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Aim: The selective use of defunctioning stomas in anterior resection for rectal cancer hinges on accurately predicting anastomotic leakage. The aim of this study was to develop a prediction model for use in a prospective randomized clinical trial.

Method: Colorectal Cancer Database (CRCBaSe) Sweden was used to identify patients who underwent low anterior resection for rectal cancer 2007–2021. Eligibility criteria mirrored the forthcoming SELective defunctioning Stoma Approach in low anterior resection for rectal cancer (SELSA) trial, including patients <80 years of age and with American Society of Anaesthesiologists' (ASA) physical status grade of <III; further, patients without a defunctioning stoma were excluded. The outcome comprised anastomotic leakage within 30 days or in-hospital. Candidate predictors included age, sex, ASA grade, cardiovascular disease, diabetes, body mass index (BMI), tumour stage, tumour height, and neoadjuvant therapy. Seven models were developed and internally validated using bootstrapping. A threshold of a predicted leakage risk of ≤10% was chosen for trial implementation. Validation was conducted using chart-reviewed data from a nested cohort.

Results: Of the 2727 eligible patients, 199 (7.3%) were registered with an anastomotic leakage. All models demonstrated similar performance, with prediction instability observed for risks exceeding 12.5%. The preferred model included three significant predictors: male sex (OR 2.00; 95% CI: 1.45–2.75), BMI >30 kg/m2 (OR 1.82; 95% CI: 1.21–2.74), and radiotherapy (OR 1.90; 95% CI: 1.35–2.69). The bootstrapped area under the curve (AUC) was 0.64 (95% CI: 0.62–0.65), with a negative predictive value of 94.6% (95% CI: 93.7%–95.6%). For the validation cohort, the corresponding estimates were 0.66 (95% CI: 0.59–0.74) and 89.5% (95% CI: 86.2%–92.5%).

Conclusion: Accuracy of anastomotic leakage prediction using registry-based data is moderate; however, the model's ability to rule out a >10% risk is considered appropriate for trial use.

Background: Postoperative death measured 30 days after surgery is a conventional quality metric, whereas intervals up to 90 days are increasingly used, although data-driven time windows have scarcely been investigated.

Methods: The Swedish Colorectal Cancer Registry was used to identify all patients subjected resection for colorectal cancer between 2007 and 2020. All patients were followed up until 180 days after surgery. A join-point statistical hazard model was used to model a declining hazard to a transition point, followed by a stable death rate. This method was subsequently applied to describe postoperative deaths for the entire cohort and subgroups according to tumour location (colon and rectum).

Results: Some 56 096 patients electively operated on for colorectal cancer during the study interval were included, with a 30-day and 90-day fatality of 805 (1.43%) and 1458 (2.60%) patients respectively. The derived postoperative fatality window, after which the death rate transitioned to a stable rate, was 23.8 (95% c.i. 21.5 to 28.2) days after surgery. There was no significant difference in the time window between rectal cancer (22.9 days; 95% c.i. 15.1 to 28.4) and colon cancer (27.3 days; 95% c.i. 21.4 to 31.8) patients (P = 0.455). However, postoperative fatality time windows were extended in patients aged at least 80 years and with American Society of Anesthesiologists’ grade III or IV.

Conclusion: The traditional postoperative time window of 30 days was confirmed to be an appropriate metric in elective colorectal cancer surgery when evaluated with a hazards-based statistical framework. Importantly, this time window is influenced by older age and advanced co-morbidity, which could prompt increased vigilance for these patient groups.

Purpose: To evaluate current MRI-based criteria for malignancy in mesorectal nodal structures in rectal cancer.

Method: Mesorectal nodal structures identified on baseline MRI as lymph nodes were anatomically compared to their corresponding structures histopathologically, reported as lymph nodes, tumour deposits or extramural venous invasion. All anatomically matched nodal structures from patients with primary surgery and all malignant nodal structures from patients with neoadjuvant treatment were included. Mixed-effects logistic regression models were used to evaluate the morphological criteria irregular margin, round shape, heterogeneous signal and nodal size, as well as the combined 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus criteria, with histopathological nodal status as the gold standard.

Results: In total, 458 matched nodal structures were included from 46 patients (mean age, 67.7 years ± 1.5 [SD], 27 men), of which 19 received neoadjuvant treatment. The strongest associations in the univariable model were found for short-axis diameter ≥ 5 mm (OR 21.43; 95% CI: 4.13–111.29, p < 0.001) and heterogeneous signal (OR 9.02; 95% CI: 1.33–61.08, p = 0.024). Only size remained significant in multivariable analysis (OR 12.32; 95% CI: 2.03–74.57, p = 0.006). When applying the ESGAR consensus criteria to create a binary classification of nodal status, the OR of malignant outcome for nodes with positive ESGAR was 8.23 (95% CI: 2.15–31.50, p = 0.002), with corresponding sensitivity and specificity of 54% and 85%, respectively.

Conclusion: The results confirm the role of morphological and size criteria in predicting lymph node metastases. However, the current criteria might not be accurate enough for nodal staging.

PURPOSE: Defunctioning stoma (DS) has been suggested to mitigate the consequences of anastomotic leak (AL) after low anterior resection. Stoma reversal (SR) is commonly delayed for nonmedical reasons in many healthcare systems. This study investigated the impact of the elapsed time from AR to SR on postoperative 90-day complications. The secondary aim was to explore the independent factors associated with a delayed SR.

M&M: This multicenter retrospective cohort study included rectal cancer patients who underwent anterior resection (AR) and DS between 2014 and 2018. Multivariable logistic regression was used to evaluate the influence of the elapsed time from AR to SR on postoperative complications within 90 days.

RESULTS: Out of 905 patients subjected to AR with DS, 116 (18%) patients experienced at least one postoperative 90-day complication after SR. Multivariable analysis revealed an association between the elapsed time to SR and complications within 90 days from SR (OR 1.02; 95% CI, 1.00-1.04). The association with SR complications was further highlighted in patients who experienced delayed SR > 6 months after AR (OR 1.73; 95% CI, 1.04-2.86). AL after AR and nodal disease were both related to delayed SR.

CONCLUSION: This study demonstrated that postoperative 90-day complications are associated with the time elapsed to SR. These findings emphasize the importance of early SR, preferably within 6 months, to prevent complications.

Aim: Accumulated data suggest that routine use of defunctioning stoma in low anterior resection for rectal cancer may cause kidney injury, bowel dysfunction and a higher risk of permanent stomas. We aim to study whether avoidance of a diverting stoma in selected patients is safe and reduces adverse consequences.

Methods: SELSA is a multicentre international prospective observational study nesting an open-label randomized clinical trial. All patients with primary rectal cancer planned for low anterior resection are eligible. Patients operated with curative intent, aged <80 years, with an American Society of Anaesthesiologists' fitness grade I or II, and a low predicted risk of anastomotic leakage are eligible to 1:1 randomization between no defunctioning stoma (experimental arm) or a defunctioning stoma (control arm). The primary outcome is the composite measure of 2-year stoma-free survival without major low anterior resection syndrome (LARS). Secondary outcomes include anastomotic leakage, postoperative mortality, reinterventions, stoma-related complications, quality of life measures, LARS score, and permanent stoma rate. To be able to state superiority of any study arm regarding the main outcome, with 90% statistical power and assuming 25% attrition, we aim to enrol 212 patients. Patient inclusion will commence in the autumn of 2024.

Conclusion: The SELSA study is investigating a tailored approach to defunctioning stoma use in low anterior resection for rectal cancer in relation to the risk of anastomotic leakage. Our hypothesis is that long-term effects will favour the selective approach, enabling some patients to avoid a defunctioning stoma.

Background: Large bowel obstruction is a possible complication in patients undergoing neoadjuvant treatment for rectal cancer; however, it may be prevented by placing a pretreatment defunctioning stoma. The aim of this retrospective study was to investigate complication rates in patients with rectal cancer undergoing long-course neoadjuvant therapy, comparing those with and without a prophylactic stoma.

Methods: All patients with rectal cancer undergoing neoadjuvant therapy between 2007 and 2022 in Region Västerbotten, Sweden, were identified using the Swedish Colorectal Cancer Registry. Patients not planned for curative long-course neoadjuvant therapy and those requiring a stoma due to urgent bowel-related issues before treatment were excluded. The primary outcome was the incidence of complications between diagnosis and resection surgery or end of follow-up. The secondary outcomes were 30-day complications following resection, time to treatment (neoadjuvant therapy and surgery), and overall survival. Multivariable regression analysis was used, with adjustment for age, sex, American Society of Anesthesiologists fitness grade, and clinical tumour stage.

Results: Of 482 identified patients, 105 were analysed after exclusion. Among these, 22.9% (24 of 105) received a pretreatment stoma, whereas 77.1% (81 of 105) received upfront neoadjuvant therapy. The complication incidence before resection in the group with a defunctioning stoma and in the group without a defunctioning stoma was 75.0% (18 of 24) and 29.6% (24 of 81) respectively. A considerable number of complications were directly caused by the stoma surgery. Patients in the stoma group had an adjusted OR of 6.71 (95% c.i. 2.17 to 20.76) for any complication. However, for 30-day complications following resection, an adjusted non-significant OR of 2.05 (95% c.i. 0.62 to 6.81) was documented for the stoma group, in comparison with the control group. Neoadjuvant treatment was also delayed for the stoma group (adjusted mean time difference: 21 (95% c.i. 14 to 27) days), whereas the difference was not significant for the time to resection surgery. The median survival after diagnosis was 4.7 years in the stoma group and 12.2 years in the control group (P = 0.015); however, adjustment in the multivariable analysis rendered the estimate non-significant (HR 1.71 (95% c.i. 0.93 to 3.14)).

Conclusion: Patients with rectal cancer who receive a stoma before long-course neoadjuvant therapy, in the absence of urgent symptoms, experience more complications than those without a stoma and a delay with regard to the start of neoadjuvant treatment.

BACKGROUND: Pulmonary complications are the most common cause of death after surgery. This study aimed to derive and externally validate a novel prognostic model that can be used before elective surgery to estimate the risk of postoperative pulmonary complications and to support resource allocation and prioritisation during pandemic recovery.

METHODS: Data from an international, prospective cohort study were used to develop a novel prognostic risk model for pulmonary complications after elective surgery in adult patients (aged ≥18 years) across all operation and disease types. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery, which was a composite of pneumonia, acute respiratory distress syndrome, and unexpected mechanical ventilation. Model development with candidate predictor variables was done in the GlobalSurg-CovidSurg Week dataset (global; October, 2020). Two structured machine learning techniques were explored (XGBoost and the least absolute shrinkage and selection operator [LASSO]), and the model with the best performance (GSU-Pulmonary Score) underwent internal validation using bootstrap resampling. The discrimination and calibration of the score were externally validated in two further prospective cohorts: CovidSurg-Cancer (worldwide; February to August, 2020, during the COVID-19 pandemic) and RECON (UK and Australasia; January to October, 2019, before the COVID-19 pandemic). The model was deployed as an online web application. The GlobalSurg-CovidSurg Week and CovidSurg-Cancer studies were registered with ClinicalTrials.gov, NCT04509986 and NCT04384926.

FINDINGS: Prognostic models were developed from 13 candidate predictor variables in data from 86 231 patients (1158 hospitals in 114 countries). External validation included 30 492 patients from CovidSurg-Cancer (726 hospitals in 75 countries) and 6789 from RECON (150 hospitals in three countries). The overall rates of pulmonary complications were 2·0% in derivation data, and 3·9% (CovidSurg-Cancer) and 4·7% (RECON) in the validation datasets. Penalised regression using LASSO had similar discrimination to XGBoost (area under the receiver operating curve [AUROC] 0·786, 95% CI 0·774-0·798 vs 0·785, 0·772-0·797), was more explainable, and required fewer covariables. The final GSU-Pulmonary Score included ten predictor variables and showed good discrimination and calibration upon internal validation (AUROC 0·773, 95% CI 0·751-0·795; Brier score 0·020, calibration in the large [CITL] 0·034, slope 0·954). The model performance was acceptable on external validation in CovidSurg-Cancer (AUROC 0·746, 95% CI 0·733-0·760; Brier score 0·036, CITL 0·109, slope 1·056), but with some miscalibration in RECON data (AUROC 0·716, 95% CI 0·689-0·744; Brier score 0·045, CITL 1·040, slope 1·009).

INTERPRETATION: This novel prognostic risk score uses simple predictor variables available at the time of a decision for elective surgery that can accurately stratify patients' risk of postoperative pulmonary complications, including during SARS-CoV-2 outbreaks. It could inform surgical consent, resource allocation, and hospital-level prioritisation as elective surgery is upscaled to address global backlogs.

FUNDING: National Institute for Health Research.

Background: Anastomotic leakage after rectal cancer surgery is linked to reduced survival and higher recurrence rates. While an aggravated inflammatory response may worsen outcomes, few studies have explored the combined effects of leakage and inflammation.

Methods: This is a retrospective multicenter cohort study including patients operated with anterior resection for rectal cancer in Sweden during 2014–2018. Anastomotic leakage within 12 months was exposure and primary outcome was recurrence-free survival. Mediation analysis was performed to evaluate the potential effect of systemic inflammatory response, as measured by the highest postoperative C-reactive protein (CRP) level within 14 days of surgery. Confounders were chosen using a causal diagram.

Results: Some 1036 patients were eligible for analysis, of whom 218 (21%) experienced an anastomotic leakage. At the end of follow-up at a median of 61 months after surgery, recurrence-free survival amounted to 82.6% and 77.8% in the group with and without leakage, respectively. The median highest postoperative CRP value after surgery was higher in the leakage group (219 mg/l), compared with the group without leakage (108 mg/l). Leakage did not lead to worse recurrence-free survival (HR 0.66; 95% CI 0.43–0.94), and there was no apparent effect through postoperative highest CRP (HR 1.12; 95% CI 0.93–1.29).

Conclusions: In conclusion, anastomotic leakage, with its accompanying CRP increase, was not found to be associated with recurrence-free survival after anterior resection for rectal cancer in this patient cohort. Larger, even more detailed studies are needed to further investigate this topic.

BACKGROUND: Anastomotic leakage after anterior resection for rectal cancer is more common after total mesorectal excision compared to partial mesorectal excision but might be mitigated by a defunctioning stoma.

OBJECTIVE: The aim is to assess how anastomotic leakage is affected by type of mesorectal excision and defunctioning stoma use.

DESIGN: This is a retrospective multicenter cohort study evaluating anastomotic leakage after anterior resection. Multivariable Cox regression with HRs and 95% CIs was used to contrast mesorectal excision types and defunctioning stoma use with respect to anastomotic leakage, with adjustment for confounding.

SETTINGS: This multicenter study included patients from 11 Swedish hospitals between 2014 and 2018.

PATIENTS: Patients who underwent anterior resection for rectal cancer were included.

MAIN OUTCOMES MEASURES: Anastomotic leakage rates within and after 30 days of surgery are described up to 1 year after surgery.

RESULTS: Anastomotic leakage occurred in 24.2% and 9.0% of 1126 patients operated with total and partial mesorectal excision, respectively. Partial compared to total mesorectal excision was associated with a reduction in leakage, with an adjusted HR of 0.46 (95% CI, 0.29-0.74). Early leak rates within 30 days were 14.9% with and 12.5% without a stoma, whereas late leak rates after 30 days were 7.5% with and 1.9% without a stoma. After adjustment, defunctioning stoma was associated with a lower early leak rate (HR 0.47; 95% CI, 0.28-0.77). However, the late leak rate was nonsignificantly higher in patients with defunctioning stomas (HR 1.69; 95% CI, 0.59-4.85).

LIMITATIONS: This study was limited by its retrospective observational study design.

CONCLUSIONS: Anastomotic leakage is common up to 1 year after anterior resection for rectal cancer, where partial mesorectal excision is associated with a lower leak rate. Defunctioning stomas seem to decrease the occurrence of leakage, although partially by only delaying the diagnosis. See Video Abstract.