Pub Date : 2023-01-01DOI: 10.20517/2394-5079.2022.51
M. Fasano, Mariacristina Poliseno, M. Milella, Francesco Rosario Paolo Ieva, M. Ciarallo, B. Caccianotti, T. Santantonio
Aim: In long-term nucleos(t)ide analog (NA) suppressed patients with chronic hepatitis B (CHB), hepatocellular carcinoma (HCC) can still develop. Few data exist on the incidence and the predictors of HCC development beyond the first five years in long-term treated patients. To assess the prevalence, incidence, and risk factors for HCC development in a real-life cohort of successfully NA-treated CHB patients for more than five years. Methods: All CHB patients under NAs for ≥ 60 months with stable virologic response were enrolled. HCC surveillance was carried out using liver ultrasound and dosing of serum alpha-fetoprotein every year in patients with CHB and every six months in cirrhotic patients. The baseline PAGE-B score was calculated for each patient. Results: 343 patients (76% male, 86% HBeAg-negative, 30% cirrhotic) were enrolled. During a median (IQR) follow-up of 144 (105-182) months, 21 patients (6%) developed HCC despite virologic suppression (incidence rate 40 cases/1000 person-years follow-up). In multivariate analysis, higher PAGE B score [adjusted Hazard Ratio, aHR 1.26 (95%CI: 1.13-1.54), P = .022] and cirrhosis [aHR 9.71 (95%CI: 2.02-46.48), P = .005] were predictors of HCC development. PAGE B score showed a significant association with HCC (R2 0.225, P < .001) and good prognostic capacity (AUC 0.863) of HCC. Conclusions: Our results confirm that in successfully NA-treated CHB patients, sustained viral replication suppression does not abolish the risk of HCC. The PAGE-B score could be a useful tool for identifying high-risk subjects.
目的:长期NA抑制的慢性乙型肝炎(CHB)患者仍可发生肝细胞癌(HCC)。在长期治疗的患者中，很少有关于5年后HCC发病率和发展预测因素的数据。评估5年以上接受na治疗的CHB患者的流行率、发病率和HCC发展的危险因素。方法:纳入所有接受NAs治疗≥60个月且病毒学反应稳定的CHB患者。对CHB患者每年和肝硬化患者每6个月分别使用肝脏超声和血清甲胎蛋白给药进行HCC监测。计算每位患者的基线PAGE-B评分。结果:共纳入343例患者(76%为男性，86%为hbeag阴性，30%为肝硬化)。在144(105-182)个月的中位(IQR)随访期间，尽管有病毒学抑制，仍有21例(6%)患者发生HCC(发病率为40例/1000人年随访)。在多因素分析中，较高的PAGE B评分[校正危险比，aHR 1.26 (95%CI: 1.13-1.54)， P = 0.022]和肝硬化[aHR 9.71 (95%CI: 2.02-46.48)， P = 0.005]是HCC发展的预测因子。PAGE B评分与HCC (R2 0.225, P < 0.001)及预后良好(AUC 0.863)呈正相关。结论:我们的研究结果证实，在na治疗成功的CHB患者中，持续的病毒复制抑制并不能消除HCC的风险。PAGE-B分数可能是识别高风险受试者的有用工具。
{"title":"Risk of hepatocellular carcinoma development in long-term nucles(t)ide analog suppressed patients with chronic hepatitis B","authors":"M. Fasano, Mariacristina Poliseno, M. Milella, Francesco Rosario Paolo Ieva, M. Ciarallo, B. Caccianotti, T. Santantonio","doi":"10.20517/2394-5079.2022.51","DOIUrl":"https://doi.org/10.20517/2394-5079.2022.51","url":null,"abstract":"Aim: In long-term nucleos(t)ide analog (NA) suppressed patients with chronic hepatitis B (CHB), hepatocellular carcinoma (HCC) can still develop. Few data exist on the incidence and the predictors of HCC development beyond the first five years in long-term treated patients. To assess the prevalence, incidence, and risk factors for HCC development in a real-life cohort of successfully NA-treated CHB patients for more than five years. Methods: All CHB patients under NAs for ≥ 60 months with stable virologic response were enrolled. HCC surveillance was carried out using liver ultrasound and dosing of serum alpha-fetoprotein every year in patients with CHB and every six months in cirrhotic patients. The baseline PAGE-B score was calculated for each patient. Results: 343 patients (76% male, 86% HBeAg-negative, 30% cirrhotic) were enrolled. During a median (IQR) follow-up of 144 (105-182) months, 21 patients (6%) developed HCC despite virologic suppression (incidence rate 40 cases/1000 person-years follow-up). In multivariate analysis, higher PAGE B score [adjusted Hazard Ratio, aHR 1.26 (95%CI: 1.13-1.54), P = .022] and cirrhosis [aHR 9.71 (95%CI: 2.02-46.48), P = .005] were predictors of HCC development. PAGE B score showed a significant association with HCC (R2 0.225, P < .001) and good prognostic capacity (AUC 0.863) of HCC. Conclusions: Our results confirm that in successfully NA-treated CHB patients, sustained viral replication suppression does not abolish the risk of HCC. The PAGE-B score could be a useful tool for identifying high-risk subjects.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67654324","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 : 2023-01-01DOI: 10.20517/2394-5079.2023.26
P. Gavriilidis, Natalie M. Bath, T. Pawlik
Intrahepatic cholangiocarcinoma (iCCA) is a rare liver cancer generally associated with poor patient outcomes. Curative intent liver resection has been established as a standard treatment of care of resectable disease. However, the role of lymphadenectomy, including the extent of resection and therapeutic value, continues to be an area of controversy. The objective of this review was to highlight the role of lymph node dissection (LND) relative to therapeutic value and prognosis in the surgical management of iCCA. A comprehensive review was performed using MEDLINE/PubMed. Search terms included “intrahepatic cholangiocarcinoma”, “bile duct cancer”, lymphadenectomy”, “lymph node metastasis”, and lymph node staging”. Treatment for iCCA should include an R0 resection with regional lymphadenectomy. The prognostic and therapeutic value of regional lymphadenectomy has been an increased area of research and debate. An increased number of lymph node metastases has correlated with inferior overall survival versus lymph node-negative disease. In addition to surgical resection, regional lymphadenectomy with the removal of at least six lymph nodes in the appropriate nodal basins based on primary tumor location should be standard. The identification of lymph node metastasis provides additional important information to guide providers in determining adjuvant therapy and surveillance strategies.
{"title":"The impact of lymphadenectomy on intrahepatic cholangiocarcinoma management and prognosis: a comprehensive review","authors":"P. Gavriilidis, Natalie M. Bath, T. Pawlik","doi":"10.20517/2394-5079.2023.26","DOIUrl":"https://doi.org/10.20517/2394-5079.2023.26","url":null,"abstract":"Intrahepatic cholangiocarcinoma (iCCA) is a rare liver cancer generally associated with poor patient outcomes. Curative intent liver resection has been established as a standard treatment of care of resectable disease. However, the role of lymphadenectomy, including the extent of resection and therapeutic value, continues to be an area of controversy. The objective of this review was to highlight the role of lymph node dissection (LND) relative to therapeutic value and prognosis in the surgical management of iCCA. A comprehensive review was performed using MEDLINE/PubMed. Search terms included “intrahepatic cholangiocarcinoma”, “bile duct cancer”, lymphadenectomy”, “lymph node metastasis”, and lymph node staging”. Treatment for iCCA should include an R0 resection with regional lymphadenectomy. The prognostic and therapeutic value of regional lymphadenectomy has been an increased area of research and debate. An increased number of lymph node metastases has correlated with inferior overall survival versus lymph node-negative disease. In addition to surgical resection, regional lymphadenectomy with the removal of at least six lymph nodes in the appropriate nodal basins based on primary tumor location should be standard. The identification of lymph node metastasis provides additional important information to guide providers in determining adjuvant therapy and surveillance strategies.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67654361","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 : 2023-01-01DOI: 10.20517/2394-5079.2022.37
Yi-Chia (Jasmine) Wu, A. Wakil, F. Salomon, N. Pyrsopoulos
Treatment for hepatocellular carcinoma (HCC) has been challenging as most patients present with late, advanced disease, where curative options are limited. For years, locoregional therapy (LRT) has been the first-line therapy for intermediate-stage HCC and sorafenib for advanced HCC. However, these treatments are often palliative since they are plagued by tumor recurrence or progression. Therefore, there is growing interest in combined therapy to utilize their respective strengths to produce synergistic effects. This review outlines past and current research on the efficacy and safety of combined LRT and systemic therapy.
{"title":"Issue on combined locoregional and systemic treatment for hepatocellular carcinoma","authors":"Yi-Chia (Jasmine) Wu, A. Wakil, F. Salomon, N. Pyrsopoulos","doi":"10.20517/2394-5079.2022.37","DOIUrl":"https://doi.org/10.20517/2394-5079.2022.37","url":null,"abstract":"Treatment for hepatocellular carcinoma (HCC) has been challenging as most patients present with late, advanced disease, where curative options are limited. For years, locoregional therapy (LRT) has been the first-line therapy for intermediate-stage HCC and sorafenib for advanced HCC. However, these treatments are often palliative since they are plagued by tumor recurrence or progression. Therefore, there is growing interest in combined therapy to utilize their respective strengths to produce synergistic effects. This review outlines past and current research on the efficacy and safety of combined LRT and systemic therapy.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67653624","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 : 2023-01-01DOI: 10.20517/2394-5079.2022.94
T. Colasanti, H. Vakifahmetoglu-Norberg, C. Mancone
Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy that originates from the biliary tract located within the liver parenchyma. While the incidence rate of iCCA is increasing worldwide, the existing therapeutic options still remain limited. Thus, the spread of iCCA is the foremost cause of treatment failure representing a major clinical challenge. The aggressive nature and refractoriness of the iCCA are strictly related to the desmoplastic tumor microenvironment, in which cancer cells are surrounded by inflammatory cells, cancer-associated fibroblasts, and the aberrant deposition of members of the collagen family. In recent years, accumulating evidence revealed that remodeling of collagens is pivotal in driving the dissemination of desmoplastic cancers. In this review, we describe the expression profile of collagens and their unique architecture in iCCA and how this can dictate neoplastic cell behavior. The emerging view argues for specific strategies aimed at targeting the collagen architecture that may be useful to hamper iCCA metastasis.
{"title":"Expression and function of collagens in intrahepatic cholangiocarcinoma","authors":"T. Colasanti, H. Vakifahmetoglu-Norberg, C. Mancone","doi":"10.20517/2394-5079.2022.94","DOIUrl":"https://doi.org/10.20517/2394-5079.2022.94","url":null,"abstract":"Intrahepatic cholangiocarcinoma (iCCA) is an aggressive malignancy that originates from the biliary tract located within the liver parenchyma. While the incidence rate of iCCA is increasing worldwide, the existing therapeutic options still remain limited. Thus, the spread of iCCA is the foremost cause of treatment failure representing a major clinical challenge. The aggressive nature and refractoriness of the iCCA are strictly related to the desmoplastic tumor microenvironment, in which cancer cells are surrounded by inflammatory cells, cancer-associated fibroblasts, and the aberrant deposition of members of the collagen family. In recent years, accumulating evidence revealed that remodeling of collagens is pivotal in driving the dissemination of desmoplastic cancers. In this review, we describe the expression profile of collagens and their unique architecture in iCCA and how this can dictate neoplastic cell behavior. The emerging view argues for specific strategies aimed at targeting the collagen architecture that may be useful to hamper iCCA metastasis.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67654116","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 : 2023-01-01DOI: 10.20517/2394-5079.2022.97
Theresa Hydes, D. Cuthbertson, D. Palmer, O. Elshaarawy, P. J. Johnson, Rashika Fernando, T. Cross
International guidelines recommend six monthly ultrasounds as the primary surveillance tool for patients at risk of hepatocellular carcinoma (HCC). The dominant driver of liver disease in HCC surveillance populations is shifting, particularly in Europe and the United States, from chronic viral hepatitis (B or C), towards non-alcoholic fatty liver disease (NAFLD). Today, the population requiring HCC surveillance is also characterised by a high prevalence of overweight/obesity. These patient characteristics significantly impair ultrasound quality which can impede the detection of early HCC lesions. This diagnostic limitation has significant implications considering that eligibility for curative treatment depends upon the stage at which the cancer is detected. In this narrative review, we provide a comprehensive overview of the published evidence and national/international guidelines regarding ultrasound surveillance for HCC in people with NAFLD. We examine ultrasound sensitivity in this cohort for the detection of all stage and early HCC, the impact of steatosis and abdominal obesity on ultrasound performance, evidence for the addition of serum alpha-fetoprotein measurement, optimal timing of surveillance, emerging modalities for risk stratification and screening, and outline the challenges of case finding and surveillance eligibility criteria in this patient cohort. Finally, amalgamating all available evidence, we propose a pragmatic surveillance pathway for patients with NAFLD.
{"title":"Ultrasonography in surveillance for hepatocellular carcinoma in patients with non-alcoholic fatty liver disease","authors":"Theresa Hydes, D. Cuthbertson, D. Palmer, O. Elshaarawy, P. J. Johnson, Rashika Fernando, T. Cross","doi":"10.20517/2394-5079.2022.97","DOIUrl":"https://doi.org/10.20517/2394-5079.2022.97","url":null,"abstract":"International guidelines recommend six monthly ultrasounds as the primary surveillance tool for patients at risk of hepatocellular carcinoma (HCC). The dominant driver of liver disease in HCC surveillance populations is shifting, particularly in Europe and the United States, from chronic viral hepatitis (B or C), towards non-alcoholic fatty liver disease (NAFLD). Today, the population requiring HCC surveillance is also characterised by a high prevalence of overweight/obesity. These patient characteristics significantly impair ultrasound quality which can impede the detection of early HCC lesions. This diagnostic limitation has significant implications considering that eligibility for curative treatment depends upon the stage at which the cancer is detected. In this narrative review, we provide a comprehensive overview of the published evidence and national/international guidelines regarding ultrasound surveillance for HCC in people with NAFLD. We examine ultrasound sensitivity in this cohort for the detection of all stage and early HCC, the impact of steatosis and abdominal obesity on ultrasound performance, evidence for the addition of serum alpha-fetoprotein measurement, optimal timing of surveillance, emerging modalities for risk stratification and screening, and outline the challenges of case finding and surveillance eligibility criteria in this patient cohort. Finally, amalgamating all available evidence, we propose a pragmatic surveillance pathway for patients with NAFLD.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67654151","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 : 2023-01-01DOI: 10.20517/2394-5079.2022.80
F. Cipriani, G. Fornoni, M. Rimini, F. Pedica, F. Invernizzi, A. Casadei‐Gardini, F. de Cobelli, M. Colombo, L. Aldrighetti
The aim of this review is to describe the relevance of minimally invasive liver resection (MILR) for the treatment of most common primary liver tumors. The uptake has been slow but steady, and thus MILR has become a well-established field of hepatobiliary surgery and is considered a landmark change of the past 30 years. There is evidence that the advantage of MILR regarding specific complications of liver surgery for HCC (reduced incidence of postoperative hepatic decompensation and ascites) can be a tool to potentially expand the indications to surgical treatment. Evidence for intrahepatic cholangiocarcinoma is early and exploratory; however, it is beginning to be documented that the fundamental principles of surgical oncology for this tumor can be respected while offering patients the advantages of minimal invasiveness.
{"title":"Surgery for hepatocellular carcinoma and intrahepatic cholangiocarcinoma: milestone changes in the last two decades potentially affecting current guidelines","authors":"F. Cipriani, G. Fornoni, M. Rimini, F. Pedica, F. Invernizzi, A. Casadei‐Gardini, F. de Cobelli, M. Colombo, L. Aldrighetti","doi":"10.20517/2394-5079.2022.80","DOIUrl":"https://doi.org/10.20517/2394-5079.2022.80","url":null,"abstract":"The aim of this review is to describe the relevance of minimally invasive liver resection (MILR) for the treatment of most common primary liver tumors. The uptake has been slow but steady, and thus MILR has become a well-established field of hepatobiliary surgery and is considered a landmark change of the past 30 years. There is evidence that the advantage of MILR regarding specific complications of liver surgery for HCC (reduced incidence of postoperative hepatic decompensation and ascites) can be a tool to potentially expand the indications to surgical treatment. Evidence for intrahepatic cholangiocarcinoma is early and exploratory; however, it is beginning to be documented that the fundamental principles of surgical oncology for this tumor can be respected while offering patients the advantages of minimal invasiveness.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67654062","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 : 2023-01-01DOI: 10.20517/2394-5079.2022.98
M. Argenziano, Michele Montori, Chiara Scorzoni, A. Benedetti, M. Marzioni, L. Maroni
Cholangiocarcinoma (CCA) is an extremely aggressive neoplasia, mostly because of diagnostic delay and lack of effective therapies. CCA is typically surrounded by a peculiar microenvironment that includes abundant desmoplastic stroma and various cell types, which support and enhance CCA development. Among the tumor microenvironment (TME) cells, there are tumor infiltrating lymphocytes (TILs), such as CD8+ and CD4+ cells, Tregs, natural killers (NKs) and B lymphocytes. TILs contribute to an immunosuppressive microenvironment that leads to tumor immune escape. Dendritic cells (DCs) may lead to immunotolerance by maturation or antigen-presentation deficiency. Hepatic stellate cells (HSCs) are one of the major precursors of cancer-associated fibroblast (CAFs), which are distinguished in various subpopulations, each with different functions and interactions with other TME cells. CAFs can promote lymphangiogenesis, early lymph-node metastasis and proinflammatory environment, but they can also provide a physical and chemical barrier to protect CCA. Tumor-associated macrophages (TAMs) could be differentiated between two phenotypes, pro- and anti-inflammatory, and they may sustain invasiveness and immunosuppression. Myeloid-derived suppressor cells (MDSCs) impair cytotoxic T lymphocytes (CTLs) function, stimulating tumor proliferation and angiogenesis. Tumor-associated neutrophils (TANs) function is influenced by the TME, leading to tumor-suppressing or tumor-promoting functions. This paper aims to provide an overview of the CCA microenvironment cells, their role in tumor progression and possible correlated diagnostic, therapeutic and prognostic implications.
{"title":"The role of tumor microenvironment in cholangiocarcinoma","authors":"M. Argenziano, Michele Montori, Chiara Scorzoni, A. Benedetti, M. Marzioni, L. Maroni","doi":"10.20517/2394-5079.2022.98","DOIUrl":"https://doi.org/10.20517/2394-5079.2022.98","url":null,"abstract":"Cholangiocarcinoma (CCA) is an extremely aggressive neoplasia, mostly because of diagnostic delay and lack of effective therapies. CCA is typically surrounded by a peculiar microenvironment that includes abundant desmoplastic stroma and various cell types, which support and enhance CCA development. Among the tumor microenvironment (TME) cells, there are tumor infiltrating lymphocytes (TILs), such as CD8+ and CD4+ cells, Tregs, natural killers (NKs) and B lymphocytes. TILs contribute to an immunosuppressive microenvironment that leads to tumor immune escape. Dendritic cells (DCs) may lead to immunotolerance by maturation or antigen-presentation deficiency. Hepatic stellate cells (HSCs) are one of the major precursors of cancer-associated fibroblast (CAFs), which are distinguished in various subpopulations, each with different functions and interactions with other TME cells. CAFs can promote lymphangiogenesis, early lymph-node metastasis and proinflammatory environment, but they can also provide a physical and chemical barrier to protect CCA. Tumor-associated macrophages (TAMs) could be differentiated between two phenotypes, pro- and anti-inflammatory, and they may sustain invasiveness and immunosuppression. Myeloid-derived suppressor cells (MDSCs) impair cytotoxic T lymphocytes (CTLs) function, stimulating tumor proliferation and angiogenesis. Tumor-associated neutrophils (TANs) function is influenced by the TME, leading to tumor-suppressing or tumor-promoting functions. This paper aims to provide an overview of the CCA microenvironment cells, their role in tumor progression and possible correlated diagnostic, therapeutic and prognostic implications.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67654162","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 : 2023-01-01DOI: 10.20517/2394-5079.2023.09
A. Cigliano, A. Strain, M. Cadamuro
Intrahepatic cholangiocarcinoma (iCCA) is a rare neoplasm of the bile ducts with a low survival rate, whose incidence is continuously increasing and is associated with a rich and varied tumor microenvironment (TME). Although the main mutations characterizing iCCA are known, there are several unresolved issues regarding the processes leading to the accumulation of mutations in the normal cholangiocyte. The inflammatory mediators and the molecular pathways involved in cholangiocarcinogenesis, which regulate the transition from normal to dysplastic cells, resulting in neoplastic cholangiocytes, are poorly understood. Moreover, once the tumor is established, it is unclear which effects of the interaction between the tumor and TME constituent cells, in particular cancer-associated fibroblasts (CAFs), are responsible for stimulating the malignant behavior of iCCA. In this review, we described the main mutations affecting the bile ducts leading to iCCA development as well as the putative inflammatory mediators and morphogenetic pathways involved in the establishment of the malignant transition of the bile ducts. We also described the main signaling pathways involved in TME-tumor cell interactions, with particular emphasis on the effect of CAFs in cancer. Finally, we wanted to analyze possible new therapeutic approaches aimed at modifying the composition of TME and the possible role of immunotherapy in improving the treatment of this cancer.
{"title":"Signaling and molecular networks related to development and inflammation involved in CCA initiation and progression","authors":"A. Cigliano, A. Strain, M. Cadamuro","doi":"10.20517/2394-5079.2023.09","DOIUrl":"https://doi.org/10.20517/2394-5079.2023.09","url":null,"abstract":"Intrahepatic cholangiocarcinoma (iCCA) is a rare neoplasm of the bile ducts with a low survival rate, whose incidence is continuously increasing and is associated with a rich and varied tumor microenvironment (TME). Although the main mutations characterizing iCCA are known, there are several unresolved issues regarding the processes leading to the accumulation of mutations in the normal cholangiocyte. The inflammatory mediators and the molecular pathways involved in cholangiocarcinogenesis, which regulate the transition from normal to dysplastic cells, resulting in neoplastic cholangiocytes, are poorly understood. Moreover, once the tumor is established, it is unclear which effects of the interaction between the tumor and TME constituent cells, in particular cancer-associated fibroblasts (CAFs), are responsible for stimulating the malignant behavior of iCCA. In this review, we described the main mutations affecting the bile ducts leading to iCCA development as well as the putative inflammatory mediators and morphogenetic pathways involved in the establishment of the malignant transition of the bile ducts. We also described the main signaling pathways involved in TME-tumor cell interactions, with particular emphasis on the effect of CAFs in cancer. Finally, we wanted to analyze possible new therapeutic approaches aimed at modifying the composition of TME and the possible role of immunotherapy in improving the treatment of this cancer.","PeriodicalId":12959,"journal":{"name":"Hepatoma Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67654251","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 : 2022-10-17DOI: 10.20517/2394-5079.2021.147
S. Khouzam, D. Pagano, M. Barbara, V. Di Marco, G. Pietrosi, M. Maringhini, M. Canzonieri, S. Calamia, S. Gruttadauria
Aim: The purpose of this study is to assess the benefit of laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) given recurrence and future need for liver transplantation (LT). Methods: Data on liver resections were gathered from the Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione (IRCCS-ISMETT) from 2003-2021. A retrospective analysis of 1408 consecutive adult patients who had a liver resection was performed with categorization based on the underlying disease process. A sub-analysis studied the 291 patients who had an LLR with an intention to transplant approach after LLR. Results: From 2012 to 2020, ISMETT’s mean annual LLR rate was 45%. Data suggests that a laparoscopic approach to iterative surgical treatment for HCC has demonstrated protective benefits. Compared to open surgery or LT, LLR is protective against the risk of de-listing, post-transplant patient death, tumor recurrence, adhesions, and bleeding in a cirrhotic patient. Kaplan Meier’s analysis showed no difference between post-LT survival curves for those with prior open abdominal surgery or LLR (P = 0.658). Conclusion: Laparoscopic surgery has important protective advantages over laparotomy surgery for the surgical treatment of HCC, particularly since treatment is not always curative. LLR can be considered a bridge therapy for transplantation, ensuring less crowding of waiting lists, a desirable condition in areas of donor storage.
目的:本研究的目的是评估腹腔镜肝切除术(LLR)对肝细胞癌(HCC)复发和未来需要肝移植(LT)的益处。方法:从2003年至2021年，收集来自意大利科学院(instituto di Ricovero e Cura a caratere scientificere)和地中海科学院(instituto Mediterraneo per i Trapianti - Terapie and alta specialzazione)的肝脏切除术数据。回顾性分析了1408例连续行肝切除术的成年患者，并根据潜在疾病进程进行了分类。一项亚分析研究了291例LLR术后有意移植入路的患者。结果:2012 - 2020年，ISMETT的年平均LLR率为45%。数据显示，腹腔镜下反复手术治疗HCC具有保护作用。与开放手术或肝移植相比，LLR对肝硬化患者的摘除术、移植后患者死亡、肿瘤复发、粘连和出血具有保护作用。Kaplan Meier的分析显示，术前腹部开腹手术或LLR患者术后生存曲线无差异(P = 0.658)。结论:对于肝细胞癌的手术治疗，腹腔镜手术比剖腹手术具有重要的保护优势，特别是在治疗并不总是治愈的情况下。LLR可以被认为是移植的桥梁疗法，确保等待名单不那么拥挤，这是供体储存区域的理想条件。
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