TACE combined Lenvatinib plus Camrelizumab versus TACE alone in efficacy and safety for unresectable hepatocellular carcinoma: a propensity score-matching study.

BACKGROUNDS: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined Lenvatinib plus Camrelizumab (TLC) in unresectable hepatocellular carcinoma (uHCC) with those of TACE alone . METHODS: A retrospective analysis was performed on 222 patients with uHCC who were treated between September 2013 and Jun 2023. One group received TACE + lenvatinib + camrelizumab (TLC) (n = 97) and another group received TACE alone (n = 151). Efficacy and safety were compared after propensity score matching between the TLC and TACE groups. RESULTS: After propensity matching, the TLC group had higher objective response rate (ORR) (88.6% vs. 28.6%, P < 0.001), disease control rate (DCR) (94.3%% vs. 72.9%, P < 0.001), and conversion rates before and after propensity matching were 44.1% and 41.4%, respectively, compared with the TACE group. The median progression free survival (PFS) was longer in the TLC group than in the TACE group (12.7 vs. 6.1 months, P = 0.005). The median overall survival (OS) was longer in the TLC group than in the TACE group (19.4 vs. 13.0 months, P = 0.023). Cox multivariate analysis with different modes of adjustment showed that treatment was an independent influencing factor of PFS and OS. The interaction analysis showed that cirrhosis and Child-Pugh stage an interactive role in the PFS of different treatment. Decreased AFP after treatment portends higher ORR and DCR. CONCLUSION: TACE combined Lenvatinib plus Camrelizumab regimen was safe and superior to TACE alone in improving PFS, OS, and tumor response rates for unresectable recurrent HCC patients.

A novel surgical scheme for hepatectomy in hepatocellular carcinoma patients with clinically significant portal hypertension.

OBJECTIVE: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. BACKGROUNDS: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. METHODS: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. RESULTS: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. CONCLUSION: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

Radiotherapy is superior to transarterial chemoembolization as adjuvant therapy after narrow-margin hepatectomy in patients with hepatocellular carcinoma: A single-center prospective randomized study.

BACKGROUND: This study was recruited to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) as postoperative adjuvant therapy after narrow-margin hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: This single-center prospective randomized study was conducted in the Cancer Hospital, Guang Xi Medical University, Nanning. A total of 72 patients who received treatment in this hospital between August 2017 and July 2019 were included and randomly allocated to TACE group (n = 48) and RT group (n = 24). Next, overall survival (OS) and progression-free survival (PFS) rates, recurrence patterns, financial burden, and safety were evaluated. RESULTS: The difference between the RT and TACE groups was not significant in one-, three-, and five-year OS (87.5%, 79.0%, and 62.5% vs. 93.8%, 75.9%, and 63.4%, respectively, P = 0.071) and PFS rates (79.0%, 54.2%, and 22.6% vs. 75.0%, 47.9%, and 32.6%, respectively, P = 0.071). Compared to the TACE group, the RT group had significantly lower intrahepatic recurrence rate (20.8% vs. 52.1%, P = 0.011), higher extrahepatic recurrence rate (37.5% vs. 14.6%, P = 0.034), and no marginal and diffuse recurrences (0% vs. 16.7%, P < 0.05). The mean overall treatment cost was higher (¥62,550.59 ± 4397.27 vs. ¥40,732.56 ± 9210.54, P < 0.01), the hospital stay (15.1 ± 3.7 vs. 11.8 ± 4.1 days, P < 0.01) was longer, and the overall treatment stay (13.3 ± 5.3 vs. 41.29 ± 12.4 days, P < 0.01) was shorter in the TACE group than in the RT group. Besides, both groups did not exhibit significant differences in the frequency and severity of adverse events. CONCLUSION: Both adjuvant TACE and RT can better the OS and PFS of patients with HCC. However, RT has a significantly better performance than TACE in terms of improving intrahepatic recurrence rate, treatment cost and hospital stay.

Beam quality control technology for solid-state lasers based on thermal effects.

Thermal effects under high-power pumping significantly limit the laser beam quality. To address this, we developed an M2 simulation algorithm based on ray trajectory simulation and established a corresponding experimental platform. This approach optimized the M2 factor of pulsed lasers to 2.2 and output power of 25.9 W under a repetition rate of 10 kHz. The results revealed that under specific conditions, thermal effects, typically considered detrimental to beam quality, could significantly enhance it. Compared to other methods necessitating additional optical components, our strategy offers a streamlined and straightforward solution for beam quality control under high-power pumping conditions.

D-dimer to lymphocyte ratio can serve as a potential predictive and prognostic value in colorectal cancer patients with liver metastases.

BACKGROUND: The intent of this research was to generate and investigate the D-dimer to lymphocyte ratio (DLR) capacity to forecast the risk and prognosis of colorectal cancer liver metastases (CRCLM). METHODS: From January 2010 to December 2019, 177 clinicopathologically confirmed colorectal cancer (CRC) patients (89 in the control group and 88 in the experimental group) were identified at the Affiliated Cancer Hospital of Guangxi Medical University. Multivariate Cox regression analysis was used to screen independent predictive diagnostic and prognostic factors of liver metastasis in CRC, and receiver operating characteristic (ROC) curves and Kaplan‒Meier (K‒M) curves were established to analyze the diagnostic and predictive prognostic efficacy of the DLR in the development of CRCLM. RESULTS: Patients with CRCLM had higher DLR levels and D-dimer levels in their blood, with statistically significant differences (p < 0.001). DLR might be employed as a predictor for the development of CRCLM, according to ROC curve research (sensitivity 0.670, specificity 0.775, area under the curve 0.765). D-dimer, lymphocyte count CEA, CA125, and CA199 were not linked to prognosis in patients with CRCLM in Cox regression analysis of dichotomous variables. In contrast, DLR level was a possible risk factor for the prognosis of patients with CRCLM (HR = 2.108, p = 0.047), and age, T stage, and DLR level (DLR < 0.4) were connected with the prognosis of patients with CRCLM (p < 0.05). CONCLUSION: DLR serves as a risk indicator for the development of CRCLM.

Serum immune biomarker levels combined with hepatitis B virus infection status predict early recurrence of early-stage hepatocellular carcinoma with microvascular invasion after liver resection.

INTRODUCTION: The tumor immune response plays a vital role in cancer recurrence in patients with malignancies. We aim to clarify the risk factors for early recurrence and investigate the efficacy of blood-based biomarkers to predict the risk of early recurrence in early-stage hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) after hepatectomy. MATERIALS AND METHODS: A total of 101 cases of HCC with MVI who underwent liver resection were enrolled. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors of early recurrence. We calculated the area under the receiver operating characteristic curve to evaluate the performance of the four biomarkers identified as risk factors for early recurrence. RESULTS: Multiple logistic regression analysis indicated that complement (C)4, cluster of differentiation (CD)4+, immunoglobulin A (IgA), and hepatitis B virus (HBV) DNA of greater than 500 IU/mL were correlated with early recurrence of HCC. The area under the curve was greater for the combination model than for the HBV DNA, CD4+, IgA, or C4 models alone. CONCLUSION: Preoperative serum CD4+, C4, IgA, and HBV DNA levels were linked with early recurrence of early-stage HCC with MVI and the combination model was of considerable predictive value for the prognosis of HCC with MVI.

Exosome-delivered CD44v6/C1QBP complex drives pancreatic cancer liver metastasis by promoting fibrotic liver microenvironment.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) shows a remarkable predilection for liver metastasis. Pro-oncogenic secretome delivery and trafficking via exosomes are crucial for pre-metastatic microenvironment formation and metastasis. This study aimed to explore the underlying mechanisms of how PDAC-derived exosomes (Pex) modulate the liver microenvironment and promote metastasis. DESIGN: C57BL/6 mice were 'educated' by tail vein Pex injection. The intrasplenic injection liver metastasis and PDAC orthotopic transplantation models were used to evaluate liver metastasis. Stable cell lines CD44v6 (CD44 variant isoform 6) or C1QBP (complement C1q binding protein) knockdown or overexpression was established using lentivirus transfection or gateway systems. A total of 142 patients with PDAC in Huashan Hospital were retrospectively enrolled. Prognosis and liver metastasis were predicted using Kaplan-Meier survival curves and logistic regression models. RESULTS: Pex tail vein injection induced the deposition of liver fibrotic extracellular matrix, which promoted PDAC liver metastasis. Specifically, the exosomal CD44v6/C1QBP complex was delivered to the plasma membrane of hepatic satellite cells (HSCs), leading to phosphorylation of insulin-like growth factor 1 signalling molecules, which resulted in HSC activation and liver fibrosis. Expression of Pex CD44v6 and C1QBP in PDAC patients with liver metastasis was significantly higher than in PDAC patients without liver metastasis, and simultaneous high expression of exosomal CD44v6 and C1QBP correlated with a worse prognosis and a higher risk of postoperative PDAC liver metastasis. CONCLUSION: The Pex-derived CD44v6/C1QBP complex is essential for the formation of a fibrotic liver microenvironment and PDAC liver metastasis. Highly expressed exosomal CD44v6 and C1QBP are promising biomarkers for predicting prognosis and liver metastasis in patients with PDAC.

Lenvatinib with or without immune checkpoint inhibitors for patients with unresectable hepatocellular carcinoma in real-world clinical practice.

BACKGROUND: Lenvatinib is regarded as the first-line therapy for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of lenvatinib with or without immune checkpoint inhibitors (ICIs) in patients with unresectable HCC. METHODS: In this multicentric retrospective study, patients with unresectable HCC who treated with lenvatinib with or without ICIs would be enrolled. Overall survival, progression-free survival, objective response rate, and disease control rate were calculated to assess the antitumor response. RESULTS: Between January 2019 and August 2020, 65 patients received lenvatinib plus ICIs while other 45 patients received lenvatinib. The baseline characteristics were comparable between the two groups. Lenvatinib plus ICIs provided significantly higher overall survival (hazard ratio = 0.47, 95% CI 0.26-0.85; p = 0.013) and progression-free survival (hazard ratio = 0.35, 95% CI 0.20-0.63; p < 0.001) than lenvatinib monotherapy. Moreover, patients with lenvatinib plus ICIs had significantly higher objective response rate (41.5% vs 20.0%, p = 0.023) and disease control rate (72.3% vs 46.7%, p = 0.009) per RECIST v1.1 than those with lenvatinib. No treatment-related deaths were observed. Grade 3 or greater adverse events occurring in 10% or more of patients in either treatment group were hypertension [13 (20.0%) of 65 patients treated with lenvatinib plus ICIs vs 8 (17.8%) of 45 patients treated with lenvatinib], and palmar-plantar erythrodysesthesia [seven (10.8%) vs two (4.4%)]. CONCLUSIONS: In this real-world study, lenvatinib combined with ICIs showed significantly promising efficacy and manageable safety than lenvatinib alone in patients with unresectable HCC.

Clinical implications and biological features of a novel postoperative recurrent HCC classification: A multi-centre study.

BACKGROUND & AIMS: The multiplicity of hepatocellular carcinoma (HCC) recurrence patterns is the most important determinant of patients' postsurgical survival. A systematic HCC recurrence classification is needed to help prevent and treat postoperative HCC recurrence in the era of precision medicine. METHODS: A total of 1319 patients with recurrent HCC from four hospitals were enrolled and divided into a development cohort (n = 916), internal validation cohort (n = 225) and external validation cohort (n = 178). A comprehensive study of patients' clinicopathological factors and biological features was conducted. RESULTS: Four subtypes of recurrence were identified, which integrated recurrence features, survival, effects on systemic and liver function and potential therapeutics after recurrence: type I (solitary-intrahepatic oligorecurrence); type II (multi-intrahepatic oligorecurrence); type III (progression recurrence) and type IV (hyper-progression recurrence). Type III~IV recurrence indicated exceptionally poor prognosis. Subsequently, two nomogram models were established for type III~IV recurrence prediction, and both demonstrated excellent predictive performance and applicability of pre and postoperative strategy formulation. Multiple biological analyses revealed that HCC cases with type III~IV recurrence were characterized by enrichment in p53 mutations, CCND1 amplification, high proliferation/metastasis potential, inactive metabolism and immune exhaustion features. Over-expression of high mobility group protein 2 (HMGA2) enhanced the highly malignant behaviour of HCC through multiple molecular pathways, making it a potential prognostic predictor and therapeutic target. CONCLUSIONS: This 'recurrent HCC classification' has important potential value in identifying patients with surgical benefit, predicting postsurgical survival and guiding treatment strategies. Multidimensional biological insights also increased knowledge of factors associated with HCC recurrence.

Hazard rate for postoperative recurrence in patients with hepatocellular carcinoma at Barcelona Clinic Liver Cancer stage 0 or A1: A multicenter observational study.

AIM: Surgical treatment is the first-line treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A1 hepatocellular carcinoma (HCC), and postoperative monitoring improves long-term survival. We aimed to establish a reasonable short-interval follow-up duration for patients with HCC. METHODS: The cohort for this retrospective study included 1396 HCC patients with BCLC stage 0 or A1 disease who underwent curative resection from 2013 to 2016 at five centers in China. Hazard rates for recurrence were calculated using the hazard function. RESULTS: The recurrence rates in patients with BCLC stage 0 and A1 HCC were 46.4% and 58.0%, respectively. The hazard curve for stage 0 patients was relatively flat, and the hazard rate was consistently low (peak hazard rate 0.0163). The hazard rate curve for recurrence was initially high (peak hazard rate 0.0441) in patients with BCLC stage A1 disease and showed a rapid decreasing trend within 1 year, followed by a slow decreasing trend, reaching a low level (<0.0163) at approximately 36 months. The time to low risk was 47, 41, and 51 months in patients with cirrhosis, hepatitis B virus (HBV) infection, and satellite lesions, respectively. CONCLUSIONS: A short-interval follow-up of 1 year is sufficient for HCC patients with BCLC stage 0 disease, whereas a short-interval follow-up time of 3 years should be considered for patients with stage A1 disease. The follow-up period should be appropriately prolonged for patients with cirrhosis, HBV infection, and satellite lesions.

Developmental artificial neural network model to evaluate the preoperative safe limit of future liver remnant volume for HCC combined with clinically significant portal hypertension.

Background & aims: Finding a way to comprehensively integrate the presence and grade of clinically significant portal hypertension, amount of preserved liver function and extent of hepatectomy into the guidelines for choosing appropriate candidates to hepatectomy remained challenging. This study sheds light on these issues to facilitate precise surgical decisions for clinicians. Methods: Independent risk factors associated with grade B/C post-hepatectomy liver failure were identified by stochastic forest algorithm and logistic regression in hepatitis B virus-related hepatocellular carcinoma patients. Results: The artificial neural network model was generated by integrating preoperative pre-ALB, prothrombin time, total bilirubin, AST, indocyanine green retention rate at 15 min, standard future liver remnant volume and clinically significant portal hypertension grade. In addition, stratification of patients into three risk groups emphasized significant distinctions in the risk of grade B/C post-hepatectomy liver failure. Conclusion: The authors' artificial neural network model could provide a reasonable therapeutic option for clinicians to select optimal candidates with clinically significant portal hypertension for hepatectomy and supplement the hepatocellular carcinoma surgical treatment algorithm.

Hepatectomy involves removing the tumor from the liver and is considered the most effective treatment for hepatocellular carcinoma (HCC). Clinically significant portal hypertension is characterized by the presence of gastric and/or esophageal varices and a platelet count <100 × 10⁹/l with the presence of splenomegaly, which would aggravate the risk of post-hepatectomy liver failure, and is therefore regarded as a contraindication to hepatectomy. Over the past few decades, with improvement in surgical techniques and perioperative care, the morbidity of postoperative complications and mortality have decreased greatly. Current HCC guidelines recommend the expansion of hepatectomy to HCC patients with clinically significant portal hypertension. However, determining how to select optimal candidates for hepatectomy remains challenging. The authors' artificial neural network is a mathematical tool developed by simulating the properties of neurons with large-scale information distribution and parallel structure. Here the authors retrospectively enrolled 871 hepatitis B virus-related HCC patients and developed an artificial neural network model to predict the risk of post-hepatectomy liver failure, which could provide a reasonable therapeutic option and facilitate precise surgical decisions for clinicians.

Efficacy comparison of optimal treatments for hepatocellular carcinoma patients with portal vein tumor thrombus.

INTRODUCTION AND OBJECTIVES: Optimal treatment of hepatocellular carcinoma (HCC) involving portal vein tumor thrombus (PVTT) remains controversial. MATERIALS AND METHODS: A total of 627 HCC patients with PVTT after initial treatment with one of the following at Affiliated Tumor Hospital of Guangxi Medical University: liver resection (LR, n = 225), transarterial chemoembolization (TACE, n = 298) or sorafenib (n = 104) were recruited and randomly divided into the training cohort (n = 314) and internal validation cohort (n = 313). Survival analysis were repeated after stratifying patients by Cheng PVTT type. RESULTS: Resection led to significantly higher OS than the other two treatments among patients with type I or II PVTT. TACE worked significantly better than the other two treatments for patients with type III. All three treatments were associated with similar OS among patients with type IV. These findings were supported by the internal validation cohort. CONCLUSIONS: Our results suggest that the optimal treatment for HCC involving PVTT depends on the type of PVTT. LR may be more appropriate for type I or II PVTT; TACE, for type III Sorafenib may be more appropriate than invasive treatments for patients with type IV PVTT.

Patterns, treatments, and prognosis of tumor recurrence after resection for hepatocellular carcinoma with microvascular invasion: a multicenter study from China.

BACKGROUND: Microvascular invasion (MVI) is a risk factor of post-hepatectomy tumor recurrence for hepatocellular carcinoma (HCC). The patterns, treatments, and prognosis have not been documented in HCC patients with MVI. METHODS: A multicenter database of patients with HCC and MVI following resection was analyzed. The clinicopathological and initial operative data, timing and first sites of recurrence, recurrence management, and long-term survival outcomes were analyzed. RESULTS: Of 1517 patients included, the median follow-up was 39.7 months. Tumor recurrence occurred in 928 patients, with 49% within 6 months of hepatectomy and 60% only in the liver. The incidence of intrahepatic only recurrence gradually increased with time after 6 months. Patients who developed recurrence within 6 months of hepatectomy had worse survival outcomes than those who developed recurrence later. Patients who developed intrahepatic only recurrence had better prognosis than those with either extrahepatic only recurrence or those with intra- and extrahepatic recurrence. Repeat resection of recurrence with curative intent resulted in better outcomes than other treatment modalities. CONCLUSION: Post-hepatectomy tumor recurrence in patients with HCC and MVI had unique characteristics and recurrence patterns. Early detection of tumor recurrence and repeat liver resection with curative intent resulted in improved long-term survival outcomes.

Development and Validation of a Nomogram to Preoperatively Estimate Post-hepatectomy Liver Dysfunction Risk and Long-term Survival in Patients With Hepatocellular Carcinoma.

OBJECTIVE: To develop a nomogram to estimate the risk of SPLD (International Study Group of Liver Surgery definition grade B or C) and long-term survival in patients with HCC before hepatectomy. BACKGROUND: SPLD is the leading cause of post-hepatectomy mortality. The decision to refer an HCC patient for hepatectomy is mainly based on the survival benefit and SPLD risk. Prediction of SPLD risk before hepatectomy is of great significance. METHODS: A total of 2071 consecutive patients undergoing hepatectomy for HCC were recruited and randomly divided into the development cohort (n = 1036) and internal validation cohort (n = 1035). Five hundred ninety patients from another center were enrolled as the external validation cohort. A nomogram was developed based on independent preoperative predictors of SPLD determined in multivariable logistic regression analysis. RESULTS: The SPLD incidences in the development, internal, and external validation cohorts were 10.1%, 9.5%, and 8.6%, respectively. Multivariable analysis identified total bilirubin, albumin, gamma-glutamyl transpeptidase, prothrombin time, clinically significant portal hypertension, and major resection as independent predictors for SPLD. Incorporating these variables, the nomogram showed good concordance statistics of 0.883, 0.851, and 0.856, respectively in predicting SPLD in the 3 cohorts. Its predictive performance in SPLD, 90-day mortality, and overall survival (OS) outperformed Child-Pugh, model for end-stage liver disease, albumin-bilirubin, and European Association for the Study of the Liver recommended algorithm. With a nomogram score of 137, patients were stratified into low and high risk of SPLD. High-risk patients also had decreased OS. CONCLUSIONS: The nomogram showed good performance in predicting both SPLD and OS. It could help surgeons select suitable HCC patients for hepatectomy.

Macrophage polarization-associated lnc-Ma301 interacts with caprin-1 to inhibit hepatocellular carcinoma metastasis through the Akt/Erk1 pathway.

BACKGROUND: Epithelial-mesenchymal transition (EMT) promotes migration, invasion, and metastasis of hepatocellular carcinoma (HCC) cells. The molecular mechanisms behind EMT and metastasis in HCC remain unclear. METHODS: Microarray analysis was used to identify lncRNAs expression during polarization of U937 macrophages from M2 to M1 phenotype. The expression of the identified lncRNA was compared between clinical samples of HCC tissues or adjacent normal tissues, as well as between HCC and normal liver cell lines. lnc-Ma301 was overexpressed or knocked-down in HCC cell lines, and the effects were assessed in vitro and in vivo. Interactions among lnc-Ma301 and its potential downstream targets caprin-1 were investigated in HCC cell lines. Effects of lnc-Ma301 over- and underexpression on the Akt/Erk1 signaling pathways were examined. RESULTS: Microarray analyses identified lnc-Ma301 as one of the most overexpressed long non-coding RNAs during polarization of U937 macrophages from M2 to M1 phenotype. Lnc-Ma301 showed lower expression in HCC tissues than in adjacent normal tissues, and lower expression was associated with worse prognosis. Activation of lnc-Ma301 inhibited cell proliferation, migration and EMT in HCC cell cultures, and it inhibited lung metastasis of HCC tumors in mice. Mechanistic studies suggested that lnc-Ma301 interacts with caprin-1 to inhibit HCC metastasis and EMT through Akt/Erk1 pathway. CONCLUSIONS: Lnc-Ma301 may help regulate onset and metastasis of HCC.

Artificial neural network model to predict post-hepatectomy early recurrence of hepatocellular carcinoma without macroscopic vascular invasion.

BACKGROUND: The accurate prediction of post-hepatectomy early recurrence (PHER) of hepatocellular carcinoma (HCC) is vital in determining postoperative adjuvant treatment and monitoring. This study aimed to develop and validate an artificial neural network (ANN) model to predict PHER in HCC patients without macroscopic vascular invasion. METHODS: Nine hundred and three patients who underwent curative liver resection for HCC participated in this study. They were randomly divided into derivation (n = 679) and validation (n = 224) cohorts. The ANN model was developed in the derivation cohort and subsequently verified in the validation cohort. RESULTS: PHER morbidity in the derivation and validation cohorts was 34.8 and 39.2%, respectively. A multivariable analysis revealed that hepatitis B virus deoxyribonucleic acid load, γ-glutamyl transpeptidase level, α-fetoprotein level, tumor size, tumor differentiation, microvascular invasion, satellite nodules, and blood loss were significantly associated with PHER. These factors were incorporated into an ANN model, which displayed greater discriminatory abilities than a Cox's proportional hazards model, preexisting recurrence models, and commonly used staging systems for predicting PHER. The recurrence-free survival curves were significantly different between patients that had been stratified into two risk groups. CONCLUSION: When compared to other models and staging systems, the ANN model has a significant advantage in predicting PHER for HCC patients without macroscopic vascular invasion.

Safe standard remnant liver volume after hepatectomy in HCC patients in different stages of hepatic fibrosis.

BACKGROUND: To determine the standard remnant liver volume (SRLV) threshold to avoid postoperative hepatic insufficiency inpatients in different stages of hepatic fibrosis who undergo right hemi-hepatectomy. METHODS: Data for 85 patients at our single medical center were analysed prospectively to examine whether the following factors differed significantly between those who experienced postoperative hepatic insufficiency and those who did not: height, prothrombin time, remnant liver volume, SRLV or hepatic fibrosis stage. RESULTS: Logistic regression showed SRLV and hepatic fibrosis stage to be independent risk factors for postoperative hepatic insufficiency. The threshold SRLV for predicting insufficiency was 203.2 ml/m2 across all patients [area under receiver operating characteristic curve (AUC) 0.778, sensitivity 66.67%, specificity 83.64%, p<0.0001), 193.8 ml/m2 for patients with severe hepatic fibrosis (AUC 0.938, sensitivity 91.30%, specificity 85.71%, p<0.0001), and 224.3 ml/m2 for patients with cirrhosis (AUC 0.888, sensitivity 100%, specificity 64.29%, p<0.0001). CONCLUSIONS: Right hemi-hepatectomy may be safer in Chinese patients when the standard remnant liver volume is more than 203.2 ml/m2 in the absence of hepatic fibrosis or cirrhosis, 193.8 ml/m2 in the presence of severe hepatic fibrosis or 224.3 ml/m2 in the presence of cirrhosis.

The lncRNA SNHG16 affects prognosis in hepatocellular carcinoma by regulating p62 expression.

Long noncoding RNAs (lncRNAs) regulate tumor development and progression by promoting proliferation, invasion, and metastasis. The oncogenic role of lncRNA SNHG16 in hepatocellular carcinoma (HCC) has not been revealed. LncRNA SNHG16 is upregulated in HCC and correlates with poorer prognosis. Patients with high SNHG16 expression showed lower rates of overall and disease-free survival than patients with low SNHG16 expression. Multivariate Cox regression revealed that SNHG16 expression was an independent predictor of poor overall and disease-free survival. In vitro, SNHG16 promoted HCC cell proliferation, migration, and invasion while inhibiting apoptosis; in vivo, it accelerated tumor development. Altering SNHG16 expression altered levels of miR-17-5p, which in turn modified expression of p62, which has been shown to regulate the mTOR and NF-κB pathways. Indeed, altering SNHG16 expression in HCC cells activated mTOR and NF-κB signaling. These results reveal a potential mechanism for the oncogenic role of SNHG16 in HCC. SNHG16 may therefore be a promising diagnostic marker as well as therapeutic target in HCC.

The chances of hepatic resection curing hepatocellular carcinoma.

BACKGROUND & AIMS: The popular sense of the word "cure" implies that a patient treated for a specific disease will return to have the same life expectancy as if he/she had never had the disease. In analytic terms, it translates into the concept of statistical cure which occurs when a group of patients returns to having similar mortality to a reference population. The aim of this study was to assess the probability of being cured from hepatocellular carcinoma (HCC) by hepatic resection. METHODS: Data from 2,523 patients undergoing resection for HCC were used to fit statistical cure models, to compare disease-free survival (DFS) after surgery to the survival expected for patients with chronic hepatitis and/or cirrhosis and the general population, matched by sex, age, race/ethnicity and year of diagnosis. RESULTS: The probability of resection enabling patients with HCC to achieve the same life expectancy as those with chronic hepatitis and/or cirrhosis was 26.3%. The conditional probability of achieving this result was time-dependent, requiring about 8.9 years to be accomplished with 95% certainty. Considering the general population as a reference, the cure fraction decreased to 17.1%. Uncured patients had a median DFS of 1.5 years. In multivariable analysis, patient's age and the risk of early HCC recurrence (within 2 years) were independent determinants of the chance of cure (p <0.001). The chances of being cured ranged between 36.0% for individuals at low risk of early recurrence to approximately 3.6% for those at high risk. CONCLUSION: Estimates of the chance of being cured of HCC by resection showed that cure is achievable, and its likelihood increases with the passing of recurrence-free time. The data presented herein can be used to inform decision making and to provide patients with accurate information. LAY SUMMARY: Data from 2,523 patients who underwent resection for hepatocellular carcinoma were used to estimate the probability that resection would enable treated patients to achieve the same life expectancy as patients with chronic hepatitis and/or cirrhosis, and the general population. Herein, the cure model suggests that in patients with hepatocellular carcinoma, resection can enable patients to achieve the same life expectancy as those with chronic liver disease in 26.3% of cases and as the general population in 17.1% of cases.

An Eastern Hepatobiliary Surgery Hospital/Portal Vein Tumor Thrombus Scoring System as an Aid to Decision Making on Hepatectomy for Hepatocellular Carcinoma Patients With Portal Vein Tumor Thrombus: A Multicenter Study.

Portal vein tumor thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first-order branch of the main portal vein (MPV) or above could benefit from negative margin (R0) liver resection (LR). An Eastern Hepatobiliary Surgery Hospital (EHBH)/PVTT scoring system was established to predict the prognosis of HCC patients with PVTT after R0 LR and guide selection of subgroups of patients that could benefit from LR. HCC patients with PVTT limited to a first-order branch of the MPV or above who underwent R0 LR as an initial therapy were included. The EHBH-PVTT score was developed from a retrospective cohort in the training cohort using a Cox regression model and validated in a prospective internal validation cohort and three external validation cohorts. There were 432 patients in the training cohort, 285 in the prospective internal validation cohort, and 286, 189, and 135 in three external validation cohorts, respectively. The score was calculated using total bilirubin, α-fetoprotein (AFP), tumor diameter, and satellite lesions. The EHBH-PVTT score differentiated two groups of patients (≤/>3 points) with distinct long-term prognoses (median overall survival [OS], 17.0 vs. 7.9 months; P < 0.001). Predictive accuracy, as determined by the area under the time-dependent receiver operating characteristic curves (AUCs; 0.680-0.721), was greater than that of the other commonly used staging systems for HCC and PVTT. Conclusion: The EHBH-PVTT scoring system was more accurate in predicting the prognosis of HCC patients with PVTT than other staging systems after LR. It selected appropriate HCC patients with PVTT limited to a first-order branch of the MPV or above for LR. It can be used to supplement the other HCC staging systems.