with dCCA seem to present a better prognosis. Moreover, although precision oncology-based approaches are still limited in both entities, their most important targets are different and include alterations affecting BRCA1/2 and related genes in PDAC, as well as HER2 amplification in dCCA. Along this line, microsatellite instability represents a potential contact point in terms of tailored treatments, but its prevalence is very low in both tumor types. This review aims at defining the most important similarities and differences in terms of clinicopathological and molecular features between these two entities, also discussing the main theranostic implications derived from this challenging differential diagnosis. Full article
(This article belongs to the Special Issue New Insights in Biliary Tract Cancers Therapy)
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19 pages, 352 KiB  
Review
Evolving Role of Immunotherapy in Advanced Biliary Tract Cancers
by Sandra Kang, Bassel F. El-Rayes and Mehmet Akce
Cancers 2022, 14(7), 1748; https://doi.org/10.3390/cancers14071748 - 29 Mar 2022
Cited by 22 | Viewed by 3202
Abstract
Biliary tract cancers (BTC) comprise a rare and diverse group of malignancies that involve the gallbladder and biliary tree. These cancers typically present in later stages because they are aggressive in nature and affected patients are often asymptomatic in earlier stages of disease. [...] Read more.
Biliary tract cancers (BTC) comprise a rare and diverse group of malignancies that involve the gallbladder and biliary tree. These cancers typically present in later stages because they are aggressive in nature and affected patients are often asymptomatic in earlier stages of disease. Moreover, BTCs are generally refractory to cytotoxic chemotherapy, which further contributes to their associated poor survival outcomes. Novel therapy approaches are clearly needed. Molecular targeted agents have been developed based on our expanding knowledge of the genetic mutations underlying BTCs and represent a promising treatment strategy in molecularly selected subgroups of patients. In addition, the advent of immunotherapy over recent years has dramatically changed the bleak outcomes observed in malignancies such as melanoma. Our growing understanding of the complex tumor microenvironment in BTC has identified mechanisms of tumor immune evasion that could potentially be targeted with immunotherapy. As a result, different immunotherapeutic approaches including immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapy, have been investigated. The use of immunotherapeutic agents is currently only approved for a small subset of treatment-refractory BTCs based on microsatellite instability (MSI) status and tumor mutational burden (TMB), but this will likely change with the potential approval of immunotherapy plus chemotherapy as a result of the TOPAZ-1 trial. Full article
(This article belongs to the Special Issue New Insights in Biliary Tract Cancers Therapy)

Other

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13 pages, 657 KiB  
Systematic Review
Minimally Invasive Surgery for Perihilar Cholangiocarcinoma: A Systematic Review of the Short- and Long-Term Results
by Giammauro Berardi, Alessio Lucarini, Marco Colasanti, Germano Mariano, Stefano Ferretti, Roberto Luca Meniconi, Nicola Guglielmo, Marco Angrisani, Sofia Usai, Maria Carola Borcea, Giulia Canali, Giovanni Moschetta and Giuseppe Maria Ettorre
Cancers 2023, 15(11), 3048; https://doi.org/10.3390/cancers15113048 - 3 Jun 2023
Cited by 5 | Viewed by 1977
Abstract
Surgery and postoperative systemic chemotherapy represent the standard treatment for patients with perihilar cholangiocarcinoma (PHC). Minimally Invasive Surgery (MIS) for hepatobiliary procedures has spread worldwide in the last two decades. Since resections for PHC are technically demanding, the role of MIS in this [...] Read more.
Surgery and postoperative systemic chemotherapy represent the standard treatment for patients with perihilar cholangiocarcinoma (PHC). Minimally Invasive Surgery (MIS) for hepatobiliary procedures has spread worldwide in the last two decades. Since resections for PHC are technically demanding, the role of MIS in this field is yet to be established. This study aimed to systematically review the existing literature on MIS for PHC, to evaluate its safety and its surgical and oncological outcomes. A systematic literature review on PubMed and SCOPUS was performed according to the PRISMA guidelines. Overall, a total of 18 studies reporting 372 MIS procedures for PHC were included in our analysis. A progressive increase in the available literature was observed over the years. A total of 310 laparoscopic and 62 robotic resections were performed. A pooled analysis showed an operative time ranging from 205.3 ± 23.9 and 840 (770–890) minutes, and intraoperative bleeding between 101.1 ± 13.6 and 1360 ± 809 mL. Minor and major morbidity rates were 43.9% and 12.7%, respectively, with a 5.6% mortality rate. R0 resections were achieved in 80.6% of patients and the number of retrieved lymph nodes ranged between 4 (3–12) and 12 (8–16). This systematic review shows that MIS for PHC is feasible, with safe postoperative and oncological outcomes. Recent data has shown encouraging results and more reports are being published. Future studies should address differences between robotic and laparoscopic approaches. Given the management and technical challenges, MIS for PHC should be performed by experienced surgeons, in high-volume centers, on selected patients. Full article
(This article belongs to the Special Issue New Insights in Biliary Tract Cancers Therapy)
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29 pages, 5712 KiB  
Systematic Review
Efficacy and Safety of First-Line Targeted Treatment and Immunotherapy for Patients with Biliary Tract Cancer: A Systematic Review and Meta-Analysis
by Xin Yan, Huimin Zou, Yunfeng Lai, Carolina Oi Lam Ung and Hao Hu
Cancers 2023, 15(1), 39; https://doi.org/10.3390/cancers15010039 - 21 Dec 2022
Cited by 2 | Viewed by 1798
Abstract
Background: Biliary tract cancer is one of the most aggressive and fatal tumours. Gemcitabine with cisplatin chemotherapy has long been the first-line treatment, but the prognosis is poor. In recent years, targeted treatment and immunotherapy have produced encouraging outcomes requiring a thorough review [...] Read more.
Background: Biliary tract cancer is one of the most aggressive and fatal tumours. Gemcitabine with cisplatin chemotherapy has long been the first-line treatment, but the prognosis is poor. In recent years, targeted treatment and immunotherapy have produced encouraging outcomes requiring a thorough review and meta-analysis. Method: For this systematic review and meta-analysis, we searched four databases, starting from the inception dates of databases to 11 January 2022. This study comprised randomised clinical trials and cohort studies that used immunotherapy or targeted treatment as the first line of treatment for patients with biliary tract cancer. Results: From the 888 studies extracted, 33 trials were examined and found to meet the criteria. These included 3087 patients, 16 single-arm trials, 13 RCTs, one nRCT, a prospective single-arm pilot study, and a clinical setting in the real world. From 2010 to 2020, 33 studies were conducted using targeted treatment or immunologic therapies as first-line treatments for BTC patients, and 18 of those studies had positive outcomes. Conclusion: This study demonstrates that immunotherapy combined with chemotherapy as first-line treatment can provide survival benefits by improving the objective response rate for patients with unresectable biliary tract cancer. The potential for combination therapy to become a new trend in clinical treatment is promising but needs further clinical evaluation. Full article
(This article belongs to the Special Issue New Insights in Biliary Tract Cancers Therapy)
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