Pub Date : 2023-12-29DOI: 10.20517/2394-5079.2023.110
A. Lonardo
My invited commentary discusses a recent paper published by Ebrahimi et al. [28 ]. To this end, the definitions of nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and the most recently proposed metabolic dysfunction-associated steatotic liver disease (MASLD) are reviewed. For brevity, the overarching definition of metabolic fatty liver syndromes (MFLS) is utilized to allude to NAFLD/MAFLD/MASLD collectively, although each nomenclature identifies different diagnostic criteria and identifies distinct patient populations. Ebrahimi and colleagues conducted an analysis using data from the National Swedish Multigeneration archive, involving 38,018 MASLD first-degree relatives (FDRs) and 9,381 MASLD spouses, alongside 197,303 comparator FDRs and 47,572 comparator spouses. They followed these groups for a median of 17.6 years and reported a definite familial aggregation of adverse liver-related events among families of MASLD individuals. These events comprise increased relative risks of hepatocellular carcinoma (HCC), major chronic liver disease, and mortality owing to hepatic causes. I comment on this study with reference to the ongoing changes in terminology describing MFLS and to sexual dimorphism exhibited by MFLS. It is concluded that the study by Ebrahimi adds another piece to the puzzle of knowledge requested to implement those precision medicine approaches that are eagerly awaited in the field of MFLS.
{"title":"MASLD co-aggregates with HCC in families-names change, fa(c)ts remain","authors":"A. Lonardo","doi":"10.20517/2394-5079.2023.110","DOIUrl":"https://doi.org/10.20517/2394-5079.2023.110","url":null,"abstract":"My invited commentary discusses a recent paper published by Ebrahimi et al. [28 ]. To this end, the definitions of nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and the most recently proposed metabolic dysfunction-associated steatotic liver disease (MASLD) are reviewed. For brevity, the overarching definition of metabolic fatty liver syndromes (MFLS) is utilized to allude to NAFLD/MAFLD/MASLD collectively, although each nomenclature identifies different diagnostic criteria and identifies distinct patient populations. Ebrahimi and colleagues conducted an analysis using data from the National Swedish Multigeneration archive, involving 38,018 MASLD first-degree relatives (FDRs) and 9,381 MASLD spouses, alongside 197,303 comparator FDRs and 47,572 comparator spouses. They followed these groups for a median of 17.6 years and reported a definite familial aggregation of adverse liver-related events among families of MASLD individuals. These events comprise increased relative risks of hepatocellular carcinoma (HCC), major chronic liver disease, and mortality owing to hepatic causes. I comment on this study with reference to the ongoing changes in terminology describing MFLS and to sexual dimorphism exhibited by MFLS. It is concluded that the study by Ebrahimi adds another piece to the puzzle of knowledge requested to implement those precision medicine approaches that are eagerly awaited in the field of MFLS.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139147774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-21DOI: 10.20517/2394-5079.2023.88
S. Shalaby, Patrizia Burra, M. Senzolo
Liver transplantation is considered the gold standard for curative treatment of hepatocellular carcinoma (HCC) in patients with cirrhosis, but limited organ availability and high costs necessitate alternative options. Hepatic resection (HR) is preferred for select patients, providing tumor removal and prognostic information. However, HR has been associated with life-threatening complications, especially in the presence of clinically significant portal hypertension (CSPH). Current guidelines recommend HR only for patients with well-preserved liver function, normal bilirubin levels, good performance status, and no CSPH. However, advancements in surgical techniques and portal hypertension management are challenging these guidelines, potentially allowing the consideration of hepatic resection for HCC in cirrhotic patients with CSPH. Indeed, minimally invasive approaches improve safety and outcomes for selected CSPH patients and accurate assessment of CSPH allows risk stratification according to liver function, tumor location, and extent of resection. Thus, despite the negative impact of CSPH on HR outcomes, careful patient selection and minimally invasive techniques expand the potential for HR in CSPH patients. This comprehensive review examines the evidence on HR in HCC treatment for cirrhotic patients with CSPH, highlighting challenges in surgical decision-making, the importance of direct measurement of hepatic venous pressure gradient, and exploring the benefits and risks associated with HR. Moreover, it underscores the need for refined prediction models and algorithms to optimize patient selection and enhance surgical outcomes.
{"title":"Hepatic venous pressure gradient in hepatic resection for hepatocellular carcinoma","authors":"S. Shalaby, Patrizia Burra, M. Senzolo","doi":"10.20517/2394-5079.2023.88","DOIUrl":"https://doi.org/10.20517/2394-5079.2023.88","url":null,"abstract":"Liver transplantation is considered the gold standard for curative treatment of hepatocellular carcinoma (HCC) in patients with cirrhosis, but limited organ availability and high costs necessitate alternative options. Hepatic resection (HR) is preferred for select patients, providing tumor removal and prognostic information. However, HR has been associated with life-threatening complications, especially in the presence of clinically significant portal hypertension (CSPH). Current guidelines recommend HR only for patients with well-preserved liver function, normal bilirubin levels, good performance status, and no CSPH. However, advancements in surgical techniques and portal hypertension management are challenging these guidelines, potentially allowing the consideration of hepatic resection for HCC in cirrhotic patients with CSPH. Indeed, minimally invasive approaches improve safety and outcomes for selected CSPH patients and accurate assessment of CSPH allows risk stratification according to liver function, tumor location, and extent of resection. Thus, despite the negative impact of CSPH on HR outcomes, careful patient selection and minimally invasive techniques expand the potential for HR in CSPH patients. This comprehensive review examines the evidence on HR in HCC treatment for cirrhotic patients with CSPH, highlighting challenges in surgical decision-making, the importance of direct measurement of hepatic venous pressure gradient, and exploring the benefits and risks associated with HR. Moreover, it underscores the need for refined prediction models and algorithms to optimize patient selection and enhance surgical outcomes.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"93 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139251197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-15DOI: 10.20517/2394-5079.2023.68
Facai Yang, Yinghe Qiu, Bin Yi
Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive primary liver cancer with limited treatment options and poor prognosis. Although gemcitabine combined with cisplatin (GEMCIS) or newly GEMCIS plus durvalumab is the first-line systemic therapy for iCCA, several promising treatment targets have been identified in the past decade in both first- and subsequent-line settings, including neurotrophic tropomyosin-receptor tyrosine kinase (NTRK) fusions, RET fusions, high microsatellite instability (MSI-H), high tumor mutation burden (TMB-H), as well as fibroblast growth factor receptor 2 (FGFR2) fusions, BRAF V600E mutation, isocitrate dehydrogenase (IDH)-1 and IDH-2 mutations, and human epidermal growth factor receptor 2 [HER2 (ERBB2)] amplifications. Corresponding small molecule inhibitors and monoclonal antibodies have demonstrated improved efficacy and survival benefits in phase 2 or phase 3 studies, gained regulatory approvals or recommendations in guidelines, and reshaped the therapeutic management for advanced cholangiocarcinoma. Numerous novel targeted drugs and combination therapies have been developed and are under evaluation. Despite the progress made in targeted therapy, it still faces challenges such as acquired drug resistance, precise patient selection, and serious adverse events. Therefore, large-scale randomized phase 3 trials of novel targeted agents and innovative regimens are warranted to benefit this population. Herein, we present a comprehensive review of the literature of clinical significance on targeted therapy for iCCA in recent years, focusing on the advances in mutation-based targeted therapy.
{"title":"Targeted mutation-based therapy for intrahepatic cholangiocarcinoma","authors":"Facai Yang, Yinghe Qiu, Bin Yi","doi":"10.20517/2394-5079.2023.68","DOIUrl":"https://doi.org/10.20517/2394-5079.2023.68","url":null,"abstract":"Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive primary liver cancer with limited treatment options and poor prognosis. Although gemcitabine combined with cisplatin (GEMCIS) or newly GEMCIS plus durvalumab is the first-line systemic therapy for iCCA, several promising treatment targets have been identified in the past decade in both first- and subsequent-line settings, including neurotrophic tropomyosin-receptor tyrosine kinase (NTRK) fusions, RET fusions, high microsatellite instability (MSI-H), high tumor mutation burden (TMB-H), as well as fibroblast growth factor receptor 2 (FGFR2) fusions, BRAF V600E mutation, isocitrate dehydrogenase (IDH)-1 and IDH-2 mutations, and human epidermal growth factor receptor 2 [HER2 (ERBB2)] amplifications. Corresponding small molecule inhibitors and monoclonal antibodies have demonstrated improved efficacy and survival benefits in phase 2 or phase 3 studies, gained regulatory approvals or recommendations in guidelines, and reshaped the therapeutic management for advanced cholangiocarcinoma. Numerous novel targeted drugs and combination therapies have been developed and are under evaluation. Despite the progress made in targeted therapy, it still faces challenges such as acquired drug resistance, precise patient selection, and serious adverse events. Therefore, large-scale randomized phase 3 trials of novel targeted agents and innovative regimens are warranted to benefit this population. Herein, we present a comprehensive review of the literature of clinical significance on targeted therapy for iCCA in recent years, focusing on the advances in mutation-based targeted therapy.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"41 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139273142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-03DOI: 10.20517/2394-5079.2023.94
Massimiliano Cadamuro, Giorgia Nuozzi, Paolo Simioni, Luca Fabris
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, deriving from the neoplastic transformation of hepatocytes, most often forced to long-lasting regeneration by the cirrhotic background. HCC is an extremely aggressive tumor with still limited effective treatments, and is characterized by the presence of a very complex and multifaceted tumor microenvironment (TME). Among the variety of cell types populating the TME of HCC, cancer-associated fibroblasts (CAFs) are the most prevalent. CAFs are a specific population of fibroblasts in a persistent state of activation, with a high level of heterogeneity, partly dependent on a wide range of cell origin, which are endowed with a repertoire of functions, profoundly modulating the biology of the tumor. Given the close relationship of HCC with cirrhosis, CAFs are paradigmatic of the role played by activated fibroblasts in promoting the evolution of a chronic, non-resolving, fibro-inflammatory condition towards a neoplastic disease and its aggressive phenotype. In this review, we will discuss the most recent findings regarding the interplay of CAFs with the tumoral epithelial compartment, with the multiple cell elements of the TME (macrophages, neutrophils, myeloid-derived suppressor cells, vascular cells), and with the extracellular matrix. Finally, we will address the translational value of CAF manipulation in HCC to unveil possible ameliorations for the treatment of a still worrisome disease.
{"title":"The tumor microenvironment in hepatocarcinoma: dissecting the functions of cancer-associated fibroblasts","authors":"Massimiliano Cadamuro, Giorgia Nuozzi, Paolo Simioni, Luca Fabris","doi":"10.20517/2394-5079.2023.94","DOIUrl":"https://doi.org/10.20517/2394-5079.2023.94","url":null,"abstract":"Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, deriving from the neoplastic transformation of hepatocytes, most often forced to long-lasting regeneration by the cirrhotic background. HCC is an extremely aggressive tumor with still limited effective treatments, and is characterized by the presence of a very complex and multifaceted tumor microenvironment (TME). Among the variety of cell types populating the TME of HCC, cancer-associated fibroblasts (CAFs) are the most prevalent. CAFs are a specific population of fibroblasts in a persistent state of activation, with a high level of heterogeneity, partly dependent on a wide range of cell origin, which are endowed with a repertoire of functions, profoundly modulating the biology of the tumor. Given the close relationship of HCC with cirrhosis, CAFs are paradigmatic of the role played by activated fibroblasts in promoting the evolution of a chronic, non-resolving, fibro-inflammatory condition towards a neoplastic disease and its aggressive phenotype. In this review, we will discuss the most recent findings regarding the interplay of CAFs with the tumoral epithelial compartment, with the multiple cell elements of the TME (macrophages, neutrophils, myeloid-derived suppressor cells, vascular cells), and with the extracellular matrix. Finally, we will address the translational value of CAF manipulation in HCC to unveil possible ameliorations for the treatment of a still worrisome disease.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"6 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135868796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-30DOI: 10.20517/2394-5079.2023.85
Jin Wang, Yali Yang, Jingyi Lu, Xia Wang
Hepatocellular carcinoma (HCC) stands as one of the most prevalent malignant tumors globally. Despite considerable advancements in HCC therapies, therapeutic resistance remains a significant challenge that compromises patient prognosis. Increasing evidence indicates that exosomes, which are secreted by cells in the tumor microenvironment (TME), are pivotal players in the development of therapeutic resistance in HCC. These nano-sized vesicles mediate intercellular communication in TME through the transfer of bioactive molecules such as nucleic acids, lipids, and proteins. A comprehensive understanding of the role of exosomes in therapeutic resistance could provide promising strategies for both the diagnosis and treatment of HCC. This review mainly summarizes the involvement of exosomal cargos and elucidates their underlying mechanisms in resistance to therapeutic treatments for HCC, and further discusses the potential clinical applications of exosomes as diagnostic biomarkers and therapeutic targets to overcome drug resistance in HCC.
{"title":"The role of exosomes in therapeutic resistance of hepatocellular carcinoma","authors":"Jin Wang, Yali Yang, Jingyi Lu, Xia Wang","doi":"10.20517/2394-5079.2023.85","DOIUrl":"https://doi.org/10.20517/2394-5079.2023.85","url":null,"abstract":"Hepatocellular carcinoma (HCC) stands as one of the most prevalent malignant tumors globally. Despite considerable advancements in HCC therapies, therapeutic resistance remains a significant challenge that compromises patient prognosis. Increasing evidence indicates that exosomes, which are secreted by cells in the tumor microenvironment (TME), are pivotal players in the development of therapeutic resistance in HCC. These nano-sized vesicles mediate intercellular communication in TME through the transfer of bioactive molecules such as nucleic acids, lipids, and proteins. A comprehensive understanding of the role of exosomes in therapeutic resistance could provide promising strategies for both the diagnosis and treatment of HCC. This review mainly summarizes the involvement of exosomal cargos and elucidates their underlying mechanisms in resistance to therapeutic treatments for HCC, and further discusses the potential clinical applications of exosomes as diagnostic biomarkers and therapeutic targets to overcome drug resistance in HCC.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"56 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136102542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-24DOI: 10.20517/2394-5079.2023.71
Reto Bale, Timothy M. Pawlik
Intrahepatic cholangiocarcinoma (iCCA) is a rare cancer with generally poor prognosis. In this narrative review, we examine the role of thermal ablation and summarize the current literature. Radiofrequency ablation (RFA) and microwave ablation (MWA) are both safe and well-tolerated as a minimally invasive local curative treatment option for patients suffering from primary and secondary liver tumors. Both methods can be used in patients with medical morbidities that would preclude surgery, as well as individuals with anatomical or functional constraints that impede liver resection. In unresectable iCCA, the median OS after conventional percutaneous US- or CT-guided RFA and MWA is between 20 and 39 months and 10 and 28 months, respectively. In recurrent iCCA, percutaneous RFA and MWA achieved a median OS of 21-27 months and 21-31 months, respectively. These data are comparable to long-term outcomes after surgical resection (SR), with the number of nodules and tumor size affecting prognosis. Stereotactic radiofrequency ablation (SRFA) allows for effective treatment of large and multiple iCCA nodules within one session and achieves short- and long-term results in inoperable patients compared with resection. With the addition of SRFA as an alternative treatment option, the proportion of patients who can be treated with curative treatment has significantly increased. In the absence of prospective trials comparing thermal ablation and surgical resection, we recommend a patient-specific decision-making process. Future research to identify technical and clinical prognostic criteria, as well as molecular markers of tumor biology, may help select patients for ablation and subsequent outcomes.
{"title":"Treatment of intrahepatic cholangiocarcinoma: evidence for the role of percutaneous ablation","authors":"Reto Bale, Timothy M. Pawlik","doi":"10.20517/2394-5079.2023.71","DOIUrl":"https://doi.org/10.20517/2394-5079.2023.71","url":null,"abstract":"Intrahepatic cholangiocarcinoma (iCCA) is a rare cancer with generally poor prognosis. In this narrative review, we examine the role of thermal ablation and summarize the current literature. Radiofrequency ablation (RFA) and microwave ablation (MWA) are both safe and well-tolerated as a minimally invasive local curative treatment option for patients suffering from primary and secondary liver tumors. Both methods can be used in patients with medical morbidities that would preclude surgery, as well as individuals with anatomical or functional constraints that impede liver resection. In unresectable iCCA, the median OS after conventional percutaneous US- or CT-guided RFA and MWA is between 20 and 39 months and 10 and 28 months, respectively. In recurrent iCCA, percutaneous RFA and MWA achieved a median OS of 21-27 months and 21-31 months, respectively. These data are comparable to long-term outcomes after surgical resection (SR), with the number of nodules and tumor size affecting prognosis. Stereotactic radiofrequency ablation (SRFA) allows for effective treatment of large and multiple iCCA nodules within one session and achieves short- and long-term results in inoperable patients compared with resection. With the addition of SRFA as an alternative treatment option, the proportion of patients who can be treated with curative treatment has significantly increased. In the absence of prospective trials comparing thermal ablation and surgical resection, we recommend a patient-specific decision-making process. Future research to identify technical and clinical prognostic criteria, as well as molecular markers of tumor biology, may help select patients for ablation and subsequent outcomes.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"79 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135267320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-12DOI: 10.20517/2394-5079.2023.60
Thomas An, Eric Wehrenberg-Klee
Trans-arterial therapies performed by interventional radiology, including chemoembolization and radioembolization, have been increasingly utilized for the treatment of unresectable intrahepatic cholangiocarcinoma. There is increasing evidence demonstrating the safety and efficacy of these interventions in patients with advanced disease. This review provides an overview of trans-arterial chemoembolization and radioembolization for unresectable intrahepatic cholangiocarcinoma, summarizes current evidence, and explores future directions for locoregional therapies.
{"title":"Trans-arterial chemoembolization and radioembolization for treatment of intrahepatic cholangiocarcinoma","authors":"Thomas An, Eric Wehrenberg-Klee","doi":"10.20517/2394-5079.2023.60","DOIUrl":"https://doi.org/10.20517/2394-5079.2023.60","url":null,"abstract":"Trans-arterial therapies performed by interventional radiology, including chemoembolization and radioembolization, have been increasingly utilized for the treatment of unresectable intrahepatic cholangiocarcinoma. There is increasing evidence demonstrating the safety and efficacy of these interventions in patients with advanced disease. This review provides an overview of trans-arterial chemoembolization and radioembolization for unresectable intrahepatic cholangiocarcinoma, summarizes current evidence, and explores future directions for locoregional therapies.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135969289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-23DOI: 10.20517/2394-5079.2023.53
Adriana Romanzi, Erica Villa
The tumor microenvironment (TME) constitutes a complex structure comprising different cell types and soluble factors that surround the tumor and promote its progression. Primarily for its pivotal role in malignant growth, TME has become a potential therapeutic objective for developing new targeted therapy and a marker for assessing therapeutic response. In intrahepatic cholangiocarcinoma (iCCA), the second most common primary liver malignancy, TME has also gained a central role in understanding the mechanisms underlying tumor progression. In this review, we focused on the role of angiogenic factors and their pathway in iCCA and analyzed possible therapeutic and prognostic implications.
{"title":"Angiogenesis: the Yin and Yang in intrahepatic cholangiocarcinoma","authors":"Adriana Romanzi, Erica Villa","doi":"10.20517/2394-5079.2023.53","DOIUrl":"https://doi.org/10.20517/2394-5079.2023.53","url":null,"abstract":"The tumor microenvironment (TME) constitutes a complex structure comprising different cell types and soluble factors that surround the tumor and promote its progression. Primarily for its pivotal role in malignant growth, TME has become a potential therapeutic objective for developing new targeted therapy and a marker for assessing therapeutic response. In intrahepatic cholangiocarcinoma (iCCA), the second most common primary liver malignancy, TME has also gained a central role in understanding the mechanisms underlying tumor progression. In this review, we focused on the role of angiogenic factors and their pathway in iCCA and analyzed possible therapeutic and prognostic implications.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"57 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135570471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-18DOI: 10.20517/2394-5079.2023.47
Kanokphorn Thonglert, M. Chuong, R. Herrera, S. Apisarnthanarax
Radiotherapy (RT) is an integral component of the multidisciplinary care for intrahepatic cholangiocarcinoma (iCCA). Over the past decades, RT techniques have been developed with the aim of enhancing tumor control and minimizing toxicity. The most recent technological advancements include proton beam therapy (PBT) and magnetic resonance-guided radiotherapy (MRgRT). PBT is notable for its unique physical characteristics that allow for greater sparing of surrounding normal organs, especially the liver, from low to moderate doses of radiation. MRgRT provides advantages in other aspects, including superior tumor visualization before treatment, on-board treatment plan adaptation, and tumor tracking during treatment. These features allow for precise dose delivery and safe dose escalation, especially for patients with tumors close to luminal GI structures. In this review article, the rationale, clinical outcomes, clinical applications, challenges, and future directions of PBT and MRgRT are discussed. Additionally, the potential combination of novel therapeutics with RT in iCCA is explored.
{"title":"Advanced and emerging radiation therapy approaches for intrahepatic cholangiocarcinoma","authors":"Kanokphorn Thonglert, M. Chuong, R. Herrera, S. Apisarnthanarax","doi":"10.20517/2394-5079.2023.47","DOIUrl":"https://doi.org/10.20517/2394-5079.2023.47","url":null,"abstract":"Radiotherapy (RT) is an integral component of the multidisciplinary care for intrahepatic cholangiocarcinoma (iCCA). Over the past decades, RT techniques have been developed with the aim of enhancing tumor control and minimizing toxicity. The most recent technological advancements include proton beam therapy (PBT) and magnetic resonance-guided radiotherapy (MRgRT). PBT is notable for its unique physical characteristics that allow for greater sparing of surrounding normal organs, especially the liver, from low to moderate doses of radiation. MRgRT provides advantages in other aspects, including superior tumor visualization before treatment, on-board treatment plan adaptation, and tumor tracking during treatment. These features allow for precise dose delivery and safe dose escalation, especially for patients with tumors close to luminal GI structures. In this review article, the rationale, clinical outcomes, clinical applications, challenges, and future directions of PBT and MRgRT are discussed. Additionally, the potential combination of novel therapeutics with RT in iCCA is explored.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45934674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-10DOI: 10.20517/2394-5079.2023.33
Min Dai, Rashid N Lui, L. Lau
Liver cancer is the sixth commonest cancer and the third leading cause of cancer mortality worldwide. Accumulating evidence suggests a pivotal role of the gut microbiome in the progression of chronic liver disease and the subsequent development of liver cancer. Additionally, gut microbiome has been shown to contribute to the hosts’ antitumor responses following immunotherapy and chemotherapy for liver cancers, highlighting the therapeutic potential of gut microbiome modulation in enhancing treatment efficacy and reducing drug resistance. Fecal microbiota transplantation (FMT), a novel therapeutic modality to deliver a healthy donor's stool by endoscopy or capsule, has demonstrated potential in managing liver diseases and cancers by restoring and modulating the recipient’s gut microbiome composition. However, existing data on the clinical application of FMT in liver cancers are still limited. This review summarizes the underlying roles and mechanisms of gut microbiome in liver cancer and discusses the therapeutic potential of FMT in liver cancer treatment and the management of its related complications (e.g., hepatic encephalopathy).
{"title":"The role of gut microbiome and fecal microbiota transplantation in liver cancer and related complications: mechanisms and therapeutic potentials","authors":"Min Dai, Rashid N Lui, L. Lau","doi":"10.20517/2394-5079.2023.33","DOIUrl":"https://doi.org/10.20517/2394-5079.2023.33","url":null,"abstract":"Liver cancer is the sixth commonest cancer and the third leading cause of cancer mortality worldwide. Accumulating evidence suggests a pivotal role of the gut microbiome in the progression of chronic liver disease and the subsequent development of liver cancer. Additionally, gut microbiome has been shown to contribute to the hosts’ antitumor responses following immunotherapy and chemotherapy for liver cancers, highlighting the therapeutic potential of gut microbiome modulation in enhancing treatment efficacy and reducing drug resistance. Fecal microbiota transplantation (FMT), a novel therapeutic modality to deliver a healthy donor's stool by endoscopy or capsule, has demonstrated potential in managing liver diseases and cancers by restoring and modulating the recipient’s gut microbiome composition. However, existing data on the clinical application of FMT in liver cancers are still limited. This review summarizes the underlying roles and mechanisms of gut microbiome in liver cancer and discusses the therapeutic potential of FMT in liver cancer treatment and the management of its related complications (e.g., hepatic encephalopathy).","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42574321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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