Mesenchymal Stem Cells Versus Placebo for Perianal Fistulizing Crohn's Disease: A Systemic Review and Meta-Analysis.

BACKGROUND: Mesenchymal stem cells (MSCs)-based therapy for perianal fistulizing Crohn's disease (pfCD) has been extensively studies in the past decade. Its efficacy and safety had been preliminarily confirmed in some phase 2 or phase 3 clinical trials. This meta-analysis is performed to evaluate the efficacy and safety of MSCs-based therapy for pfCD. METHODS: Electronic databases (Pubmed, Cochrane Library, Embase) were searched for studies that reported the efficacy and safety of MSCs. And RevMan were used to assess the efficacy and safety. RESULTS: After screening, 5 randomized controlled trials (RCTs) were included in this meta-analysis. RevMan 5.4 for meta-analysis showed that: [Efficacy] Patients had definite remission after MSCs treatment, with an odds ratio (OR) of 2.06 (P < .0001, 95%CI 1.46, 2.89) vs controls. [Safety] The incidence of the most frequently reported TEAEs (treatment-emergent adverse events, TEAEs), perianal abscess and proctalgia, did not significantly increase due to the use of MSCs, with an OR of 1.07 in perianal abscess (P = .87, 95%CI 0.67, 1.72) vs controls, and an OR of 1.10 in proctalgia (P = .47, 95%CI 0.63, 1.92) vs controls. CONCLUSIONS: MSCs seem to be an effective and safe therapy for pfCD. MSCs based therapy has the potential to be used in combination with traditional therapies.

Pathologic outcomes of transanal versus laparoscopic total mesorectal excision for rectal cancer: a meta-analysis of 26 studies.

PURPOSE: Transanal total mesorectal excision (TaTME) has the potential advantages for patients with low rectal cancer. The objective of this meta-analysis was to identify the pathologic outcomes between the TaTME and laparoscopic total mesorectal excision (LaTME) in rectal cancer. METHODS: The literature searches were conducted in PubMed, Cochrane Library, and EMBASE with English language restriction. The primary endpoint was circumferential margin (CRM), and the secondary endpoints were distal resection margin (DRM), mesorectal excision quality, and harvested lymph nodes. RESULTS: Our research identified 1090 articles, and 26 studies met the inclusion criteria for the meta-analysis. The positive CRM was lower in the TaTME than the LaTME (OR = 0.72; 95% CI = 0.53, 0.98; P = 0.04). There was no significant difference in the positive CRM between the TaTME and LaTME published after 2016 (OR = 0.80; 95% CI = 0.57, 1.12; P = 0.19), prospective study (OR = 2.70; 95% CI = 0.51, 14.24; P = 0.24), respective study (OR = 0.76; 95% CI = 0.55, 1.04; P = 0.09), BMI > 26 (OR = 1.00; 95% CI = 0.63, 1.58; P = 0.98), or sample size > 100 (OR = 0.84; 95% CI = 0.57, 1.23; P = 0.38). In addition, there was no significant difference observed between the TaTME and LaTME in terms of DRM, mesorectum incompleteness, and harvested lymph nodes. CONCLUSIONS: The TaTME is associated with lower positive CRM compared to the LaTME and similar pathologic outcomes including DRM, harvested lymph node, and mesorectal excision quality.

D3 Versus D2 Lymphadenectomy in Right Hemicolectomy: A Systematic Review and Meta-analysis.

PURPOSE: D3 lymphadenectomy for right colon cancer improves oncological outcomes. This meta-analysis aimed to compare operation data, histopathological characteristics, perioperative conditions, and long-term survival after D3 and D2 lymphadenectomy in right hemicolectomy. METHODS: We searched PubMed, Embase, and the Cochrane Library for relevant articles (up to March 31, 2020). Random-effects and fixed-effects meta-analysis models were used. Review Manager (RevMan) version 5.3 and Stata version 15.1 were used for pooled estimates. RESULTS: After screening 714 articles, 7 articles with a total of 1368 patients were eligible for inclusion. Compared with D2, D3 lymphadenectomy improves results in terms of blood loss (weighted mean difference [WMD] = -20.63, 95% confidence interval [CI] -28.19 to -13.16, P < .01), harvested lymph nodes (WMD = 8.86, 95% CI 7.74 to 9.98, P < .01), 3-year overall survival (OS) (hazard ratio [HR] = 2.03, 95% CI 1.20 to 3.43, P < .01), 5-year OS (HR = 2.22, 95% CI 1.15 to 4.30, P = .02), and 5-year disease-free survival (DFS) (HR = 2.16, 95% CI 1.19 to 3.90, P = .01). There was no significant difference regarding operation time, anastomosis leakage, wound infection, overall morbidity, postoperative hospital stay, mortality, length of dissected colon, and 3-year DFS (P >= .05). CONCLUSIONS: It is suggested in this review that D3 lymphadenectomy is superior to D2 lymphadenectomy in terms of blood loss, harvested lymph nodes, 3-year OS, 5-year OS, and 5-year DFS. The conclusion must be drawn with caution due to the limited number of included studies. Further RCTs are needed for stronger evidence.

Ribosome assembly factor URB1 contributes to colorectal cancer proliferation through transcriptional activation of ATF4.

Ribosome assembly factor URB1 is essential for ribosome biogenesis. However, its latent role in cancer remains unclear. Analysis of The Cancer Genome Atlas database and clinical tissue microarray staining showed that URB1 expression was upregulated in colorectal cancer (CRC) and prominently related to clinicopathological characteristics. Silencing of URB1 hampered human CRC cell proliferation and growth in vitro and in vivo. Microarray screening, ingenuity pathway analysis, and JASPAR assessment indicated that activating transcription factor 4 (ATF4) and X-box binding protein 1 (XBP1) are potential downstream targets of URB1 and could transcriptionally interact through direct binding. Silencing of URB1 significantly decreased ATF4 and cyclin A2 (CCNA2) expression in vivo and in vitro. Restoration of ATF4 effectively reversed the malignant proliferation phenotype of URB1-silenced CRC cells. Dual-luciferase reporter and ChIP assays indicated that XBP1 transcriptionally activated ATF4 by binding with its promoter region. X-box binding protein 1 colocalized with ATF4 in the nuclei of RKO cells, and ATF4 mRNA expression was positively regulated by XBP1. This study shows that URB1 contributes to oncogenesis and CRC growth through XBP1-mediated transcriptional activation of ATF4. Therefore, URB1 could be a potential therapeutic target for CRC.

Early Versus Routine Stoma Closure in Patients With Colorectal Resection: A Meta-Analysis of 7 Randomized Controlled Trials.

Background. A substantial proportion of patients undergoing colorectal surgery receive a temporary stoma, and the timing for stoma closure remains unclear. The aim of this study was to evaluate the safety and feasibility of early stoma closure (ESC) compared with routine stoma closure (RSC) after colorectal surgery. Methods. We comprehensively searched PubMed, Embase, and the Cochrane Library for randomized controlled trials that compared ESC and RSC after colorectal surgery. Results. A total of 7 randomized controlled trials with 814 enrolled patients were identified for this meta-analysis. There were no significant differences between the ESC and RSC groups regarding the complications of stoma closure (26.8% and 16.6%, respectively; odds ratio [OR]: 1.30; 95% confidence interval [CI]: 0.89-1.90; P = .17). A subgroup analysis was conducted by Clavien-Dindo grade of complication, and no significant difference was observed in any subgroup (P > .05). However, the ESC group had a significantly higher risk of wound complications than the RSC group (17.6% and 7.8%, respectively; OR: 2.61; 95% CI: 1.43-4.76; P = .002), and the RSC group had more cases of small bowel obstruction than the ESC group (3.1% and 8.4%, respectively; OR: 0.37; 95% CI: 0.15-0.87; P = .02). Conclusions. ESC is a safe and effective therapeutic approach in patients who have undergone colorectal surgery; it is associated with a reduced risk of bowel obstruction but a higher risk of wound complications.

Comparison of three-dimensional versus two-dimensional laparoscopic surgery for rectal cancer: a meta-analysis.

PURPOSE: Three-dimensional (3D) vision technology has recently been validated for the improvement of surgical skills in a simulated setting. This study assessed the current evidence regarding the efficiency and potential advantages of 3D compared with two-dimensional (2D) laparoscopic rectal surgery for rectal cancer. METHODS: We comprehensively searched PubMed, EMBASE and the Cochrane Library and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) and non-randomized controlled trials (nRCTs) assessing the two approaches. RESULTS: Four trials including a total 331 cases were identified. The positive circumferential resection margins (CRMs) were significantly lower for the 3D group (P = 0.02). The operative time was significantly shorter in the 3D group than in the 2D group (P < 0.00001). There was less estimated blood loss (EBL) in the 3D group than in the 2D group (P = 0.02). Perioperative complication rates, conversion rate, harvested lymph nodes, first flatus, length of stay, pneumonia, wound infection, ileus, anastomotic fistula and urinary retention did not differ significantly between the two groups (P > 0.05). CONCLUSIONS: In summary, 3D laparoscopic rectal surgery appears to have advantages over 2D laparoscopic rectal surgery in terms of positive CRM and operation time; however, it is not better than 2D laparoscopic rectal surgery in terms of the conversion rate and postoperative complications.

Lymph node yield, survival benefit, and safety of high and low ligation of the inferior mesenteric artery in colorectal cancer surgery: a systematic review and meta-analysis.

PURPOSE: The aim of this meta-analysis was to compare high inferior mesenteric artery (IMA) ligation (HL) with low IMA ligation (LL) for the treatment of colorectal cancer and to evaluate the lymph node yield, survival benefit, and safety of these surgeries. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and China Biomedical Literature Database (CBM) were systematically searched for relevant articles that compared HL and LL for sigmoid or rectal cancer. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for dichotomous outcomes and the weighted mean difference (WMD) for continuous outcomes. RESULTS: In total, 30 studies were included in this analysis. There were significantly higher odds of anastomotic leakage and urethral dysfunction in patients treated with HL compared to those treated with LL (OR = 1.29; 95% CI = 1.08 to 1.55; OR = 2.45; 95% CI = 1.39 to 4.33, respectively). There were no significant differences between the groups in terms of the total number of harvested lymph nodes, the number of harvested lymph nodes around root of the IMA, local recurrence rate, and operation time. Further, no statistically significant group differences in 5-year overall survival rates and 5-year disease-free survival rates were detected among all patients nor among subgroups of stage II patients and stage III patients, respectively. CONCLUSIONS: LL can achieve equivalent lymph node yield to HL, and both procedures have similar survival benefits. However, LL is associated with a lower incidence of leakage and urethral dysfunction. Thus, LL is recommended for colorectal cancer surgery.

Robotic Versus Laparoscopic Rectal Surgery for Rectal Cancer: A Meta-Analysis of 7 Randomized Controlled Trials.

Background. Robotic surgery has been recently used as a novel tool for rectal surgery. This study assessed the current evidence regarding the efficiency, safety, and potential advantages of robotic rectal surgery (RRS) compared with laparoscopic rectal surgery (LRS). Methods. We comprehensively searched PubMed, Embase, and the Cochrane Library databases and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) assessing the 2 approaches. Results. Seven RCTs including a total of 1022 cases were identified. The conversion rate is significantly lower for RRS (odds ratio: 0.29; 95% confidence interval: 0.09 to 0.96; P = .04). The length of the distal margin was significantly shorter in the LRS group than in the RRS group (weighted mean difference: 0.60; 95% confidence interval: 0.09 to 1.10; P = .02). Perioperative complication rates, harvested lymph nodes, positive circumferential resection margins, complete total mesorectal excision, first flatus, and length of stay did not differ significantly between approaches (P > .05). Conclusions. This meta-analysis indicates that RRS is a safe and effective approach. It is not inferior to LRS in terms of oncologic outcomes and postoperative complications. Future large-volume, well-designed RCTs with extensive follow-up are awaited to confirm and update the findings of this analysis.

Prediction of lateral lymph node metastasis in rectal cancer patients based on MRI using clinical, deep transfer learning, radiomic, and fusion models.

Introduction: Lateral lymph node (LLN) metastasis in rectal cancer significantly affects patient treatment and prognosis. This study aimed to comprehensively compare the performance of various predictive models in predicting LLN metastasis. Methods: In this retrospective study, data from 152 rectal cancer patients who underwent lateral lymph node (LLN) dissection were collected. The cohort was divided into a training set (n=86) from Tianjin Union Medical Center (TUMC), and two testing cohorts: testing cohort (TUMC) (n=37) and testing cohort from Gansu Provincial Hospital (GSPH) (n=29). A clinical model was established using clinical data; deep transfer learning models and radiomics models were developed using MRI images of the primary tumor (PT) and largest short-axis LLN (LLLN), visible LLN (VLLN) areas, along with a fusion model that integrates features from both deep transfer learning and radiomics. The diagnostic value of these models for LLN metastasis was analyzed based on postoperative LLN pathology. Results: Models based on LLLN image information generally outperformed those based on PT image information. Rradiomics models based on LLLN demonstrated improved robustness on external testing cohorts compared to those based on VLLN. Specifically, the radiomics model based on LLLN imaging achieved an AUC of 0.741 in the testing cohort (TUMC) and 0.713 in the testing cohort (GSPH) with the extra trees algorithm. Conclusion: Data from LLLN is a more reliable basis for predicting LLN metastasis in rectal cancer patients with suspicious LLN metastasis than data from PT. Among models performing adequately on the internal test set, all showed declines on the external test set, with LLLN_Rad_Models being less affected by scanning parameters and data sources.

Total neoadjuvant therapy versus standard therapy in locally advanced rectal cancer: A systematic review and meta-analysis of 15 trials.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) before total mesorectal excision (TME) and followed systemic chemotherapy is widely accepted as the standard therapy for locally advanced rectal cancer (LARC). This meta-analysis was to evaluate the current evidence regarding nCRT in combination with induction or consolidation chemotherapy for rectal cancer in terms of oncological outcomes. METHODS: A systematic search of medical databases (PubMed, EMBASE and Cochrane Library) was conducted up to the end of July 1, 2021. This meta-analysis was performed to evaluate the efficacy of TNT in terms of pathological complete remission (pCR), nCRT or surgical complications, R0 resection, local recurrence, distant metastasis, disease-free survival (DFS) and overall survival (OS) in LARC. RESULTS: Eight nRCTs and 7 RCTs, including 3579 patients were included in the meta-analysis. The rate of pCR was significantly higher in the TNT group than in the nCRT group, (OR 1.85, 95% CI 1.39-2.46, p < 0.0001), DFS (HR 0.80, 95% CI 0.69-0.92, p = 0.001), OS (HR 0.75, 95% CI 0.62-0.89, p = 0.002), nCRT complications (OR 1.05, 95% CI 0.77-1.44, p = 0.75), surgical complications (OR 1.02, 95% CI 0.83-1.26, p = 0.83), local recurrence (OR 1.82, 95% CI 0.95-3.49, p = 0.07), distant metastasis (OR 0.77, 95% CI 0.58-1.03, p = 0.08) did not differ significantly between the TNT and nCRT groups. CONCLUSION: TNT appears to have advantages over standard therapy for LARC in terms of pCR, R0 resection, DFS, and OS, with comparable nCRT and postoperative complications, and no increase in local recurrence and distant metastasis.

Comparison of pathologic outcomes of robotic and open resections for rectal cancer: A systematic review and meta-analysis.

OBJECTIVE: The application of robotic surgery for rectal cancer is increasing steadily. The purpose of this meta-analysis is to compare pathologic outcomes among patients with rectal cancer who underwent open rectal surgery (ORS) versus robotic rectal surgery (RRS). METHODS: We systematically searched the literature of EMBASE, PubMed, the Cochrane Library of randomized controlled trials (RCTs) and nonrandomized controlled trials (nRCTs) comparing ORS with RRS. RESULTS: Fourteen nRCTs, including 2711 patients met the predetermined inclusion criteria and were included in the meta-analysis. Circumferential resection margin (CRM) positivity (OR: 0.58, 95% CI, 0.29 to 1.16, P = 0.13), number of harvested lymph nodes (WMD: -0.31, 95% CI, -2.16 to 1.53, P = 0.74), complete total mesorectal excision (TME) rates (OR: 0.93, 95% CI, 0.48 to 1.78, P = 0.83) and the length of distal resection margins (DRM) (WMD: -0.01, 95% CI, -0.26 to 0.25, P = 0.96) did not differ significantly between the RRS and ORS groups. CONCLUSION: Based on the current evidence, robotic resection for rectal cancer provided equivalent pathological outcomes to ORS in terms of CRM positivity, number of harvested lymph nodes and complete TME rates and DRM.

RAPTOR promotes colorectal cancer proliferation by inducing mTORC1 and upregulating ribosome assembly factor URB1.

Mammalian target of rapamycin complex 1 (mTORC1) is evolutionally conserved and frequently activated in various tumors, including colorectal cancer (CRC). It has been reported that the ribosome assembly factor Urb1 acts downstream of mTORC1/raptor signaling and contributes to digestive organ development in zebrafish. Previously, we highlighted that URB1 was overexpressed in CRC. Here, we assessed the mTORC1/regulatory associated protein with mTOR (RAPTOR)-URB1 axis in CRC tumorigenesis. We found that RAPTOR was overexpressed in CRC tissues and cell lines, was a favorable predictor in patients with CRC, and positively correlated with URB1. Silencing of RAPTOR suppressed CRC cell proliferation and migration and induced cell cycle arrest and apoptosis in vitro and inhibited xenograft growth in vivo. Moreover, ectopic overexpression of RAPTOR exerted an inverse biological phenotype. Knockdown of RAPTOR quenched mTORC1 activity and reduced the expression of URB1 and cyclinA2 (CCNA2). In contrast, overexpression of RAPTOR activated mTORC1 and upregulated URB1 and CCNA2. Furthermore, URB1 and CCNA2 expression were also impeded by rapamycin, which is a specific inhibitor of mTORC1. Thus, RAPTOR promoted CRC proliferation, migration, and cell cycle progression by inducing mTORC1 signaling and transcriptional activation of both URB1 and CCNA2. Taken together, we concluded that RAPTOR has the potential to serve as a novel biomarker and therapeutic target for CRC.

Meta-analysis of the effectiveness of laparoscopic adjustable gastric banding versus laparoscopic sleeve gastrectomy for obesity.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) are common weight loss procedures. Our meta-analysis compared these procedures for the treatment of morbid obesity and related diseases. METHODS: We systematically searched the PubMed, Embase, and the Cochrane Library through January 2018. The percentage of excess weight loss (%EWL), improvement or remission of type 2 diabetes mellitus (T2DM) and hypertension were analyzed and compared. RESULTS: Thirty-three studies with 4109 patients were included. Greater decreases in excess weight were found in patients who received LSG at 6 months (weighted mean difference (WMD) -9.29, 95% confidence interval (CI): -15.19 to -3.40, P = .002), 12 months (WMD -16.67 95% CI: -24.30 to -9.05, P < .0001), 24 months (WMD -19.63, 95% CI: -29.00 to -10.26, P < .0001), and 36 months (WMD -19.28, 95% CI: -27.09 to -11.47, P < .0001) than in patients who received LAGB. However, there were no significant differences in the 3-month outcomes between the 2 groups (WMD -1.61, 95% CI: -9.96 to 6.73, P = .70). T2DM patients after LSG experience more significant improvement or remission of diabetes (odds ratio (OR): 0.22, 95% CI: 0.06-0.87, P = .03). The 2 groups did not significantly differ regarding improvement or remission of hypertension (OR 0.80, 95% CI: 0.46-1.38, P = .42). CONCLUSION: LSG is a more effective procedure than LAGB for morbidly obese patients, contributing to a higher %EWL and greater improvement in T2DM.

The Effects of Sleeve Gastrectomy on Glucose Metabolism and Glucagon-Like Peptide 1 in Goto-Kakizaki Rats.

PURPOSE: To investigate the effects of sleeve gastrectomy (SG) on glucose metabolism and changes in glucagon-like peptide 1 (GLP-1) in Goto-Kakizaki (GK) rats. METHODS: GK rats were randomly assigned to one of three groups: SG, SG pair-fed plus sham surgery (PF-sham), and ad libitum-fed no surgery (control). Food intake, body weight, blood glucose, GLP-1 and insulin levels, and GLP-1 expression in the jejunum and ileum were compared. RESULTS: The SG rats exhibited lower postoperative food intake, body weight, and fasting glucose than did the control rats (P < 0.05). SG significantly improved glucose and insulin tolerance (P < 0.05). Plasma GLP-1 levels were higher in SG rats than in control or PF-sham rats in the oral glucose tolerance test (OGTT) (P < 0.05). Blood glucose levels expressed as a percentage of baseline were higher in SG rats than in control rats after exendin (9-39) administration (P < 0.05). The levels of GLP-1 expression in the jejunum and ileum were higher in SG rats than in PF-sham and control rats (P < 0.05). CONCLUSIONS: Improvement of glucose metabolism by SG was associated with increased GLP-1 secretion. SG contributes to an increase in plasma GLP-1 levels via increased GLP-1 expression in the mucosa of the jejunum and/or ileum.