To Örebro University

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.

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.

TRIAL REGISTRATION: Swedish Ethical Review Authority approval (2023-04347-01, 2024-02418-02 and 2024-03622-02), Regional Ethics Committee Denmark (H-24014463), and ClinicalTrials.gov (NCT06214988).

BACKGROUND: Despite absence of level 1 evidence on the long-term oncological safety of non-operative management for rectal cancer (watch and wait), increased implementation has occurred globally over the past decades. In Sweden, a pan-national prospective non-randomized study was initiated in 2017 to assess its implementation.

METHOD: Patients with biopsy-proven rectal cancer receiving neoadjuvant therapy according to national guidelines in whom a clinical complete response was detected at reassessment were eligible for inclusion following informed consent. Only patients with an opportunistic watch-and-wait approach were included. Inclusion and follow-up, according to the study protocol, was managed at the participating study centres. The primary outcome measure of the study is 3-year disease-free survival. Here, the secondary short-term outcomes local regrowth rate, distant metastasis rate and outcomes after surgery for regrowth, at 6 months follow-up, are reported.

RESULTS: Between January 2017 and February 2023, 211 patients with a clinical complete response were included in the study. Thirty-three (16%) patients developed suspicious regrowth within 6 months of inclusion. Thirty-two of 33 patients had abdominal resectional surgery for regrowth. The curative intention rate was 94% for patients with regrowth. Three patients (1.4%) developed distant metastases within 6 months of inclusion.

CONCLUSION: This Swedish national study on watch and wait reports regrowth rates after 6 months are in line with previous reports in the literature. Nearly all patients with early regrowth could be treated with salvage surgery and curative intent.

Introduction: Anastomotic leakage following resection surgery for rectal cancer is often linked with reduced overall survival and higher rates of recurrence. Some data suggest that an aggravated inflammatory response as well might lead to worse oncological outcomes, but few attempts have been made to investigate leakage and inflammation in conjunction.

Method: This is a retrospective multicentre 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, while multiple imputation was used to handle missing data.

Result: Some 1036 patients were eligible for analysis, of which 218 (21%) experienced an anastomotic leakage. At the end of follow-up at a median of 1865 days after surgery, recurrence-free survival amounted to 82.6% and 77.8% in the group with and without leakage, respectively. The median maximum postoperative CRP value after surgery was higher in the leakage group (218.5 mg/l), compared with the group without leakage (108 mg/l). Leakage did not confer 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).

Discussion: In conclusion, anastomotic leakage, with its accompanying CRP increase, was not found to be associated with recurrence and long-term death after anterior resection for rectal cancer in this patient cohort.

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 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 hazard ratios and 95% confidence intervals was employed 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 one 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, while 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 non-significantly higher in defunctioned patients (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 one 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, though partially by only delaying the diagnosis.

Introduction: In rectal cancer minimally invasive surgery (MIS) is recommended with either robotic-assisted or laparoscopic technique. Randomized controlled studies have shown similar outcomes between the techniques. This study aimed to compare population-based data on short-term outcomes between robotic-assisted and laparoscopic surgery for rectal cancer.

Method: Data from the Swedish Colorectal Cancer Registry for patients undergoing MIS for rectal cancer between 2014-2021 with 30-day follow-up were analysed. Primary outcome was positive circumferential resection margin (CRM+). Secondary outcomes were conversion to open surgery, total mesorectal excision (TME) specimen quality and overall or surgical complications. Analyses were conducted by intention-to-treat, with data grouped according to surgical technique. Multivariable analyses were performed.

Result: A total of 5874 patients were analysed (3578 robotic-assisted; 2296 laparoscopic). There was no difference in CRM+ between the groups (6.5 versus 5.9 per cent; P=0.291). Increased rates of conversion were found in the laparoscopic group (16.1 versus 9.1 per cent; P<0.001) and of incomplete TME specimen (4.9 versus 2.7 per cent; P=0.04) and surgical complications (21.5 versus 19.3 per cent; P=0.044) in the robotic-assisted group. In multivariable analysis (Table 1), neither of the techniques was an independent predictor of CRM+ (Odds ratio (OR) 0.99, 95 per cent c.i. 0.75 to 1.30; P=0.925). For secondary outcomes laparoscopic technique was a predictor of conversion (P<0.001) and robotic-assisted of incomplete TME specimen (P<0.001).

Discussion: This population-based study could not show superiority regarding short-term outcomes of any of MIS techniques. Findings regarding conversion rates and incomplete TME specimen warrant further investigation.

AIM: Extramural venous invasion detected by MRI (mrEMVI) has in several expert centre studies been identified as an important prognostic factor in rectal cancer, and in guiding neoadjuvant therapy. However, population-based evidence for mrEMVI as a predictor for recurrent disease is lacking.

METHOD: This was a multicentre retrospective study based on the Swedish Colorectal Cancer Registry. The study period encompassed patients operated with abdominal resection for rectal cancer 2017-2021, with follow-up until January 2023. Patients diagnosed at hospitals with radiological registry data coverage <90% or with metastatic disease were excluded. Pretreatment mrEMVI constituted exposure, while recurrence-free survival was the main outcome. Distant and local recurrence, and overall survival were secondary outcomes, and pretreatment and postoperative scenarios were explored using multivariable Cox regression with multiple imputation. Hazard ratios (HRs) with 95% confidence intervals (CIs) were reported.

RESULTS: A total of 2737 patients from 13 hospitals were eligible for analysis. Pretreatment mrEMVI was reported in 14.5% of patients, while 71.9% had negative findings and 13.6% had missing data. In the pretreatment scenario, mrEMVI was an independent predictor for worse recurrence-free survival with an adjusted HR of 1.64 (95% CI: 1.31-2.06). In the postoperative MDT setting, the influence of mrEMVI on recurrence-free survival decreased with an adjusted HR of 1.27 (95% CI: 1.00-1.61).

CONCLUSION: mrEMVI at diagnosis is an independent predictor of recurrence-free survival in an unselected population of rectal cancer patients undergoing abdominal resection.

Introduction: Rectal cancer has historically been treated with resection surgery. (Chemo)radiotherapy results in a clinical complete response (cCR) in some patients, which enables a nonoperative management; “watch and wait”. Low Anterior Resection Syndrome (LARS) is a consequence after sphincter-preserving surgery, however similar symptoms can occur after treatment with (chemo) radiotherapy. The aim of this study was to report the prevalence of LARS in Swedish patients treated as watch and wait within a research protocol and to identify trends over time.

Method: The WoW study is a multicenter prospective national cohort study including patients with cCR after (chemo)radiotherapy for rectal cancer. The study population consists of 211 patients with stage I-III rectal cancer and cCR included between January 2017 and February 2023. LARS-score was analyzed at baseline, six months and one year.

Result: Demography and clinical characteristics are presented in the table. Questionnaires were available for 182 patients in total. LARS-score was possible to analyze for 170 patients at baseline, 136 at six months and 118 at one year, patients reporting a stoma wereexcluded. Major LARS was reported by 41 (24%) patients at baseline, 35 (26%) at 6 months and 26 (22%) at 12 months.

Discussion: One of four patients in this WoW-cohort reported major LARS and it is persistent after one year. Long-term follow-up is required to see if symptoms change over time to understand the functional outcome of the treatment offered to be able to provide adequate information about possible long-lasting life changes due to treatment.