Tumor burden score-AFP-albumin-bilirubin grade score predicts the survival of patients with hepatocellular carcinoma after liver resection.

PURPOSE: There is little information regarding the overall survival (OS) predictive ability of the combination of tumor burden score (TBS), α-fetoprotein (AFP), and albumin-bilirubin (ALBI) grade for patients with hepatocellular carcinoma (HCC). Here, we aimed to develop a model including TBS, AFP, and ALBI grade to predict HCC patient OS following liver resection. METHODS: Patients (N = 1556) from six centers were randomly divided 1:1 into training and validation sets. The X-Tile software was used to determine the optimal cutoff values. The time-dependent area under the receiver operating characteristic curve (AUROC) was calculated to assess the prognostic ability of the different models. RESULTS: In the training set, tumor differentiation, TBS, AFP, ALBI grade, and Barcelona Clinic Liver Cancer (BCLC) stage were independently related to OS. According to the coefficient values of TBS, AFP, and ALBI grade, we developed the TBS-AFP-ALBI (TAA) score using a simplified point system (0, 2 for low/high TBS, 0, 1 for low/high AFP and 0,1 for ALBI grade 1/2). Patients were further divided into low TAA (TAA ≤ 1), medium TAA (TAA = 2-3), and high TAA (TAA= 4) groups. TAA scores (low: referent; medium, HR = 1.994, 95% CI = 1.492-2.666; high, HR = 2.413, 95% CI = 1.630-3.573) were independently associated with patient survival in the validation set. The TAA scores showed higher AUROCs than BCLC stage for the prediction of 1-, 3-, and 5-year OS in both the training and validation sets. CONCLUSION: TAA is a simple score that has better OS prediction performance than the BCLC stage in predicting OS for HCC patients after liver resection.

Preoperative aspartate aminotransferase to albumin ratio correlates with tumor characteristics and predicts outcome of hepatocellular carcinoma patients after curative hepatectomy: a multicenter study.

AIMS: This study aimed to evaluate the clinical significance of the preoperative aminotransferase to albumin ratio (AAR) in patients with hepatocellular carcinoma (HCC) after hepatectomy. METHODS: From five hospitals, a total of 991 patients with HCC admitted between December 2014 and December 2019 were included as the primary cohort and 883 patients with HCC admitted between December 2010 and December 2014 were included as the validation cohort. The X-tile software was conducted to identify the optimal cut-off value of AAR. RESULTS: In the primary cohort, the optimal cut-off value of the AAR was defined as 0.7 and 1.6, respectively. Compared to patients with AAR 0.7-1.6, those with AAR > 1.6 showed significantly worse overall survival (OS) and RFS, whereas those with AAR < 0.7 showed significantly better OS and RFS (all p < 0.001). Pathologically, patients with AAR > 1.6 had more aggressive tumour characteristics, such as larger tumour size, higher incidence of microvascular invasion, and severe histologic activity, and higher AFP level than patients with AAR < 0.7. Consistently, the abovementioned clinical significance of AAR was confirmed in the validation cohort. CONCLUSIONS: A high AAR was significantly correlated with advanced tumours and severe hepatic inflammation, and a worse prognosis of HCC.

Tenofovir vs. entecavir on recurrence of hepatitis B virus-related hepatocellular carcinoma beyond Milan criteria after hepatectomy.

BACKGROUND: Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria. METHODS: Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence. RESULTS: The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS. CONCLUSIONS: Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.

Comparison of nucleoside and nucleotide analogs in the recurrence of hepatitis B virus-related hepatocellular carcinoma after surgical resection: A multicenter study.

BACKGROUND: Antiviral therapy should reduce the recurrence of hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) after surgical resection. However, there is little research on whether various antiviral drugs have different prognostic effects in patients with HBV-related HCC after curative liver resection. The present study compared the effects of nucleotide analog (NtA) and nucleoside analog (NsA) antiviral therapies after surgical resection on the prognosis of HBV-related HCC. METHODS: A total of 1303 patients with HBV-related HCC who received curative hepatectomy at five institutes between April 2014 and April 2019 were retrospectively enrolled and analyzed. Propensity matching analysis was used to compare the outcomes of HCC patients given NsA versus NtA therapy. Subgroup analysis of patients treated with entecavir (ETV) and tenofovir disoproxil fumarate (TDF) was also performed. RESULTS: Among 1303 patients, 759 (58.2%) patients developed recurrence, and 460 (35.3%) patients died. Multivariable analyses revealed that NtA therapy significantly decreased the risk of HCC recurrence (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.51-0.80; p < 0.001) and HCC-related death (HR, 0.52; 95% CI, 0.36-0.76; p = 0.001) compared to that with NsA therapy. Subgroup analysis showed that TDF treatment was associated with significantly lower rates of HCC recurrence (HR, 0.64; 95% CI, 0.49-0.83; p = 0.001) and death (HR, 0.32; 95% CI, 0.20-0.50; p < 0.001) than ETV treatment. CONCLUSIONS: Nucleotide analog treatment, but not NsA treatment, significantly reduced the risk of HCC recurrence in patients with HBV-related HCC and improved overall survival after curative hepatic resection.

LLGL2 Increases Ca2+ Influx and Exerts Oncogenic Activities via PI3K/AKT Signaling Pathway in Hepatocellular Carcinoma.

BACKGROUND: Lethal giant larvae (Lgl), scaffolding proteins, regulate the epithelial cell apicobasal polarity in Drosophila. They play important roles in asymmetric cell division, cell migration, and progenitor cells self-renewal as tumor suppressors. One of Lgl mammalian homologues proteins, LLGL2 overexpression has been reported in ER+ breast cancer and promotes tumor proliferation through regulating leucine uptake. Nonetheless, the role of LLGL2 in hepatocellular carcinoma (HCC) is still unknown. METHODS: TCGA dataset mining, qRT-PCR, Western blot along with immunohistochemistry assays were employed to explore LLGL2 expression in human HCC samples and cell lines. Moreover, the clinical value of LLGL2 was investigated in 156 HCC patients. Furthermore, the role as well as the molecular mechanism of LLGL2 in the progression of HCC was explored through a series of in vitro and in vivo experiments. RESULTS: LLGL2 was up-regulated in HCC tissues, which was related with certain clinicopathological features including tumor number, vascular invasion as well as advanced stage. High expression of LLGL2 predicted poor prognosis after hepatectomy. LLGL2 promoted HCC cells proliferation, migration and invasion through PI3K/ATK signaling by promoting calcium ion influx. CONCLUSION: Our study identified that LLGL2 is a tumor promoter in HCC for the first time, which could potentially be utilized as a new biomarker and a therapeutic target for HCC.

A Novel Score Predicts HBV-Related Hepatocellular Carcinoma Recurrence After Hepatectomy: a Retrospective Multicenter Study.

BACKGROUND: In China, hepatitis B virus (HBV) is an important causative factor of hepatocellular carcinoma (HCC). The contribution and interaction of fibrosis-4 (FIB-4) score and total tumor volume (TTV) in association with HCC recurrence is unknown. A reliable point score based on the FIB-4 score, TTV, and differentiation grade was established to predict the postoperative recurrence of HBV-related HCC patients who underwent hepatic resection (HR). METHODS: Three hundred thirty-eight HBV-related HCC patients from three institutions treated by HR were enrolled in this retrospective study. Prognostic factors were also evaluated by univariate and multivariate analysis using Cox's proportional hazards model in the training cohort. The DFT score was established by a Cox regression model and validated in the internal cohort and the external cohorts from the other two institutions. RESULTS: The DFT score differentiated four groups of HBV-related HCC patients (0, 1-2, 3, 4-5 points) with distinct prognosis (median recurrence-free survival (RFS), 72.7 vs. 53.0 vs. 23.2 vs. 5.7 months; P < 0.05). Its predictive accuracy as determined by the area under the receiver operating characteristic curve (AUC) at 1, 3, and 5 years (AUCs 0.7319, 0.7031, and 0.6972) was greater than the other three staging systems for HCC. These findings were supported by the validation cohorts. CONCLUSIONS: The DFT model is a reliable and objective model to predict the RFS of HBV-related HCC patients after HR.

Pulmonary function impairment predicted poor prognosis of patients with hepatocellular carcinoma after hepatectomy.

Tumor hypoxia can influence the progression and metastasis of various cancers, including hepatocellular carcinoma (HCC). Clinical studies have indicated that hyperbaric oxygen may improve the prognosis and reduce complications in HCC patients; however, whether pulmonary function can influence the prognosis of HCC remains unknown. In this study, we found that pulmonary function was associated with clinicopathological features, including smoking, liver cirrhosis, tumor size Edmondson-Steiner grade, total operative blood loss and perioperative blood transfusion. Through Cox proportional hazard regression analysis, smoking, tumor number, tumor size, liver cirrhosis, total operative blood loss and pulmonary function were independent risk factors for overall survival (OS) and disease-free survival (DFS). In addition, poor pulmonary function was independently associated with shorter survival and increased HCC recurrence in patients. Notably, we also found that HCC with liver cirrhosis predicted worse prognosis. In summary, our study found pulmonary function could influence HCC progression. Improve pulmonary function may enhance the OS and DFS of patients with HCC.

PTIP promotes recurrence and metastasis of hepatocellular carcinoma by regulating epithelial-mesenchymal transition.

Hepatocellular carcinoma (HCC) is one of the most lethal tumors worldwide, which is mainly due to the high recurrence and metastasis rate after hepatectomy. In this study, we found that PTIP expression was dramatically upregulated in human HCC tissues and cell lines. High expression of PTIP was shown to be associated with aggressive clinicopathological features, including liver cirrhosis, vascular invasion and advanced stage. In addition, PTIP overexpression was independently associated with shorter survival and increased HCC recurrence in patients. Knockdown of the PTIP expression significantly inhibited invasion and metastasis in vitro and in vivo, whereas ectopic expression of PTIP significantly promoted invasion and metastasis. Mechanistically, PTIP promotes HCC progress by facilitating epithelial-mesenchymal transition (EMT). Notably, we also found that PTIP might increase miR-374a expression to promote EMT and metastasis in HCC. In summary, our study identified PTIP as a new potential prognostic indicator and therapeutic target for HCC.

Absorbable polymeric surgical clips for appendicular stump closure: A randomized control trial of laparoscopic appendectomy with lapro-clips.

A randomized control trial was performed to evaluate the effectiveness and safety of absorbable polymeric clips for appendicular stump closure in laparoscopic appendectomy (LA). Patients were randomly enrolled into an experimental group (ligation of the appendicular base with Lapro-Clips, L-C group) or control group (ligation of the appendicular base with Hem-o-lok Clips, H-C group). We identified 1,100 patients who underwent LA between April 1, 2012 and February 3, 2015. Overall, 99 patients (9.0%, 99/1,100) developed a complication following LA (47 [8.5%] in the L-C group and 52 [9.5%] in the H-C group (P = 0.598). No statistically significant differences were observed in intra-abdominal abscesses, stump leakage, superficial wound infections, post-operative abdominal pain, overall adverse events, or the duration of the operations and hospital stays between the groups (all p > 0.05). Adverse risk factors associated with the use of absorbable clips in LA included body mass index ≥ 27.5 kg/m2, diabetes, American Society of Anesthesiologists degree ≥ III, gangrenous appendicitis, severe inflammation of the appendix base, appendix perforation, and the absence of peritoneal drainage. The results indicate that the Lapro-Clip is a safe and effective device for closing the appendicular stump in LA in select patients with appendicitis.

Tumor deposits counted as positive lymph nodes in TNM staging for advanced colorectal cancer: a retrospective multicenter study.

We investigated the possibility of counting tumor deposits (TDs) as positive lymph nodes (pLNs) in the pN category and evaluated its prognostic value for colorectal cancer (CRC) patients. A new pN category (npN category) was calculated using the numbers of pLNs plus TDs. The npN category included 4 tiers: npN1a (1 tumor node), npN1b (2-3 tumor nodes), npN2a (4-6 tumor nodes), and npN2b (≥7 tumor nodes). We identified 4,121 locally advanced CRC patients, including 717 (11.02%) cases with TDs. Univariate and multivariate analyses were performed to evaluate the disease-free and overall survival (DFS and OS) for npN and pN categories. Multivariate analysis showed that the npN and pN categories were both independent prognostic factors for DFS (HR 1.614, 95% CI 1.541 to 1.673; HR 1.604, 95% CI 1.533 to 1.679) and OS (HR 1.633, 95% CI 1.550 to 1.720; HR 1.470, 95% CI 1.410 to 1.532). However, the npN category was superior to the pN category by Harrell's C statistic. We conclude that it is thus feasible to consider TDs as positive lymph nodes in the pN category when evaluating the prognoses of CRC patients, and the npN category is potentially superior to the TNM (7th edition) pN category for predicting DFS and OS among advanced CRC patients.

Wait-and-see or radical surgery for rectal cancer patients with a clinical complete response after neoadjuvant chemoradiotherapy: a cohort study.

A wait-and-see policy might be considered instead of surgery for rectal cancer patients with no residual tumor or involved lymph nodes on imaging or endoscopy after neoadjuvant chemoradiotherapy (clinical complete response, cCR). In this cohort study, we compared the oncologic outcomes of rectal cancer patients with a cCR who were managed according to a wait-and-see policy (observation group) or with surgery (surgery group). In the observation group, follow-up was performed every 3 months for the first year and consisted of MRI, endoscopy with biopsy, computed tomography and transrectal ultrasonography. In the surgery group, patients received radical surgery. Long-term oncologic outcomes were estimated using Kaplan-Meier curves. Thirty patients were enrolled in the observation group (median follow-up, 60 months; range, 18-100 months), and 92 patients were enrolled in the surgery group (median follow-up, 58 months; range, 18-109 months). The 5-year disease free survival and overall survival rates were similar in the two groups: 90.0% vs. 94.3% (P = 0.932) and 100.0% vs. 95.6% (P = 0.912), respectively. We conclude that for rectal cancer patients with a cCR after neoadjuvant chemoradiotherapy, a wait-and-see policy with strict selection criteria, follow-up and salvage treatments achieves outcomes at least as good as radical surgery. Additionally, we declare that the pCR (pathologic complete regression) and non-pCR subgroups of patients with a cCR have similar long-term failure (local recurrence and/or distant metastasis) rate.