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Cancers
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New Insights into the Management of Intrahepatic Cholangiocarcinoma
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New Insights into the Management of Intrahepatic Cholangiocarcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 6529

Special Issue Editor

Dr. Gianluca Rompianesi

E-Mail Website1 Website2
Guest Editor
Department of Clinical Medicine and Surgery, Federico II University Hospital, 80131 Naples, Italy
Interests: surgical oncology; liver cancers; pancreatic cancers; biliary cancers; liver surgery; pancreatic surgery; biliary surgery; minimally invasive surgery; robotic surgery

Special Issue Information

Dear Colleagues,

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer, showing a steady increase in its incidence and mortality over time in most locations worldwide. It appears above the second-order bile ducts and can also present in a mixed form with hepatocellular carcinoma (HCC).

Only a minority of patients diagnosed with iCCA are amenable of surgical resection (<20%), which represents the only curative option, and are still burdened with dismal survival (15–40% at 5 years) and a high recurrence rate.

The diagnostic and therapeutic management of iCCA is complex, due to significant variations in disease course and outcome in relation to tumor stages and different molecular profiling, mandating a multidisciplinary approach involving histopathology, interventional radiology, oncology, surgical oncology, and radiotherapy professionals.

Recently, several genomic and immunohistochemistry biomarkers have been analyzed, risk models and nomograms have been developed, and surgical and non-surgical treatment options have been explored in an effort to guide clinicians to identify the best strategies and improve the prognosis of both patients with resectable and unresectable disease.

Due to such an intricated scenario, this Special Issue aims to focus on the latest advances in iCCA classification, diagnosis, prognosis, and treatments.

Dr. Gianluca Rompianesi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • intrahepatic cholangiocarcinoma
  • liver cancer
  • biliary tract neoplasm
  • diagnosis
  • therapies
  • treatment
  • outcome

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Published Papers (4 papers)

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Research

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17 pages, 2938 KiB  
Article
Active Autophagy Is Associated with Favorable Outcome in Patients with Surgically Resected Cholangiocarcinoma
by Katrin Bankov, Falko Schulze, Steffen Gretser, Henning Reis, Nada Abedin, Fabian Finkelmeier, Jörg Trojan, Stefan Zeuzem, Andreas A. Schnitzbauer, Dirk Walter, Peter J. Wild and Maximilian N. Kinzler
Cancers 2023, 15(17), 4322; https://doi.org/10.3390/cancers15174322 - 29 Aug 2023
Cited by 1 | Viewed by 1584
Abstract
Data on the impact of autophagy in primary cholangiocarcinoma (CCA) remain scarce. Here, we therefore investigated the role of active autophagy and its impact on survival in CCA patients. All CCA patients who underwent surgical resection with curative intent between 08/2005 and 12/2021 [...] Read more.
Data on the impact of autophagy in primary cholangiocarcinoma (CCA) remain scarce. Here, we therefore investigated the role of active autophagy and its impact on survival in CCA patients. All CCA patients who underwent surgical resection with curative intent between 08/2005 and 12/2021 at University Hospital Frankfurt were evaluated. Autophagic key proteins were studied by immunohistochemistry. iCCA processed for gene expression profiling of immune-exhaustion gene sets was used for an autophagy approach in silico. Active autophagy was present in 23.3% of the 172 CCA patients. Kaplan–Meier curves revealed median OS of 68.4 months (95% CI = 46.9–89.9 months) and 32.7 months (95% CI = 23.6–41.8 months) for active and non-active autophagy, respectively (p ≤ 0.001). In multivariate analysis, absence of active autophagy (HR = 2, 95% CI = 1.1–3.5, p = 0.015) was an independent risk factor for OS. Differential-expression profiling revealed significantly upregulated histone deacetylases (HDAC) mRNA in patients showing non-active autophagy. In line with this, pan-acetylated lysine was significantly more prominent in CCA patients with ongoing autophagy (p = 0.005). Our findings strengthen the role of active autophagy as a prognostically relevant marker and a potential therapeutic target. Full article
(This article belongs to the Special Issue New Insights into the Management of Intrahepatic Cholangiocarcinoma)
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Review

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40 pages, 1338 KiB  
Review
Unveil Intrahepatic Cholangiocarcinoma Heterogeneity through the Lens of Omics and Multi-Omics Approaches
by Veronica Porreca, Cristina Barbagallo, Eleonora Corbella, Marco Peres, Michele Stella, Giuseppina Mignogna, Bruno Maras, Marco Ragusa and Carmine Mancone
Cancers 2024, 16(16), 2889; https://doi.org/10.3390/cancers16162889 - 20 Aug 2024
Viewed by 1011
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is recognized worldwide as the second leading cause of morbidity and mortality among primary liver cancers, showing a continuously increasing incidence rate in recent years. iCCA aggressiveness is revealed through its rapid and silent intrahepatic expansion and spread through the [...] Read more.
Intrahepatic cholangiocarcinoma (iCCA) is recognized worldwide as the second leading cause of morbidity and mortality among primary liver cancers, showing a continuously increasing incidence rate in recent years. iCCA aggressiveness is revealed through its rapid and silent intrahepatic expansion and spread through the lymphatic system leading to late diagnosis and poor prognoses. Multi-omics studies have aggregated information derived from single-omics data, providing a more comprehensive understanding of the phenomena being studied. These approaches are gradually becoming powerful tools for investigating the intricate pathobiology of iCCA, facilitating the correlation between molecular signature and phenotypic manifestation. Consequently, preliminary stratifications of iCCA patients have been proposed according to their “omics” features opening the possibility of identifying potential biomarkers for early diagnosis and developing new therapies based on personalized medicine (PM). The focus of this review is to provide new and advanced insight into the molecular pathobiology of the iCCA, starting from single- to the latest multi-omics approaches, paving the way for translating new basic research into therapeutic practices. Full article
(This article belongs to the Special Issue New Insights into the Management of Intrahepatic Cholangiocarcinoma)
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56 pages, 2661 KiB  
Review
Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma
by Philipp Heumann, Andreas Albert, Karsten Gülow, Denis Tümen, Martina Müller and Arne Kandulski
Cancers 2024, 16(9), 1690; https://doi.org/10.3390/cancers16091690 - 26 Apr 2024
Viewed by 2159
Abstract
We conducted a comprehensive review of the current literature of published data, clinical trials (MEDLINE; ncbi.pubmed.com), congress contributions (asco.org; esmo.org), and active recruiting clinical trains (clinicaltrial.gov) on targeted therapies in cholangiocarcinoma. Palliative treatment regimens were analyzed as well as preoperative and perioperative treatment [...] Read more.
We conducted a comprehensive review of the current literature of published data, clinical trials (MEDLINE; ncbi.pubmed.com), congress contributions (asco.org; esmo.org), and active recruiting clinical trains (clinicaltrial.gov) on targeted therapies in cholangiocarcinoma. Palliative treatment regimens were analyzed as well as preoperative and perioperative treatment options. We summarized the current knowledge for each mutation and molecular pathway that is or has been under clinical evaluation and discussed the results on the background of current treatment guidelines. We established and recommended targeted treatment options that already exist for second-line settings, including IDH-, BRAF-, and NTRK-mutated tumors, as well as for FGFR2 fusion, HER2/neu-overexpression, and microsatellite instable tumors. Other options for targeted treatment include EGFR- or VEGF-dependent pathways, which are known to be overexpressed or dysregulated in this cancer type and are currently under clinical investigation. Targeted therapy in CCA is a hallmark of individualized medicine as these therapies aim to specifically block pathways that promote cancer cell growth and survival, leading to tumor shrinkage and improved patient outcomes based on the molecular profile of the tumor. Full article
(This article belongs to the Special Issue New Insights into the Management of Intrahepatic Cholangiocarcinoma)
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Other

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17 pages, 924 KiB  
Systematic Review
Multi-Omics Classification of Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis
by Laura Alaimo, Sara Boggio, Giovanni Catalano, Giuseppe Calderone, Edoardo Poletto, Mario De Bellis, Tommaso Campagnaro, Corrado Pedrazzani, Simone Conci and Andrea Ruzzenente
Cancers 2024, 16(14), 2596; https://doi.org/10.3390/cancers16142596 - 20 Jul 2024
Viewed by 1295
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous disease characterized by a dismal prognosis. Various attempts have been made to classify ICC subtypes with varying prognoses, but a consensus has yet to be reached. This systematic review aims to gather relevant data on the multi-omics-based [...] Read more.
Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous disease characterized by a dismal prognosis. Various attempts have been made to classify ICC subtypes with varying prognoses, but a consensus has yet to be reached. This systematic review aims to gather relevant data on the multi-omics-based ICC classification. The PubMed, Embase, and Cochrane databases were searched for terms related to ICC and multi-omics analysis. Studies that identified multi-omics-derived ICC subtypes and investigated clinicopathological predictors of long-term outcomes were included. Nine studies, which included 910 patients, were considered eligible. Mean 3- and 5-year overall survival were 25.7% and 19.6%, respectively, for the multi-omics subtypes related to poor prognosis, while they were 70.2% and 63.3%, respectively, for the subtypes linked to a better prognosis. Several negative prognostic factors were identified, such as genes’ expression profile promoting inflammation, mutations in the KRAS gene, advanced tumor stage, and elevated levels of oncological markers. The subtype with worse clinicopathological characteristics was associated with worse survival (Ref.: good prognosis subtype; pooled hazard ratio 2.06, 95%CI 1.67–2.53). Several attempts have been made to classify molecular ICC subtypes, but they have yielded heterogeneous results and need a clear clinical definition. More efforts are required to build a comprehensive classification system that includes both molecular and clinical characteristics before implementation in clinical practice to facilitate decision-making and select patients who may benefit the most from comprehensive molecular profiling in the disease’s earlier stages. Full article
(This article belongs to the Special Issue New Insights into the Management of Intrahepatic Cholangiocarcinoma)
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