Short-term and Long-term Clinical Outcomes of Combined Caudate Lobectomy for Intrahepatic Cholangiocarcinoma Involving the Hepatic Hilus: A Propensity Score Analysis.

Background/Aims: Extended hepatectomy combined with caudate lobe resection has been approved for the radical resection of hilar cholangiocarcinoma. There was a lack of credible research on the clinical value of caudate lobectomy (CL) for intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. We aimed to compare the short-term and long-term outcomes of the combined procedure with those of only CL for curative resection of intrahepatic cholangiocarcinoma involving the hepatic hilus. Methods: This single-center retrospective cohort study of patients with hilar cholangiocarcinoma was conducted from January 2007 to December 2021. Patients who underwent radical resection were enrolled in this study. The short-term and long-term clinical outcomes of the groups were compared before and after propensity score matching (PSM). Results: A total of 282 patients were included. There were no statistically significant differences in perioperative clinical outcomes between the CL group and the non-CL group before and after PSM. Compared to patients in the non-CL group, patients in the CL group had significantly longer overall survival before and after PSM (p=0.007 before PSM, p=0.033 after PSM). Moreover, compared to the non-CL group, the CL group had longer disease-free survival before and after PSM (p<0.001 before PSM, p=0.019 after PSM). Conclusions: The postoperative complications of the CL group were comparable to those of the non-CL group. CL improved the long-term survival of patients with intrahepatic cholangiocarcinoma involving the hepatic hilus when combined with hepatectomy. Therefore, hepatectomy combined with caudate lobe resection should be performed for patients with hilar cholangiocarcinoma.

Incidental gallbladder cancer detected during laparoscopic cholecystectomy: conversion to extensive resection is a feasible choice.

Background: Re-resection is recommended for patients with incidental gallbladder carcinoma (iGBC) at T1b stage and above. It is unclear whether continuation of laparoscopic re-resection (CLR) for patients with intraoperatively detected iGBC (IDiGBC) is more beneficial to short- and long-term clinical outcomes than with conversion to radical extensive-resection (RER). Methods: This single-centre, retrospective cohort study of patients with iGBC was conducted between June 2006 and August 2021. Patients who underwent immediate reresection for T1b or higher ID-iGBC were enrolled. Propensity score matching (PSM) was used to match the two groups (CLR and RER) of patients, and differences in clinical outcomes before and after matching were analyzed. Result: A total of 102 patients with ID-iGBC were included in this study. 58 patients underwent CLR, and 44 underwent RER. After 1:1 propensity score matching, 56 patients were matched to all baselines. Patients in the RER group had a lower total postoperative complication rate, lower pulmonary infection rate, and shorter operation time than those in the CLR group did. Kaplan-Meier analysis showed that the overall survival rate of patients who underwent CLR was significantly lower than that of patients who underwent RER. Multivariate analysis showed that CLR, advanced T stage, lymph node positivity, and the occurrence of postoperative ascites were adverse prognostic factors for the overall survival of patients. Conclusion: Patients with ID-iGBC who underwent RER had fewer perioperative complications and a better prognosis than those who underwent CLR. For patients with ID-iGBC, conversion to radical extensive-resection appears to be a better choice.

The prognostic value of preoperative peripheral blood inflammatory biomarkers in extrahepatic cholangiocarcinoma: a systematic review and meta-analysis.

Background: Recent evidence indicates that inflammation plays a major role in the pathogenesis and progression of CCA. This meta-analysis seeks to evaluate the prognostic implications of preoperative inflammatory markers, specifically NLR, PLR, and LMR, in patients with eCCA. By focusing on these preoperative biomarkers, this study aims to provide valuable insights into their prognostic value and potential utility in clinical practice. Methods: For this analysis, comprehensive searches were conducted in PubMed, Embase, and Web of Science databases from inception to May 2024. The primary outcomes of interest focused on the association between the levels of NLR, PLR, and LMR and the prognosis of eCCA patients. Statistical analyses were conducted using STATA 17.0 software. Results: The meta-analysis, involving 20 retrospective studies with 5553 participants, revealed significant correlations between preoperative biomarkers and the prognosis of eCCA patients. Elevated NLR, PLR, and decreased LMR levels were extensively studied regarding overall survival (OS) in eCCA patients. Elevated NLR was an independent predictor of poor OS (HR 1.86, p < 0.001), similar to elevated PLR (HR 1.76, p < 0.001), while decreased LMR predicted poor OS (HR 2.16, p < 0.001). Subgroup analyses based on eCCA subtypes and curative surgery status showed consistent results. Conclusions: In conclusion, our study emphasizes the clinical significance of assessing NLR, PLR, and LMR preoperatively to predict patient prognosis. Elevated NLR and PLR values, along with decreased LMR values, were linked to poorer overall survival (OS). Large-scale prospective cohort studies are required to confirm their independent prognostic value in eCCA. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024551031.

Thiostrepton induces oxidative stress, mitochondrial dysfunction and ferroptosis in HaCaT cells.

TST has been mainly studied for its anti-tumor proliferation and antimicrobial effects, but not widely used in dermatological diseases. The mechanism of cellular damage by TST in response to H2O2-mediated oxidative stress was investigated in human skin immortalized keratinocytes (HaCaT) as an in vitro model. The findings reveal that TST treatment leads to increased oxidative stress in the cells by reducing levels of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). This effect is further supported by an upsurge in the expression of malondialdehyde (MDA, a pivotal marker of lipid peroxidation). Additionally, dysregulation of FoxM1 at both gene and protein levels corroborates its involvement TST associated effects. Analysis of ferroptosis-related genes confirms dysregulation following TST treatment in HaCaT cells. Furthermore, TST treatment exhibits effects on mitochondrial morphology and function, affirming its induction of apoptosis in the cells through heightened oxidative stress due to mitochondrial damage and dysregulation of mitochondrial membrane potential.

Development and validation of nomogram to predict overall survival and disease-free survival after surgical resection in elderly patients with hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the common causes of tumor death in elderly patients. However, there is a lack of individualized prognostic predictors for elderly patients with HCC after surgery. Method: We retrospectively analyzed HCC patients over 65 years old who underwent hepatectomy from 2015 to 2018, and randomly divided them into training cohort and validation cohort in a ratio of 3:1. Univariate Cox regression was used to screen the risk factors related to prognosis. Prognostic variables were further selected by least absolute shrinkage and selection operator regression model (LASSO) and multivariate Cox regression to identify the predictors of overall survival (OS) and disease-free survival (DFS). These indicators were then used to construct a predictive nomogram. The receiver operating characteristic curve (ROC curve), calibration curve, consistency index (C-index) and decision analysis curve (DCA) were used to test the predictive value of these independent prognostic indicators. Result: A total of 188 elderly HCC patients who underwent hepatectomy were enrolled in this study. The independent prognostic indicators of OS included albumin (ALB), cancer embolus, blood loss, viral hepatitis B, total bilirubin (TB), microvascular invasion, overweight, and major resection. The independent prognostic indicators of DFS included major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion. In the training cohort, the ROC curve showed that the predictive values of these indicators for OS and DFS were 0.827 and 0.739, respectively, while in the validation cohort, they were 0.798 and 0.694. The calibration curve nomogram exhibited good prediction for 1-year, 2-year, and 3-year OS and DFS. Moreover, the nomogram models exhibited superior performance compared to the T-staging suggested by C-index and DCA. Conclusion: The nomogram established in this study demonstrate commendable predictive efficacy for OS and DFS in elderly patients with HCC after hepatectomy.Core Tip: The purpose of this retrospective study is to screen the risk factors of survival and recurrence in elderly patients with HCC after hepatectomy. The nomogram included cancer embolus, viral hepatitis B, overweight, major resection, ALB, microvascular invasion, laparoscopic surgery, blood loss, TB, and pleural effusion as predictors. The calibration curve of this nomogram was good, indicating credible predictive value and clinical feasibility.

Cholangiocarcinoma combined with biliary obstruction: an exosomal circRNA signature for diagnosis and early recurrence monitoring.

Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic approaches. We present a novel system to monitor CCA using exosomal circular RNA (circRNA) via serum and biliary liquid biopsies. A pilot cohort consisting of patients with CCA-induced biliary obstruction (CCA-BO, n = 5) and benign biliary obstruction (BBO, n = 5) was used to identify CCA-derived exosomal circRNAs through microarray analysis. This was followed by a discovery cohort (n = 20) to further reveal a CCA-specific circRNA complex (hsa-circ-0000367, hsa-circ-0021647, and hsa-circ-0000288) in both bile and serum exosomes. In vitro and in vivo studies revealed the three circRNAs as promoters of CCA invasiveness. Diagnostic and prognostic models were established and verified by two independent cohorts (training cohort, n = 184; validation cohort, n = 105). An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature (Bile-DS, AUROC = 0.947, RR = 6.05) and serum exosomal circRNA signature (Serum-DS, AUROC = 0.861, RR = 4.04) compared with conventional CA19-9 (AUROC = 0.759, RR = 2.08). A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score, verified with bile samples (Bile-ERS, C-index=0.783) and serum samples (Serum-ERS, C-index = 0.782). These models, combined with other prognostic factors revealed by COX-PH model, enabled the establishment of nomograms for recurrence monitoring of CCA. Our study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

Prognostic factors associated with early recurrence following liver resection for colorectal liver metastases: a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is the 3rd most common malignancy with the liver being the most common site of metastases. The recurrence rate of colorectal liver metastases (CRLM) after liver resection (LR) is notably high, with an estimated 40% of patients experiencing recurrence within 6 months. In this context, we conducted a meta-analysis to synthesize and evaluate the reliability of evidence pertaining to prognostic factors associated with early recurrence (ER) in CRLM following LR. METHODS: Systematic searches were conducted from the inception of databases to July 14, 2023, to identify studies reporting prognostic factors associated with ER. The Quality in Prognostic Factor Studies (QUIPS) tool was employed to assess risk-of-bias for included studies. Meta-analysis was then performed on these prognostic factors, summarized by forest plots. The grading of evidence was based on sample size, heterogeneity, and Egger's P value. RESULTS: The study included 24 investigations, comprising 12705 individuals, during an accrual period that extended from 2007 to 2023. In the evaluation of risk-of-bias, 22 studies were rated as low/moderate risk, while two studies were excluded because of high risk. Most of the studies used a postoperative interval of 6 months to define ER, with 30.2% (95% confidence interval [CI], 24.1-36.4%) of the patients experiencing ER following LR. 21 studies were pooled for meta-analysis. High-quality evidence showed that poor differentiation of CRC, larger and bilobar-distributed liver metastases, major hepatectomy, positive surgical margins, and postoperative complications were associated with an elevated risk of ER. Additionally, moderate-quality evidence suggested that elevated levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA199), lymph node metastases (LNM) of CRC, and a higher number of liver metastases were risk factors for ER. CONCLUSION: This review has the potential to enhance the efficacy of surveillance strategies, refine prognostic assessments, and guide judicious treatment decisions for CRLM patients with high risk of ER. Additionally, it is essential to undertake well-designed prospective investigations to examine additional prognostic factors and develop salvage therapeutic approaches for ER of CRLM.

Combining a glycolysis­related prognostic model based on scRNA­Seq with experimental verification identifies ZFP41 as a potential prognostic biomarker for HCC.

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis, and its heterogeneity affects the response to clinical treatments. Glycolysis is highly associated with HCC therapy and prognosis. The present study aimed to identify a novel biomarker for HCC by exploring the heterogeneity of glycolysis in HCC. The intersection of both marker genes of glycolysis­related cell clusters from single­cell RNA sequencing analysis and mRNA data of liver HCC from The Cancer Genome Atlas were used to construct a prognostic model through Cox proportional hazard regression and the least absolute shrinkage and selection operator Cox regression. Data from the International Cancer Genome Consortium were used to validate the results of the analysis. Immune status analysis was then conducted. A significant gene in the prognostic model was identified as a potential biomarker and was verified through in vitro experiments. The results revealed that the glycolysis­related prognostic model divided patients with HCC into high­ and low­risk groups. A nomogram combining the model and clinical features exhibited accurate predictive ability, with an area under the curve of 0.763 at 3 years. The high­risk group exhibited a higher expression of checkpoint genes and lower tumor immune dysfunction and exclusion scores, suggesting that this group may be more likely to benefit from immunotherapy. The tumor tissues had a higher zinc finger protein (ZFP)41 mRNA and protein expression compared with the adjacent tissues. In vitro analyses revealed that ZFP41 played a crucial role in cell viability, proliferation, migration, invasion and glycolysis. On the whole, the present study demonstrates that the glycolysis­related prognostic gene, ZFP41, is a potential prognostic biomarker and therapeutic target, and may play a crucial role in glycolysis and malignancy in HCC.

METTL3-mediated m6A modification of lncRNA TSPAN12 promotes metastasis of hepatocellular carcinoma through SENP1-depentent deSUMOylation of EIF3I.

In a previous study, we discovered that the level of lnc-TSPAN12 was significantly elevated in hepatocellular carcinoma (HCC) and correlated with a low survival rate. However, the function and mechanism of lnc-TSPAN12 in modulating epithelial-mesenchymal transition (EMT) and metastasis in HCC remains poorly understood. This study demonstrates that lnc-TSPAN12 positively influences migration, invasion, and EMT of HCC cells in vitro and promotes hepatic metastasis in vivo. The modification of N6-methyladenosine, driven by METTL3, is essential for the stability of lnc-TSPAN12, which may partially contribute to the upregulation of lnc-TSPAN12. Mechanistically, lnc-TSPAN12 exhibits direct interactions with EIF3I and SENP1, acting as a scaffold to enhance the SENP1-EIF3I interaction. As a result, the SUMOylation of EIF3I is inhibited, preventing its ubiquitin-mediated degradation. Ultimately, this activates the Wnt/ß-catenin signaling pathway, stimulating EMT and metastasis in HCC. Our findings shed light on the regulatory mechanism of lnc-TSPAN12 in HCC metastasis and identify the lnc-TSPAN12-EIF3I/SENP1 axis as a novel therapeutic target for HCC.

Short-term and long-term clinical outcomes of combined major vessel resection for hilar cholangiocarcinoma: a propensity score analysis.

Purpose: In the treatment of hilar cholangiocarcinoma (HCCA), combined resection of important hepatic vessels remains controversial. The purpose of this study was to compare the postoperative complications and prognosis of combined and non-combined major vessel resections in patients undergoing radical resection for HCCA. Methods: In this study, patients with HCCA who underwent curative resection between January 2007 and December 2018 were retrospectively enrolled. Postoperative complications and prognosis between the groups were compared using propensity score-matching (PSM) analysis. Results: There were 310 patients included in this study. The portal vein resection (PVR) and hepatic artery resection (HAR) groups had a higher incidence of postoperative complications than the control group. Patients in the HAR group had an increased risk of abdominal and pleural effusion after surgery. Patients who underwent combined PVR had better overall survival (OS; P = 0.020) and disease-free survival (DFS; P = 0.020). After curative-intent resection, patients in the HAR group had improved OS (P = 0.027) and DFS (P = 0.023). The postoperative complications of combined vascular resection (VR) did not worsen long-term survival for patients. Conclusion: In patients with HCCA, combined VR improved prognosis. The postoperative complications of combined VR do not worsen patient survival. Therefore, radical surgical resection is recommended.

Epidemiology, risk factors, diagnosis, and treatment of intra-abdominal traumatic neuromas - a narrative review.

Traumatic neuroma (TN) is a disorganized proliferation of injured nerves arising from the axons and Schwann cells. Although TN rarely occurs in the abdominal cavity, the incidence of TN may be underestimated because of the large number of asymptomatic patients. TN can cause persistent pain, which seriously affects quality of life. TN of the biliary system can cause bile duct obstruction, leading to acute cholangitis. It is difficult to differentiate TN from malignancies or recurrence of malignancy, which results in a number of patients receiving aggressive treatment. We collected cases reports of intra-abdominal TN over the past 30 years form PubMed and cases diagnosed in our medical center over the past 20 years, which is the largest case series of intra-abdominal TN to the best of our knowledge. In this review, we discuss the epidemiology, pathophysiology, risk factors, classification, diagnosis, and management of intra-abdominal TN.

Single-cell analysis of human prepuce reveals dynamic changes in gene regulation and cellular communications.

BACKGROUND: The cellular and molecular dynamics of human prepuce are crucial for understanding its biological and physiological functions, as well as the prevention of related genital diseases. However, the cellular compositions and heterogeneity of human prepuce at single-cell resolution are still largely unknown. Here we systematically dissected the prepuce of children and adults based on the single-cell RNA-seq data of 90,770 qualified cells. RESULTS: We identified 15 prepuce cell subtypes, including fibroblast, smooth muscle cells, T/natural killer cells, macrophages, vascular endothelial cells, and dendritic cells. The proportions of these cell types varied among different individuals as well as between children and adults. Moreover, we detected cell-type-specific gene regulatory networks (GRNs), which could contribute to the unique functions of related cell types. The GRNs were also highly dynamic between the prepuce cells of children and adults. Our cell-cell communication network analysis among different cell types revealed a set of child-specific (e.g., CD96, EPO, IFN-1, and WNT signaling pathways) and adult-specific (e.g., BMP10, NEGR, ncWNT, and NPR1 signaling pathways) signaling pathways. The variations of GRNs and cellular communications could be closely associated with prepuce development in children and prepuce maintenance in adults. CONCLUSIONS: Collectively, we systematically analyzed the cellular variations and molecular changes of the human prepuce at single-cell resolution. Our results gained insights into the heterogeneity of prepuce cells and shed light on the underlying molecular mechanisms of prepuce development and maintenance.

Timing of surgery in patients with synchronous colorectal cancer liver metastases undergoing neoadjuvant chemotherapy: a propensity score analysis.

BACKGROUND: The optimal timing of surgery after neoadjuvant chemotherapy (NAC) in patients with synchronous colorectal cancer liver metastases (SLM) remains controversial. We plan to analyze whether the choice of different surgical timings will have different effects on the perioperative and oncologic outcomes of patients. METHOD: We retrospectively collected all patients who met the inclusion and exclusion criteria from 2010 to 2020 in West China Hospital. Patients were grouped according to time interval (TI) after NAC to surgery. The perioperative and oncologic outcomes of the two groups were compared after propensity score matching. Univariate and multivariate analyzes were used to screen factors associated with prognosis. RESULT: Among 255 enrolled patients, 188 were matched with comparable baseline (94 each group). Patients in the 6≦TI≦8 group had longer operation time, less intraoperative blood loss, and less postoperative complications than those in the 4≦TI < 6 group. However, the overall survival (OS) (p = 0.012) and disease-free survival (DFS) (p = 0.013) of the patients in the 4≦TI < 6 group were better than those in the 6≦TI≦8 group. Subgroup analysis found that the above conclusions still apply in age ≥ 60, non-anemic patients, and patients who underwent R0 resection. OS was inversely correlated with TI in patients without preoperative jaundice. DFS was negatively correlated with TI in patients with preoperative jaundice. Multivariate analysis showed that the prolongation of TI after NAC to surgery was an independent prognostic risk factor for OS and DFS. CONCLUSIONS: Patients with SLM may be a better choice for surgery within 4-6 weeks after receiving NAC. Although patients with SLM undergoing surgery 4-6 weeks after NAC has a higher rate of postoperative complications, radical surgery is still recommended for a better survival benefit.

Biliary drainage in malignant biliary obstruction: an umbrella review of randomized controlled trials.

Background: There are still many controversies about biliary drainage in MBO, and we aimed to summarize and evaluate the evidence associated with biliary drainage. Methods: We conducted an umbrella review of SRoMAs based on RCTs. Through July 28, 2022, Embase, PubMed, WOS, and Cochrane Database were searched. Two reviewers independently screened the studies, extracted the data, and appraised the methodological quality of the included studies. GRADE was used to evaluate the quality of the evidence. Results: 36 SRoMAs were identified. After excluding 24 overlapping studies, 12 SRoMAs, including 76 RCTs, and 124 clinical outcomes for biliary drainage in MBO were included. Of the 124 pieces of evidence evaluated, 13 were rated "High" quality, 38 were rated "Moderate", and the rest were rated "Low" or "Very low". For patients with MBO, 125I seeds+stent can reduce the risk of stent occlusion, RFA+stent can improve the prognosis; compared with PC, SEMS can increase the risk of tumor ingrowth and reduce the occurrence of sludge formation, and the incidence of tumor ingrowth in C-SEMS/PC-SEMS was significantly lower than that in U-SEMS. There was no difference in the success rate of drainage between EUS-BD and ERCP-BD, but the use of EUS-BD can reduce the incidence of stent dysfunction. For patients with obstructive jaundice, PBD does not affect postoperative mortality compared to direct surgery. The use of MS in patients with periampullary cancer during PBD can reduce the risk of re-intervention and stent occlusion compared to PC. In addition, we included four RCTs that showed that when performing EUS-BD on MBO, hepaticogastrostomy has higher technical success rates than choledochoduodenostomy. Patients who received Bilateral-ENBD had a lower additional drainage rate than those who received Unilateral-ENBD. Conclusions: Our study summarizes a large amount of evidence related to biliary drainage, which helps to reduce the uncertainty in the selection of biliary drainage strategies for MBO patients under different circumstances.

Risk factors for recurrent common bile duct stones: a systematic review and meta-analysis.

BACKGROUND: Common bile duct stones (CBDS) have a reported recurrence rate of 4%-24% after stone extraction. The most commonly applied stone extraction method is endoscopic cholangiopancreatography (ERCP). We conducted a systematic review and meta-analysis to identify all available risk factors for recurrent CBDS following stone retraction. RESEARCH DESIGN AND METHODS: A literature search of studies with case-control design was performed to identify potential risk factors for recurrent CBDS. The impact of different risk factors on stone recurrence was analyzed. Pooled odds ratios (ORs) with 95% CIs and heterogeneity were calculated. Identified risk factors were graded as 'strong,' 'moderate,' or 'weak' after quality assessment. RESULTS: A total of 46 studies discussing stone recurrence following ERCP treatment were included. CBD diameter≥1.5 cm, sharp CBD angulation, multiple ERCP sessions, postoperative pneumobilia, history of CBD incision, and biliary stent placement were identified as strong risk factors; larger CBD diameter, periampullary diverticulum, mechanical lithotripsy, and history of cholecystectomy were identified as moderate. Other weak risk factors were also listed. CONCLUSIONS: In this comprehensive study, we identified 14 risk/protective factors for recurrent CBDS following ERCP. Pooled odds ratios were calculated and evaluated the quality of evidence. These findings may shed light on the assessment and management of CBDS.

A meta-analysis of prognostic factors for early recurrence in perihilar cholangiocarcinoma after curative-intent resection.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is a type of cancer that has a high rate of recurrence after curative-intent surgery, with about half of all recurrences occurring within the first year. The primary aim of this study was to identify prognostic factors (PFs) for early recurrence (ER, within 12 months) after surgery. METHODS: Systematic searching was conducted from database inception to September 28th, 2022, with duplicate independent review and data extraction. Data on eight predefined PFs were collected, and meta-analysis was performed on PFs for ER, summarized using forest plots. RESULTS: The study enrolled 11 studies comprising 2877 patients. In the risk-of-bias assessment, seven studies were rated as low risk and four as moderate risk. More than 34.3% (95% confidence interval [CI], 26.1-42.5%) of the patients experienced ER after curative-intent pCCA resection. Of the PFs, vascular invasion (HR, 2.41; 95% CI, 1.47-3.95; OR, 1.60; 95% CI, 1.17-2.18), lymph node metastases (HR, 2.54; 95% CI, 1.92-3.37; OR, 4.26; 95% CI, 2.40-7.57), and R1 resection (HR, 3.27; 95% CI, 1.81-5.92; OR, 2.40; 95% CI, 1.36-4.22) were associated with an increased hazard for ER. The combined OR values also showed that tumor size, poor tumor differentiation, and perineural invasion were linked to an elevated risk of ER, but all of them had apparent heterogeneity. CONCLUSION: These findings from the review could be used to plan surveillance of ER and guide post-operative individualized management in pCCA. Furthermore, prospective studies are needed to explore more prognostic factors for ER of pCCA.

Chemotherapy and targeted therapy for advanced biliary tract cancers: an umbrella review.

BACKGROUND: Malignant tumors of the biliary system are characterized by a high degree of malignancy and strong invasiveness, and they are usually diagnosed at late stages with poor prognosis. For patients with advanced biliary tract cancer, chemotherapy and targeted therapy are two of the options available to improve prognosis and delay tumor progression. This study aimed to comprehensively evaluate the safety and effectiveness of various chemotherapy schemes for the treatment of advanced biliary tract cancer in published systematic reviews and meta-analyses (SRoMAs). METHODS: An umbrella review method was adopted, which aims to summarize the existing evidence from multiple studies around a research topic. SRoMAs up to April 9, 2022, were identified using PubMed, Web of Science, the Cochrane database, and manual screening. Eligible studies were screened according to inclusion and exclusion criteria. This study had been registered at PROSPERO (CRD42022324548). For each eligible study, we extracted the data of general characteristics and the main findings. The methodological quality of the included studies were assessed by the AMSTAR2 scale, and the quality of evidence was evaluated by the GRADE tools. RESULTS: A total of 1833 articles were searched; 14 unique articles with 94 outcomes were identified by eligibility criteria. The incidence of skin rash (RR = 18.11, 95% CI 5.13-63.91, GRADE: Moderate) and diarrhea (RR = 2.48, 95% CI 1.2-5.10, GRADE: Moderate) was higher in patients receiving gemcitabine-based chemotherapy plus targeted therapy than in patients receiving gemcitabine monotherapy. The number of patients receiving gemcitabine-based chemotherapy who developed leukopenia (OR = 7.17, 95% CI 1.43-36.08, GRADE: Moderate), anemia (OR = 7.04, 95% CI 2.59-19.12, GRADE: High), thrombocytopenia (RR = 2.45, 95% CI 1.39-4.32, GRADE: Moderate), and neutropenia (RR = 3.30, 95% CI 1.04-10.50, GRADE: Moderate) was significantly higher than that of patients who received gemcitabine-free regimens. In addition, patients receiving S-1 monotherapy had significantly better ORR (RR = 2.46, 95% CI 1.27-4.57, GRADE: Moderate) than patients receiving S-1 + gemcitabine. Patients receiving fluoropyrimidine-based chemotherapy had longer OS (HR = 0.83, 95% CI 0.7-0.99, GRADE: Moderate), higher DCR (0R = 5.18, 95% CI 3.3-10.23, GRADE: Moderate), and higher ORR (0R = 3.24, 95% CI 1.18-8.92, GRADE: Moderate) compared with patients who received 5-FU/LV monotherapy or supportive therapy. Surprisingly, we found evidence that gemcitabine-based chemotherapy did not improve postoperative patients' OS (HR = 0.91, 95% CI 0.74-1.12, GRADE: Moderate) when compared with best supportive care. CONCLUSIONS: This study comprehensively evaluated the safety and efficacy of chemotherapy or targeted therapy regimens for advanced biliary tract cancer and found 11 outcomes with "Moderate" or "High" levels; however, most of the outcomes were still at "low" or "very low" levels. More randomized controlled studies are needed in the future to further summarize high levels of evidence.

CRISPR-based quantum dot nanobead lateral flow assay for facile detection of varicella-zoster virus.

Varicella-zoster virus (VZV) infects more than 90% of the population worldwide and has a high incidence of postherpetic neuralgia in elderly patients, seriously affecting their quality of life. Combined with clustered regularly interspaced short palindromic repeats (CRISPR) system, we develop a quantum dot nanobeads (QDNBs) labeled lateral flow assay for VZV detection. Our assay allows the identification of more than 5 copies of VZV genomic DNA in each reaction. The entire process, from sample preparation to obtaining the results, takes less than an hour. In 86 clinical vesicles samples, the test shows 100% concordance with quantitative real-time PCR for VZV detection. Notably, when vesicles are present in specific areas, such as the genitals, our method outperforms clinical diagnosis. Compared to traditional detection methods, only a minute amount of blister fluid is required for accurate detection. Therefore, we anticipate that our method could be translated to clinical applications for specific and rapid VZV detection. KEY POINTS: • CRISPR/Cas12a and quantum dot nanobead-based lateral flow assay achieved 5 copies per reaction for VZV detection • Specific identification of VZV in atypical skin lesions • Results read by the naked eye within one hour.

Cuproptosis-related genes score: A predictor for hepatocellular carcinoma prognosis, immunotherapy efficacy, and metabolic reprogramming.

Background: Cuproptosis is a newly identified type of programmed cell death, characterized by aggregation of mitochondrial lipoylated proteins and the destabilization of Fe-S cluster proteins triggered by copper. However, its role in hepatocellular carcinoma (HCC) remains unclear. Methods: We analyzed the expression and prognostic significance of cuproptosis-related genes using the data obtained from TCGA and ICGC datasets. A cuproptosis-related genes (CRG) score was constructed and validated via least absolute shrinkage and selection operator (LASSO) Cox regression, multivariate Cox regression and nomogram model. The metabolic features, immune profile and therapy guidance of CRG-classified HCC patients were processed via R packages. The role of kidney-type glutaminase (GLS) in cuproptosis and sorafenib treatment has been confirmed via GLS knockdown. Results: The CRG score and its nomogram model performed well in predicting prognosis of HCC patients based on the TCGA cohort (training set), ICGC cohort and GEO cohort (validation set). The risk score was proved as an independent predictor for overall survival (OS) of HCC. The area under the curves (AUCs) of the model in the training and validation cohorts were all around 0.83 (TCGA, 1- year), 0.73 (TCGA, 3- year), 0.92 (ICGC, 1- year), 0.75 (ICGC, 3- year), 0.77 (GEO, 1- year), 0.76(GEO, 3- year). Expression levels of metabolic genes and subtypes of immune cells, and sorafenib sensitiveness varied significantly between the high-CRG group and low-CRG group. One of the model-included gene, GLS, might be involved in the process of cuproptosis and sorafenib treatment in HCC cell line. Conclusion: The five cuproptosis-related genes model contributed to prognostic prediction and provided a new sight for cuproptosis-related therapy in HCC.

The Efficacy and Safety of Proton Pump Inhibitors Combining Dual Antiplatelet Therapy in Patients with Coronary Intervention: A Systematic Review, Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials.

Background: Proton pump inhibitors (PPIs) are used to prevent gastrointestinal hemorrhage in patients with coronary treatment undergoing dual antiplatelet therapy (DAPT). Methods: A systematic review was performed to compare the outcomes between DAPT and DAPT + PPI in acute coronary syndrome (ACS) patients or patients who took percutaneous coronary intervention (PCI) with coronary stent implantation (PCI patients), and to estimate, for the first time, the sample size needed for reliable results via trial sequential analysis (TSA). The PubMed, EMBASE, the Cochrane Library and Web of Science databases were searched for articles authored from the onset until November 1, 2022, for randomized controlled trials (RCTs) comparing outcomes in ACS or PCI patients who undertook DAPT or DAPT + PPI. The primary outcomes were the incidence rate of gastrointestinal events and major adverse cardiovascular events (MACEs). Results: The initial web search retrieved 786 literature references. Eventually, eight articles published between 2009 and 2020 were incorporated into the systematic review and meta-analysis. The combined results established a non-significant variation in MACEs incidences between the DAPT group and DAPT + PPI group [risk ratio (RR) = 0.93, 95% confidence interval (CI) = 0.81-1.06, p = 0.27, I 2 = 0%]; conversely, the incidence of gastrointestinal events was significantly decreased in the DAPT + PPI group in comparison with the DAPT group (RR = 0.33, 95% CI = 0.24-0.45, p < 0.00001, I 2 = 0%). TSA of MACEs and gastrointestinal events revealed that meta-analysis included adequate trials (required sample size = 6874) in the pool to achieve 80% study power. Conclusions: Based on our results, DAPT + PPI can significantly reduce gastrointestinal outcomes without affecting cardiovascular outcomes in PCI and ACS patients compared to DAPT.