Management of acute and chronic pelvic sepsis after total mesorectal excision for rectal cancer-a 10-year experience of a national referral centre.

AIM: Uncontrolled pelvic sepsis following rectal cancer surgery may lead to dramatic consequences with significant impact on patients' quality of life. The aim of this retrospective observational study is to evaluate management of pelvic sepsis after total mesorectal excision for rectal cancer at a national referral centre. METHOD: Referred patients with acute or chronic pelvic sepsis after sphincter preserving rectal cancer resection, with the year of referral between 2010 and 2014 (A) or between 2015 and 2020 (B), were included. The main outcome was control of pelvic sepsis at the end of follow-up, with healed anastomosis with restored faecal stream (RFS) as co-primary outcome. RESULTS: In total 136 patients were included: 49 in group A and 87 in group B. After a median follow-up of 82 months (interquartile range 35-100) in group A and 42 months (interquartile range 22-60) in group B, control of pelvic sepsis was achieved in all patients who received endoscopic vacuum assisted surgical closure (7/7 and 2/2), in 91% (19/21) and 89% (31/35) of patients who received redo anastomosis (P = 1.000) and in 100% (18/18) and 95% (41/43) of patients who received intersphincteric resection (P = 1.000), respectively. Restorative procedures resulted in a healed anastomosis with RFS in 61% (17/28) of patients in group A and 68% (25/37) of patients in group B (P = 0.567). CONCLUSION: High rates of success can be achieved with surgical salvage of pelvic sepsis in a dedicated tertiary referral centre, without significant differences over time. In well selected and motivated patients a healed anastomosis with RFS can be achieved in the majority.

Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients.

BACKGROUND: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied. METHODS: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2 : 1). RESULTS: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days). CONCLUSION: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding.

Stoma-free Survival After Rectal Cancer Resection With Anastomotic Leakage: Development and Validation of a Prediction Model in a Large International Cohort.

OBJECTIVE: To develop and validate a prediction model (STOMA score) for 1-year stoma-free survival in patients with rectal cancer (RC) with anastomotic leakage (AL). BACKGROUND: AL after RC resection often results in a permanent stoma. METHODS: This international retrospective cohort study (TENTACLE-Rectum) encompassed 216 participating centres and included patients who developed AL after RC surgery between 2014 and 2018. Clinically relevant predictors for 1-year stoma-free survival were included in uni and multivariable logistic regression models. The STOMA score was developed and internally validated in a cohort of patients operated between 2014 and 2017, with subsequent temporal validation in a 2018 cohort. The discriminative power and calibration of the models' performance were evaluated. RESULTS: This study included 2499 patients with AL, 1954 in the development cohort and 545 in the validation cohort. Baseline characteristics were comparable. One-year stoma-free survival was 45.0% in the development cohort and 43.7% in the validation cohort. The following predictors were included in the STOMA score: sex, age, American Society of Anestesiologist classification, body mass index, clinical M-disease, neoadjuvant therapy, abdominal and transanal approach, primary defunctioning stoma, multivisceral resection, clinical setting in which AL was diagnosed, postoperative day of AL diagnosis, abdominal contamination, anastomotic defect circumference, bowel wall ischemia, anastomotic fistula, retraction, and reactivation leakage. The STOMA score showed good discrimination and calibration (c-index: 0.71, 95% CI: 0.66-0.76). CONCLUSIONS: The STOMA score consists of 18 clinically relevant factors and estimates the individual risk for 1-year stoma-free survival in patients with AL after RC surgery, which may improve patient counseling and give guidance when analyzing the efficacy of different treatment strategies in future studies.

Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): a multicentre, open-label, randomised, controlled trial.

BACKGROUND: A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. METHODS: In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1-2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. FINDINGS: Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55-2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87-4·58]; p<0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). INTERPRETATION: Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. FUNDING: Vifor Pharma.

International expert opinion on optimal treatment of anastomotic leakage after rectal cancer resection: a case-vignette study.

PURPOSE: Little is known about the optimal treatment of anastomotic leakage after low anterior resection (LAR) for rectal cancer and whether treatment strategy depends on leakage features and patient characteristics. The objective of this study was to determine which treatment principles are used by expert colorectal surgeons worldwide. METHODS: In this international case-vignette study, participants completed a survey on their preferred treatment for 11 clinical cases with varying leakage features and two patient scenarios depending on surgical risk (a total of 22 cases). RESULTS: In total, 42 of 64 invited surgeons completed the survey from 18 countries worldwide. The majority worked at a university training hospital (62%) and had more than 15 years of experience performing LAR for rectal cancer (52%). Early leaks in septic patients were preferably treated by major salvage surgery, to some extent depending on the patient scenario. In early leaks in non-septic patients, drainage and faecal diversion were the cornerstones of the proposed treatment. Endoscopic vacuum therapy was more often proposed than percutaneous drainage. A minority proposed anastomotic reconstruction, more often for larger defects. Treatment of late leaks ranged from watchful waiting, drainage, or transanal repair to major (non-)restorative salvage surgery, with minimal influence of the degree of symptoms on the proposed strategy. Leaks of the blind loop and rectovaginal fistulae showed high variability in the proposed treatment strategy. CONCLUSION: This TENTACLE-Rectum case-vignette study demonstrates tailored treatment strategies depending on the clinical type of leak and patient characteristics, with variable degrees of consensus and knowledge gaps which should be addressed in future studies.

Endoscopic vacuum therapy and early surgical closure after pelvic anastomotic leak: meta-analysis of bowel continuity rates.

BACKGROUND: Endoscopic vacuum therapy (EVT) with or without early surgical closure (ESC) is considered an effective option in the management of pelvic anastomotic leakage. This meta-analysis evaluated the effectiveness of EVT in terms of stoma reversal rate and the added value of ESC. METHODS: A systematic search of PubMed, MEDLINE, and the Cochrane Library was conducted in November 2021 to identify articles on EVT in adult patients with pelvic anastomotic leakage. The primary outcome was restored continuity rate. Following PRISMA guidelines, a meta-analysis was undertaken using a random-effects model. RESULTS: Twenty-nine studies were included, accounting for 827 patients with leakage who underwent EVT. There was large heterogeneity between studies in design and reported outcomes, and a high risk of bias. The overall weighted mean restored continuity rate was 66.8 (95 per cent c.i. 58.8 to 73.9) per cent. In patients undergoing EVT with ESC, the calculated restored continuity rate was 82 per cent (95 per cent c.i. 50.1 to 95.4) as compared to 64.7 per cent (95 per cent c.i. 55.7 to 72.7) after EVT without ESC. The mean number of sponge exchanges was 4 (95 per cent c.i. 2.7 to 4.6) and 9.8 (95 per cent c.i. 7.3 to 12.3), respectively. Sensitivity analysis showed a restored continuity rate of 81 per cent (95 per cent c.i. 55.8 to 99.5) for benign disease, 69.0 per cent (95 per cent c.i. 57.3 to 78.7) for colorectal cancer, and 65 per cent (95 per cent c.i. 48.8 to 79.1) if neoadjuvant radiotherapy was given. CONCLUSION: EVT is associated with satisfactory stoma reversal rates that may be improved if it is combined with ESC.

Endoscopic vacuum-assisted surgical closure (EVASC) of anastomotic defects after low anterior resection for rectal cancer; lessons learned.

BACKGROUND: Endoscopic vacuum-assisted surgical closure (EVASC) is an emerging treatment for AL, and early initiation of treatment seems to be crucial. The objective of this study was to report on the efficacy of EVASC for anastomotic leakage (AL) after rectal cancer resection and determine factors for success. METHODS: This retrospective cohort study included all rectal cancer patients treated with EVASC for a leaking primary anastomosis after LAR at a tertiary referral centre (July 2012-April 2020). Early initiation (≤ 21 days) or late initiation of the EVASC protocol was compared. Primary outcomes were healed and functional anastomosis at end of follow-up. RESULTS: Sixty-two patients were included, of whom 38 were referred. Median follow-up was 25 months (IQR 14-38). Early initiation of EVASC (≤ 21 days) resulted in a higher rate of healed anastomosis (87% vs 59%, OR 4.43 [1.25-15.9]) and functional anastomosis (80% vs 56%, OR 3.11 [1.00-9.71]) if compared to late initiation. Median interval from AL diagnosis to initiation of EVASC was significantly shorter in the early group (11 days (IQR 6-15) vs 70 days (IQR 39-322), p < 0.001). A permanent end-colostomy was created in 7% and 28%, respectively (OR 0.18 [0.04-0.93]). In 17 patients with a non-defunctioned anastomosis, and AL diagnosis within 2 weeks, EVASC resulted in 100% healed and functional anastomosis. CONCLUSION: Early initiation of EVASC for anastomotic leakage after rectal cancer resection yields high rates of healed and functional anastomosis. EVASC showed to be progressively more successful with the implementation of highly selective diversion and early diagnosis of the leak.

A systematic review and meta-analysis on complications of transanal total mesorectal excision.

AIM: Transanal total mesorectal excision (TaTME) is a surgical approach for treating mid to low rectal cancer as well as other colorectal diseases. Since the procedure is difficult to master, perioperative complications of TaTME should be examined precisely, especially during the early implementation phase of this procedure. The primary aim of this review was to determine a pooled morbidity and anastomotic leakage (AL) rate after TaTME surgery, and the secondary aim was to show the completeness of reporting of complications among the included studies, as well as the correlation between completeness and reported incidence of complications. METHOD: A systematic review of literature was conducted using Medline, Embase and Cochrane databases, searching for observational studies reporting on complications after TaTME. Studies published between 1 January 2010 and 15 October 2019 were included. Meta-analysis on the proportion of morbidity, AL and intraoperative complications was performed. RESULTS: Forty-one studies (2446 TaTME cases), consisting of 27 noncomparative studies and 14 comparative studies, were included, after screening 1711 possible studies. The pooled rates of overall morbidity and AL were 30.0% (95% CI 26.4%-34.0%) and 6.8% (95% CI 5.2%-8.9%), respectively. Subgroup analysis showed that the morbidity rate in studies that reported 30-day results (35.5%; 95% CI 31.8%-39.4%) was significantly higher than the rate in studies that did not define the follow-up length for complications (23.4%; 95% CI 17.8%-30.1%; p = 0.003). The rates of intraoperative urethral injury, rectal injury, vaginal injury and bladder injury were 0.3% (95% CI 0.1%-1.7%), 0.4% (95% CI 0.1%-2.2%), 0.3% (95% CI 0.1%-0.8%) and 0.3% (95% CI 0.1%-1.7%), respectively. CONCLUSION: This meta-analysis shows that pooled perioperative complication rates were within acceptable ranges. However, the significant difference in overall morbidity rate between the studies with 30-day results and the studies without a specified follow-up time, indicates a large under-reporting of complications in many studies.

Treatment of anastomotic leakage after rectal cancer resection: The TENTACLE-Rectum study.

AIM: Anastomotic leakage is a severe complication after low anterior resection (LAR) for rectal cancer and occurs in up to 20% of patients. Most research focuses on reducing its incidence and finding predictive factors for anastomotic leakage. There are no robust data on severity and treatment strategies with associated outcomes. The aims of this work were (1) to investigate the factors that contribute to severity of anastomotic leakage and to compose an anastomotic leakage severity score and (2) to evaluate the effects of different treatment approaches on prespecified outcome parameters, stratified for severity score and other leakage characteristics. METHOD: TENTACLE-Rectum is an international multicentre retrospective cohort study. Patients with anastomotic leakage after LAR for primary rectal cancer between 1 January 2014 and 31 December 2018 will be included by each centre. We aim to include 1246 patients in this study. The primary outcome is 1-year stoma-free survival (i.e. patients alive at 1 year without a stoma). Secondary outcomes include number of reinterventions and unplanned readmissions within 1 year, total length of hospital stay, total time with a stoma, the type of stoma present at 1 year (defunctioning, permanent), complications related to secondary leakage and mortality. For aim (1) regression models will be used to create an anastomotic leakage severity score. For aim (2) the effectiveness of different treatment strategies for leakage will be tested after correction for severity score and leakage characteristics, in addition to other potential related confounders. CONCLUSION: TENTACLE-Rectum will be an important step towards drawing up evidence-based recommendations and improving outcomes for patients who experience severe treatment-related morbidity.