Iron Is Critical for Mucosal-Associated Invariant T Cell Metabolism and Effector Functions.

Mucosal-Associated Invariant T (MAIT) cells are a population of innate T cells that play a critical role in host protection against bacterial and viral pathogens. Upon activation, MAIT cells can rapidly respond via both TCR-dependent and -independent mechanisms, resulting in robust cytokine production. The metabolic and nutritional requirements for optimal MAIT cell effector responses are still emerging. Iron is an important micronutrient and is essential for cellular fitness, in particular cellular metabolism. Iron is also critical for many pathogenic microbes, including those that activate MAIT cells. However, iron has not been investigated with respect to MAIT cell metabolic or functional responses. In this study, we show that human MAIT cells require exogenous iron, transported via CD71 for optimal metabolic activity in MAIT cells, including their production of ATP. We demonstrate that restricting iron availability by either chelating environmental iron or blocking CD71 on MAIT cells results in impaired cytokine production and proliferation. These data collectively highlight the importance of a CD71-iron axis for human MAIT cell metabolism and functionality, an axis that may have implications in conditions where iron availability is limited.

Management Strategies for Malignant Left-Sided Colonic Obstruction: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials and Propensity Score Matching Studies.

BACKGROUND: The optimal treatment strategy for left-sided malignant colonic obstruction remains controversial. Emergency colonic resection has been the standard of care; however, self-expanding metallic stenting as a bridge to surgery may offer short-term advantages, although oncological concerns exist. Decompressing stoma may provide a valid alternative, with limited evidence. OBJECTIVE: To perform a systematic review and Bayesian arm random-effects model network meta-analysis comparing the approaches for management of malignant left-sided colonic obstruction. DATA SOURCES: A systematic review of PubMed, Embase, Cochrane Library, and Google Scholar databases was conducted from inception to August 22, 2023. STUDY SELECTION: Randomized controlled trials and propensity score-matched studies. INTERVENTIONS: Emergency colonic resection, self-expanding metallic stent, and decompressing stoma. MAIN OUTCOME MEASURES: Oncologic efficacy, morbidity, successful minimally invasive surgery, primary anastomosis, and permanent stoma rates. RESULTS: Nineteen of 5225 articles identified met our inclusion criteria. Stenting (risk ratio 0.57; 95% credible interval, 0.33-0.79) and decompressing stomas (risk ratio 0.46, 95% credible interval: 0.18-0.92) resulted in a significant reduction in the permanent stoma rate. Stenting facilitated minimally invasive surgery more frequently (risk ratio 4.10; 95% credible interval, 1.45-13.13) and had lower overall morbidity (risk ratio 0.58; 95% credible interval, 0.35-0.86). A pairwise analysis of primary anastomosis rates showed increased stenting (risk ratio 1.40; 95% credible interval, 1.31-1.49) compared with emergency resection. There was a significant decrease in the 90-day mortality with stenting (risk ratio 0.63; 95% credible interval, 0.41-0.95) compared with resection. There were no differences in disease-free and overall survival rates, respectively. LIMITATIONS: There is a lack of randomized controlled trials and propensity score matching data comparing short-term and long-term outcomes for diverting stomas compared to self-expanding metallic stents. Two trials compared self-expanding metallic stents and diverting stomas in left-sided malignant colonic obstruction. CONCLUSIONS: This study provides high-level evidence that a bridge-to-surgery strategy is safe for the management of left-sided malignant colonic obstruction and may facilitate minimally invasive surgery, increase primary anastomosis rates, and reduce permanent stoma rates and postoperative morbidity compared with emergency colonic resection.

Evaluating mesh fixation techniques for ventral hernia repair: A systematic review and network meta-analysis of randomised control trials.

INTRODUCTION: There is uncertainty regarding the optimal mesh fixation techniques for laparoscopic ventral and incisional hernia repair. AIM: To perform a systematic review and network meta-analysis of randomised control trials (RCTs) to investigate the advantages and disadvantages associated with absorbable tacks, non-absorbable tacks, non-absorbable sutures, non-absorbable staples, absorbable synthetic glue, absorbable sutures and non-absorbable tacks, and non-absorbable sutures and non-absorbable tacks. METHODS: A systematic review was performed as per PRISMA-NMA guidelines. Odds ratios (ORs) and mean differences (MDs) were extracted to compare the efficacy of the surgical approaches. RESULTS: Nine RCTs were included with 707 patients. Short-term pain was significantly reduced in non-absorbable staples (MD; -1.56, confidence interval (CI); -2.93 to -0.19) and non-absorbable sutures (MD; -1.00, CI; -1.60 to -0.40) relative to absorbable tacks. Recurrence, length of stay, operative time, conversion to open surgery, seroma and haematoma formation were unaffected by mesh fixation technique. CONCLUSION: Short-term post-operative pain maybe reduced by the use of non-absorbable sutures and non-absorbable staples. There is clinical equipoise between each modality in relation to recurrence, length of stay, and operative time.

Comparing neoadjuvant therapy followed by local excision to total mesorectal excision in the treatment of early stage rectal cancer: a systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Total mesorectal excision (TME) is the standard-of-care in early, clinical stage (cT2-3 N0 M0) rectal cancer. Local excision (LE) may be an alternative after adequate response to neoadjuvant therapy (NAT), with either long-course chemoradiotherapy (nCRT) or short-course radiotherapy (SCRT), as a means of preserving the rectum and potentially obviating the morbidity of TME. METHODS: A systematic review was performed according to PRISMA guidelines for studies that randomly assigned patients with cT2-3 N0 M0 rectal cancer to either NAT + LE or TME that reported radiologic, oncologic, surgical, and morbidity outcomes. RESULTS: A total of 4 RCTs comprise 462 patients (232 patients receiving NAT + LE; nCRT n = 205; SCRT n = 27) and 230 undergoing TME, respectively. NAT compliance was 98.86%. The rate of early completion TME in the NAT + LE group was 22.3%, while the proportion of patients achieving durable organ preservation was 75.4% at mean follow-up of 5.6 years. There was no difference in disease-free survival (DFS) (HR [hazard ratio] 1.19; 95% CI 0.95, 1.49; p = 0.13) or overall survival (OS) (HR 0.94; 95% CI 0.72, 1.23; p = 0.63]) according to the assigned treatment arm. The local recurrence rate (LRR) (HR 1.22; 95% CI 0.5-3.02; p = 0.66) and distant metastases (HR 0.92; 95% CI 0.45, 1.90; p = 0.82) were also comparable between the groups. There was a significant reduction in major (OR 0.45; 95% CI 0.21, 0.95; p = 0.04) and minor morbidity (OR 0.45; 95% CI 0.24, 0.85; p = 0.01) for patients undergoing NAT + LE. Overall stoma formation was decreased in the NAT + LE group (OR 0.03; 95% CI 0.0, 0.23; p ≤ 0.00001). CONCLUSION: NAT + LE reduces adverse effects of TME, without any compromise in oncological outcomes, and the potential for an organ preserving strategy should be discussed with patients with T2-3N0 rectal cancers prior to treatment.

Surgical management strategies for colorectal malignancies of the splenic flexure - A systematic review and network meta-analysis.

BACKGROUND: Extended right hemicolectomy (ERHC) or left hemicolectomy (LHC) are accepted as the standard-of-care for colonic tumours of the splenic flexure. Lymphatic drainage at this site is poorly defined and subject to significant heterogeneity. Nevertheless, emerging evidence demonstrates the potential oncological safety of segmental splenic flexure colectomy (SFC). AIM: To perform a systematic review and network meta-analysis (NMA) to compare outcomes following ERHC, LHC and SFC for splenic flexure tumours (SFTs). METHODS: A systematic review was performed as per PRISMA guidelines. NMA was performed using R Shiny and Netmeta packages. RESULTS: A total of 13 studies, involving 6176 patients (ERHC n = 785; LHC n = 1527; SFC n = 3864) were included in the NMA. There was no difference in overall survival (OS) (SFC vs LHC Hazard Ratio [HR] 1.0, 95% Credible Interval [CrI] 0.76,1.34; SFC vs ERHC HR 1.18, 95% CrI 0.85,1.58) between the groups. SFC had a shorter operation time (Mean 176.37 min; Mean Difference [MD] SFC vs LHC 20.34 min 95% CrI 10.9, 29.97; SFC vs ERHC MD 22.19 95% CrI 11.09, 33.29) but also had a lower average lymph node yield (LNY) compared with ERHC (MD 7.15, 95% CrI 5.71, 8.60). ERHC had a significantly higher incidence of post-operative ileus (Odds Ratio [OR] 3.47, 95% CrI 1.11, 10.84). There was also no difference observed for minimally invasive approaches, anastomotic leak rate, perioperative mortality, reoperation rates or length of stay. CONCLUSIONS: While SFC may allow for reduced operative duration and improved bowel function postoperatively. SFC, LHC, ERHC are all acceptable approaches for curative resection of cancers of the splenic flexure, with no difference in OS observed. Thus, surgeon preference and candidate-specific factors will likely determine the management of SFTs.

Evaluating the oncological safety of neoadjuvant chemotherapy in locally advanced colon carcinoma: a systematic review and meta-analysis of randomised clinical trials and propensity-matched studies.

PURPOSE: Use of neoadjuvant chemotherapy (NAC) for locally advanced colon cancer (LACC) remains controversial. An integrated analysis of data from high-quality studies may inform the long-term safety of NAC for this cohort. Our aim was to perform a systematic review and meta-analysis of randomised clinical trials (RCTs) and propensity-matched studies to assess the oncological safety of NAC in patients with LACC. METHODS: A systematic review was performed as per preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Survival was expressed as hazard ratios using time-to-effect generic inverse variance methodology, while surgical outcomes were expressed as odds ratios (ORs) using the Mantel-Haenszel method. Data analysis was performed using Review Manager version 5.4. RESULTS: Eight studies (4 RCTs and 4 retrospective studies) including 31,047 patients with LACC were included. Mean age was 61.0 years (range: 19-93 years) and mean follow-up was 47.6 months (range: 2-133 months). Of those receiving NAC, 4.6% achieved a pathological complete response and 90.6% achieved R0 resection (versus 85.9%, P < 0.001). At 3 years, patients receiving NAC had improved disease-free survival (DFS) (OR: 1.28, 95% confidence interval (CI): 1.02-1.60, P = 0.030) and overall survival (OS) (OR: 1.76, 95% CI: 1.10-2.81, P = 0.020). When using time-to-effect modelling, a non-significant difference was observed for DFS (HR: 0.79, 95% CI: 0.57-1.09, P = 0.150) while a significant difference in favour of NAC was observed for OS (HR: 0.75, 95% CI: 0.58-0.98, P = 0.030). CONCLUSION: This study highlights the oncological safety of NAC for patients being treated with curative intent for LACC using RCT and propensity-matched studies only. These results refute current management guidelines which do not advocate for NAC to improve surgical and oncological outcomes in patients with LACC. TRIAL REGISTRATION: International Prospective Register of Systematic Review (PROSPERO) registration: CRD4202341723.

Glycogen-fuelled metabolism supports rapid mucosal-associated invariant T cell responses.

Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells which recognize a limited repertoire of ligands presented by the MHC class-I like molecule MR1. In addition to their key role in host protection against bacterial and viral pathogens, MAIT cells are emerging as potent anti-cancer effectors. With their abundance in human, unrestricted properties, and rapid effector functions MAIT cells are emerging as attractive candidates for immunotherapy. In the current study, we demonstrate that MAIT cells are potent cytotoxic cells, rapidly degranulating and inducing target cell death. Previous work from our group and others has highlighted glucose metabolism as a critical process for MAIT cell cytokine responses at 18 h. However, the metabolic processes supporting rapid MAIT cell cytotoxic responses are currently unknown. Here, we show that glucose metabolism is dispensable for both MAIT cell cytotoxicity and early (<3 h) cytokine production, as is oxidative phosphorylation. We show that MAIT cells have the machinery required to make (GYS-1) and metabolize (PYGB) glycogen and further demonstrate that that MAIT cell cytotoxicity and rapid cytokine responses are dependent on glycogen metabolism. In summary, we show that glycogen-fueled metabolism supports rapid MAIT cell effector functions (cytotoxicity and cytokine production) which may have implications for their use as an immunotherapeutic agent.

Total neoadjuvant therapy versus standard neoadjuvant treatment strategies for the management of locally advanced rectal cancer: network meta-analysis of randomized clinical trials.

BACKGROUND: This study compared the advantages and disadvantages of total neoadjuvant therapy (TNT) strategies for patients with locally advanced rectal cancer, compared with the more traditional multimodal neoadjuvant management strategies of long-course chemoradiotherapy (LCRT) or short-course radiotherapy (SCRT). METHODS: A systematic review and network meta-analysis of exclusively RCTs was undertaken, comparing survival, recurrence, pathological, radiological, and oncological outcomes. The last date of the search was 14 December 2022. RESULTS: In total, 15 RCTs involving 4602 patients with locally advanced rectal cancer, conducted between 2004 and 2022, were included. TNT improved overall survival compared with LCRT (HR 0.73, 95 per cent credible interval 0.60 to 0.92) and SCRT (HR 0.67, 0.47 to 0.95). TNT also improved rates of distant metastasis compared with LCRT (HR 0.81, 0.69 to 0.97). Reduced overall recurrence was observed for TNT compared with LCRT (HR 0.87, 0.76 to 0.99). TNT showed an improved pCR compared with both LCRT (risk ratio (RR) 1.60, 1.36 to 1.90) and SCRT (RR 11.32, 5.00 to 30.73). TNT also showed an improvement in cCR compared with LCRT (RR 1.68, 1.08 to 2.64). There was no difference between treatments in disease-free survival, local recurrence, R0 resection, treatment toxicity or treatment compliance. CONCLUSION: This study provides further evidence that TNT has improved survival and recurrence benefits compared with current standards of care, and may increase the number of patients suitable for organ preservation, without negatively influencing treatment toxicity or compliance.

Minimally Invasive and Open Gastrectomy for Gastric Cancer: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials.

BACKGROUND AND OBJECTIVES: Optimal surgical management for gastric cancer remains controversial. We aimed to perform a network meta-analysis (NMA) of randomized clinical trials (RCTs) comparing outcomes after open gastrectomy (OG), laparoscopic-assisted gastrectomy (LAG), and robotic gastrectomy (RG) for gastric cancer. METHODS: A systematic search of electronic databases was undertaken. An NMA was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-NMA guidelines. Statistical analysis was performed using R and Shiny. RESULTS: Twenty-two RCTs including 6890 patients were included. Overall, 49.6% of patients underwent LAG (3420/6890), 46.6% underwent OG (3212/6890), and 3.7% underwent RG (258/6890). At NMA, there was a no significant difference in recurrence rates following LAG (odds ratio [OR] 1.09, 95% confidence interval [CI] 0.77-1.49) compared with OG. Similarly, overall survival (OS) outcomes were identical following OG and LAG (OS: OG, 87.0% [1652/1898] vs. LAG: OG, 87.0% [1650/1896]), with no differences in OS in meta-analysis (OR 1.02, 95% CI 0.77-1.52). Importantly, patients undergoing LAG experienced reduced intraoperative blood loss, surgical incisions, distance from proximal margins, postoperative hospital stays, and morbidity post-resection. CONCLUSIONS: LAG was associated with non-inferior oncological and surgical outcomes compared with OG. Surgical outcomes following LAG and RG superseded OG, with similar outcomes observed for both LAG and RG. Given these findings, minimally invasive approaches should be considered for the resection of local gastric cancer, once surgeon and institutional expertise allows.

The Impact of Bariatric Surgery on the Incidence of Colorectal Cancer in Patients with Obesity-a Systematic Review and Meta-analysis of Registry Data.

PURPOSE: Cancer and obesity represent two of the most significant global health concerns. The risk of malignancy, including colorectal cancer (CRC), increases with obesity. The aim of this study was to perform a systematic review and meta-analysis to determine the value of bariatric surgery in reducing CRC risk in patients with obesity using registry data. MATERIALS AND METHODS: A systematic review and meta-analysis were performed as per PRISMA guidelines. The risk of CRC was expressed as a dichotomous variable and reported as odds ratios (OR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method. A multi-treatment comparison was performed, examining the risk reduction associated with existing bariatric surgery techniques. Analysis was performed using RevMan, R packages, and Shiny. RESULTS: Data from 11 registries including 6,214,682 patients with obesity were analyzed. Of these, 14.0% underwent bariatric surgery (872,499/6,214,682), and 86.0% did not undergo surgery (5,432,183/6,214,682). The mean age was 49.8 years, and mean follow-up was 5.1 years. In total, 0.6% of patients who underwent bariatric surgery developed CRC (4,843/872,499), as did 1.0% of unoperated patients with obesity (54,721/5,432,183). Patients with obesity who underwent bariatric surgery were less likely to develop CRC (OR: 0.53, 95% CI: 0.36-0.77, P < 0.001, I2 = 99%). Patients with obesity undergoing gastric bypass surgery (GB) (OR: 0.513, 95% CI: 0.336-0.818) and sleeve gastrectomy (SG) (OR: 0.484, 95% CI: 0.307-0.763) were less likely to develop CRC than unoperated patients. CONCLUSION: At a population level, bariatric surgery is associated with reduced CRC risk in patients with obesity. GB and SG are associated with the most significant reduction in CRC risk. PROSPERO REGISTRATION: CRD42022313280.

Comparing surgical outcomes of approaches to adrenalectomy - a systematic review and network meta-analysis of randomised clinical trials.

BACKGROUND: No randomised clinical trials (RCTs) have simultaneously compared the safety of open (OA), transperitoneal laparoscopic (TLA), posterior retroperitoneal (PRA), and robotic adrenalectomy (RA) for resecting adrenal tumours. AIM: To evaluate outcomes for OA, TLA, PRA, and RA from RCTs. METHODS: A NMA was performed according to PRISMA-NMA guidelines. Analysis was performed using R packages and Shiny. RESULTS: Eight RCTs with 488 patients were included (mean age: 48.9 years). Overall, 44.5% of patients underwent TLA (217/488), 37.3% underwent PRA (182/488), 16.4% underwent RA (80/488), and just 1.8% patients underwent OA (9/488). The mean tumour size was 35 mm in largest diameter with mean sizes of 44.3 mm for RA, 40.9 mm for OA, 35.5 mm for TLA, and 34.4 mm for PRA (P < 0.001). TLA had the lowest blood loss (mean: 50.6 ml), complication rates (12.4%, 14/113), and conversion to open rates (1.3%, 2/157), while PRA had the shortest intra-operative duration (mean: 94 min), length of hospital stay (mean: 3.7 days), lowest visual analogue scale pain scores post-operatively (mean: 3.7), and was most cost-effective (mean: 1728 euros per case). At NMA, there was a significant increase in blood loss for OA (mean difference (MD): 117.00 ml (95% confidence interval (CI): 1.41-230.00)) with similar blood loss observed for PRA (MD: - 10.50 (95% CI: - 83.40-65.90)) compared to TLA. CONCLUSION: LTA and PRA are important contemporary options in achieving favourable outcomes following adrenalectomy. The next generation of RCTs may be more insightful for comparison surgical outcomes following RA, as this approach is likely to play a future role in minimally invasive adrenalectomy. PROSPERO REGISTRATION: CRD42022301005.

Comparing minimally invasive surgical and open approaches to pelvic exenteration for locally advanced or recurrent pelvic malignancies - Systematic review and meta-analysis.

INTRODUCTION: Pelvic exenteration (PE) is a complex multivisceral surgical procedure indicated for locally advanced or recurrent pelvic malignancies. It poses significant technical challenges which account for the high risk of morbidity and mortality associated with the procedure. Developments in minimally invasive surgical (MIS) approaches and enhanced peri-operative care have facilitated improved long term outcomes. However, the optimum approach to PE remains controversial. METHODS: A systematic literature search was conducted in accordance with PRISMA guidelines to identify studies comparing MIS (robotic or laparoscopic) approaches for PE versus the open approach for patients with locally advanced or recurrent pelvic malignancies. The methodological quality of the included studies was assessed systematically and a meta-analysis was conducted. RESULTS: 11 studies were identified, including 2009 patients, of whom 264 (13.1%) underwent MIS PE approaches. The MIS group displayed comparable R0 resections (Risk Ratio [RR] 1.02, 95% Confidence Interval [95% CI] 0.98, 1.07, p = 0.35)) and Lymph node yield (Weighted Mean Difference [WMD] 1.42, 95% CI -0.58, 3.43, p = 0.16), and although MIS had a trend towards improved towards improved survival and recurrence outcomes, this did not reach statistical significance. MIS was associated with prolonged operating times (WMD 67.93, 95% CI 4.43, 131.42, p < 0.00001) however, this correlated with less intra-operative blood loss, and a shorter length of post-operative stay (WMD -3.89, 955 CI -6.53, -1.25, p < 0.00001). Readmission rates were higher with MIS (RR 2.11, 95% CI 1.11, 4.02, p = 0.02), however, rates of pelvic abscess/sepsis were decreased (RR 0.45, 95% CI 0.21, 0.95, p = 0.04), and there was no difference in overall, major, or specific morbidity and mortality. CONCLUSION: MIS approaches are a safe and feasible option for PE, with no differences in survival or recurrence outcomes compared to the open approach. MIS also reduced the length of post-operative stay and decreased blood loss, offset by increased operating time.

Comparison of Restorative Proctocolectomy with and Without Defunctioning Loop Ileostomy in Patients with Ulcerative Colitis: A Systematic Review and Meta-analysis.

BACKGROUND: Restorative proctocolectomy [RPC] without a defunctioning loop ileostomy [DLI] in patients with ulcerative colitis [UC] remains controversial. AIM: To compare safety and efficacy of RPC with and without DLI in patients exclusively with UC. METHODS: A systematic review was performed according to PRISMA/MOOSE guidelines. Dichotomous variables were pooled as odds ratios [OR]. Continuous variables were pooled as weighted mean differences [WMD]. Quality assessment was performed using the Newcastle-Ottawa score [NOS]. RESULTS: A total of 20 studies [five paediatric and 15 adult] with 4550 UC patients [without DLI, n = 2370, 52.09%; with DLI, n = 2180, 47.91%] were eligible for inclusion. The median NOS was 8 [range 6-9]. There was no increased risk of anastomotic leak [AL] (OR 1.13, 95% confidence interval [CI]: 0.92, 1.39; p = 0.25), pouch excision [OR 1.01, 95% CI: 0.68, 1.50; p = 0.97], or overall major morbidity [OR 1.44, 95% CI, 0.91, 2.29; p = 0.12] for RPC without DLI, and this technique was associated with fewer anastomotic strictures [OR 0.45, 95% CI: 0.29, 0.68; p = 0.0002] and less bowel obstruction [OR 0.73, 95% CI: 0.57, 0.93; p = 0.01]. However, RPC without DLI increased the likelihood of pelvic sepsis [OR 1.68, 95% CI: 1.03, 2.75; p = 0.04] and emergency reoperation [OR 1.74, 95% CI: 1.22, 2.50; p = 0.002]. CONCLUSION: RPC without DLI is not associated with increased clinically overt AL or pouch excision rates. However, it is associated with increased risk of pelvic sepsis and emergency reoperation. RPC without DLI is feasible, but should only be performed judiciously in select UC patient cohorts in high-volume, specialist, tertiary centres.

Surgical approach for rectal cancer: A network meta-analysis comparing open, laparoscopic, robotic and transanal TME approaches.

BACKGROUND: The optimal approach for total mesorectal excision (TME) of rectal cancer remains controversial. AIM: To compare short- and long-term outcomes after open (OpTME), laparoscopic (LapTME), robotic (RoTME) and transanal TME (TaTME). METHODS: A systematic search of electronic databases was performed up to January 1, 2020 for randomized controlled trials (RCTs) comparing at least 2 TME strategies. A Bayesian arm-based random effect network meta-analysis (NMA) was performed, specifically, a mixed treatment comparison (MTC). RESULTS: 30 RCTs (and six updates) of 5586 patients with rectal cancer were included. No significant differences were identified in recurrence rates or survival rates. Operating time was shorter with OpTME (surface under the cumulative ranking curve [SUCRA] 0.96) compared to LapTME, RoTME and TaTME. Although OpTME was associated with the most blood loss (SUCRA 0.90) and had a slower recovery with increased length of stay (SUCRA 0.90) compared to the minimally invasive techniques, there was no difference in postoperative morbidity. OpTME was associated with a more complete TME specimen compared to LapTME (Risk Ratio [RR] 1.05, 95% Credible Interval [CrI] 1.01, 1.11), and TaTME had less involved CRMs (RR 0.173, 95% CrI 0.02, 0.76) versus LapTME. There were no differences between the modalities in terms of deep TME defects, DRM distance, or lymph node yield. CONCLUSIONS: While OpTME was the most effective TME modality for short term histopathological resection quality, there was no difference in long-term oncologic outcomes. Minimally invasive approaches enhance postoperative recovery, at the cost of longer operating times. Technique selection should be based on individual tumour characteristics and patient expectations, as well as surgeon and institutional expertise.