Comparing treatment modalities for hepatocellular carcinoma: the value of network meta-analyses

2022 ◽  
pp. 1-1
Author(s):  
Ronald Chow ◽  
Charles B. Simone ◽  
Meghan Pooja Jairam ◽  
Anand Swaminath ◽  
Gabriel Boldt ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Modalities ◽  
Meta Analyses

scholarly journals The GNAQ T96S Mutation Affects Cell Signaling and Enhances the Oncogenic Properties of Hepatocellular Carcinoma

2021 ◽  
Vol 22 (6) ◽  
pp. 3284
Author(s):  
Eugene Choi ◽  
Sung Jean Park ◽  
Gunhee Lee ◽  
Seung Kew Yoon ◽  
Minho Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Expression Vector ◽  
Signal Transduction Pathway ◽  
Inhibitory Effect ◽  
The Cancer Genome Atlas ◽  
Treatment Modalities ◽  
Protein Signaling ◽  
Wild Type ◽  
Anchorage Independent Growth ◽  
Mapk Pathways

Hepatocellular carcinoma (HCC), the most common malignant tumor in the liver, grows and metastasizes rapidly. Despite advances in treatment modalities, the five-year survival rate of HCC remains less than 30%. We sought genetic mutations that may affect the oncogenic properties of HCC, using The Cancer Genome Atlas (TCGA) data analysis. We found that the GNAQ T96S mutation (threonine 96 to serine alteration of the Gαq protein) was present in 12 out of 373 HCC patients (3.2%). To examine the effect of the GNAQ T96S mutation on HCC, we transfected the SK-Hep-1 cell line with the wild-type or the mutant GNAQ T96S expression vector. Transfection with the wild-type GNAQ expression vector enhanced anchorage-independent growth, migration, and the MAPK pathways in the SK-Hep-1 cells compared to control vector transfection. Moreover, cell proliferation, anchorage-independent growth, migration, and the MAPK pathways were further enhanced in the SK-Hep-1 cells transfected with the GNAQ T96S expression vector compared to the wild-type GNAQ-transfected cells. In silico structural analysis shows that the substitution of the GNAQ amino acid threonine 96 with a serine may destabilize the interaction between the regulator of G protein signaling (RGS) protein and GNAQ. This may reduce the inhibitory effect of RGS on GNAQ signaling, enhancing the GNAQ signaling pathway. Single nucleotide polymorphism (SNP) genotyping analysis for Korean HCC patients shows that the GNAQ T96S mutation was found in only one of the 456 patients (0.22%). Our data suggest that the GNAQ T96S hotspot mutation may play an oncogenic role in HCC by potentiating the GNAQ signal transduction pathway.

scholarly journals Combining tissue and circulating tumor DNA increases the detection rate of a CTNNB1 mutation in hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stine Karlsen Oversoe ◽  
Michelle Simone Clement ◽  
Britta Weber ◽  
Henning Grønbæk ◽  
Stephen Jacques Hamilton-Dutoit ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mutation Rate ◽  
Detection Rate ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Treatment Modalities ◽  
Advanced Hepatocellular Carcinoma ◽  
Tissue Samples ◽  
The Impact ◽  
Tumor Dna

Abstract Background and aims Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC. Methods We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up. Results In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients. Conclusion Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.

scholarly journals Current Trends and Characteristics of Hepatocellular Carcinoma in Patients with Autoimmune Liver Diseases

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1023
Author(s):  
Eirini I. Rigopoulou ◽  
George N. Dalekos
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Diseases ◽  
Treatment Modalities ◽  
Primary Biliary Cholangitis ◽  
Autoimmune Liver Diseases ◽  
Increased Risk ◽  
Liver Cancers ◽  
Medium Risk ◽  
Causes Of Mortality

Hepatocellular carcinoma (HCC), the commonest among liver cancers, is one of the leading causes of mortality among malignancies worldwide. Several reports demonstrate autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) to confer increased risk of hepatobiliary malignancies, albeit at lower frequencies compared to other liver diseases. Several parameters have been recognized as risk factors for HCC development in AIH and PBC, including demographics such as older age and male sex, clinical features, the most decisive being cirrhosis and other co-existing factors, such as alcohol consumption. Moreover, biochemical activity and treatment response have been increasingly recognized as prognostic factors for HCC development in AIH and PBC. As available treatment modalities are effective only when HCC diagnosis is established early, surveillance has been proven essential for HCC prognosis. Considering that the risk for HCC is not uniform between and within disease groups, refinement of screening strategies according to prevailing demographic, clinical, and molecular risk factors is mandated in AILDs patients, as personalized HCC risk prediction will offer significant advantage in patients at high and/or medium risk. Furthermore, future investigations should draw attention to whether modification of immunosuppression could benefit AIH patients after HCC diagnosis.

scholarly journals Diagnostic and therapeutic treatment modalities for acute lower gastrointestinal bleeding: a systematic review

2017 ◽  
Vol 05 (10) ◽  
pp. E959-E973 ◽  
Author(s):  
Kathryn Oakland ◽  
Jennifer Isherwood ◽  
Conor Lahiff ◽  
Petra Goldsmith ◽  
Michael Desborough ◽  
...  
Keyword(s):  
Gastrointestinal Bleeding ◽  
Flexible Sigmoidoscopy ◽  
Meta Analysis ◽  
Computed Tomographic Angiography ◽  
Lower Gastrointestinal Bleeding ◽  
Treatment Modalities ◽  
Computed Tomographic ◽  
Meta Analyses ◽  
Tomographic Angiography ◽  
Risk Ratios

Abstract Background and study aims Investigations for lower gastrointestinal bleeding (LGIB) include flexible sigmoidoscopy, colonoscopy, computed tomographic angiography (CTA), and angiography. All may be used to direct endoscopic, radiological or surgical treatment, although their optimal use is unknown. The aims of this study were to determine the diagnostic and therapeutic yields of endoscopy, CTA, and angiography for managing LGIB, and their influence on rebleeding, transfusion, and hospital stay. Patients and methods A systematic search of MEDLINE, PubMed, EMBASE, and CENTRAL was undertaken to identify randomized controlled trials (RCTs) and nonrandomized studies of intervention (NRSIs) published between 2000 and 12 November 2015 in patients hospitalized with LGIB. Separate meta-analyses were conducted, presented as pooled odds (ORs) or risk ratios (RR) with 95 % confidence intervals (CIs). Results Two RCTs and 13 NRSIs were included, none of which examined flexible sigmoidoscopy, or compared endotherapy with embolization, or investigated the timing of CTA or angiography. Two NRSIs (57 – 223 participants) comparing colonoscopy and CTA were of insufficient quality for synthesis but showed no difference in diagnostic yields between the two interventions. One RCT and 4 NRSIs (779 participants) compared early colonoscopy (< 24 hours) with colonoscopy performed later; meta-analysis of the NRSIs demonstrated higher diagnostic and therapeutic yields with early colonoscopy (OR 1.86, 95 %CI 1.12 to 2.86, P = 0.004 and OR 3.08, 95 %CI 1.93 to 4.90, P < 0.001, respectively) and reduced length of stay (mean difference 2.64 days, 95 %CI 1.54 to 3.73), but no difference in transfusion or rebleeding. Conclusions In LGIB there is a paucity of high-quality evidence, although the limited studies on the timing of colonoscopy suggest increased rates of diagnosis and therapy with early colonoscopy.

A year of hepatocellular carcinoma at a glance. Demographics, biochemical and radiological characteristics and treatment modalities from a specialized facility of Pakistan

2021 ◽  
pp. 1-6
Author(s):  
Laima Alam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cross Sectional Study ◽  
Treatment Modalities ◽  
Fisher Exact Test ◽  
Tumour Staging ◽  
Chi Square ◽  
Cross Sectional ◽  
Exact Test ◽  
Team Meetings ◽  
Contrast Enhanced Ct

Objectives:Relation of demographics of hepatocellular-carcinoma with the aetiology.Tumour characteristics in relation to anti-viral therapy and presence of viral-DNA/RNATreatment modalities offeredMethods: This cross-sectional study enrolled all the patients aged 18-70 years with diagnosed hepatocellular carcinoma either through Triphasic Contrast-Enhanced-CT scan and/or Magnetic Resonance Imaging or biopsy presenting to the Outpatient-Department or multi-disciplinary-team meetings for the year 2019. Demographic variables, biochemical analysis including liver profile and stage of cirrhosis, viral-status, tumour staging and the treatment modalities offered were all noted. ANOVA (normal) and Kruskal-Wallis (non-normal) tests were used to compare quantitative data whereas chi-square-test and fisher-exact-test were used to compare qualitative-data.Results: Out of 195 patients with hepatocellular carcinoma, 76% were males in their fifth to sixth decades of life, 96% had cirrhosis, 94% corresponded to viral hepatocellular-carcinoma (82% Hepatitis-C-Virus, 9% Hepatitis-B-Virus and 3% coinfection), 60% of the cirrhotics landed in Child-Pugh A category with tumour staging BCLC-B being the predominant one (43.6%) and single and multiple bilateral nodules were the commonest lesions encountered. Platelets and Alanine-Transaminase had a significant relation across aetiological groups. Lymph-nodes were the most common extra-hepatic organs for metastasis and the presence of viral PCR had a significant impact on the tumour aggressiveness. Thirty-two percent of the patients were amenable to curative treatment.Conclusion: Viral infection is the main cause of rising prevalence of this tumour in Pakistan. Treatment modalities are expensive and expertise are lacking. A nationwide cancer registry is required for the exact disease burden and tumour behaviour for our population. Continuous....

scholarly journals The contribution of serum hepatitis B virus load in the carcinogenesis and prognosis of hepatocellular carcinoma: evidence from two meta-analyses

Oncotarget ◽  
2016 ◽  
Vol 7 (31) ◽  
pp. 49299-49309 ◽  
Author(s):  
Xueqin Chen ◽  
Fan Wu ◽  
Yanmei Liu ◽  
Jiao Lou ◽  
Beibei Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Serum Hepatitis ◽  
Virus Load ◽  
B Virus ◽  
Meta Analyses

scholarly journals How Much Time Should Be Waited and What Are the Main Findings to Evaluate the Hepatocellular Carcinoma Response to Regorafenib? A Real-Life Experience

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Gustavo Hideki Kawanami ◽  
Leopoldo Katsuda ◽  
Thiara Barcelos Rocha ◽  
Fabio da Silva Yamashiro ◽  
Leonardo Pelafsky ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Kinase Inhibitors ◽  
Life Experience ◽  
Real Life ◽  
Treatment Modalities ◽  
Screening Methods ◽  
Second Line ◽  
Imaging Findings ◽  
Sorafenib Treatment

Background. Hepatocellular carcinoma is a relevant cause of mortality worldwide, mainly among patients who have a prior liver disease. In spite of clear recommendations regarding surveillance and screening methods, most patients are still diagnosed only when they are no longer candidates to curative treatment modalities, while others do not achieve the goals of such treatments, thus increasing the need of anticancer drugs. Moreover, when cirrhotic patients begin to receive these drugs, many types of adverse events are seen as a reason to withdrawal, even when there are findings suggesting a good response to the treatment. Case Summary. This case report is about a cirrhotic patient who received many types of treatment, from surgery and chemoembolization during early stages to first- and second-line systemic therapy when the disease turned to be advanced. Since he had no signs of liver dysfunction and suffered tumor progression during sorafenib treatment, regorafenib was initiated. The main findings that make this case important are the adverse events after taking this second-line agent, which would certainly be considered unacceptable and would lead to the drug withdrawal. The reasons why regorafenib was maintained are explained based on clinical and imaging findings, showing how this decision led to an excellent response. Conclusions. The knowledge of the main adverse events described in the pilot clinical trials can avoid unnecessary withdrawal of regorafenib. In addition, some clinical and imaging findings can be deemed as predictors of good response to tyrosine kinase inhibitors.

Medical Treatment of Hepatocellular Carcinoma: Any Progress?

1994 ◽  
Vol 80 (5) ◽  
pp. 315-326 ◽  
Author(s):  
Marco Colleoni ◽  
Fernando Gaion ◽  
Guido Liessi ◽  
Giorgio Mastropasqua ◽  
Patrizia Nelli ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Options ◽  
Arterial Embolization ◽  
Percutaneous Ethanol Injection ◽  
High Response Rate ◽  
New Drugs ◽  
Treatment Modalities ◽  
Ethanol Injection ◽  
Hormonal Manipulation ◽  
Number Of Patients

Background Hepatocellular carcinoma (HCC) remains one of the most common neoplasms worldwide. Curative treatment options include liver transplantation or resection. Unfortunately, most patients still have unresectable or untransplantable HCC due to disease extension or comorbid factors and are therefore candidate only for palliative treatments. Methods In this review we have analyzed the different medical approaches employed in the treatment of HCC in an attempt to better define their roles. Results Palliative medical treatments including systemic chemotherapy, immunotherapy or hormonal manipulation rarely influence survival of the patients. Although a high response rate is often reported with new local therapies such as transcatheter arterial embolization, intraarterial chemotherapy or percutaneous ethanol injection, the real impact of these treatment modalities on patient survival remains to be determined. Conclusion One way to improve the diagnosis of HCC patients would be an appropriate approach to evaluate new drugs or treatment modalities. To answer all the open questions, further trials, possibly randomized, should be conducted on a substantial number of patients with homogeneous prognostic factors.

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