Prediction of microvascular invasion in hepatocellular carcinoma with expert-inspiration and skeleton sharing deep learning.

BACKGROUND AND AIMS: Radiological prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) is essential but few models were clinically implemented because of limited interpretability and generalizability. METHODS: Based on 2096 patients in three independent HCC cohorts, we established and validated an MVI predicting model. First, we used data from the primary cohort to train a 3D-ResNet network for MVI prediction and then optimised the model with "expert-inspired training" for model construction. Second, we implemented the model to the other two cohorts using three implementation strategies, the original model implementation, data sharing model implementation and skeleton sharing model implementation, the latter two of which used part of the cohorts' data for fine-tuning. The areas under the receiver operating characteristic curve (AUCs) were calculated to compare the performances of different models. RESULTS: For the MVI predicting model, the AUC of the expert-inspired model was 0.83 (95% CI: 0.77-0.88) compared to 0.54 (95% CI: 0.46-0.62) of model before expert-inspiring. Taking this model as an original model, AUC on the second cohort was 0.76 (95% CI: 0.67-0.84). The AUC was improved to 0.83 (95% CI: 0.77-0.90) with the data-sharing model, and further improved to 0.85 (95% CI: 0.79-0.92) with the skeleton sharing model. The trend that the skeleton sharing model had an advantage in performance was similar in the third cohort. CONCLUSIONS: We established an expert-inspired model with better predictive performance and interpretability than the traditional constructed model. Skeleton sharing process is superior to data sharing and direct model implementation in model implementation.

Hornerin promotes tumor progression and is associated with poor prognosis in hepatocellular carcinoma.

BACKGROUND: The function of hornerin (HRNR), a member of the S100 protein family, is poorly clarified in the development of human tumors. The role of HRNR in hepatocellular carcinoma (HCC) progression is investigated in the study. METHODS: The expression levels of HRNR were assessed in tumor samples from a cohort of 271 HCC patients. The effect of HRNR on proliferation, colony formation and invasion of tumor cells was examined. We further determined the role of HRNR in tumor growth in vivo by using xenograft HCC tumor models. The possible mechanism of the HRNR promotion of HCC progression was explored. RESULTS: We found that HRNR was overexpressed in HCC tissues. The high expression of HRNR in HCCs was significantly associated with vascular invasion, poor tumor differentiation, and advanced TNM stage. The disease-free survival (DFS) and overall survival (OS) of HCC patients with high HRNR expression were poorer than those in the low HRNR expression group. HRNR expression was an independent risk factor linked to both poor DFS (HR = 2.209, 95% CI = 1.627-2.998,P <  0.001) and OS (HR = 2.459,95% CI = 1.736-3.484, P <  0.001). In addition, the knockdown of HRNR by shRNAs significantly inhibited the proliferation, colony formation, migration and invasion of HCC tumor cells. HRNR silencing led to the decreased phosphorylation of AKT signaling. Notably, tumor growth was markedly inhibited by HRNR silencing in a xenograft model of HCC. CONCLUSIONS: HRNR promotes tumor progression and is correlated with a poor HCC prognosis. HRNR may contribute to HCC progression via the regulation of the AKT pathway.

A simplified multivisceral transplantation procedure for patients with combined end-stage liver disease and type 2 diabetes mellitus.

In liver transplant patients with type 2 diabetes mellitus (DM), the disease worsens after transplantation because of longterm use of diabetogenic immunosuppressive drugs, making management of those patients a great challenge. The objective of our study was to evaluate the safety and efficacy of a simplified multivisceral transplantation (SMT) procedure for the treatment of patients with end-stage liver disease and concurrent type 2 DM. Forty-four patients who had pretransplant type 2 DM were included. A total of 23 patients received SMT, and 21 patients received orthotopic liver transplantation (OLT). Patient and graft survivals, complications, diabetic control, and quality of life (QOL) were retrospectively analyzed in both groups. The 1-, 3-, and 5-year cumulative patient and graft survival rates were 91.5%, 75.4%, and 75.4% in the SMT group and were 94.4%, 64.4%, and 64.4% in the OLT group, respectively (P = 0.70). Interestingly, 95.7% (22/23) of patients achieved complete remission from DM after SMT compared with 16.7% (3/18) of patients after OLT. The occurrence of biliary complication was significantly higher in the OLT group than that in the SMT group (23.8% versus 0.0%; P = 0.01). Moreover, better QOL was observed in the SMT group than that in the OLT group. In conclusion, the SMT procedure we described here is a safe and viable option for patients with end-stage live disease and concurrent type 2 DM. This SMT procedure offers excellent transplant outcomes and QOL. Liver Transplantation 23 1161-1170 2017 AASLD.

Prognostic value of combined preoperative prognostic nutritional index and body mass index in HCC after hepatectomy.

BACKGROUND: Malnutrition and immunological status are associated with survival in many cancers. Prognostic nutritional index (PNI) and body mass index (BMI) are recognized immune-nutritional indices and associated with postoperative outcome in hepatocellular carcinoma (HCC) patients. However, this association is still controversial. Our aim was to determine whether the combination of PNI and BMI is better than either alone in HCC patients' prognosis. MATERIAL AND METHODS: Preoperative PNI and BMI, patient demographics, clinical and pathological data from 322 HCC patients were collected and analyzed. RESULTS: Low PNI was correlated with age, cirrhosis, total bilirubin (TBIL) ≥34.2 µmol/L, and recurrence. Likewise, low BMI was associated with TBIL ≥34.2 µmol/L, portal vein tumor thrombi (PVTT), tumor size, tumor differentiation, TNM stage, and recurrence. Multivariate analysis identified TNM stage, PVTT, tumor size, PNI, and BMI as independent predictors of outcome in HCC patients. Low PNI combined with BMI (PNI + BMI) accurately predicted poorer outcome, particularly in patients with TNM stage I HCC. The predictive range of PNI + BMI was more sensitive than that of either alone. CONCLUSIONS: preoperative PNI/BMI is an independent predictor of outcome for HCC patients, especially in patients with early stage HCC. Intriguingly, the PNI + BMI combination can enhance the accuracy of prognosis.

Prognostic value of preoperative serum gamma-glutamyltranspeptidase in patients with hepatocellular carcinoma after hepatectomy.

Gamma-glutamyltranspeptidase (γ-GGT), an oxidative stress marker, is correlated with inflammation in the extracellular hepatic microenvironment. This study aimed to evaluate the prognostic value of serum γ-GGT levels in patients with hepatocellular carcinoma (HCC) after hepatectomy. Three hundred and eight patients who underwent hepatic resection for HCC were included in the study. Preoperative serum γ-GGT levels, as well as demographic, clinical, and pathologic data, were analyzed. The optimal cutoff value of γ-GGT was 88 U/L. All patients were divided into γ-GGT ≤ 88 U/L group (n = 146) and γ-GGT > 88 U/L group (n = 162). The disease-free survival (DFS) and overall survival (OS) rates of patients in the γ-GGT > 88 U/L group were poorer than those in γ-GGT ≤ 88 U/L group. Preoperative serum γ-GGT levels, associating with gender, HBsAg status, tumor size, capsulation, tumor number, and vascular invasion, was an independent prognostic predictor of disease-free survival [hazard ratio (HR) = 1.616; 95 % confidence interval (CI), 1.223-2.135; P = 0.001] and overall survival (HR = 2.043; 95 % CI, 1.509-2.766; P < 0.001). Furthermore, γ-GGT was also associated with DFS and OS in small HCC (tumor size ≤5 cm) and alpha-fetoprotein (AFP) ≤ 200 ng/mL subgroup. In conclusion, γ-GGT is a promising and reliable prognostic biomarker in HCC patients after hepatic resection, especially for patients with small HCC or AFP ≤ 200 ng/mL.

Prognostic value of preoperative peripheral monocyte count in patients with hepatocellular carcinoma after liver transplantation.

Prognostic value of peripheral monocyte, as a member of inflammatory cells, was widely being investigated. The aim of this study was to evaluate the prognostic value of preoperative peripheral blood monocyte count for hepatocellular carcinoma (HCC) patients who underwent liver transplantation (LT) and the relationship between monocyte count and tumor-related characteristics. We retrospectively analyzed the clinical data of 101 HCC patients after LT. Preoperative monocyte count and demographic, clinical, and pathologic data were analyzed. The optimal cutoff value of monocyte count was 456/mm(3), with the sensitivity and specificity of 69.4 and 61.5 %, respectively. Elevated preoperative peripheral blood monocyte count was significantly associated with large tumor size. The 1-, 3-, and 5-year disease-free survival (DFS) (80.9, 70.1, and 53.3 % vs 55.1, 38.7, and 38.7 %, P = 0.007) and overall survival (OS) rates (95.7, 76.6, and 64.8 % vs 72.2, 44.1, and 36.1 %, P = 0.002) of HCC patients in the peripheral blood monocyte count ≤456/mm(3) group were higher than those in the peripheral blood monocyte count >456/mm(3) group. In conclusion, elevated preoperative peripheral blood monocyte count was significantly associated with advanced tumor stage and it can be considered as a prognostic factor for HCC patients after LT.

A novel and accurate predictor of survival for patients with hepatocellular carcinoma after surgical resection: the neutrophil to lymphocyte ratio (NLR) combined with the aspartate aminotransferase/platelet count ratio index (APRI).

BACKGROUND: The occurrence and development of hepatocellular carcinoma (HCC) depends largely on such non-tumor factors as inflammatory condition, immune state, viral infection and liver fibrosis. Various inflammation-based prognostic scores have been associated with survival in patients with HCC, such as the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR) and the prognostic nutritional index (PNI). The aspartate aminotransferase/platelet count ratio index (APRI) is thought to be a biomarker of liver fibrosis and cirrhosis. This study aims to evaluate the ability of these indices to predict survival in HCC patients after curative hepatectomy, and probe the increased prognostic accuracy of APRI combined with established inflammation-based prognostic scores. METHODS: Data were collected retrospectively from 321 patients who underwent curative resection for HCC. Preoperative NLR, PLR, PNI, APRI and clinico-pathological variables were analyzed. Univariate and multivariate analyses were performed to identify the predictive value of the above factors for disease-free survival (DFS) and overall survival (OS). RESULTS: Univariate analysis showed that NLR, PLR, PNI and APRI were significantly associated with DFS and OS in HCC patients with curative resection. Multivariate analysis showed that NLR and APRI were superior to PLR and PNI, and both were independently correlated with DFS and OS. Preoperative NLR >2 or APRI >1.68 predicted poor prognosis of patients with HCC after hepatectomy. Furthermore, the predictive range of NLR combined with APRI was more sensitive than that of either measure alone. CONCLUSIONS: Preoperative NLR and APRI are independent predictors of DFS and OS in patients with HCC after surgical resection. Higher levels of NLR or APRI predict poorer outcomes in HCC patients. Intriguingly, combining NLR and APRI increases the prognostic accuracy of testing.

The prognostic value of combined TGF-ß1 and ELF in hepatocellular carcinoma.

BACKGROUND: Tumor suppression of Transforming Growth Factor (TGF-ß) signaling pathway requires an adaptor protein, Embryonic Liver Fodrin (ELF). Disruption of ELF expression resulted in miscolocalization of Smad3 and Smad4, then disruption of TGF-ß signaling. However, the prognostic significance of ELF for hepatocellular carcinoma (HCC) hasn't been clarified. This study aimed to investigate whether measuring both TGF-ß1 and ELF provides a more powerful predictor for HCC prognosis than either marker alone. METHODS: TGF-ß1 and ELF protein were detected by immunohistochemistry. The relationship between TGF-ß1/ELF expression and patients' clinicopathologic factors was analyzed. The association between TGF-ß1/ELF expression and disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and Multivariate Cox regression analyses. RESULTS: The expression of TGF-ß1 in HCC tissues was significantly higher than that in normal liver tissues. Conversely, the expression of ELF in HCC tissues declined markedly. ELF protein was correlated with HBsAg, tumor size, tumor number, TNM and recurrence. Data also indicated a significant negative correlation between ELF and TGF-ß1. Patients with high TGF-ß1 expression or/and low ELF expression appeared to have a poor postoperative disease-free survival and overall survival compared with those with low TGF-ß1 expression or/and high ELF expression. Furthermore, the predictive range of ELF combined with TGF-ß1 was more sensitive than that of either one alone. CONCLUSIONS: TGF-ß1 and ELF protein are potential and reliable biomarkers for predicting prognosis in HCC patients after hepatic resection. Our current study has demonstrated that the prognostic accuracy of testing can be enhanced by their combination.

Risk factors and outcomes of postoperative pancreatic fistula after pancreatico-duodenectomy: an audit of 532 consecutive cases.

BACKGROUND: Pancreatic fistula (PF) remains the most challenging complication after pancreaticoduodenectomy (PD). The purpose of this study was to identify the risk factors of PF and delineate its impact on patient outcomes. METHODS: We retrospectively reviewed clinical data of 532 patients who underwent PD and divided them into PF group and no PF group. Risk factors and outcomes of PF following PD were examined. RESULTS: PF was found in 65 (12.2%) cases, of whom 11 were classified into ISGPF grade A, 42 grade B, and 12 grade C. Clinically serious postoperative complications in the PF versus no PF group were mortality, abdominal bleeding, bile leak, intra-abdominal abscess and pneumonia. Univariate and multivariate analysis showed that blood loss ≥ 500 ml, pancreatic duct diameter ≤ 3 mm and pancreaticojejunostomy type were independent risk factors of PF after PD. CONCLUSIONS: Blood loss ≥ 500 ml, pancreatic duct diameter ≤ 3 mm and pancreatico-jejunostomy type were independent risk factors of PF after PD. PF was related with higher mortality rate, longer hospital stay, and other complications.

Preoperative aspartate aminotransferase to platelet ratio is an independent prognostic factor for hepatitis B-induced hepatocellular carcinoma after hepatic resection.

BACKGROUND: There is conflicting evidence concerning platelet status and hepatocellular carcinoma (HCC) prognosis. We evaluated the prognostic value of platelet-based indices, including platelet count, platelet/lymphocyte ratio (PLR), and aspartate aminotransferase to platelet ratio index (APRI) in HCC after hepatic resection. METHODS: We retrospectively reviewed 332 patients with HCC treated with hepatectomy between 2006 and 2009. Preoperative platelet count, as well as demographic, clinical, and pathologic data, were analyzed. RESULTS: Both disease-free survival (DFS) and overall survival (OS) were significantly improved for patients with low platelet count, PLR, and APRI compared to patients with elevated values. On multivariate analysis, APRI, tumor size ≥5 cm, noncapsulation, and multiple tumors were all associated with both poor DFS and OS. The 1-, 3-, and 5-year DFS rates were 52, 36, and 32 % for patients with APRI <0.62 and were 35, 22, and 19 % for patients with APRI ≥0.62. Correspondingly, the 1-, 3-, and 5-year OS rates were 77, 51, and 42, and 63, 35, and 29 % for both groups. Both DFS and OS of patients with APRI <0.62 were significantly better compared to patients with an elevated APRI (P = 0.009 and 0.002, respectively). Patients with elevated APRI tended to have cirrhosis, hepatitis B virus (HBV) infection, surgical margin <1 cm, and noncapsulated tumors. CONCLUSIONS: Elevated platelets based inflammatory indices, especially APRI, was associated with adverse characteristic features and poor prognosis in HCC, especially for patients with HBV infection or cirrhosis. Antiplatelet treatment may represent a potential therapy for HBV-induced HCC recurrence.

Prognostic significance of neutrophil-lymphocyte ratio in hepatocellular carcinoma: a meta-analysis.

BACKGROUNDS: Neutrophil-lymphocyte ratio (NLR) has recently been reported as a predictor of Hepatocellular carcinoma (HCC). However, its prognostic value in HCC still remains controversial. In this study, we aimed to evaluate the association between NLR and clinical outcome of HCC patients by performing meta-analysis. METHODS: A comprehensive literature search for relevant studies published up to August 2013 was performed by using PubMed, Ovid, the Cochrane Library and Web of Science databases. Meta-analysis was performed using hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (95% CIs) as effect measures. RESULTS: A total of 15 studies encompassing 3094 patients were included in this meta-analysis. Our pooled results showed that high NLR was associated with poor overall survival (OS) and disease free survival (DFS) in HCC initially treated by liver transplantation (HR = 3.42, 95% CI:2.41-4.85,P = 0.000; HR = 5.90, 95% CI:3.99-8.70,P = 0.000, respectively) and surgical resection (HR = 3.33, 95% CI:2.23-4.98, P = 0.000; HR = 2.10, 95% CI: 2.06-2.14, respectively). High NLR was also associated with poor OS in HCC treated by radiofrequency-ablation (HR = 1.28, 95%CI: 1.10-1.48, P = 0.000), TACE (HR = 2.52, 95% CI: 1.64-3.86, P = 0.000) and mixed treatment (HR = 1.85, 95% CI: 1.40-2.44, P = 0.000), respectively. In addition, high NLR was significantly correlated with the presence of vascular invasion (OR = 2.69, 95% CI: 2.01-3.59, P = 0.000), tumor multifocality (OR = 1.74, 95% CI: 1.30-2.34, P = 0.000) and higher incidence of AFP ≥ 400 ng/ml (OR = 1.46, 95% CI: 1.01-2.09, P = 0.04). CONCLUSION: Elevated NLR indicates a poor prognosis for patients with HCC. NLR may be a convenient, easily-obtained, low cost and reliable biomarker with prognostic potential for HCC.

Elevated preoperative peripheral blood monocyte count predicts poor prognosis for hepatocellular carcinoma after curative resection.

BACKGROUND: Peripheral blood monocyte count is an easily assessable parameter of systemic inflammatory response. The aim of this study was to determine whether monocyte count was prognostic in hepatocellular carcinoma (HCC) following hepatic resection. METHODS: We retrospectively reviewed 351 patients with HCC treated with hepatic resection from 2006 to 2009. Preoperative absolute peripheral monocyte count, demographics, and clinical and pathological data were analyzed. RESULTS: On univariate and multivariate analysis, elevated monocyte counts (≥ 545/mm(3)), tumor size ≥ 5 cm, non-capsulation, and multiple tumors were associated with poor disease-free survival (DFS) and overall survival (OS). The 1-, 3- and 5-year DFS rates were 58%, 41% and 35%, respectively, for patients with monocyte counts <545/mm(3), and 36%, 23% and 21% for patients with monocyte counts ≥ 545/mm(3). Correspondingly, the 1-, 3- and 5-year OS rates were 79%, 53% and 46% for monocyte counts <545/mm(3), and 64%, 36% and 29% for monocyte counts ≥ 545/mm(3). Subgroup analysis indicated that DFS after hepatic resection in hepatitis B virus (HBV)-infected patients was significantly better in those with a peripheral blood monocyte counts <545/mm(3), but it did not differ between patients without HBV infection. In addition, DFS was significantly better for patients with a peripheral blood monocyte count <545/mm(3), whether or not cirrhosis was present. Patients with elevated monocyte counts tended to have larger tumors. CONCLUSIONS: Elevated preoperative monocyte count is an independent predictor of worse prognosis for patients with HCC after hepatic resection, especially for those with HBV infection. Postoperative adjuvant treatment might be considered for patients with elevated preoperative monocyte counts.

Prognostic significance of glypican-3 in hepatocellular carcinoma: a meta-analysis.

BACKGROUNDS: Glypican-3(GPC3) has been implicated in tumor development and progression for several years. However, the prognostic significance of GPC3 expression in patients with hepatocellular carcinoma (HCC) is controversial. We performed a meta-analysis of available studies to assess whether GPC3 can be used as a prognostic factor in patients with HCC. METHODS: We searched PubMed and Ovid EBM Reviews databases and evaluated the reference list of relevant articles for studies that assessed the prognostic relevance of GPC3 in patients with HCC. Meta-analysis was performed using hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (95% CIs) as effect measures. RESULTS: A meta-analysis of eight studies included 1070 patients was carried out to evaluate the association between GPC3 and overall survival (OS) and disease-free survival (DFS) in HCC patients. The relation between GPC3 and tumor pathological features was also assessed. Our analysis results indicated that high GPC3 expression predicted poor OS (HR: 1.96, 95% CI: 1.51-2.55) and DFS (HR: 1.99, 95% CI: 1.57-2.51) of patients with HCC. GPC3 overexpression was significantly associated with high tumor grade (OR: 3.30, 95% CI: 2.04-5.33), late TNM stage (OR: 2.26, 95% CI: 1.00-5.12), and the presence of vascular invasion (OR: 2.43, 95% CI: 1.23-4.82). CONCLUSIONS: GPC3 overexpression indicates a poor prognosis for patients with HCC, and it may also have predictive potential for HCC invasion and metastasis.

Radiofrequency-assisted versus clamp-crush liver resection: a systematic review and meta-analysis.

BACKGROUND: Conflicting results were found between radiofrequency-assisted liver resection (RF-LR) and clamp-crush liver resection (CC-LR) during liver surgery. We conducted a systematic review and meta-analysis that included randomized controlled trials (RCTs) and non-RCTs to compare the effectiveness and safety of RF-LR versus CC-LR during liver surgery. METHODS: Articles comparing RF-LR and CC-LR that were published before December 2012 were retrieved and subjected to a systematic review and meta-analysis. Data synthesis and statistical analysis were carried out by Review Manager Version 5.2 software. RESULTS: In all, four RCTs and five nonrandomized studies evaluating 728 patients were included. Compared with CC-LR, the RF-LR group had significantly reduced total intraoperative blood loss (weighted mean difference [WMD] = -187 mL; 95% confidence interval [CI] = -312, -62; data on 628 patients), and blood loss during liver transection (WMD = -143.7 mL; 95% CI = -200, -87; data on 190 patients). However, RF-LR is associated with a higher rate of intra-abdominal abscess than the clamp-crushing method (odds ratio = 3.61; 95% CI = 1.26, 10.32; data on 366 patients). No significant difference was observed between both the groups for the incidence of both blood transfusion and bile leak. CONCLUSIONS: There is currently not sufficient evidence to support or refute the use of RF-LR in liver surgery. RF-LR has advantages in terms of reducing blood loss. However, RF-LR may increase the rates of both bile leak and abdominal abscess. So, the safety of RF-LR has not been established. Future well-designed RCTs are awaited to further investigate the efficacy and safety of RF devices in liver resection.

GPC3 DNA vaccine elicits potent cellular antitumor immunity against HCC in mice.

BACKGROUND/AIMS: DNA-based tumor vaccine immunotherapy which elicits exclusively cellular immune response against cancer cells in an antigen-specific fashion has been documented to be an effective treatment for cancers in the past decade. Glypican 3 (GPC3) is especially overexpressed in hepatocellular carcinoma (HCC), but not in benign liver lesions and normal adult tissues, which makes it an ideal tumor antigen designed for HCC immunotherapy. METHODOLOGY: We constructed a GPC3 cDNA vaccine by using a recombinant plasmid encoding murine GPC3 cDNA for treatment of HCC in a C57BL/6 mouse model. The specificity and effectiveness of anti-tumor immunity were assessed in vitro and in vivo studies. RESULTS: In vitro studies showed that GPC3 DNA vaccine induced potent specific cytotoxic T lymphoctyes (CTLs) immune response against C57BL/6 homogenous HCC cell line Hepa 1-6 (GPC3+). However, there was no detectable immune response against GPC3-negative SP 2/0 cells and Sk-Hep-1 cells. In vivo study indicated that GPC3 DNA vaccine could significantly suppress homogenous tumor growth and prolong survival time of tumor bearing mice. CONCLUSIONS: This study demonstrated the first time that the GPC3 DNA vaccine could elicit specific and effective cellular antitumor immunity against GPC3 HCC. This may provide an alternative option for immunotherapy of HCC.

Laparoscopic Anterior Right Hepatectomy: A Single-Center Experience.

Laparoscopic anterior right hepatectomy (LARH) has been used in some hospitals. However, data on the feasibility and safety of this procedure are still limited, due to the demanding technical requirements. The primary objective of this study was to compare the clinical outcomes of LARH with those of laparoscopic conventional right hepatectomy (LCRH) in patients with large right hepatocellular carcinoma, as well as to confirm the safety and feasibility of LARH. Furthermore, the article presents a step-by-step description of the surgical procedures for LARH to help perform this surgery in the clinic. The principle of LARH is to first prioritize the hepatic inlet duct separation while separating the right hepatic perihepatic ligament after transecting the liver. From December 2015 to June 2022, 82 patients with large right hepatocellular carcinoma (maximum tumor diameter ≥ 5 cm), were recruited for the study. In this cohort, 54 and 28 patients underwent LARH and LCRH, respectively. The perioperative clinical data and survival outcomes of the two groups were compared. Compared with LCRH, LARH exhibited the advantages of less contact and extrusion, thereby leading to the achievement of superior results. Thus, we propose that LARH is the optimal choice for patients with large right hepatocellular carcinoma.

Plasma-only circulating tumor DNA analysis detects minimal residual disease and predicts early relapse in hepatocellular carcinoma patients undergoing curative resection.

Background: Minimal residual disease (MRD) is considered an essential factor leading to relapse within 2 years (early relapse) after radical surgery, which is challenging to be detected by conventional imaging. Circulating tumor DNA (ctDNA) provides a novel approach for detecting MRD and predicting clinical outcomes. Here, we tried to construct a fixed panel for plasma-only ctDNA NGS to enable tumor-uninformed MRD detection in hepatocellular carcinoma (HCC). Methods: Here, we performed the followings: (i) profiling genomic alteration spectrum of ctDNA from the Chinese HCC cohort consisting of 493 individuals by NGS; (ii) screening of MRD monitoring genes; and (iii) performance evaluation of MRD monitoring genes in predicting early relapse in the ZJZS2020 cohort comprising 20 HCC patients who underwent curative resection. Results: A total of 493 plasma samples from the Chinese HCC cohort were detected using a 381/733-gene NGS panel to characterize the mutational spectrum of ctDNA. Most patients (94.1%, 464/493) had at least one mutation in ctDNA. The variants fell most frequently in TP53 (45.1%), LRP1B (20.2%), TERT (20.2%), FAT1 (16.2%), and CTNNB1 (13.4%). By customized filtering strategy, 13 MRD monitoring genes were identified, and any plasma sample with one or more MRD monitoring gene mutations was considered MRD-positive. In the ZJZS2020 cohort, MRD positivity presented a sensitivity of 75% (6/8) and a specificity of 100% (6/6) in identifying early postoperative relapse. The Kaplan-Meier analysis revealed a significantly short relapse-free survival (RFS; median RFS, 4.2 months vs. NR, P=0.002) in the MRD-positive patients versus those with MRD negativity. Cox regression analyses revealed MRD positivity as an independent predictor of poor RFS (HR 13.00, 95% CI 2.60-69.00, P=0.002). Conclusions: We successfully developed a 13-gene panel for plasma-only MRD detection, which was effective and convenient for predicting the risk of early postoperative relapse in HCC.

Aberrant expression of circular RNA DHPR facilitates tumor growth and metastasis by regulating the RASGEF1B/RAS/MAPK axis in hepatocellular carcinoma.

BACKGROUND: Circular RNAs (circRNAs) are noncoding RNAs. Accumulating evidence suggests that circRNAs play a critical role in human biological processes, especially tumorigenesis, and development. However, the exact mechanisms of action of circRNAs in hepatocellular carcinoma (HCC) remain unclear. METHODS: Bioinformatic tools and RT-qPCR were used to identify the role of circDHPR, a circRNA derived from the dihydropteridine reductase (DHPR) locus, in HCC and para-carcinoma tissues. Kaplan-Meier analysis and the Cox proportional hazard model were used to analyze the correlation between circDHPR expression and patient prognosis. Lentiviral vectors were used to establish stable circDHPR-overexpressing cells. In vitro and in vivo studies have shown that tumor proliferation and metastasis are affected by circDHPR. Mechanistic assays, including Western blotting, immunohistochemistry, dual-luciferase reporter assays, fluorescence in situ hybridization, and RNA immunoprecipitation, have demonstrated the molecular mechanism underlying circDHPR. RESULTS: CircDHPR was downregulated in HCC, and low circDHPR expression was associated with poor overall survival and disease-free survival rates. CircDHPR overexpression inhibits tumor growth and metastasis in vitro and in vivo. Further systematic studies revealed that circDHPR binds to miR-3194-5p, an upstream regulator of RASGEF1B. This endogenous competition suppresses the silencing effect of miR-3194-5p. We confirmed that circDHPR overexpression inhibited HCC growth and metastasis by sponging miR-3194-5p to upregulate the expression of RASGEF1B, which is regarded as a suppressor of the Ras/MAPK signaling pathway. CONCLUSIONS: Aberrant circDHPR expression leads to uncontrolled cell proliferation, tumorigenesis, and metastasis. CircDHPR may serve as a biomarker and therapeutic target for HCC.

Bloodless Laparoscopic Partial Splenectomy Assisted by Bipolar Radiofrequency Excision Hemostatic Device.

Among the lymphatic system in the human body, the spleen is the most extensive one and has hematopoietic, hemofiltration, blood storage, and immune functions. As a new method of preserving the spleen, laparoscopic partial splenectomy (LPS) has been increasingly applied in clinical practice with people's deeper insights into minimally invasive treatment and the development of technical equipment. Compared with conventional open splenectomy, LPS can preserve normal spleen tissue as much as possible, decrease the occurrence of complications after total splenectomy, and reduce postoperative hospital stay. The bipolar radiofrequency excision hemostatic device used for LPS can solidify the splenic tissue and close the small blood vessels, which reduces the hemorrhage of the spleen cross-section and clears the operative field, thus achieving the ideal effect of "bloodless partial splenectomy". Therefore, under the premise of strictly mastering the indications and fully understanding the vascular anatomy of the spleen, the application of the bipolar radiofrequency excision hemostatic device in LPS is worthy of clinical promotion.