Resected Hepatocellular Carcinoma Patients Research Articles

Metabolic dysfunction-associated fatty liver disease increases the risk of complications after radical resection in patients with hepatocellular carcinoma

Background and aimsThe prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) in hepatocellular carcinoma (HCC) patients is increasing, yet its association with postoperative complications of HCC remains unclear. The aim of this study was to investigate the impact of MAFLD on complications after radical resection in HCC patients.MethodsPatients with HCC who underwent radical resection were included. Patients were stratified into MAFLD group and non-MAFLD group. Clinical features and post-hepatectomy complications were compared between the two groups, and logistic regression analysis was used to determine independent risk factors associated with post-hepatectomy complications.ResultsAmong the 936 eligible patients with HCC who underwent radical resection, concurrent MAFLD was diagnosed in 201 (21.5%) patients. Compared to the non-MAFLD group, the MAFLD group exhibited a higher incidence of complications, including infectious and major complications after radical resection in HCC patients. The logistic regression analysis found that MAFLD was an independent risk factor for complications, including infectious and major complications in HCC patients following radical resection (OR 1.565, 95%CI 1.109–2.343, P = 0.012; OR 2.092, 95%CI 1.386–3.156, P < 0.001; OR 1.859, 95% CI 1.106–3.124, P = 0.019; respectively). Subgroup analysis of HBV-related HCC patients yielded similar findings, and MAFLD patients with type 2 diabetes mellitus (T2DM) exhibited a higher incidence of postoperative complications compared to those without T2DM (all P < 0.05).ConclusionsConcurrent MAFLD was associated with an increased incidence of complications after radical resection in patients with HCC, especially MAFLD with T2DM.

Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion.

For resectable hepatocellular carcinoma (HCC), radical hepatectomy is commonly used as a curative treatment. However, postoperative recurrence significantly diminishes the overall survival (OS) of HCC patients, especially with microvascular invasion (MVI) as an independent high-risk factor for recurrence. While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients, the specific role of adjuvant therapies in those with MVI remains unclear. To conduct a network meta-analysis (NMA) to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen. A systematic literature search was conducted on PubMed, EMBASE, and Web of Science until April 6, 2023. Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included. Hazard ratios (HRs) with 95% confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA. Fourteen eligible trials (2268 patients) reporting five different therapies were included. In terms of reducing the risk of recurrence, radiotherapy (RT) [HR = 0.34 (0.23, 0.5); surface under the cumulative ranking curve (SUCRA) = 97.7%] was found to be the most effective adjuvant therapy, followed by hepatic artery infusion chemotherapy [HR = 0.52 (0.35, 0.76); SUCRA = 65.1%]. Regarding OS improvement, RT [HR: 0.35 (0.2, 0.61); SUCRA = 93.1%] demonstrated the highest effectiveness, followed by sorafenib [HR = 0.48 (0.32, 0.69); SUCRA = 70.9%]. Adjuvant therapy following hepatectomy may reduce the risk of recurrence and provide a survival benefit for HCC patients with MVI. RT appears to be the most effective adjuvant regimen.

Neoadjuvant Immune Checkpoint Inhibitors in hepatocellular carcinoma: a meta-analysis and systematic review.

Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular carcinoma (HCC) are currently lacking. This systematic review and meta-analysis aims to investigate the reliability of neoadjuvant immunotherapy's efficacy and safety in the context of HCC. A systematic search was conducted across PubMed (MEDLINE), EMBASE, the Web of Science, the Cochrane Library, and conference proceedings to identify clinical trials involving resectable HCC and neoadjuvant immunotherapy. Single-arm meta-analyses were employed to compute odds ratios and 95% confidence intervals (CIs). Heterogeneity analysis, data quality assessment, and subgroup analyses based on the type of immunotherapy drugs and combination therapies were performed. This meta-analysis is registered in PROSPERO (identifier CRD42023474276). This meta-analysis included 255 patients from 11 studies. Among resectable HCC patients, neoadjuvant immunotherapy exhibited an overall major pathological response (MPR) rate of 0.47 (95% CI 0.31-0.70) and a pathological complete response (pCR) rate of 0.22 (95% CI 0.14-0.36). The overall objective response rate (ORR) was 0.37 (95% CI 0.20-0.69), with a grade 3-4 treatment-related adverse event (TRAE) incidence rate of 0.35 (95% CI 0.24-0.51). Furthermore, the combined surgical resection rate was 3.08 (95% CI 1.66-5.72). Subgroup analysis shows no significant differences in the efficacy and safety of different single-agent immunotherapies; the efficacy of dual ICIs (Immune Checkpoint Inhibitors) combination therapy is superior to targeted combined immunotherapy and monotherapy, while the reverse is observed in terms of safety. Neoadjuvant immunotherapy presents beneficial outcomes in the treatment of resectable HCC. However, large-scale, high-quality experiments are warranted in the future to provide robust data support.

Aberrant Expressions of PSMD14 in Tumor Tissue are the Potential Prognostic Biomarkers for Hepatocellular Carcinoma after Curative Resection.

Hepatocellular carcinoma (HCC) has a high mortality rate, with curative resection being the primary treatment. However, HCC patients have a large possibility of recurrence within 5 years after curative resection. Thus, identifying biomarkers to predict recurrence is crucial. In our study, we analyzed data from CCLE, GEO, and TCGA, identifying eight oncogenes associated with HCC. Subsequently, the expression of 8 genes was tested in 5 cases of tumor tissues and the adjacent non-tumor tissues. Then ATP6AP1, PSMD14 and HSP90AB1 were selected to verify the expression in 63 cases of tumor tissues and the adjacent non-tumor tissues. The results showed that ATP6AP1, PSMD14, HSP90AB1 were generally highly expressed in tumor tissues. A five-year follow-up of the 63 clinical cases, combined with Kaplan-Meier Plotter's relapse-free survival (RFS) analysis, found a significant correlation between PSMD14 expression and recurrence in HCC patients. Subsequently, we analyzed the PSMD14 mutations and found that the PSMD14 gene mutations can lead to a shorter disease-free survival time for HCC patients. The results of enrichment analysis indicated that the differentially expressed genes related to PSMD14 are mainly enriched in the signal release pathway. In conclusion, our research showed that PSMD14 might be related to recurrence in HCC patients, and the expression of PSMD14 in tumor tissue might be a potential prognostic biomarker after tumor resection in HCC patients.

Does perioperative allogeneic blood transfusion worsen the prognosis of patients with hepatocellular carcinoma? A meta-analysis of propensity score-matched studies.

Allogeneic blood transfusion is required in a part of liver resection. The effect of allogeneic blood transfusion on the prognosis of patients with hepatocellular carcinoma (HCC) remains controversial. To investigate whether perioperative allogeneic blood transfusion (PBT) affects the long-term prognosis of patients with HCC, we conducted a meta-analysis that included only propensity score-matched (PSM) studies. The Cochrane Library, Embase, PubMed, and Web of Science databases were systematically searched to identify PSM studies that compared the long-term outcomes of allogeneic blood transfusion in resected HCC patients. Overall survival (OS) and recurrence-free survival (RFS) rates were calculated. This meta-analysis included 9 PSM studies with 12 datasets involving 2476 patients. Lower OS and RFS in HCC patients receiving allogeneic blood transfusion were observed than those in patients not receiving blood transfusion (OS: hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.10-1.64; p < 0.01; RFS: HR, 1.29; 95% CI, 1.07-1.56; p < 0.01). Subgroup analysis revealed that among patients with BCLC A HCC, those receiving allogeneic blood transfusion had lower OS and RFS (OS: HR, 2.27; 95% CI, 1.61-3.21; RFS: HR, 2.11; 95% CI, 1.30-3.41). OS and RFS were similar in both groups of patients with BCLC B and C HCC. The receipt of perioperative allogeneic blood transfusion is associated with a decrease in OS and RFS. These results seem to be reliable for patients in BCLC stage A. But more high-quality research is needed to confirm this conclusion.

Survival benefit of neoadjuvant hepatic arterial infusion chemotherapy followed by hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus.

Background/purpose: The prognosis of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) is generally poor and hepatectomy is optional for these patients. This study aims to explore the survival benefits of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) for resectable HCC with PVTT. Methods: This retrospective study included 120 resectable HCC patients with PVTT who underwent hepatectomy, from January 2017 to January 2021 at Sun Yat-sen University Cancer Center. Of these patients, the overall survival (OS) and recurrence-free survival (RFS) of 55 patients who received hepatectomy alone (Surgery group) and 65 patients who received neoadjuvant HAIC followed by hepatectomy (HAIC-Surgery group) were compared. Logistic regression analysis was conducted to develop a model predicting the response to neoadjuvant HAIC. Results: The OS rates for the HAIC-Surgery group at 1, 3, and 5years were 94.9%, 78%, and 66.4%, respectively, compared with 84.6%, 47.6%, and 37.2% in the Surgery group (p < 0.001). The RFS rates were 88.7%, 56.2%, and 38.6% versus 84.9%, 38.3%, and 22.6% (p = 0.002). The subgroup analysis revealed that the survival benefit of neoadjuvant HAIC was limited to patients who responded to it. The logistic model, consisting of AFP and CRP, that predicted the response to neoadjuvant HAIC performed well, with an area under the ROC curve (AUC) of 0.756. Conclusion: Neoadjuvant HAIC followed by hepatectomy is associated with a longer survival outcome than hepatectomy alone for HCC patients with PVTT and the survival benefit is limited to patients who respond to neoadjuvant FOLFOX-HAIC.

CT-derived extracellular volume and liver volumetry can predict posthepatectomy liver failure in hepatocellular carcinoma

ObjectivesPosthepatectomy liver failure (PHLF) is a severe complication of liver resection. We aimed to develop and validate a model based on extracellular volume (ECV) and liver volumetry derived from computed tomography (CT) for preoperative predicting PHLF in resectable hepatocellular carcinoma (HCC) patients.MethodsA total of 393 resectable HCC patients from two hospitals were enrolled and underwent multiphasic contrast-enhanced CT before surgery. A total of 281 patients from our hospital were randomly divided into a training cohort (n = 181) and an internal validation cohort (n = 100), and 112 patients from another hospital formed the external validation cohort. CT-derived ECV was measured on nonenhanced and equilibrium phase images, and liver volumetry was measured on portal phase images. The model is composed of independent predictors of PHLF. The under the receiver operator characteristic curve (AUC) and calibration curve were used to reflect the predictive performance and calibration of the model. Comparison of AUCs used the DeLong test.ResultsCT-derived ECV, measured future liver remnant (mFLR) ratio, and serum albumin were independent predictors for PHLF in resectable HCC patients. The AUC of the model was significantly higher than that of the ALBI score in the training cohort, internal validation cohort, and external validation cohort (all p < 0.001). The calibration curve of the model showed good consistency in the training cohort and the internal and external validation cohorts.ConclusionsThe novel model contributes to the preoperative prediction of PHLF in resectable HCC patients.Critical relevance statementThe novel model combined CT–derived extracellular volume, measured future liver remnant ratio, and serum albumin outperforms the albumin–bilirubin score for predicting posthepatectomy liver failure in patients with resectable hepatocellular carcinoma.Key points• CT-derived ECV correlated well with the fibrosis stage of the background liver.• CT-derived ECV and mFLR ratio were independent predictors for PHLF in HCC.• The AUC of the model was higher than the CT-derived ECV and mFLR ratio.• The model showed a superior predictive performance than that of the ALBI score.Graphical

Ultra-sensitive baseline-informed MRD assay to predict prognosis outcomes in patients with resectable hepatocellular carcinoma.

e16228 Background: The detection of minimal residual disease (MRD) has been shown to be a potential biomarker for the prognosis and post-surgery treatment of resectable hepatocellular carcinoma (HCC). However, the application of MRD in HCC has been limited by the traditional requirement of carrying out MRD over 30 days post-surgery, which is often incompatible with the time window for adjuvant treatment decisions. Additionally, MRD results may be impacted by post-surgery imbalances if assayed too soon after surgery. Methods: This retrospective study enrolled 255 early-stage HCC patients who received surgical resections and had complete information on relapse and survival. Matched tumor and normal tissue samples were collected at the time of surgery and plasma samples were collected as early as 7 days post-surgery. An ultra-sensitive, baseline-informed MRD assay (PredicineBEACON) was used to evaluate the correlation between peri-surgical MRD status and prognosis outcomes. Somatic mutations were identified through PredicineWES+ whole exon sequencing, and up to 50 somatic mutations were selected for the design of a patient-specific capture panel, in addition to a fixed panel of 500 actionable variants. Results: The study has completed MRD tests for 58 patients, of which 8 were called MRD positive with ≥0.005% tumor fractions. The tumor fraction proportion of MRD-positive patients ranged from 0.008% to 5.653% (median 0.315%). The relapse-free survival (RFS) and overall survival (OS) were correlated with MRD status: the median RFS of MRD-positive patients was 13.9 months compared to not reached after 44.4 months for MRD-negative patients (p = 0.1), and the median OS of MRD-positive patients was 27.2 months compared to not reached after 55.5 months for MRD-negative patients (p = 0.03). Conclusions: Our results demonstrate the feasibility of using an ultra-sensitive, baseline-informed MRD assay to detect strong correlations between MRD status and prognosis outcomes in peri-surgical plasma samples collected as early as 7 days post-surgery in resectable HCC patients. This study highlights the clinical utility of MRD testing in peri-surgical settings.

Uridine Inhibits Hepatocellular Carcinoma Cell Development by Inducing Ferroptosis.

Uridine is a key metabolite used as a substrate for the production of DNA, RNA, and glucose, and it is mainly synthesized in the liver. Currently, it is not known whether uridine levels are altered in the tumor microenvironment of patients with hepatocellular carcinoma (HCC) and whether uridine can be a target for tumor therapy. In this study, the detection of genes associated with de novo uridine synthesis, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) (n = 115), and dihydroorotate dehydrogenase (DHODH) (n = 115) in HCC tissues through tissue microarrays revealed that the expression of CAD and DHODH was higher in tumor compared with paraneoplastic tissues. Next, we collected tumor tissues from surgically resected HCC patients and the corresponding adjacent non-tumor tissues (n = 46) for LC-MS/MS assays. The results showed that the median and interquartile ranges of uridine content in non-tumor and tumor tissues were 640.36 (504.45-807.43) and 484.22 (311.91-626.73) nmol/g, respectively. These results suggest that uridine metabolism is disturbed in HCC patients. To further investigate whether uridine can be used as a tumor-therapeutic target, a series of high concentrations of uridine were incubated with HCC cells in vitro and in vivo. It was observed that uridine dose-dependently inhibited the proliferation, invasion, and migration of HCC cells by activating the ferroptosis pathway. Overall, these results reveal for the first time the range of uridine content in human HCC tissues and suggest that uridine may be a new target for HCC therapy.

Influence of Child-Pugh B7 and B8/9 cirrhosis on laparoscopic liver resection for hepatocellular carcinoma: a retrospective cohort study.

BackgroundLaparoscopic liver resection for hepatocellular carcinoma (HCC) in patients with Child–Pugh A cirrhosis has been shown to be beneficial. However, less is known regarding the outcomes of such treatment in patients with Child–Pugh B cirrhosis. We conducted a retrospective study to evaluate the outcomes of laparoscopic liver resection for HCC in patients with Child–Pugh B cirrhosis, focusing on surgical risks, recurrence, and survival.Methods357 patients with HCC who underwent laparoscopic liver resection from 2007 to 2021 were identified from our single-institute database. The patients were divided into three groups by their Child–Pugh score: the Child–Pugh A (n = 280), Child–Pugh B7 (n = 42), and Child–Pugh B8/9 groups (n = 35). Multivariable Cox regression models for recurrence-free survival (RFS) and overall survival (OS) were constructed with adjustment for preoperative and postoperative clinicopathological factors.ResultsThe Child–Pugh B8/9 group had a significantly higher complication rate, but the complication rates were comparable between the Child–Pugh B7 and Child–Pugh A groups (Child–Pugh A vs. B7 vs. B8/9: 8.2% vs. 9.6% vs. 26%, respectively; P = 0.010). Compared with the Child–Pugh A group, the risk-adjusted hazard ratios (95% confidence intervals) in the Child–Pugh B7 and B8/9 groups for RFS were 1.39 (0.77–2.50) and 3.15 (1.87–5.31), respectively, and those for OS were 0.60 (0.21–1.73) and 1.80 (0.86–3.74), respectively. There were no significant differences in major morbidities (Clavien–Dindo grade > II) (P = 0.117) or the proportion of retreatment after HCC recurrence (P = 0.367) among the three groups.ConclusionAmong patients with HCC, those with Child–Pugh A and B7 cirrhosis can be good candidates for laparoscopic liver resection in terms of complications and recurrence. Despite poor postoperative outcomes in patients with Child–Pugh B8/9 cirrhosis, laparoscopic liver resection is less likely to interfere with retreatment and can be performed as part of multidisciplinary treatment.Graphical abstract

Protocol of notable-HCC: a phase Ib study of neoadjuvant tislelizumab with stereotactic body radiotherapy in patients with resectable hepatocellular carcinoma

IntroductionLiver resection is the mainstay of curative-intent treatment for hepatocellular carcinoma (HCC), but the postoperative 5-year recurrence rate reaches 70%, and there are no adjuvant or neoadjuvant therapies recommended by...

Laparoscopic versus open liver resection for resectable HCC with BCLC stage B: a propensity score-matched analysis

To date, there is little knowledge about the value of laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) patients with Barcelona Clinic Liver Cancer (BCLC) stage B. Thus, this study was performed to assess the perioperative and oncological outcomes of LLR for these patients by comparison with open liver resection (OLR). Between April 2015 and October 2018, a total of 217 resectable HCC patients with BCLC stage B were eligible for this study. Patients were divided into the LLR group and the OLR group according to different procedures. Propensity score matching (PSM) was conducted to adjust for known confounders. Short- and long-term outcomes were compared between the two groups. LLR was performed in 75 of the 217 included patients. After PSM, 72 patients with well-balanced baseline levels were enrolled into each group. Although the operative time was significantly longer in the LLR group than in the OLR group (median, 237.5 vs. 210min, P = 0.024), the intraoperative blood loss was significantly less in the LLR group than in the OLR group (median, 200 vs. 350ml, P = 0.005). Patients in the LLR group had fewer complications than those in the OLR group (P = 0.035). Furthermore, overall survival (OS, P = 0.827) and recurrence-free survival (RFS, P = 0.694) were comparable between the two groups. LLR for resectable HCC patients with BCLC stage B is safe and feasible in carefully selected patients and has superior perioperative outcomes and similar survival rates compared with OLR.

Tumor and peritumor radiomics analysis based on contrast-enhanced CT for predicting early and late recurrence of hepatocellular carcinoma after liver resection

BackgroundIn China, liver resection has been proven to be one of the most important strategies for hepatocellular carcinoma patients, but the recurrence rate is high. This study sought to investigate the prognostic value of pretreatment tumor and peritumor contrast-enhanced CT radiomics features for early and late recurrence of BCLC stage 0-B hepatocellular carcinoma after liver resection.MethodsThis study involved 329 hepatocellular carcinoma patients after liver resection. A radiomics model was built by using Lasso-Cox regression model. Association between radiomics model and recurrence-free survival was explored by using Harrell’s concordance index (C-Index) and receiver operating characteristic (ROC) curves. Then, we combined the radiomics model and clinical factors to establish a nomogram whose calibration and discriminatory ability were revealed.ResultsTen significant tumor and peritumor features were screened to build the radiomics model whose C-indices were 0.743 [95% CI, 0.707 to 0.778] and 0.69 [95% CI, 0.629 to 0.751] in the training and validation cohorts. Moreover, the discriminative accuracy of the radiomics model improved with peritumor features entry. The C-indices of the combined model were 0.773 [95% CI, 0.739 to 0.806] and 0.727 [95% CI, 0.667 to 0.787] in the training and validation cohorts, outperforming the radiomics model.ConclusionsThe tumor and peritumor contrast-enhanced CT radiomic signature is a quantitative imaging biomarker that could improve the prediction of early and late recurrence after liver resection for hepatocellular carcinoma patients when used in addition to clinical predictors.

Antidiabetic treatment improves prognosis after radical resection in hepatocellular carcinoma patients with diabetes mellitus: a retrospective cohort study from 2000 to 2013.

It remains unclear whether diabetic medications, such as metformin and insulin, affect the post-liver resection prognosis of hepatocellular carcinoma (HCC) patients complicated with diabetes mellitus (DM). This study try to find out the prognostic factors in HCC patients with DM and provide a better antidiabetic therapy after liver resection. Patients presenting with HCC complicated with DM undergoing liver resection were enrolled in this study. They were examined and followed up every 3-6 months after surgery. Patients were divided into the antidiabetic treatment group and no antidiabetic treatment group according to whether they received medications for diabetes or not. Then patients in the antidiabetic treatment group were further divided into insulin group, metformin group, insulin plus metformin group and others group, according to the medications they received. Overall survival (OS) and recurrence-free survival (RFS) were compared among two groups and four subgoups. Comparative and multivariate analyses were performed to investigate the effects of DM medication on the prognosis of these HCC patients, using Cox proportional hazards model. The 1-, 3-, 5-, and 7-year OS rates for the antidiabetic treatment group were 87.5%, 75.5%, 48.7%, and 29.1%, respectively, and for the no antidiabetic treatment group, the OS rates were 85.4%, 57.7%, 33.6%, and 19.1%, respectively (P=0.007). The 1-, 3-, 5-, 7-year RFS rates for the antidiabetic treatment group were 76.4%, 53.5%, 28.5%, and 17.5%, respectively, and for the no antidiabetic treatment group, the RFS rates were 69.5%, 32.5%, 16.5%, and 10.7%, respectively (P=0.001). In subgroup analysis, There was no significant difference in either RFS (P=0.934) nor OS (P=0.412) among the different types of antidiabetic treatment regimens. Cox proportional hazard regression analysis revealed that tumor size (HR: 1.048), tumor number (HR: 1.626), vascular invasion (HR: 2.074, P=0.003), satellite tumor (HR: 1.592), Edmondson classification (HR: 1.468) and antidiabetic treatment (HR: 0.722) were independent prognostic factors of DFS, while tumor size (HR: 1.048), tumor number (HR: 1.779), vascular invasion (HR: 2.545), Edmondson classification (HR: 1.596) and antidiabetic treatment (HR: 0.713) were independent prognostic factors of OS. For HCC patients with DM, antidiabetic treatment should be recommended aggressively in order to improve the surgical outcome, regardless of which antidiabetic drugs are used.

The Safety Profile of Hepatectomy Following Preoperative Systemic Therapy with Lenvatinib Plus Anti-PD-1 Antibodies Versus Hepatectomy Alone in Patients With Hepatocellular Carcinoma.

To determine the safety of hepatectomy after combined lenvatinib and anti-PD-1 preoperative systemic therapy (PST) in patients with marginally resectable hepatocellular carcinoma (HCC). PST followed by hepatectomy (PSTH) is an emerging treatment for HCC. However, the impact of PST with lenvatinib plus anti-PD-1 antibodies on surgical safety is unknown. Medical records from consecutive patients with marginally resectable advanced HCC who underwent hepatectomy after PST with lenvatinib and anti-PD-1 antibodies between January 2018 and August 2021 were retrieved from a prospectively designed database. Propensity score matching (1:2) was performed with a further 2318 HCC patients who underwent upfront hepatectomy (UH) without initial antitumor treatment during the same period. In total, 49 and 98 matched patients were included in the PSTH and UH groups, respectively. Compared to the UH group, individuals in the PSTH group experienced more intraoperative blood loss, blood transfusions, and longer postoperative hospital stays. Moreover, posthepatectomy liver failure was more common in the PSTH group, who also had worse albumin-bilirubin (ALBI) scores on postoperative days 1-7. A significantly greater amount of drainage was also required in the PSTH group. However, the 30-day morbidity and 90-day mortality were similar among the two groups. Additionally, the duration of surgery, use of hepatic inflow occlusion during surgery, and the levels of postoperative inflammation-based markers were not statistically different between the two groups. Despite more intraoperative and postoperative adverse events, PSTH had comparable 30-day morbidity and 90-day mortality as UH. Thus, PSTH appears to be a viable treatment option for marginally resectable HCC patients with careful preoperative evaluation.

Realization of improved outcomes following liver resection in hepatocellular carcinoma patients 75 years of age and older

Realization of improved outcomes following liver resection in hepatocellular carcinoma patients 75 years of age and older

Association of CK19 expression with efficacy of adjuvant TACE after hepatic resection in hepatocellular carcinoma patients at high risk of recurrence

This study retrospectively explored the potential association between CK19 expression and efficacy of adjuvant conventional transarterial chemoembolization (TACE) after hepatic resection in patients with hepatocellular carcinoma (HCC) at high risk of recurrence. Read more at JCTRes.com

Preoperative Chemotherapy Followed by Hepatectomy for Potentially Resectable UICC7 Stage IIIA, IIIB Hepatocellular Carcinoma; A Phase II Clinical Trial.

The Japanese guideline for therapeutic strategy in HCC does not recognize any benefit of preoperative chemotherapy for potentially resectable hepatocellular carcinoma (HCC), and only upfront resec tion is recommended even for an advanced HCC. Data on preoperative chemotherapy for advanced HCC is still limited. Poor prognostic factors of HCC after resection are tumor more than 5 cm in diameter, multiple lesions, and gross tumor thrombosis, which constitute UICC7 Stage IIIA and IIIB HCC. There are no prospective studies about preoperative chemotherapy in these patients. To evaluate the benefit of preoperative chemotherapy for UICC7 Stage IIIA and IIIB potentially resectable HCC. Our recent study demonstrated that the 5-year overall survival rate (OS) of patients diagnosed as UICC7 Stage IIIA and IIIB who had received upfront resection was only 16.5%. In contrast, the 5-year OS of UICC7 Stage IIIA and IIIB initially unresectable patients who had achieved conversion from unresectable to resect able status under successful hepatic infusion chemotherapy prior to resection was as high as 61.3%. Additionally, recent studies reported transarterial chemoembolization achieved outcomes comparable with those of resection. Therefore, we believe that patients with UICC7 Stage IIIA and IIIB should be considered borderline resectable. To evaluate this hypothesis we registered the present phase II clinical trial to assess the benefit of preoperative chemo therapy followed by hepatectomy in potentially resectable UICC7 Stage IIIA and IIIB HCC patients.

RNA sequencing analysis reveals the competing endogenous RNAs interplay in resected hepatocellular carcinoma patients who received interferon-alpha therapy

BackgroundInterferon-alpha (IFN-α) is a general therapeutic regimen to be utilized in hepatocellular carcinoma (HCC). However, regulatory mechanisms of IFN-α on competing endogenous RNAs (ceRNAs) level in anti-HCC relapse are rarely understood.MethodsHCC patients with and without IFN-α treatment were calculated to analyze the expression profile of mRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) by RNA sequence, and significant differential expression (DE) of these types of RNAs were selected for further analysis. A ceRNA regulatory network was constructed to explore the potential mechanisms of IFN-α intervention on anti-HCC relapse. Finally, the potential prognostic associated genes among these DE RNAs were identified.ResultsTotally, 556 mRNAs, 120 circRNAs, 87 lncRNAs, and 96 miRNAs were differentially expressed in patients who received IFN-α treatment. A ceRNA regulatory network including a circRNA-miRNA-mRNA network which composed of 4 up- and 10 down-regulated circRNAs, 8 up- and 5 down-regulated miRNAs, 28 up- and 9 down-regulated mRNAs, and a lncRNA-miRNA-mRNA network which composed of 10 up- and 3 down-regulated lncRNAs, 11 up- and 5 down-regulated miRNAs, 28 up- and 10 down-regulated mRNAs was constructed. Gene enrichment and pathway analysis revealed that the ceRNA network was associated with immune-related pathway and corresponding molecular function in patients who accepted IFN-α treatment. Next, we identified 3 most relevant to IFN-α treatment to HCC among these DE RNAs, namely FAM20A, IGFBP4 and MARCH3, as the prognostic associated genes for HCC. Furthermore, MARCH3 expression correlated with infiltrating levels of tumor infiltrating immune cells (TICCs) in HCC. MARCH3 expression also showed strong correlations with the gene markers of diverse immune cells in HCC.ConclusionOur data discovered a novel ceRNA network in HCC patients receiving IFN-α therapy, which might lay the foundation for better understand the regulatory mechanism of IFN-α treatment.

Establishment, validation and evaluation of predictive model for early relapse after R0 resection in hepatocellular carcinoma patients with microvascular invasion

BackgroundsThis is the first study to build and evaluate a predictive model for early relapse after R0 resection in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI).MethodsThe consecutive HCC patients with MVI who underwent hepatectomy in Cancer Hospital of Chinese Academy of Medical Science from Jan 2014 to June 2019 were retrospectively enrolled and randomly allocated into a derivation (N = 286) and validation cohort (N = 120) in a ratio of 7:3. Cox regression and Logistic regression analyses were performed and a predictive model for postoperative early-relapse were developed.ResultsA total of 406 HCC patients with MVI were included in our work. Preoperative blood alpha-fetoprotein (AFP) level, hepatitis B e antigen (HBeAg) status, MVI classification, largest tumor diameter, the status of serosal invasion, number of tumors, and the status of satellite nodules were incorporated to construct a model. The concordance index (C-index) was 0.737 and 0.736 in the derivation and validation cohort, respectively. The calibration curves showed a good agreement between actual observation and nomogram prediction. The C-index of the nomogram was obviously higher than those of the two traditional HCC staging systems.ConclusionWe have developed and validated a prediction model for postoperative early-relapse in HCC patient with MVI after R0 resection.