Association between type 2 diabetes, alcohol intake frequency, age at menarche, and gallbladder cancer: a two-sample Mendelian randomization study.

Background: Gallbladder cancer (GBC) is a rare malignancy of the digestive tract, characterized by a remarkably poor prognosis. Currently, there is a controversy on the relationship between type 2 diabetes (T2D) and GBC. Additionally, no definitive conclusions were established regarding the causal relationships between alcohol intake frequency (AIF), age at menarche (AAM) and GBC. The objective of this study was to elucidate the causal association between T2D, AIF, AAM, and GBC. Methods: Single-nucleotide polymorphisms (SNPs) associated with exposures and outcomes were sourced from the Integrative Epidemiology Unit (IEU) Open Genome-Wide Association Study (GWAS) database. Specifically, the data of GBC comprised 907 East Asians (pathological results of all cases were registered into Biobank Japan) and 425,707 SNPs; T2D comprised 655,666 Europeans with 5,030,727 SNPs; AIF comprised 462,346 Europeans and 9,851,867 SNPs; AAM comprised 243,944 Europeans and 9,851,867 SNPs. The measurement of exposure traits is collected uniformly from the UK Biobank (UKB) database and presented in the form of standard deviation (SD) or the logarithmic form of the odds ratio (logOR). We employed a two-sample Mendelian randomization (MR) analysis to discern the causalities between T2D, AIF, AAM, and GBC. Sensitivity analyses were conducted to identify and address potential heterogeneity, horizontal pleiotropy, and outliers. Results: Our findings indicated that T2D reduced GBC risk [odds ratio (OR) =0.044; 95% confidence interval (CI): 0.004-0.55; P=0.015, inverse variance-weighted (IVW)]. However, no causal relationship was observed between AIF (OR =0.158; 95% CI: 5.33E-05 to 466.84; P=0.65, IVW), AAM (OR =0.19; 95% CI: 0.0003-140.34; P=0.62, IVW), and GBC. Sensitivity analysis revealed no evidence of horizontal pleiotropy, heterogeneity, or outliers, suggesting the robustness and reliability of our conclusions. Conclusions: T2D emerged as a potentially protective factor against GBC, whereas neither AIF nor AAM demonstrated a causal relationship with GBC risk. Regulation of glucose metabolism may be one of the methods for preventing GBC.

Simulation training of laparoscopic biliary-enteric anastomosis with a three-dimensional-printed model leads to better skill transfer: a randomized controlled trial.

AIM: A new simulation model and training curriculum for laparoscopic bilioenteric anastomosis has been developed. Currently, this concept lacks evidence for the transfer of skills from simulation to clinical settings. This study was conducted to determine whether training with a three-dimensional (3D) bilioenteric anastomosis model result in greater transfer of skills than traditional training methods involving video observation and a general suture model. METHODS: Fifteen general surgeons with no prior experience in laparoscopic biliary-enteric anastomosis were included in this study and randomised into three training groups: video observation only, practice using a general suture model, and practice using a 3D-printed biliary-enteric anastomosis model. Following five training sessions, each surgeon was asked to perform a laparoscopic biliary-enteric anastomosis procedure on an isolated swine organ model. The operative time and performance scores of the procedure were recorded and compared among the three training groups. RESULTS: The operation time in the 3D-printed model group was significantly shorter than the suture and video observation groups ( P =0.040). Furthermore, the performance score of the 3D-printed model group was significantly higher than those of the suture and video observation groups ( P =0.001). Finally, the goal score for laparoscopic biliary-enteric anastomosis in the isolated swine organ model was significantly higher in the 3D model group than in the suture and video observation groups ( P =0.004). CONCLUSIONS: The utilisation of a novel 3D-printed model for simulation training in laparoscopic biliary-enteric anastomosis facilitates improved skill acquisition and transferability to an animal setting compared with traditional training techniques.

Wedge resection versus segment IVb and V resection of the liver for T2 gallbladder cancer: a systematic review and meta-analysis.

Objectives: Although guidelines recommend extended cholecystectomy for T2 gallbladder cancer (GBC), the optimal hepatectomy strategy remains controversial. The study aims to compare the prognosis of T2 GBC patients who underwent wedge resection (WR) versus segment IVb and V resection (SR) of the liver. Methods: A specific search of online databases was performed from May 2001 to February 2023. The postoperative efficacy outcomes were synthesized and meta-analyses were conducted. Results: A total of 9 studies involving 2,086 (SR = 627, WR = 1,459) patients were included in the study. The primary outcomes included disease-free survival (DFS) and overall survival (OS). For DFS, the 1-year DFS was statistically higher in patients undergoing SR than WR [risk ratio (RR) = 1.07, 95% confidence interval (CI) = 1.02-1.13, P = 0.007]. The 3-year DFS (P = 0.95), 5-year DFS (P = 0.77), and hazard ratio (HR) of DFS (P = 0.72) were similar between the two groups. However, the 3-year OS was significantly lower in patients who underwent SR than WR [RR = 0.90, 95% CI = 0.82-0.99, P = 0.03]. Moreover, SR had a higher hazard HR of OS [HR = 1.33, 95% CI = 1.01-1.75, P = 0.04]. No significant difference was found in 1-year (P = 0.32) and 5-year (P = 0.9) OS. For secondary outcomes, patients who received SR tended to develop postoperative complications (POC) [RR = 1.90, 95% CI = 1.00-3.60, P = 0.05]. In addition, no significant differences in intrahepatic recurrence (P = 0.12) were observed. Conclusions: In conclusion, SR can improve the prognosis of T2 GBC patients in DFS. In contrast to WR, the high HR and complications associated with SR cannot be neglected. Therefore, surgeons should evaluate the condition of the patients and take their surgical skills into account when selecting SR. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier, CRD42022362974.

Cytoskeleton remodeling mediated by circRNA-YBX1 phase separation suppresses the metastasis of liver cancer.

Metastasis, especially intrahepatic, is a major challenge for hepatocellular carcinoma (HCC) treatment. Cytoskeleton remodeling has been identified as a vital process mediating intrahepatic spreading. Previously, we reported that HCC tumor adhesion and invasion were modulated by circular RNA (circRNA), which has emerged as an important regulator of various cellular processes and has been implicated in cancer progression. Here, we uncovered a nuclear circRNA, circASH2, which is preferentially lost in HCC tissues and inhibits HCC metastasis by altering tumor cytoskeleton structure. Tropomyosin 4 (TPM4), a critical binding protein of actin, turned out to be the major target of circASH2 and was posttranscriptionally suppressed. Such regulation is based on messenger RNA (mRNA)/precursormRNA splicing and degradation process. Furthermore, liquid-liquid phase separation of nuclear Y-box binding protein 1 (YBX1) enhanced by circASH2 augments TPM4 transcripts decay. Together, our data have revealed a tumor-suppressive circRNA and, more importantly, uncovered a fine regulation mechanism for HCC progression.

Comparison of short-term outcomes between robotic and laparoscopic distal gastrectomy performed by the same surgical team during the same period.

Objective: To evaluate the short-term outcomes of laparoscopic distal gastrectomy and robotic distal gastrectomy performed during the same period. Methods: This study enrolled 46 cases of laparoscopic distal gastrectomy and 67 cases of robotic distal gastrectomy that were performed by a single surgeon between April 2020 to October 2021. Baseline characteristics and short-term outcomes of these two groups were then compared. Moreover, the robotic distal gastrectomy group was further divided into two subgroups according to the learning curve. Finally, the baseline characteristics and short-term outcomes of both subgroups were compared with the laparoscopic group, respectively. Results: The baseline characteristics and short-term outcomes of the LDG group and RDG group were comparable. In contrast, the operation time in the laparoscopic group was significantly shorter than that in the early experience robotic group (191.3 ± 37.6 VS 225.1 ± 49, P=0.001). However, the operation time (191.3 ± 37.6 VS 185.3 ± 25.3, P=0.434) was comparable between the laparoscopic group and the late experience robotic group. Likewise, the bleeding volume was comparable between the laparoscopic and early experience robotic groups. However, bleeding volume was significantly lower in the late experience robotic group compared to that in the laparoscopic group (37.5 ± 18.8 VS 49.2 ± 29.0, P=0.049). Conclusions: With surgeons stepping into the stable stage of the robotic learning curve, RDG showed a comparable operation time and lower volume of blood loss compared with LDG. Collectively, our study supports the application of robotic distal gastrectomy in patients diagnosed with gastric cancer.

Clinical utility of resected pancreatic volume ratio calculation for predicting postoperative new-onset diabetes mellitus after distal pancreatectomy-a propensity-matched analysis.

Background: Limited literature is available on new-onset diabetes mellitus (NODM) after distal pancreatectomy. This study aimed to investigate the correlation between surgery-related factors and the incidence of NODM after distal pancreatectomy. Methods: Patients were divided into the NODM-positive or NODM-negative group according to the diagnosis of NODM. After propensity score matching, the correlation between operation-related factors and the incidence of NODM was analyzed. The diagnostic threshold for predicting NODM was determined using the receiver operating characteristic (ROC) curve and the Youden index. Results: No significant correlation was observed between the NODM incidence after distal pancreatectomy and operative blood loss, spleen preservation, surgical method (open or laparoscopy), postoperative ALB and HB (first day after surgery), and postoperative pathology. However, a significant correlation was found between the NODM incidence and the postoperative pancreatic volume or the resected pancreatic volume ratio. Resected pancreatic volume ratio was identified as a predictive risk factor for NODM. Youden index of the ROC curve was 0.548, with a cut off value of 32.05% for resected pancreatic volume ratio. The sensitivity and specificity of the cut off values were 0.952 and 0.595, respectively. Conclusions: This study demonstrated that the volume ratio of pancreatic resection is a risk factor for the incidence of NODM after distal pancreatectomy. This can be used to predict the incidence of NODM and may have further clinical applications.

Recent advances in the role of exosomes in liver fibrosis.

BACKGROUND AND AIM: We aim to summarize the current status of research on the role of exosomes in liver fibrosis. METHODS: A review of the relevant literature was performed and the key findings were presented. RESULTS: Most studies focused on the role of exosomes derived from mesenchymal stem cells, other types of stem cells, and liver resident cells including hepatocytes, cholangiocytes, and hepatic stellate cells in liver fibrosis. Exosomes have been reported to play an essential role in the inactivation or activation of hepatic stellate cells through the delivery of non-coding RNAs and proteins. In recent years, this exosome cargo has become a research hotspot. CONCLUSIONS: Recent studies have indicated the potential therapeutic benefit of exosomes in liver fibrosis.

Adhesive cryogel particles for bridging confined and irregular tissue defects.

BACKGROUND: Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging. METHODS: This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery. RESULTS: ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface. CONCLUSIONS: ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.

Evaluation of PD-L1 as a biomarker for immunotherapy for hepatocellular carcinoma: systematic review and meta-analysis.

Aim: To determine if PD-L1 can be used as a biomarker to predict the efficacy of anti-PD-1/PD-L1 inhibitors in hepatocellular carcinoma (HCC). Methods: Relevant studies from a specific search of the four databases from October 2014 to December 2022 were included in this meta-analysis. Results: Higher PD-L1 expression levels were associated with a higher objective response rate (ORR). Higher PD-L1 expression levels on tumor cells and tumor proportion score were associated with higher ORR. PD-L1 was capable of predicting the effectiveness of nivolumab. Dako 28-8 is a promising assay for HCC. Conclusion: PD-L1 is a predictive biomarker for ORR in HCC. Tumor proportion score and PD-L1 expression levels on tumor cells are potential scoring algorithms.

Clinically, liver cancer patients with high PD-L1 levels may not benefit from immunotherapy. Conversely, some patients with low PD-L1 level can benefit from it. Therefore, the concept of PD-L1 as a predictive indicator in liver cancer is defective. Whether PD-L1 can serve as an indicator in liver cancer patients receiving immunotherapy needs urgent confirmation. In this work, we evaluated the feasibility of PD-L1 as a prognostic biomarker for immunotherapy. The results suggested that high expression of PD-L1 by tumor cells rather than tumor tissue was correlated with better prognosis.

The Learning Curve Study of Robotic Distal Gastrectomy: an Analysis of Outcomes of the First 67 Consecutive Cases at a High-Volume Gastric Center.

BACKGROUND: Robotic distal gastrectomy (RDG) is performed increasingly; a sound understanding of the learning curve in robotic distal gastrectomy has taken on great importance METHODS: Data on the 67 RDG cases were collected from one surgeon with rich experience in laparoscopic gastrectomy. Cumulative sum (CUSUM) analysis based on operative time was used to identify inflexion points. RESULTS: Thirty-five cases, on average, were needed to complete operation time-learning curve sufficiently. A reduction in surgical time was observed in the last 32 cases compared with the first 35 cases (185.3 ± 25.3 min vs. 225.1 ± 49 min, P < 0.01). CONCLUSIONS: Surgeons with extensive laparoscopic experience can master robotic distal gastrectomy techniques after some training.