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Biomedicine & Pharmacotherapy =... May 2023Treatment resistance is one of the major barriers for therapeutic strategies in hepatocellular carcinoma (HCC). Many studies have indicated that chemotherapy and... (Review)
Review
Treatment resistance is one of the major barriers for therapeutic strategies in hepatocellular carcinoma (HCC). Many studies have indicated that chemotherapy and radiotherapy induce autophagy machinery (cell protective autophagy) in HCC cells. In addition, many experiments report a remarkable crosstalk between treatment resistance and autophagy pathways. Thus, autophagy could be one of the key factors enabling tumor cells to hinder induced cell death after medical interventions. Therefore, extensive research on the molecular pathways involved in resistance induction and autophagy have been conducted to achieve the desired therapeutic response. The key molecular pathways related to the therapy resistance are TGF-β, MAPK, NRF2, NF-κB, and non-coding RNAs. In addition, EMT, drug transports, apoptosis evasion, DNA repair, cancer stem cells, and hypoxia could have considerable impact on the hepatoma cell's response to therapies. These mechanisms protect tumor cells against various treatments and many studies have shown that each of them is connected to the molecular pathways of autophagy induction in HCC. Hence, autophagy inhibition may be an effective strategy to improve therapeutic outcome in HCC patients. In this review, we further highlight how autophagy leads to poor response during treatment through a complex molecular network and how it enhances resistance in primary liver cancer. We propose that combinational regimens of approved HCC therapeutic protocols plus autophagy inhibitors may overcome drug resistance in HCC therapy.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Drug Resistance, Neoplasm; Autophagy; Cell Line, Tumor; Apoptosis
PubMed: 36963361
DOI: 10.1016/j.biopha.2023.114487 -
Experimental and Clinical... Jan 2022In patients who receive liver transplant to treat hepatocellular carcinoma, 10% to 15% posttransplant recurrence is observed. In the present study, we evaluated the...
OBJECTIVES
In patients who receive liver transplant to treat hepatocellular carcinoma, 10% to 15% posttransplant recurrence is observed. In the present study, we evaluated the long-term outcomes of patients who had received liver transplant for treatment of hepatocellular carcinoma.
MATERIALS AND METHODS
Of the 683 livertransplants that we performed, 72 were in response to hepatocellular carcinoma. The physical examination and laboratory and imaging results of the patients were retrospectively analyzed and recorded. The recipients were evaluated according to the Başkent criteria and divided into 2 groups: early diagnosis and late diagnosis.
RESULTS
Among 72 total patients in our study, 19 (26.3%) were pediatric recipients. Hepatocellular carcinoma recurred in 7 patients (9.7%; 5 adult, 2 pediatric). Except for one patient, all were in the late diagnosis group.The mean survivaltime of all patients was 137.45 ± 10 months.The mean survival in the early diagnosis group was longer than in the late diagnosis group. During follow-up, 11 patients died from recurrence and distant metastasis.
CONCLUSIONS
In patients with hepatocellular carcinoma who received liver transplant, we found that postoperative recurrence of hepatocellular carcinoma and distant metastasis can be treated with surgery and/or with interventional radiology methods, which may improve patient survival after liver transplant.
Topics: Adult; Carcinoma, Hepatocellular; Child; Humans; Liver Neoplasms; Neoplasm Recurrence, Local; Retrospective Studies; Risk Factors; Treatment Outcome
PubMed: 35060449
DOI: 10.6002/ect.2021.0450 -
World Journal of Gastroenterology Jul 2015Hepatocellular carcinoma (HCC) represents a unique challenge for physicians and patients. There is no definitively curative treatment. Rather, many treatment and... (Review)
Review
Hepatocellular carcinoma (HCC) represents a unique challenge for physicians and patients. There is no definitively curative treatment. Rather, many treatment and management modalities exist with differing advantages and disadvantages. Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC. In addition, quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies. Thus, considering all the options and their various pros and cons can quickly become complex for both clinicians and patients. In this review, we systematically discuss the current treatment modalities available for HCC, detailing relevant clinical data, risks and rewards and overall outcomes for each approach. Surgical options discussed include resection, transplantation and ablation. We also discuss the radiation modalities: conformal radiotherapy, yttrium 90 microspheres and proton and heavy ion radiotherapy. The biologic agent Sorafenib is discussed as a promising new approach, and recent clinical trials are reviewed. We then detail currently described molecular pathways implicated in the initiation and progression of HCC, and we explore the potential of each pathway as an avenue for drug exploitation. We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Early Detection of Cancer; Humans; Liver Neoplasms; Neoplasm Staging; Palliative Care; Patient Selection; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 26229392
DOI: 10.3748/wjg.v21.i28.8478 -
Journal of Cellular and Molecular... May 2024Liver diseases include all types of viral hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), cirrhosis, liver failure (LF) and... (Review)
Review
Liver diseases include all types of viral hepatitis, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), cirrhosis, liver failure (LF) and hepatocellular carcinoma (HCC). Liver disease is now one of the leading causes of disease and death worldwide, which compels us to better understand the mechanisms involved in the development of liver diseases. Anoctamin 1 (ANO1), a calcium-activated chloride channel (CaCC), plays an important role in epithelial cell secretion, proliferation and migration. ANO1 plays a key role in transcriptional regulation as well as in many signalling pathways. It is involved in the genesis, development, progression and/or metastasis of several tumours and other diseases including liver diseases. This paper reviews the role and molecular mechanisms of ANO1 in the development of various liver diseases, aiming to provide a reference for further research on the role of ANO1 in liver diseases and to contribute to the improvement of therapeutic strategies for liver diseases by regulating ANO1.
Topics: Humans; Anoctamin-1; Liver Diseases; Animals; Signal Transduction; Neoplasm Proteins; Liver Neoplasms; Carcinoma, Hepatocellular; Gene Expression Regulation
PubMed: 38685684
DOI: 10.1111/jcmm.18320 -
Arquivos Brasileiros de Cirurgia... 2017Hepatocellular carcinoma is an aggressive malignant tumor with high lethality. (Review)
Review
INTRODUCTION
Hepatocellular carcinoma is an aggressive malignant tumor with high lethality.
AIM
To review diagnosis and management of hepatocellular carcinoma.
METHODS
Literature review using web databases Medline/PubMed.
RESULTS
Hepatocellular carcinoma is a common complication of hepatic cirrhosis. Chronic viral hepatitis B and C also constitute as risk factors for its development. In patients with cirrhosis, hepatocelular carcinoma usually rises upon malignant transformation of a dysplastic regenerative nodule. Differential diagnosis with other liver tumors is obtained through computed tomography scan with intravenous contrast. Magnetic resonance may be helpful in some instances. The only potentially curative treatment for hepatocellular carcinoma is tumor resection, which may be performed through partial liver resection or liver transplantation. Only 15% of all hepatocellular carcinomas are amenable to operative treatment. Patients with Child C liver cirrhosis are not amenable to partial liver resections. The only curative treatment for hepatocellular carcinomas in patients with Child C cirrhosis is liver transplantation. In most countries, only patients with hepatocellular carcinoma under Milan Criteria are considered candidates to a liver transplant.
CONCLUSION
Hepatocellular carcinoma is potentially curable if discovered in its initial stages. Medical staff should be familiar with strategies for early diagnosis and treatment of hepatocellular carcinoma as a way to decrease mortality associated with this malignant neoplasm.
Topics: Algorithms; Carcinoma, Hepatocellular; Hepatectomy; Humans; Liver Neoplasms
PubMed: 29340553
DOI: 10.1590/0102-6720201700040011 -
Radiology May 2023
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Neoplasm Recurrence, Local; Tomography, X-Ray Computed; Biomarkers
PubMed: 37097138
DOI: 10.1148/radiol.230657 -
World Journal of Gastroenterology Nov 2015Hepatocellular carcinoma (HCC) is an increasing health problem, representing the second cause of cancer-related mortality worldwide. The major risk factor for HCC is... (Review)
Review
Hepatocellular carcinoma (HCC) is an increasing health problem, representing the second cause of cancer-related mortality worldwide. The major risk factor for HCC is cirrhosis. In developing countries, viral hepatitis represent the major risk factor, whereas in developed countries, the epidemic of obesity, diabetes and nonalcoholic steatohepatitis contribute to the observed increase in HCC incidence. Cirrhotic patients are recommended to undergo HCC surveillance by abdominal ultrasounds at 6-mo intervals. The current diagnostic algorithms for HCC rely on typical radiological hallmarks in dynamic contrast-enhanced imaging, while the use of α-fetoprotein as an independent tool for HCC surveillance is not recommended by current guidelines due to its low sensitivity and specificity. Early diagnosis is crucial for curative treatments. Surgical resection, radiofrequency ablation and liver transplantation are considered the cornerstones of curative therapy, while for patients with more advanced HCC recommended options include sorafenib and trans-arterial chemo-embolization. A multidisciplinary team, consisting of hepatologists, surgeons, radiologists, oncologists and pathologists, is fundamental for a correct management. In this paper, we review the diagnostic and therapeutic management of HCC, with a focus on the most recent evidences and recommendations from guidelines.
Topics: Algorithms; Biomarkers, Tumor; Carcinoma, Hepatocellular; Critical Pathways; Diagnostic Imaging; Humans; Liver Neoplasms; Neoplasm Staging; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 26576088
DOI: 10.3748/wjg.v21.i42.12003 -
Diagnostic and Interventional Imaging 2020The purpose of this study was to perform a systematic review of current literature describing the efficacy and technical outcomes of transarterial liver therapies using... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The purpose of this study was to perform a systematic review of current literature describing the efficacy and technical outcomes of transarterial liver therapies using automated feeder detection (AFD) software.
MATERIALS AND METHODS
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A structured search was performed in the PubMed, SCOPUS, and Embase databases of patients undergoing locoregional therapy of liver tumors utilizing AFD software. Demographic data, procedure data (including radiometrics) and tumor response rate were recorded. Where available, performance of AFD was compared to conventional digital subtraction angiography (DSA) and cone-beam CT (CBCT) without AFD.
RESULTS
A total of 14 full-text manuscripts met inclusion criteria, comprising 1042 tumors in 604 patients (305 men, 156 women; mean age, 68.6±6.0 [SD] years), including 537 patients with hepatocellular carcinoma, 8 with metastases from neuroendocrine tumors, and 59 patients without reported etiology. Reported sensitivity of AFD ranged between 86% and 98.5%, compared to DSA alone (38% - 64%) or DSA in combination with CBCT (69% - 81%). Three studies reported tumor response by modified response evaluation criteria in solid tumors (mRECIST) guidelines, with complete response in the range of 60% - 69%.
CONCLUSION
AFD is a promising new technology for the identification of intrahepatic and extrahepatic tumor-feeding arteries and should be considered a useful adjunct to conventional DSA and CBCT in the treatment of liver tumors.
Topics: Aged; Angiography, Digital Subtraction; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cone-Beam Computed Tomography; Female; Humans; Liver Neoplasms; Male; Middle Aged; Software
PubMed: 32035822
DOI: 10.1016/j.diii.2020.01.011 -
Clinical and Molecular Hepatology Sep 2016There has been ongoing debate that the Milan criteria may be too strict that a significant number of patients who could benefit from liver transplantation (LT) might... (Review)
Review
There has been ongoing debate that the Milan criteria may be too strict that a significant number of patients who could benefit from liver transplantation (LT) might have been excluded. Based on this idea, various studies have been conducted to further expand the Milan criteria and give more HCC patients a chance of cure. In deceased donor LT (DDLT) setting, expansion of the criteria is relatively tempered because the results of LT for HCC should be comparable to those of patients with non-malignant indications. On the other hand, in living donor LT (LDLT) situation, liver grafts are not public resources. The acceptable target outcomes for LDLT might be much lower than those for DDLT. Patients with biologically favorable tumors might have excellent survivals after LT despite morphological advanced HCCs. Therefore, the significance and utility of biological tumor parameters for selecting suitable LT candidates have been increased to predict HCC recurrence after LT. Although there is no consensus regarding the use of prognostic biomarkers in LT selection criteria for HCC, the combination of conventional morphological parameters and new promising biomarkers could help us refine and expand the LT criteria for HCC in the near future.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Liver Transplantation; Neoplasm Recurrence, Local; Neoplasm Staging; Patient Selection; Positron-Emission Tomography
PubMed: 27729631
DOI: 10.3350/cmh.2016.0042 -
World Journal of Gastroenterology Jun 2017Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. However, there are several case reports resulted in the regression of hepatocellular... (Review)
Review
Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. However, there are several case reports resulted in the regression of hepatocellular carcinoma (HCC) and the accumulation of clinical information and analyses of the mechanism can contribute to the development of a novel therapy. For this purpose, we have carefully reviewed 23 cases of spontaneously regressed HCC published in recent 5 years and our case. The information regarding the tumor size, tumor marker, treatments, ., have been summarized. The mechanism of spontaneous regression has been discussed to date and presumed to be due to many factors, including hypoxia and immunological reactions. In this careful review of the 24 cases based on the clinical information, hypoxia, systemic inflammation, and both upon spontaneous regression were seen in 3, 8, and 4 cases, respectively among the 15 cases for which the information regarding the proposed mechanisms are available. Recent development of immunotherapeutic approaches in oncology shows promising results, therefore, accumulation of additional cases and analysis of mechanisms underlying the spontaneous regression of HCC are essential and could lead to the development of a new generation of immunotherapies including antibodies directed against immune reactions.
Topics: Antibodies; Carcinoma, Hepatocellular; Cell Hypoxia; Cytotoxicity, Immunologic; Humans; Immunotherapy; Liver; Liver Neoplasms; Neoplasm Regression, Spontaneous; Prognosis; T-Lymphocytes; Tomography, X-Ray Computed
PubMed: 28638219
DOI: 10.3748/wjg.v23.i21.3797