Treatment Of Early Hepatocellular Carcinoma Research Articles

Effectiveness and Safety of Radiofrequency Ablation versus Liver Resection in the Treatment of Early-stage Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

To systematically evaluate the efficacy and safety of radiofrequency ablation and liver resection in the therapeutic management of early-stage hepatocellular carcinoma. We conducted a comprehensive search of domestic and foreign databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang to retrieve literature on radiofrequency ablation and liver resection for the treatment of early hepatocellular carcinoma. The retrieved literature underwent thorough screening, and relevant data were extracted. Following the evaluation of the literature's quality, Meta-analysis was performed using RevMan 5.4 software. In this study, a total of 11 documents were selected, comprising 1334 patients with hepatocellular carcinoma. Meta-analysis results indicated that there was no statistically significant difference in the 1-year overall survival rate [Relative risk (RR) = 1.01, 95% confidence intervals (CI) (0.98; 1.04)] and the 3-year overall survival rate [RR = 0.95, 95% CI (0.90; 1.01)] between the radiofrequency ablation and liver resection groups (p > 0.05). Similarly, there was no statistically significant difference in the 1-year disease-free survival rate [RR = 0.94, 95% CI (0.87; 1.01)] between the two groups. However, the 3-year disease-free survival rate [RR = 0.84, 95% CI (0.74; 0.96)] of patients in the radiofrequency ablation group was significantly lower than that in the hepatectomy group (p < 0.05). Notably, the incidence of complications [RR = 0.42, 95% CI (0.33; 0.55)] was significantly lower in the radiofrequency ablation group compared to the hepatectomy group. Conversely, the local recurrence rate [RR = 1.45, 95% CI (1.22; 1.73)] was significantly higher in the radiofrequency ablation group compared to the hepatectomy group (p < 0.05). During the treatment of hepatocellular carcinoma, hepatectomy demonstrates superior clinical efficacy compared to radiofrequency ablation, particularly in its ability to control tumor recurrence. However, radiofrequency ablation presents with fewer complications and a higher level of safety. These findings can serve as a valuable foundation for clinicians when selecting the most suitable treatment approaches for liver cancer.

Loco-regional therapies competing with radiofrequency ablation in potential indications for hepatocellular carcinoma: a network meta-analysis.

There is no clear consensus on the relative ranking of interventional and radiation techniques with indications similar to those of radiofrequency ablation (RFA) for the treatment of early hepatocellular carcinoma (HCC). We used a network meta-analysis to compare the efficacy of non-surgical treatments for early HCC. We searched databases for randomized trials assessing the efficacy of loco-regional treatments for HCCs ≤5 cm with no extrahepatic spread or portal invasion. The primary outcome was the pooled hazard ratio (HR) for overall survival (OS), and secondary outcomes included overall and local progression-free survival (PFS). A frequentist network meta-analysis was performed, and the relative ranking of therapies was assessed with P-scores. Nineteen studies comparing 11 different strategies in 2,793 patients were included. Chemoembolization plus RFA improved OS better than RFA alone (HR 0.52, 95% confidence interval [CI] 0.33-0.82; P-score=0.951). Cryoablation, microwave ablation, laser ablation, and proton beam therapy had similar effects on OS compared with RFA. For overall PFS, but not local PFS, only chemoembolization plus RFA performed significantly better than RFA (HR 0.61, 95% CI 0.42-0.88; P-score=0.964). Injection of percutaneous ethanol or acetic acid was significantly less effective than RFA for all measured outcomes, while no differences in progression outcomes were identified for other therapies included in the network. Our results suggest that chemoembolization combined with RFA is the best option for local treatment of early HCC. Cases with potential contraindications for RFA may benefit from a tailored approach using thermal or radiation modalities.

Multi-database Based Study of the Pharmacological Mechanisms of Resveratrol in the Treatment of Early Hepatocellular Carcinoma

Multi-database Based Study of the Pharmacological Mechanisms of Resveratrol in the Treatment of Early Hepatocellular Carcinoma

Hepatic resection versus microwave ablation for the treatment of early hepatocellular carcinoma: a comparative analysis of treatment outcomes and survival predictors

IntroductionLiver resection and local ablation are the two primary curative treatments for early-stage hepatocellular carcinoma (HCC). Microwave ablation (MWA) shows promising performance in terms of early tumor response, recurrence, and survival. This study aims to determine whether MWA would be comparable to liver resection in treating early-stage HCC.MethodsThis study included patients with hepatitis C-related HCC attending the multidisciplinary HCC clinic, Kasr Al-Ainy Hospital (March 2018 to September 2020). We included adults with early-stage HCC (BCLC stages 0-A). We studied patients and tumor characteristics, HCC treatment response, recurrence, and overall survival.ResultsThirty-one patients were treated with liver resection and 41 patients were treated with MWA, including 4 patients who received intraoperative MWA. By the end of the study, 21 patients (28.77%) died. Patients who underwent MWA were younger compared to the hepatectomy group with lower baseline AFP (21 (6.7–54) versus 77 (31.3–136.0), respectively, (P value 0.024) and tumor size (2.78 (0.87) cm versus 3.77 (0.97) cm, respectively, (P value < 0.001). We found no differences between the studied groups in terms of treatment response, post-treatment decompensation, recurrence, or overall survival. One-year survival probability in the MWA and resection groups was 75.5% and 76.3% respectively. Post-procedure hepatic decompensation was the only independent predictor of lower survival by multivariate logistic regression analysis (OR 37.74, 95%CI 6.251–227.87, P value < 0.001) after adjusting for age, AFP, and tumor size.ConclusionLiver resection and MWA showed similar satisfactory results in the treatment of early-stage HCC, in terms of treatment response, recurrence, and overall survival.

Risk factors for the recurrence of early hepatocellular carcinoma treated by percutaneous radiofrequency ablation with a multiple-electrode switching system: a multicenter prospective study

Purpose To investigate the long-term efficacy of radiofrequency ablation (RFA) with a multiple-electrode switching system (MESS) in the treatment of early hepatocellular carcinoma (HCC) and evaluate the patterns and risk factors of intrahepatic recurrence of HCC after RFA. Methods In total, 139 patients with early HCC who underwent RFA with MESS as primary treatment at multiple centers were prospectively enrolled according to the inclusion criteria. We evaluated the local tumor progression (LTP), intrahepatic distant recurrence (IDR), the incidence of cumulative disease-free survival (DFS), LTP-free survival, IDR-free survival, and overall survival. We also analyzed the associated risk factors. Results A total of 139 patients were included in the study and the median follow-up time was 64 months, ranging from 11 to 72 months. The complete ablation rate was 98.56%. Sixty-nine (49.64%) were found to have intrahepatic recurrence (LTP, n = 15; IDR, n = 55) during follow-up. The 1-year, 3-year and 5-year cumulative DFS, LTP-free survival, and IDR-free survival rates were 74.82, 94.46 and 78.75%; 54.68, 88.03 and 61.79%; and 51.80, 85.67 and 60.17%, respectively. In the multivariable analysis, tumor size > 4 cm was the only important risk factor for LTP. The alkaline phosphatase (ALP) level and the number of tumors were independent risk factors for IDR; α-fetoprotein (AFP) level > 400 µg/L and recurrence interval were risk factors for the overall survival period. Conclusions The MESS-RFA is an effective method for local control of tumors in early HCC. Early HCC with multiple high-ALP tumors has a higher rate of recurrence, which mainly occurs in an IDR pattern. Early HCC with high AFP levels and a shorter initial recurrence interval resulted in a poorer prognosis. Thus, treatments such as liver transplantation or surgical resection may be a good strategy in those cases. ClinicalTrials.gov ID NCT02046356.

Preferred Treatment with Curative Intent for Left Lateral Segment Early Hepatocellular Carcinoma under the Era of Minimal Invasive Surgery.

Background: Hepatocellular carcinoma (HCC) occurring at the left lateral segment (LLS) is relatively susceptible to treatment with curative intent in terms of tumor location. However, outcomes might vary depending on the selection of treatment modalities. This study aimed to analyze patients who had undergone curative treatment for early HCC at LLS. Methods: A retrospective analysis of 179 patients who underwent curative treatment for early HCC at LLS was performed. Patients were grouped based on treatment modalities, including radiofrequency ablation (RFA) and liver resection (LR). The long-term outcomes of the two groups were compared. Additionally, the impact of the LR approach on patient outcomes was analyzed. Results: Among these patients, 60 received RFA and 119 underwent LR as primary treatment with curative intent. During follow-up, a significantly higher incidence of HCC recurrence was observed in the RFA group (37/60, 61.7%) than in the LR group (45/119, 37.8%) (p = 0.0025). The median time of HCC recurrence was 10.8 (range: 1.1–60.9 months) and 17.6 (range: 2.4–94.8 months) months in the RFA and LR groups, respectively. In addition, multivariate analysis showed that liver cirrhosis, multiple tumors, and RFA treatment were significant risk factors for HCC recurrence. The 1-, 2-, and 5-year overall survival rates in the RFA and LR groups were 96.4%, 92.2%, and 71.5% versus 97.3%, 93.6%, and 87.7%, respectively. (p = 0.047). Moreover, outcomes related to LR were comparable between laparoscopic and conventional open methods. The 1-, 2-, and 5-year recurrence free survival rates in the laparoscopic (n = 37) and conventional open (n = 82) LR groups were 94.1%, 82.0%, and 66.9% versus 86.1%, 74.6%, and 53.1%, respectively. (p = 0.506) Conclusion: Early HCC at LLS had satisfactory outcomes after curative treatment, in which LR seems to have a superior outcome, as compared to RFA treatment. Moreover, laparoscopic LR could be considered a preferential option in the era of minimally invasive surgery.

Comparative Study of Laparoscopic Hepatectomy, Open Hepatectomy and Percutaneous Radiofrequency Ablation for Small Hepatocellular Carcinoma: An Ancillary Study of Randomized Controlled Trial (SURF Trial)

Introduction: To evaluate the efficacy of laparoscopic hepatectomy (LH) for small hepatocellular carcinoma (≤3 tumors within 3 cm), we compared short- and long-term outcomes between LH, open hepatectomy (OH), and radiofrequency ablation (RFA) as an ancillary study of a nationwide multicenter randomized controlled trial (RCT), SURF trial. Methods: This study enrolled 398 patients who underwent treatment of early hepatocellular carcinoma (HCC): SURF RCT: n=137, SURF cohort: n=261. Primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Secondary endpoints were short-term outcomes, and relationship between tumor conditions and prognosis by each therapy. Results: There were 38 patients in the LH group, 139 patients in the OH group, and 221 patients in the RFA group. Clinicopathological data were adjusted using an inverse probability of treatment-weighted analysis. The 5-year rates of RFS and OS were not significantly different in the LH, OH, and RFA groups: 50%, 41.6%, and 41.8%, respectively (p=0.89); 85.2%, 80.1%, and 80.1%, respectively (p=0.83). The median postoperative hospital stays in the LH, OH, and RFA groups were 11, 13, and 7 days (p <0.01). The OH rate was significantly higher than RFA for the following factors: maximum tumor diameter >2 cm (OR=3.13; 95% CI=1.72–5.69), proximity to major vessels (OR=2.08; 95% CI=1.01–4.30), and good liver function (OR=0.46; 95% CI=0.22–0.93). Conclusions: Prognosis after LH for early HCC treatment was not significantly different from that of OH and RFA. LH is a feasible and effective treatment for early HCC with wide variety of tumor conditions.

Diagnostic Accuracy of Circular RNAs in Different Types of Samples for Detecting Hepatocellular Carcinoma: A Meta-Analysis.

The lack of accurate biomarkers impeded the screening, diagnosis and early treatment of hepatocellular carcinoma (HCC). As a result of the development of high-throughput transcriptome analysis techniques, circular RNAs, a newly discovered class of noncoding RNAs, were recognized as potential novel biomarkers. This meta-analysis was performed to update the diagnostic roles of circular RNAs for HCC. We acquired 23 articles from PubMed, Web of Science, EMBASE, and Cochrane Library databases up to September 2021. The overall sensitivity was 0.80 (95% CI: 0.77–0.84), and the specificity was 0.83 (95% CI: 0.79–0.85), with an AUC of 0.88 (0.85–0.91). Considering of the significant heterogeneity, studies were divided into four groups based on the control types. The circular RNAs in exosomes had a sensitivity of 0.69 (95% CI: 0.61–0.75), and a highest specificity of 0.91 (95% CI: 0.83–0.96). The pooled sensitivity of circular RNAs in serum/plasma was 0.84 (95% CI: 0.81–0.87), and the pooled specificity was 0.83 (95% CI: 0.79–0.86). The pooled sensitivity of circular RNAs distinguishing tumor tissue from chronic hepatitis/cirrhosis tissues was 0.56 (95% CI: 0.48–0.64), and specificity was 0.76 (95% CI: 0.67–0.82). When the controls were adjacent tissues, the sensitivity was 0.78 (95% CI: 0.70–0.84), and the specificity was 0.78 (95% CI: 0.71–0.85). Hsa_circ_0001445 with a pooled sensitivity of 0.81, a specificity of 0.76 and an AUC of 0.85 in two studies, might be a suitable diagnostic blood biomarker for HCC. Relying on function in HCC, the AUC of subgroups were 0.88 (95%CI: 0.84–0.90) (function group) and 0.87 (95%CI: 0.84–0.90) (unknown function group). As for only reported in HCC or not, these circular RNAs had an AUC of 0.89 (95%CI: 0.86–0.91) (only in HCC) and 0.85 (95%CI: 0.82–0.88) (not only in HCC). In conclusion, the results suggested that circular RNAs were acceptable biomarkers for detecting HCC, especially those circular RNAs existing in exosomes or serum/plasma.

Predictors of recurrence in early hepatocellular carcinoma patients treated with surgical resection

AbstractAlthough surgical resection is a curative treatment for early hepatocellular carcinoma (HCC), the incidence of recurrence is still high. The factors associated with HCC recurrence are unclear and deserve investigation. The early HCC patients receiving surgical resection in Taipei Tzu Chi Hospital were enrolled retrospectively. Those with histologically microvascular invasion and largest tumor size &gt;5 cm were excluded. Aggressive recurrence was defined as multiple recurrence (&gt;3), invasion to vessel or extrahepatic metastasis at the first time of recurrence. A total of 125 HCC patients (86 male; mean age 68.74 ± 11.57 year‐old) were included for final analysis. The survival rate was 96%, 91.2%, and 89.6%, at year 1, 3, and 5, respectively. Sixty one (48.8%) patients had HCC recurrence during the median follow‐up duration of 4.4 years. Of them, aggressive recurrence was present in 17 (27.4%) patients. Among patients with recurrent HCC, those with aggressive recurrence had worse survival rates than those without (P = .008). Multifocal tumor was the predictor associated with HCC recurrence using logistic regression analysis; tumor size was associated with earlier recurrence in aggressive recurrence of HCC using stepwise method (P = .042). Although early HCC patients had satisfactory 5‐year survival rates after surgical resection, the incidence of HCC recurrence was still high. The presence of aggressive recurrence had a negative impact on overall survival. Multifocal tumor in histology has higher risk of HCC recurrence, but not the pathologic grade of differentiation. Tumor size was associated with early recurrence in HCC patients with aggressive recurrence.

Dipeptidyl Peptidase Inhibition Enhances CD8 T Cell Recruitment and Activates Intrahepatic Inflammasome in a Murine Model of Hepatocellular Carcinoma.

Simple SummaryThis study reported, for the first time, on the expression and activity of the dipeptidyl peptidase 4 (DPP4) family during the development of hepatocellular carcinoma (HCC). We also demonstrated that the pan-DPP inhibitory compound ARI-4175 significantly reduced the number of macroscopic liver nodules in a mouse HCC model. ARI-4175 increased intrahepatic inflammatory cell infiltration, CD8+ T cell numbers and caspase-1-mediated inflammasome activation in the HCC-bearing liver. Thus, this study provides promising data on the efficacy of ARI-4175 in the treatment of early-stage HCC. Targeting the DPP4 family may be a novel and effective approach to promote anti-tumour immunity in HCC via caspase-1 activation.The mRNA expression of the dipeptidyl peptidase 4 (DPP4) gene family is highly upregulated in human hepatocellular carcinoma (HCC) and is associated with poor survival in HCC patients. Compounds that inhibit the DPP4 enzyme family, such as talabostat and ARI-4175, can mediate tumour regression by immune-mediated mechanisms that are believed to include NLRP1 activation. This study investigated the expression and activity of the DPP4 family during the development of HCC and evaluated the efficacy of ARI-4175 in the treatment of early HCC in mice. This first report on this enzyme family in HCC-bearing mice showed DPP9 upregulation in HCC, whereas intrahepatic DPP8/9 and DPP4 enzyme activity levels decreased with age. We demonstrated that ARI-4175 significantly lowered the total number of macroscopic liver nodules in these mice. In addition, ARI-4175 increased intrahepatic inflammatory cell infiltration, including CD8+ T cell numbers, into the HCC-bearing livers. Furthermore, ARI-4175 activated a critical component of the inflammasome pathway, caspase-1, in these HCC-bearing livers. This is the first evidence of caspase-1 activation by a pan-DPP inhibitor in the liver. Our data suggest that targeting the DPP4 enzyme family may be a novel and effective approach to promote anti-tumour immunity in HCC via caspase-1 activation.

Differences in the presentation and treatment of primary liver tumors at a hepatology center and an oncology center.

Primary liver cancer is a public health problem in Mexico and the world. Liver transplantation (LT) is the ideal treatment for early hepatocellular carcinoma (HCC). Our aim was to evaluate the characteristics of patients with HCC and cholangiocarcinoma (CC) at two centers and identify transplantation candidates. A retrospective observational study was conducted at the Hepatology Center (HC) and the University Center Against Cancer (UCAC), within the time frame of 2012-2018. HCC or intrahepatic CC was confirmed in 109 patients. Staging classifications, transplant selection models, and a predictive model for post-LT recurrence were applied to the HCC patients. Of the total population, 93% (n = 102) presented with cirrhosis, 86% (n = 94) had HCC (HC: 58%, UCAC: 42%), and 14% (n = 15) had intrahepatic CC (HC: 40%, UCAC: 60%). Of the HC patients with HCC, Okuda I-II, BCLC A-B, and AFP levels < 100 ng/m predominated, whereas Okuda II-III, BCLC C-D, and AFP levels > 1,000 ng/mL predominated in the UCAC patients. Half of the HC population with HCC met the criteria for LT, in contrast to 23% of the UCAC patients. Fifteen patients were evaluated for LT, and at present, six have undergone transplantation. The most frequent primary liver tumor was HCC. Patients from the HC presented with earlier-stage disease and a high number of them met the criteria for LT. Only patients from the HC underwent transplantation.

Differences in the presentation and treatment of primary liver tumors at a hepatology center and an oncology center

Introduction and aimsPrimary liver cancer is a public health problem in Mexico and the world. Liver transplantation (LT) is the ideal treatment for early hepatocellular carcinoma (HCC). Our aim was to evaluate the characteristics of patients with HCC and cholangiocarcinoma (CC) at two centers and identify transplantation candidates. Materials and methodsA retrospective observational study was conducted at the Hepatology Center (HC) and the University Center Against Cancer (UCAC), within the time frame of 2012–2018. HCC or intrahepatic CC was confirmed in 109 patients. Staging classifications, transplant selection models, and a predictive model for post-LT recurrence were applied to the HCC patients. ResultsOf the total population, 93% (n=102) presented with cirrhosis, 86% (n=94) had HCC (HC: 58%, UCAC: 42%), and 14% (n=15) had intrahepatic CC (HC: 40%, UCAC: 60%). Of the HC patients with HCC, Okuda I–II, BCLC A–B, and AFP levels <100ng/m predominated, whereas Okuda II-III, BCLC C-D, and AFP levels >1000ng/mL predominated in the UCAC patients. Half of the HC population with HCC met the criteria for LT, in contrast to 23% of the UCAC patients. Fifteen patients were evaluated for LT, and at present, six have undergone transplantation. ConclusionsThe most frequent primary liver tumor was HCC. Patients from the HC presented with earlier-stage disease and a high number of them met the criteria for LT. Only patients from the HC underwent transplantation.

Medicare/Medicaid Insurance, Rurality, and Black Race Associated With Provision of Hepatocellular Carcinoma Treatment and Survival.

Early treatment of hepatocellular carcinoma (HCC) is associated with improved survival, but many patients with HCC do not receive therapy. We aimed to examine factors associated with HCC treatment and survival among incident patients with HCC in a statewide cancer registry. All patients with HCC from 2003 through 2013 were identified in the North Carolina cancer registry. These patients were linked to insurance claims from Medicare, Medicaid, and large private insurers in North Carolina. Associations between prespecified covariates and more advanced HCC stage at diagnosis (ie, multifocal cancer), care at a liver transplant center, and provision of HCC treatment were examined using multivariate logistic regression. A Cox proportional hazards model was developed to assess the association between these factors and survival. Of 1,809 patients with HCC, 53% were seen at a transplant center <90 days from diagnosis, with lower odds among those who were Black (adjusted odds ratio [aOR], 0.54; 95% CI, 0.39-0.74), had Medicare insurance (aOR, 0.35; 95% CI, 0.21-0.59), had Medicaid insurance (aOR, 0.46; 95% CI, 0.28-0.77), and lived in a rural area; odds of transplant center visits were higher among those who had prediagnosis alpha fetoprotein screening (aOR, 1.74; 95% CI, 1.35-2.23) and PCP and gastroenterology care (aOR, 1.66; 95% CI, 1.27-2.18). Treatment was more likely among patients who had prediagnosis gastroenterology care (aOR, 1.68; 95% CI, 0.98-2.86) and transplant center visits (aOR, 2.42; 95% CI, 1.74-3.36). Survival was strongly associated with age, cancer stage, cirrhosis complications, and receipt of HCC treatment. Individuals with Medicare (adjusted hazard ratio [aHR], 1.58; 95% CI, 1.20-2.09) and Medicaid insurance (aHR, 1.55; 95% CI, 1.17-2.05) had shorter survival than those with private insurance. In this population-based cohort of patients with HCC, Medicare/Medicaid insurance, rural residence, and Black race were associated with lower provision of HCC treatment and poorer survival. Efforts should be made to improve access to care for these vulnerable populations.

New frontiers in liver resection for hepatocellular carcinoma.

SummaryLiver resection is one of the main curative options for early hepatocellular carcinoma (HCC) in patients with cirrhosis and is the treatment of choice in non-cirrhotic patients. However, careful patient selection is required to balance the risk of postoperative liver failure and the potential benefit on long-term outcomes. In the last decades, improved surgical techniques and perioperative management, as well as better patient selection, have enabled the indications for liver resection to be expanded. In this review, we aim to describe the main indications for liver resection in the management of HCC, its role compared to percutaneous ablation and liver transplantation in the therapeutic algorithm, as well as the recent advances in liver surgery that could be used to improve the prognosis of patients with HCC.

En Bloc lumpectomy of T12 vertebra for progressive hepatocellular carcinoma metastases following liver transplantation

Rationale:Liver transplantation (LT) is the preferred surgical option for the treatment of early hepatocellular carcinoma (HCC). In contrast, surgical treatment of progressive HCC metastasized to the spine following LT constitutes a considerable challenge. Here, we report the first case of progressive HCC metastasized to the T12 vertebra after local radiotherapy, treated successfully with en bloc lumpectomy following LT for HCC.Patient concerns:A 40-year-old man who had undergone LT for the treatment of HCC 2 months prior presented to our clinic with symptoms of progressive back pain. Magnetic resonance imagining (MRI) and positron emission tomography (PET) examinations showed a solitary metastasis at T12 without recurrence in the liver or metastasis to other organs.Diagnoses:The patient was diagnosed with HCC metastasized to the T12 vertebra after liver transplantation.Interventions:Local radiation therapy of the T12 vertebra was performed; however, the lesion continued to grow one month after irradiation. Accordingly, the patient was treated with en bloc lumpectomy of the T12 vertebra. After surgery, the patient reported significant pain relief. At 11 months post-surgery, a C4 metastasis with spinal cord compression was revealed by MRI. Multiple grafted liver metastases were also detected by ultrasound along with several lung metastases, which were discovered by X-ray. The patient was treated with a pedicle screw system and a mesh cage filled with frozen autografts for C4 metastasis.Outcomes:The patient died 15 months after liver transplantation due to recurrence in the liver and metastasis to the lung.Lessons:En bloc lumpectomy may be a viable therapeutic option for patients with progressive solitary spinal metastases after LT refractory to radiotherapy. Use of immunosuppressive therapy after LT may significantly inhibit immune function, making patients more susceptible to HCC recurrence and bone metastasis.

Short-term outcomes of surgical resection and radiofrequency in treatment of hepatocellular carcinoma

Backgroundand aim To evaluate surgical liver resection in comparison with radiofrequency in the treatment of early hepatocellular carcinoma (HCC) regarding intraoperative blood loss and transfusion, time of respectability, time of operation, ICU stay, hospital stay, postoperative morbidity, mortality, and overall survival.Introduction Surgical resection and radiofrequency ablation (RFA) in the treatment of HCC are different modalities for the treatment of HCC.Patients and methods This is a prospective study that included 60 patients with HCC randomized into hepatic resection and RFA groups at Al-Zahraa University Hospital from 2016 to 2019. Demographic and biochemical characteristics, intraoperative data, postsurgical complications, and overall survival rate were compared between groups.Results Surgical resection group had longer operative time, resection time, blood loss and blood transfusion, hospital stay, and ICU stay than RFA group. Postoperative hemorrhage, bile leak, and chest infection were markedly decreased in RFA group than surgical resection group. Wound infection and ascites are similar in the two patient groups. Regarding the median follow-up during the 3 years, there were no significant differences between the treatment groups in 1- and 3-year overall survival.Conclusion Surgical resection is considered the primary solution if the patient’s liver function and general conditions are good enough to undergo surgical intervention. RFA is considered superior to hepatic resection in the treatment of HCC in terms of operation duration and other complications like hemorrhage and bile leak. RFA revealed similar overall survival to surgical resection. RFA is accessible and a promising liver resection method with very good results.

A Noncoding Regulatory RNAs Network Driven by Circ-CDYL Acts Specifically in the Early Stages Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the fastest-rising causes of cancer-related death worldwide, but its deficiency of specific biomarkers and therapeutic targets in the early stages lead to severe inadequacy in the early diagnosis and treatment of HCC. Covalently closed circular RNA (circRNA), which was once considered an aberrant splicing by-product, is now drawing new interest in cancer research because of its remarkable functionality. Beneath the surface of the dominant functional proteins events, a hidden circRNA-centric noncoding regulatory RNAs network active in the very early stage of HCC is here revealed by a genome-wide analysis of mRNA, circRNA, and microRNA (miRNA) expression profiles. Circ-CDYL (chromodomain Y like) is specifically up-regulated in the early stages of HCC and therefore contributes to the properties of epithelial cell adhesion molecule (EPCAM)-positive liver tumor-initiating cells. Circ-CDYL interacts with mRNAs encoding hepatoma-derived growth factor (HDGF) and hypoxia-inducible factor asparagine hydroxylase (HIF1AN) by acting as the sponge of miR-892a and miR-328-3p, respectively. Subsequently, activation of the phosphoinositide 3-kinase (PI3K)-AKT serine/threonine kinase-mechanistic target of rapamycin kinase complex 1/β-catenin and NOTCH2 pathways, which promote the expression of the effect proteins, baculoviral IAP repeat containing 5 (BIRC5 or SURVIVIN) and MYC proto-oncogene, is influenced by circ-CDYL. A treatment incorporating circ-CDYL interference and traditional enzyme inhibitors targeting PI3K and HIF1AN demonstrated highly effective inhibition of stem-like characteristics and tumor growth in HCC. Finally, we demonstrated that circ-CDYL expression or which combined with HDGF and HIF1AN are both independent markers for discrimination of early stages of HCC with the odds ratios of 1.09 (95% confidence interval [CI], 1.02-1.17) and 124.58 (95% CI, 13.26-1170.56), respectively. Conclusion: These findings uncover a circRNA-centric noncoding regulatory RNAs network in the early stages of HCC and thus provide a possibility for surveillance and early treatment of HCC.

Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAAs. DAA-untreated patients from the ITA.LI.CA. cohort (n = 328) served as controls. After propensity score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared. In the DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in the DAA group compared to the No DAA group (hazard ratio [HR] 0.39; 95% CI0.17-0.91; p = 0.03). HCC recurrence was not significantly different between the DAA and No DAA groups (HR0.70; 95% CI0.44-1.13; p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in the DAA group compared with the No DAA group (HR0.32; 95% CI0.13-0.84; p = 0.02). In the DAA group, sustained virologic response was a significant predictor of OS (HR 0.02; 95% CI 0.00-0.19; p <0.001), HCC recurrence (HR 0.25; 95% CI 0.11-0.57; p <0.001) and hepatic decompensation (HR 0.12; 95% CI 0.02-0.38; p = 0.02). In patients with HCV-related cirrhosis who had been successfully treated for early HCC, DAAs significantly improved OS compared with No DAA treatment. We aimed to determine whether direct-acting antivirals (DAAs) significantly improve overall survival in patients with hepatitis C virus-related compensated cirrhosis and a first diagnosis of hepatocellular carcinoma (HCC) which has been successfully treated with curative resection or ablation. Using propensity-score matched patients, we found that DAAs improved overall survival and reduced the risk of hepatic decompensation. However, the risk of HCC recurrence was not significantly reduced.

Direct acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Background & Aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. Methods: We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAAs. DAA-untreated patients from the ITA.LI.CA. cohort (n = 328) served as controls. After propensity score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared. Results: In the DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in the DAA group compared to the No DAA group (hazard ratio [HR] 0.39; 95% CI0.17-0.91; p = 0.03). HCC recurrence was not significantly different between the DAA and No DAA groups (HR0.70; 95% CI0.44-1.13; p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in the DAA group compared with the No DAA group (HR0.32; 95% CI0.13-0.84; p = 0.02). In the DAA group, sustained virologic response was a significant predictor of OS (HR 0.02; 95% CI 0.00-0.19; p <0.001), HCC recurrence (HR 0.25; 95% CI 0.11-0.57; p <0.001) and hepatic decompensation (HR 0.12; 95% CI 0.02-0.38; p = 0.02). Conclusions: In patients with HCV-related cirrhosis who had been successfully treated for early HCC, DAAs significantly improved OS compared with No DAA treatment.

Effect of Donor Race-Matching on Overall Survival for African-American Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma

Liver transplantation (LT) is the preferred treatment for early hepatocellular carcinoma (HCC) in select patients. Differences in outcomes after LT have been previously described between recipient races, but the role of donor race is not well defined. This study sought to examine the effect of donor-recipient race-matching on overall survival after liver transplantation for HCC in African-American patients (AA). Adult AA patients with HCC undergoing liver transplantation were identified using the Organ Procurement and Transplantation Network database (1994 to 2015). Recipient and donor demographic and clinical characteristics were collected. Patients were separated into unadjusted cohorts based on whether the liver donor was AA (matched) or another race (unmatched). The primary outcome was overall survival, which was analyzed by log-rank test and graphed using the Kaplan-Meier method. Multivariate regression modeling was used to determine adjusted hazard ratios (HR) for overall survival. Of 1,384 AA patients identified, 325 (23.5%) were race-matched. Matched patients experienced significantly better median overall survival when compared with the unmatched cohort (135 vs 78 months, p= 0.007). Multivariate analysis revealed an adjusted hazard ratio of 0.66 for race-matched transplantation (95% CI 0.49 to 0.88; p= 0.004). Matched patients also experienced an improved 5-year survival (64.2% vs 56.9%; p= 0.019). African-American HCC patients undergoing liver transplantation experienced significantly improved overall survival when the donor race matched the recipient race. Donor-recipient race-matching remained an independent predictor of improved survival after adjusting for comorbidities and disease characteristics. Race-matching should be considered in the process of organ allocation because it may affect long-term survival in African-American HCC patients.