Despite a burgeoning literature during the last two decades regarding perioperative risk management of anal fistula, little is known about its risk factors that influence postoperative recurrence. We performed a meta-analysis to summarize and assess the credibility of evidence of potential risk factors for anal fistula recurrence (AFR) after surgery. Pubmed and EMBASE without language restriction were searched from inception to April 2018 that reported risk factors which predisposed recurrence after anal fistula surgery. We excluded studies that involved patients with anal fistula associated with Crohn's disease. MOOSE guidelines were followed when this meta-analysis was performed. We used random-effects models to pool relative risks (RRs) with 95% confidence intervals (CIs). Evidence from observational studies was graded into high-quality (Class I), moderate-quality (Class II/III) and low-quality (Class IV) based on Egger's P value, total sample size and between-study heterogeneity. Of 3514 citations screened, 20 unique observational studies comprising 6168 patients were involved in data synthesis. High-quality evidence showed that AFR was associated with high transsphincteric fistula (RR, 4.77; 95% CI, 3.83 to 5.95), internal opening unidentified (RR, 8.54; 95% CI, 5.29 to 13.80), and horseshoe extensions (RR, 1.92; 95% CI, 1.43 to 2.59). Moderate-quality evidence suggested an association with prior anal surgery (RR, 1.52; 95% CI, 1.04 to 2.23), seton placement surgery (RR, 2.97; 95% CI, 1.10 to 8.06), and multiple fistula tract (RR, 4.77; 95% CI, 1.46 to 15.51). High-quality evidence demonstrated no significant association with gender or smoking; moderate-quality evidence also suggested no association with age, tertiary referral, alcohol use, diabetes mellitus, obesity, preoperative seton drainage, high internal opening, postoperative drainage, mucosal advancement flap surgery, supralevator extensions, location or type of anal fistula. Several patient, surgery and fistula-related factors are significantly associated with postoperative AFR. These findings strengthen clinical awareness of early warning to identify patients with high-risk disease recurrence for AFR.

CD166 has been identified as an important cancer stem cell (CSC) marker in colorectal cancer (CRC). The purpose of our study was to investigate the relationship between CD166 expression and clinical features and to examine the role of CD166 expression on the survival of patients with CRC. A total of 15 studies with 3,332 cases were identified in this meta-analysis. The pooled OR indicated that CD166 expression was significantly higher in CRC than in colonic adenomas or normal colonic mucosa (OR = 3.48, P = 0.002 and OR = 55.13, P = 0.017, respectively). CD166 expression was found to be negatively correlated with vascular invasion (OR = 0.75, P = 0.017), but it was not associated with gender, tumor location, lymph node status, distant metastasis, clinical stage, T classification or tumor differentiation. Meanwhile, CD166 expression was not associated with the prognosis of overall survival (OS) (HR = 1.20, 95% CI = 0.45-3.22, P = 0.72) in multivariate regression analysis. One study reported that CD166 expression may be a predictor of survival in stage II CRC patients using multivariate logistic regression analysis (OS: OR = 9.97, P = 0.035; disease-specific survival: OR = 29.02, P = 0.011). Our findings suggest that CD166 expression may be correlated with CRC carcinogenesis and a decreased risk of vascular invasion, and it may become a predictive biomarker of survival for stage II CRC patients, but additional studies with large sample sizes are essential to validate the prognostic and predictive values of CD166 expression.

Objective: Cancer stem cell marker CD44 and its variant isoforms (CD44v) may be correlated with tumor growth, metastasis and chemo-radiotherapy resistance. However, the prognostic power of CD44 and CD44v in advanced cancer remains controversial. Therefore, the purpose of our study was to generalize the prognostic significance of these cancer stem cell markers in advanced cancer patients. Methods: Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated from multivariable analysis to assess the associations among CD44, CD44v6, and CD44v9 positivity and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), and recurrence-free survival (RFS). Trial sequential analysis (TSA) was also conducted. Results: We included 15 articles that reported on 1,201 patients with advanced cancer (CD44: nine studies with 796 cases, CD44v6: three studies with 143 cases, and CD44v9: three studies with 262 cases). CD44 expression was slightly linked to worse OS (HR = 2.03, P = 0.027), but there was no correlation between CD44 expression and DFS, RFS, or PFS. Stratified analysis showed that CD44 expression was not correlated with OS at ≥ 5 years or OS in patients receiving adjuvant therapy. CD44v6 expression was not associated with OS. CD44v9 expression was closely associated with poor 5-year CSS in patients treated with chemo/radiotherapy (HR = 3.62, P < 0.001). However, TSA suggested that additional trials were needed to confirm these conclusions. Conclusions: CD44 or CD44v9 might be novel therapeutic targets for improving the treatment of advanced cancer patients. Additional prospective clinical trials are strongly needed across different cancer types.

Introduction Postoperative recurrence and related complications are common and related to poor outcomes in patients with anal fistula (AF). Due to being associated with short-term and long-term cure rates, perioperative complications have received widespread attention following AF surgery. This study aims to identify a set of predictive factors to develop risk prediction models for recurrence and related complications following AF surgery. We plan to develop and validate risk prediction models, using information collected through a WeChat patient-reported questionnaire system combined with clinical, laboratory and imaging findings from the perioperative period until 3–6 months following AF surgery. Methods and analysis This is a prospective hospital-based cohort study using a linked database of collected health data as well as the follow-up outcomes for all adult patients who suffered from AF at a tertiary referral hospital in Shanghai, China. We will perform logistic regression models to predict anal fistula recurrence (AFR) as well as related complications (eg, wound haemorrhage, faecal impaction, urinary retention, delayed wound healing and unplanned hospitalisation) during and after AF surgery, and machine learning approaches will also be applied to develop risk prediction models. This prospective study aims to develop the first risk prediction models for AFR and related complications using multidimensional variables. These tools can be used to warn, motivate and empower patients to avoid some modifiable risk factors to prevent postoperative complications early. This study will also provide alternative tools for the early screening of high-risk patients with AFR and related complications, helping surgeons better understand the aetiology and outcomes of AF in an earlier stage. Ethics and dissemination The study was approved by the Institutional Review Board of Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine (approval number: 2019-699-54-01). The results of this study will be submitted to international scientific peer-reviewed journals or conferences in surgery, anorectal surgery or anorectal diseases. Trial registration number ChiCTR1900025069; Pre-results.

Novel prognostic markers and therapeutic targets for advanced cancer are urgently needed. This report with trial sequential analysis (TSA) was first conducted to provide robust estimates of the correlation between aldehyde dehydrogenase 1 (ALDH1) and Nestin and clinical outcomes of advanced cancer patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) were summarized for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), relapse/recurrence-free survival (RFS), and metastasis-free survival (MFS) from multivariable analysis. TSA was performed to control for random errors. A total of 20 studies with 2050 patients (ALDH1: 15 studies with 1557 patients and Nestin: 5 studies with 493 patients) were identified. ALDH1 (HR = 2.28, p < 0.001) and Nestin (HR = 2.39, p < 0.001) were associated with a worse OS, as confirmed by TSA. Nestin positivity was linked to a poor PFS (HR = 2.08, p < 0.001), but ALDH1 was not linked to DFS, RFS, MFS, or PFS, and TSA showed that more studies were needed. Subgroup analysis by tumor type indicated that ALDH1 positivity may be associated with shorter OS in breast, head and neck cancers, but there was no association with colorectal cancer. Subgroup analysis by study source showed that ALDH1 positivity was correlated with a worse OS for Japanese (HR = 1.94, p = 0.002) and European patients (HR = 4.15, p < 0.001), but there was no association for Chinese patients. Subgroup analysis by survival rate showed that ALDH1 positivity correlated with poor OS at ⩾ 5 years (HR = 2.33, p < 0.001) or 10 years (HR = 1.76, p = 0.038). ALDH1 may be more valuable as an effective therapeutic target than Nestin for improving the long-term survival rate of advanced cancer. Additional prospective clinical trials are needed across different cancer types.

Ulcerative colitis (UC) is an increasing incidence of inflammatory disorder in the colon mucosa. One of the current research focuses is the alteration of metabolic networks in UC. One of the important aspects of this metabolic shift is the expression of purine metabolism genes (PMGs) vital for nucleic acid synthesis. Nevertheless, the precise function of PMGs in the pathophysiology of UC is not yet fully known. To this end, this study used state-of-the-art bioinformatics tools and approaches to discover and confirm the PMGs involved in UC. All the 114 candidate PMGs were compared for their expression levels. GSEA and GSVA were applied to define the functional and pathway implications of these PMGs. Lasso regression and SVM-RFE approaches were used for the identification of hub genes and to assess the diagnostic potential of eight PMGs in UC classification. The relationship between these critical PMGs and clinical features was also systematically evaluated as well. The expression levels of these eight PMGs were validated using datasets GSE206285 and GSE179285. Using bioinformatics and machine learning, this work seeks to establish the involvement of PMGs in UC. From the LASSO and SVM models, 114 DE PMGs were selected and investigated to build a stable predictive model. Based on these studies, the following genes: IMPDH1, GUK1, POLE3, ADCY3, ADCY4, PDE6B, PNPT1 and PDE4D were suggested as potential biomarkers of UC. Gene ontology enrichment analysis revealed that these genes are implicated in the biological processes of particular relevance to immune and inflammatory responses. The study also provided a lot of information on the interaction between immune cells and PMGs indicating that these genes may control some immune-related pathways in UC. Moreover, drug-gene interaction analysis presents potential therapeutic opportunities for potential drug targets which were further confirmed through molecular docking. Mendelian randomization analysis revealed that ADCY4 and PDAZN are involved in PMG-related processes, thus opening new possibilities for treatment. This work reveals eight PMGs closely related to UC and provides new perspectives on possible markers of this inflammatory disease. These findings not only increase the understanding of the pathogenesis of UC but also offer potential for improving the surveillance of disease and its progression.