Liquid-Liquid Phase Separation-Related Genes Associated with Tumor Grade and Prognosis in Hepatocellular Carcinoma: A Bioinformatic Study.

AIM: The aim of the present study was to identify the association between tumor grade and liquid-liquid phase separation (LLPS)-related genes, and to generate a LLPS-related gene-based risk index (LLPSRI) as a prognostic tool for hepatocellular carcinoma (HCC). METHODS: Weighted gene correlation network analysis was performed to test whether the LLPS-related gene modules were associated with tumor grade of HCC. The candidate modules were subjected to functional enrichment analysis. We generated a LLPSRI using the expression profiles of the hub genes among the candidate modules in order to identify patients at high risk. Then, the biological characteristics of the high-risk patients were revealed using gene set enrichment analysis. Additionally, an independent external data set was used to validate the LLPSRI. RESULTS: Four gene modules showed a significant positive correlation with tumor grade and involved various cancer-related pathways. Among the hub genes, six were selected to generate the LLPSRI, which was significantly associated with prognosis of HCC patients. The LLPSRI could successfully divide patients with HCC into high- and low-risk groups, and patients in the high-risk group showed shorter overall survival than those in the low-risk group. E2F, MYC, and mTORC1 signaling may be important determinants of survival in the high-risk group. The prognostic value of the LLPSRI was validated with the independent external data set. CONCLUSION: We identified LLPS-related gene modules that are associated with HCC tumor grade. The LLPSRI may be useful as a prognostic marker of HCC, and it may reliably stratify patients into groups at low or high risk of worse survival. Our analysis also suggests that certain biological characteristics of HCC may be associated with high risk of worse survival.

One-step percutaneous transhepatic cholangioscopic lithotripsy in patients with choledocholithiasis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) may be inappropriate for most patients with choledocholithiasis. This study aimed to evaluate one-step percutaneous transhepatic cholangioscopic lithotripsy (PTCSL) in the treatment of patients with choledocholithiasis who could not undergo ERCP (e.g., failed ERCP, altered anatomy, and/or contra-indications). METHOD: This was a retrospective single-centre series of 67 patients who underwent choledocholithiasis between November 2015 and March 2018: 35 with one-step PTCSL (Group A) and 32 with laparoscopic common bile duct (CBD) exploration (Group B). RESULTS: Compared with Group B, Group A showed shorter duration of operation, length of stay in the hospital, postoperative hospital stay, postoperative drainage time, and time to oral intake (all P<0.05). Intraoperative blood loss, costs, conversion to open surgery (one in group A vs. seven in group B; P=0.023), and bile leakage (none in group A vs. four in group B; P=0.047) were lower in Group A than in Group B. There were no significant differences between the two groups regarding the intraoperative clearance rate, ultimate clearance rate, and several postoperative complications. CONCLUSION: One-step PTCSL could be an alternative for patients with choledocholithiasis, especially when ERCP is not feasible.

Identification and validation of a ten-gene set variation score as a diagnostic and prognostic stratification tool in hepatocellular carcinoma.

We aimed to identify a hepatocellular carcinoma (HCC)-specific gene set during progression. Using the HCC data set from The Cancer Genome Atlas, we found that 10 genes were gradually upregulated with the progression of HCC and associated with survival, classified as HCC-unfavorable genes; 29 genes were gradually downregulated and associated with survival, classified as HCC-favorable genes. Gene set variation analysis (GSVA) was used to score individual samples against the two gene sets. Receiver operating characteristic (ROC) curve analysis showed that both the HCC-unfavorable GSVA score and HCC-favorable GSVA score were reliable biomarkers for diagnosing HCC. Moreover, tROC curve analysis and univariate/multivariate Cox proportional hazards analyses indicated that the HCC-unfavorable GSVA score was an independent prognostic biomarker. The results were validated in an external independent data set. Our results support a ten-gene set variation score as a diagnostic and predictive strategy tool in HCC.

Body Mass Index and Stump Morphology Predict an Increased Incidence of Pancreatic Fistula After Pancreaticoduodenectomy.

BACKGROUND: A majority of factors associated with the occurrence of clinical relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD) can only be identified intra- or postoperatively. There are no reports for assessing the morphological features of pancreatic stump and analyzing its influence on CR-POPF risk after PD preoperatively. METHOD: A total of 90 patients underwent PD between April 2012 and May 2014 in our hospital were included. Preoperative computed tomographic (CT) images were imported into the Medical Image Three-Dimensional Visualization System (MI-3DVS) for acquiring the morphological features of pancreatic stump. The demographics, laboratory test and morphological features of pancreatic stump were recorded prospectively. The clinical course was evaluated focusing on the occurrence of pancreatic fistula as defined by the International Study Group on Pancreatic Fistula (ISGPF). Logistic regression analysis was used to identify independent predictors of CR-POPF. RESULTS: CR-POPF occurred in 18 patients (14 grade B, 4 grade C). In univariate analysis, male gender (P = 0.026), body mass index (BMI) ≥ 25.3 kg/m(2) (P = 0.002), main pancreas duct diameter (MPDD) < 3.1 mm (P = 0.005), remnant pancreatic parenchymal volume (RPPV) > 27.8 mL (P < 0.001), and area of cut surface (AOCS) > 222.3 mm(2) (P < 0.001) were associated with an increased risk of CR-POPF. In multivariate analysis, BMI ≥ 25.3 kg/m(2) (OR 12.238, 95 % CI 1.822-82.215, P = 0.010) and RPPV > 27.8 mL (OR 12.907, 95 % CI 1.602-104.004, P = 0.016) were the only independent risk factors associated with CR-POPF. A cut-off value of 27.8 mL for RPPV established based on the receiver operating characteristic (ROC) curve, which was the strongest single predictive factor for CR-POPF, with a sensitivity and specificity of 77.8 and 86.1 %, respectively. The area under the ROC curve of RPPV was 0.770 (95 % CI 0.629-0.911, P < 0.001). CONCLUSIONS: Our study demonstrated that CR-POPF is correlated with BMI and RRPV. MI-3DVS provides us a novel and convenient method for measuring the RPPV. Preoperative acquisition of RPPV and BMI may help the surgeons in fitting postoperative management to patient's individual risk after PD.

[Application of 3D visualization, 3D printing and 3D laparoscopy in the diagnosis and surgical treatment of hepatic tumors].

OBJECTIVE: To study the value of three-dimensional (3D) visualization, 3D printing and 3D laparoscopy (3-3D techniques) in the diagnosis and surgical treatment of hepatic tumors. METHODS: From November 2013 to January 2015, 22 patients with hepatic tumors admitted in our department underwent abdominal thin-slice CT scanning. The CT images were imported into Medical Image three Dimensional Visualization System (MI-3DVS) for 3D reconstruction. Standard Template Library (STL) files were exported for 3D printing. The hepatic vascular classification and predicted liver resection were performed with the aid of MI-3DVS system. The 3D models were then printed and virtual liver resections were executed accordingly. Based on these preoperative surgical planning data, we performed anatomical hepatectomy using 3D laparoscopy, and the intraoperative blood loss, volume of virtual and actual liver resection and postoperative hospital stay were recorded. RESULTS: According to Michels's classifications, 19 patients had type I, 2 had type II, and 1 had type VIII hepatic arteries; based on Cheng classifications, the portal vein was classified into type I in 17 cases, type II in 2 cases, and type III in 2 cases, and type IV in 1 case; according to Nakamura classifications, the right hemiliver hepatic vein was classified into type I in 10 cases, type II in 7 cases, and type III in 5 cases. In the virtual operations, the mean volume of liver resected was 490 ± 228 ml and the mean remnant liver volume was 885 ± 139 ml, with a remnant to functional liver volume ratio of (71 ± 11)%. The 3D printed models stereoscopically displayed the location of the liver tumors and adjacent liver vascular structure clearly. Laparoscopic hepatectomy was performed successfully in 20 patients guided by the 3-3D techniques, and the other 2 patients required convertion to open hepatectomy. The mean operation time was 186 ± 92 min, the intraoperative blood loss was 284 ± 286 ml, the mean actual liver resection volume was 491 ± 192 ml, and the mean postoperative hospital stay of the patients was 8.6 ± 3.7 days. CONCLUSIONS: The 3-3D technique can facilitate the evaluation of preoperative risk and critical anatomical structures and navigate the surgical procedure in real time in anatomical hepatectomy for hepatic tumors.

Impact of three-dimensional reconstruction technique in the operation planning of centrally located hepatocellular carcinoma.

BACKGROUND: The aim of this retrospective study was to compare the outcomes of operations based on 3-dimensional (3D) operation planning with non 3D-assisted operations in the treatment of centrally located hepatocellular carcinoma. STUDY DESIGN: From April 2008 to March 2014, 116 patients with centrally located hepatocellular carcinoma received surgical treatment in our department. Among these cases, a total of 60 patients received resection with operation planning based on 3D reconstructions (group A); the remaining 56 received treatment with the aid of traditional imaging (group B). Three-dimensional surgical planning, including the classification system for centrally located hepatocellular carcinoma, was elaborated in the study. RESULTS: Compared with group B, group A was linked to shorter operation time (294.5 ± 61.9 minutes vs 324.3 ± 83.1 minutes; p = 0.028) and lower rate of hepatic inflow occlusion (51.7% vs 71.4%; p = 0.029). No differences were found in surgical methods, intraoperative blood transfusion, and intraoperative blood loss. The groups were similar in their rates of complications, except that group B was more liable to have Clavien Grade III to V complications (3.3% vs 14.3%; p = 0.048). In addition, a significant difference in ascites was found across the 2 cohorts (2 in group A and 8 in group B; p = 0.048), and the 2 groups also differed significantly in total bilirubin (23.2 ± 16.1 g/L vs 31.1 ± 24.1 g/L; p = 0.032) and albumin (29.3 ± 5.2 g/L vs 27.8 ± 7.9 g/L; p = 0.033). CONCLUSIONS: Compared with non 3D-assisted operations, the operation planning based on 3D reconstruction is a more effective and reasonable method in the treatment of centrally located hepatocellular carcinoma. In addition, the classification system may facilitate the 3D operation planning.