Zhiyu Xiao

High expression of trimethylated histone H3 lysine 4 is associated with poor prognosis in hepatocellular carcinoma

Tumor-associated epigenetic alterations including DNA methylation and histone modifications are important determinants in the initiation and progression of hepatocellular cancer (HCC) and represent promising biomarkers and therapeutic targets. Locus-specific trimethylation of histone H3 lysine 4 (H3K4me) is a well-known modification linked to the enhanced transcriptional expression of many genes activated in HCC. Our aim was to assess the cellular expression pattern of H3K4me3 in HCC and its association with clinicopathologic variables and outcome. Expression of H3K4me3 and the histone methyltransferase (HMT) SET and MYND domain-containing protein 3 (SMYD3) was studied by Western blotting and immunohistochemistry in cell lines and tumor tissue microarray from a well-characterized series of HCC patients (n = 168). The optimal cut-point of H3K4me3 expression for prognosis was determined by the X-tile program. The prognostic significance was evaluated using Kaplan-Meier survival estimates and log-rank tests. Tumor tissue microarray from another independent HCC patients cohort (n = 147) was used for validation studies. Expression of H3K4me3 and SMYD3 were enhanced in HCC cell lines. In tumor specimens, enhanced expression of H3K4me3 was correlated with reduced overall survival (P < .0001), especially in early-stage HCC patients (TNM I/II). Furthermore, both univariate and multivariate analyses revealed that H3K4me3 level was a significant and independent predictor of poor survival (hazard ratio, 3.592; 95% confidence interval, 2.302-5.605). In addition, H3K4m3 expression was positively correlated with SMYD3 expression in both testing and validation cohorts (P < .0001). In conclusion, H3K4me3 level defines unrecognized subsets of HCC patients with distinct epigenetic phenotype and clinical outcome and can thus be a novel predictor for poor prognosis of HCC patients, especially at TNM I/II stage.

Is the end of the T-tube drainage era in laparoscopic choledochotomy for common bile duct stones is coming? A systematic review and meta-analysis.

Objective:This study aims to compare the efficacy and safety of T-tube free (TTF) versus T-tube drainage (TTD) after laparoscopic common bile duct exploration (LCBDE). Background:LCBDE has been proven to be an effective and preferred treatment approach for uncomplicated choledocholithiasis, and the appropriateness of T-tube placement after laparoscopic choledochotomy for common bile duct (CBD) stones is still under debate. Methods:A systematic literature search (PubMed, EMBASE, Science Citation Index, Springer-Link, and Cochrane Central Register of Controlled Trials) was performed. Postoperative complications were evaluated/graded according to the modified Clavien classification. Other variables extracted including primary closures of the CBDs and the associated assistant methods, T-tube types, and placement durations. Stratified and sensitivity analyses were performed both to explore heterogeneity between studies and to assess the effects of the study qualities. Results:A total of 956 patients from 12 studies were included. The pooled odds ratio for postoperative complications and biliary-specific complications in TTF was found to be 0.59 [95% confidence interval (CI), 0.38–0.91; P = 0.02], 0.62 (95% CI, 0.36–1.06; P = 0.08), respectively, when compared with TTD. Operative time and hospital stay were significantly decreased in the TTF group, with the pooled weighted mean differences being 18.84 minutes (95% CI, −27.01 to 10.67; P < 0.01) and 3.22 days (95% CI, −4.59 to 1.84; P < 0.01), respectively. Conclusions:The results of this meta-analysis demonstrate that among patients undergoing laparoscopic choledochotomy for common bile duct stones, primary closure of the CBD alone is superior to TTD; however, there is no significant benefit in terms of primary duct closure with various internal or external drainage techniques. Further randomized controlled trials are eagerly awaited to prove these findings.

Patterns and prognostic value of lymph node dissection for resected perihilar cholangiocarcinoma

Lymph node metastasis is a major prognostic factor for perihilar cholangiocarcinoma (PHC). However, prognostic significance of extent of node dissection, lymph node ratio (LNR), and number and location of positive nodes remain unclear. We aimed to evaluate whether node status, LNR, or number or location of positive nodes are independent factors for staging in PHC and to determine the minimum requirements for node examination.

Duodenal pseudolymphoma: A case report and review of literature

We report a rare case of duodenal pseudolymphoma without any symptoms. The lesion located in front of the head of the pancreas was found accidentally during a medical examination. The findings of computed tomography and positron emission tomography-computed tomography suggested a stromal tumor or malignant lymphoma. Surgical resection was performed. The lesions were pathologically diagnosed as duodenal pseudolymphoma.

The impact of liver resection on survival outcomes of hepatocellular carcinoma patients with extrahepatic metastases: A propensity score matching study

The majority of hepatocellular carcinoma patients (HCCs) with extrahepatic metastases die of progressive intrahepatic tumor. There have been little data on the role of primary tumor resection (PTR) for HCCs with extrahepatic metastases but with resectable primary tumors.

Epithelial-Mesenchymal Transition is Superior to Vessels-Encapsulate Tumor Cluster in Promoting Metastasis of Hepatocellular Carcinoma: a Morphological Evidence

Purpose Vessels-encapsulate tumor cluster (VETC) is a vascular pattern distinct from classical capillary-like pattern. It is reported that VETC structure is common in hepatocellular carcinoma (HCC) and can promote HCC metastasis in an epithelial-mesenchymal transition (EMT)-independent but VETC-dependent manner. However, the main metastatic manner of HCC containing both VETC and classical vascular structure (we called VETC±) is unknown. Methods Vascular pattern types and E-cadherin expression were evaluated by immunohistochemical staining in 168 HCC tissues, 50 pairs of primary HCC tissues and intrahepatic metastatic lesions, as well as 12 pairs of primary HCC tissues and major portal vein tumor thrombus. Survival and recurrence rates were evaluated using Kaplan-Meier analysis. The multivariate Cox proportional hazards model was used to determine the independent prognostic factors of HCC. Results VETC± cases were more common than VETC+ cases (HCC tissues with a VETC pattern fully distributed in the HCC section) in HCC. Statistical analysis showed that VETC± was an independent predictor of survival and recurrence. Furthermore, E-cadherin was positively correlated with the presence of VETC structure. In the case of HCCs with VETC±, their metastases (both intrahepatic and major vascular) were more likely to be VETC negative. Conclusions Our findings suggest that EMT may be superior to VETC in promoting HCC metastasis. Thus, both anti-EMT and anti-VETC agents should be considered in the case of HCC with VETC±.