Mutational Landscape of Cholangiocarcinoma According to Different Etiologies: A Review

Tavolari, Simona; Brandi, Giovanni

doi:10.3390/cells12091216

Cited by 10 publications

(5 citation statements)

References 81 publications

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“…The presence of these two mutations, along with a mutation in TP53 , in post-operative ctDNA has been associated with a decreased recurrence-free survival [ 30 ]. In CCA, the mutations are thought to be more heterogeneous, though mutations in KRAS , IDH1/2 , FGFR , ERBB2 , and BRAF have been noted to be more frequently mutated [ 34 ]. In colorectal cancer, mutations in APC and TP53 are known to drive the transition from adenoma to adenocarcinoma [ 35 , 36 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

Hong,

Wehrle,

Zhang

et al. 2024

Cancers

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Introduction: Circulating tumor DNA (ctDNA) is emerging as a promising, non-invasive diagnostic and surveillance biomarker in solid organ malignancy. However, its utility before and after liver transplant (LT) for patients with primary and secondary liver cancers is still underexplored. Methods: Patients undergoing LT for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM) with ctDNA testing were included. CtDNA testing was conducted pre-transplant, post-transplant, or both (sequential) from 11/2019 to 09/2023 using Guardant360, Guardant Reveal, and Guardant360 CDx. Results: 21 patients with HCC (n = 9, 43%), CRLM (n = 8, 38%), CCA (n = 3, 14%), and mixed HCC/CCA (n = 1, 5%) were included in the study. The median follow-up time was 15 months (range: 1–124). The median time from pre-operative testing to surgery was 3 months (IQR: 1–4; range: 0–5), and from surgery to post-operative testing, it was 9 months (IQR: 2–22; range: 0.4–112). A total of 13 (62%) patients had pre-transplant testing, with 8 (62%) having ctDNA detected (ctDNA+) and 5 (32%) not having ctDNA detected (ctDNA-). A total of 18 (86%) patients had post-transplant testing, 11 (61%) of whom were ctDNA+ and 7 (33%) of whom were ctDNA-. The absolute recurrence rates were 50% (n = 5) in those who were ctDNA+ vs. 25% (n = 1) in those who were ctDNA- in the post-transplant setting, though this difference was not statistically significant (p = 0.367). Six (29%) patients (HCC = 3, CCA = 1, CRLM = 2) experienced recurrence with a median recurrence-free survival of 14 (IQR: 6–40) months. Four of these patients had positive post-transplant ctDNA collected following diagnosis of recurrence, while one patient had positive post-transplant ctDNA collected preceding recurrence. A total of 10 (48%) patients had sequential ctDNA testing, of whom n = 5 (50%) achieved ctDNA clearance (+/−). The remainder were ctDNA+/+ (n = 3, 30%), ctDNA−/− (n = 1, 10%), and ctDNA−/+ (n = 1, 11%). Three (30%) patients showed the acquisition of new genomic alterations following transplant, all without recurrence. Overall, the median tumor mutation burden (TMB) decreased from 1.23 mut/Mb pre-transplant to 0.00 mut/Mb post-transplant. Conclusions: Patients with ctDNA positivity experienced recurrence at a higher rate than the ctDNA- patients, indicating the potential role of ctDNA in predicting recurrence after curative-intent transplant. Based on sequential testing, LT has the potential to clear ctDNA, demonstrating the capability of LT in the treatment of systemic disease. Transplant providers should be aware of the potential of donor-derived cell-free DNA and improved approaches are necessary to address such concerns.

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Section: Discussionmentioning

confidence: 99%

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

Hong,

Wehrle,

Zhang

et al. 2024

Cancers

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“…The northeast region of Thailand has one of the highest incidences of CCA. CCA is a complex disease with multifactorial etiology, including parasitic infection, genetic predisposition, and environmental factors (Tavolari, & Brandi, 2023). The long-term presence of liver flukes in the biliary system induces chronic inflammation and irritation, promoting the development of CCA.…”

Section: Liver Fluke Infections and Cholangiocarcinoma In Northeaster...mentioning

confidence: 99%

School-based Training Effects on Liver Fluke and Cholangiocarcinoma Prevention: A Comparative Case Study of Individual Differences Among Elementary Teachers in Northeast Thailand

Tungkasamit,

Meekaew,

Srisurak

et al. 2024

JCT

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Liver fluke and Cholangiocarcinoma (CCA) infestations pose significant health challenges, particularly in northeastern region of Thailand. Addressing health issues through an educational lens is of paramount importance to stakeholders in various fields of education, including health education and social education. Collaboratively, stakeholders strive to develop initiatives that enhance understanding of this disease among people in the region. An essential step toward achieving this objective involves recognizing the variations in individuals' responses to educational activities, thereby facilitating the development of locally contextualized and effective learning programs. This study was to explore the differences among elementary teachers participating in training courses for the prevention of cholangiocarcinoma and liver fluke disease in Khon Kaen province. Employing a pre-experimental design, the study involved one hundred and thirty-nine elementary teachers as research participants. Pre- and post-test served as the research instrument, and data analysis entailed the use of descriptive statistics and a t-test. The findings revealed that most of the participants were female, held bachelor's degrees, and were affiliated with schools in Ban Phai district. Moreover, the study demonstrated a significant enhancement in participants’ understanding of liver fluke and CCA prevention following the training. Notably, the study identified a significant impact of the school’s geographical location on training effectiveness. This study contributes to the existing knowledge base, offering insights to tailor more precise training programs in regions where liver fluke and Cholangiocarcinoma disease are prevalent.

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“…Despite these advances, many critical questions remain to be addressed, including the need for better identification of the risk factors associated with this disease and an understanding of their role in the genetic heterogeneity of ICCA. For advancements in managing ICCA in the near future, close collaboration between basic science and clinical research is essential [230].…”

Section: Future Perspectivesmentioning

confidence: 99%

Recent Advances in Pathology of Intrahepatic Cholangiocarcinoma

Choi,

Thung

2024

Preprint

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Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: small duct type and large duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes–inflammation and proliferation–have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.

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Mutational Landscape of Cholangiocarcinoma According to Different Etiologies: A Review

Cited by 10 publications

References 81 publications

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

Circulating Tumor DNA Profiling in Liver Transplant for Hepatocellular Carcinoma, Cholangiocarcinoma, and Colorectal Liver Metastases: A Programmatic Proof of Concept

School-based Training Effects on Liver Fluke and Cholangiocarcinoma Prevention: A Comparative Case Study of Individual Differences Among Elementary Teachers in Northeast Thailand

Recent Advances in Pathology of Intrahepatic Cholangiocarcinoma

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