To Örebro University

BACKGROUND: Anastomotic leakage is a serious complication following anterior resection for rectal cancer and may increase the risk of long-term bowel dysfunction. This study aimed to assess the long-term impact of anastomotic leakage on major low anterior resection syndrome (major LARS) at a uniform follow-up time.

METHODS: We conducted a nationwide cohort study using the Swedish Colorectal Cancer Registry. Patients who underwent anterior resection for rectal cancer between 2015 and 2017 received the validated LARS questionnaire by mail 3 years after surgery. The primary outcome was major LARS among patients without a permanent stoma. Propensity score weighting was used to adjust for confounding, with covariates chosen using a directed acyclic graph. Sensitivity analyses included a dose-response analysis based on reoperation and an evaluation of a composite outcome of major LARS or permanent stoma.

RESULTS: Of 1778 patients contacted, 1178 responded (66.2%). Among 1033 stoma-free patients, 52 (5.0%) had experienced a symptomatic anastomotic leak. Major LARS was reported in 69.2% and 52.9% of patients with and without leakage, respectively. Symptomatic anastomotic leakage increased the risk of major LARS (OR 2.09; 95% CI: 1.13-3.87) and this risk was higher in patients requiring reintervention (OR 2.78; 95% CI: 0.87-8.91) and when including permanent stoma in the outcome (OR 3.90; 95% CI: 2.20-6.91).

CONCLUSION: Anastomotic leakage significantly increased the risk of major LARS 3 years after anterior resection for rectal cancer. These findings underscore the importance of preventing anastomotic leakage to reduce long-term functional morbidity in patients who survive rectal cancer.

The present nationwide population-based study compared minimally invasive surgery (MIS) with open surgery (OPEN) for colorectal cancer during a period when MIS was introduced in Sweden. The primary analyses demonstrated that MIS was not inferior compared with OPEN regarding short-term outcome for patients operated 2012-2018, nor for long-term outcome assessed as overall survival with surgery performed 2010-2016. In secondary analyses employing Cox regression models, several short-term advantages for MIS were demonstrated, such as lower early mortality, shorter hospital stay and decreased reoperation rate. Regarding long-term outcome, with adjustment for potential statistical confounders, overall survival was better with MIS as compared with OPEN both for colon and rectal cancer, with a relative decrease in risk for overall 5-year mortality by 13% and 12 %, respectively. The authors conclude that MIS was introduced in a safe and well controlled manner, and suggest that MIS should be equally offered to all suitable patients across Sweden.

Minimalinvasiv kirurgi för kolorektal cancer introducerades på bred front i Sverige under 2010-talet. Jämförelser mellan minimalinvasiv kirurgi och öppen kirurgi i Sverige har de senaste åren redovisats i flera vetenskapliga publikationer, som här sammanfattas. För ett antal korttidsutfall har minimalinvasiv kirurgi visat sig ha fördelar jämfört med öppen kirurgi. Minimalinvasiv kirurgi uppvisade i regressionsanalyser med justering för relevanta förväxlingsfaktorer bättre total överlevnad efter 5 år. Tillgången till minimalinvasiv kirurgi varierar fortfarande i Sverige, och det är av största vikt att dessa lokala skillnader kan elimineras inom en snar framtid, något som Arbetsgruppen för mini­malinvasiv kolorektal kirurgi i Sverige (AMIS) arbetar för.

BACKGROUND: Frailty is known to adversely affect post-operative mortality and morbidity following colorectal cancer resection, but its impact on long-term quality of life and functional outcomes after colon cancer surgery is less clear. This study aims to evaluate the impact of frailty at the time of diagnosis on quality of life, impact on daily activities, and contentment with treatment one year after colon cancer resection.

METHOD: Data were obtained from the prospective, multicentre Quality of Life in Colon Cancer (QoLiCOL) study. Patients aged ≥70 years who underwent colon cancer surgery in Region Västra Götaland, Sweden, were collected from the QoLiCOL database (n = 347). Clinical data were retrieved from national quality registries. Frailty was retrospectively assessed by reviewing medical records using the Clinical Frailty Scale-9 (CFS-9), with scores ≥4 classified as frail. Outcomes included self-reported quality of life, treatment-related impact on activities of daily living, and treatment satisfaction one year post-operatively. Directed Acyclic Graphs (DAGs) of variables known to affect the outcome variables were made before analyses, and potential confounders were adjusted for in the final analyses. Comparisons between frail and non-frail groups were performed using ordinal logistic regression and logistic regression, with results reported as odds ratios (OR).

RESULTS: The prevalence of frailty in the cohort was 29%, with a median CFS-9 value of 4 (range 4-6) in the frail group, indicating very mild to moderate frailty. No significant differences were observed between frail and non-frail older adults in self-assessed quality of life, treatment-related impact on daily activities or treatment satisfaction one year after surgery. Notably, both groups reported improved quality of life at one year compared with baseline. Only a small proportion of participants (n = 8; 2%) reported not being content with their treatment.

CONCLUSION: Among older adults who were alive one year after colon cancer surgery, mild to moderate frailty does not appear to negatively influence long-term quality of life, effect on daily activities, or satisfaction with treatment. Frail and non-frail patients reported similar levels of well-being and contentment with their care one year post-operatively.

BACKGROUND: This retrospective cohort study compared short-term outcomes between robotic-assisted and conventional laparoscopic surgery for rectal cancer using data from the Swedish Colorectal Cancer Registry.

METHOD: All patients undergoing elective minimally invasive surgery for rectal cancer between 2014 and 2021 and registered in the Swedish Colorectal Cancer Registry were assessed for eligibility, with patients who underwent robotic-assisted and laparoscopic rectal cancer resection included in the study. The primary outcome was a positive circumferential resection margin (CRM+). Secondary outcomes included conversion to open surgery, total mesorectal excision (TME) specimen quality, and 30-day overall and surgical complications. Multivariable logistic regression analyses were performed.

RESULTS: Of 12 703 patients registered during the study period, 10 914 underwent abdominal resection; of these, 5874 were analysed in this study (3578 robotic-assisted; 2296 conventional laparoscopic surgery). There was no difference in CRM+ between the robotic-assisted and conventional laparoscopic surgery groups (6.5% versus 5.9%, respectively; P = 0.291). Conversion to open surgery was more frequent in the conventional laparoscopic surgery group (16.1% versus 9.1%; P < 0.001). In addition, 30-day surgical complications were more common in the robotic-assisted laparoscopic surgery group (21.5% versus 19.3%; P = 0.044), including a higher rate of anastomotic leakage (10.9% versus 7.4%; P = 0.001). In multivariable analysis, neither technique was an independent predictor of CRM+ (odds ratio (OR) 0.99; 95% confidence interval (c.i.) 0.75 to 1.30; P = 0.925). For secondary outcomes robotic-assisted laparoscopic surgery reduced the risk of conversion to open surgery (OR 0.51; 95% c.i. 0.41 to 0.63; P < 0.001), but resulted in fewer complete TME specimens (OR 0.66; 95% c.i. 0.52 to 0.83; P < 0.001).

CONCLUSION: No short-term oncological advantage in terms of radial margin positivity was demonstrated between the two techniques. Findings regarding conversion rates, TME specimen quality, and anastomotic leakage warrant further investigation.

OBJECTIVE: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has improved outcomes in colorectal cancer (CRC) patients with peritoneal metastases (PM), yet evidence regarding perioperative risk and long-term survival in those 75 years or older remains uncertain. The aim of this study was to evaluate whether age ≥75 years impacts on overall survival (OS) and postoperative in-hospital morbidity, according to Clavien-Dindo classification (CD), compared with patients aged <75 years.

METHOD: This population-based study collected data from the National Swedish HIPEC Registry, including patients with colorectal PM operated with CRS-HIPEC. Patients were stratified by age (≤74 vs ≥75) with OS as primary outcome. Secondary outcomes were in-hospital mortality, postoperative morbidity and disease free survival (DFS). Potential variables assessed for association with OS were Complete Cytoreduction Score (CCS), Peritoneal Carcinomatosis Index (PCI) score, p/ypN stage of the primary tumor, postoperative morbidity and age.

RESULTS: A total of 592 patients were operated between 2004 and 2021, of which 553 were ≤74 years and 39 were ≥75 years. OS did not differ between age groups (p = .951). Factors affecting OS negatively were high CCS (p = .004), PCI ≥21 (p = .009) and p/ypN2 (p = .041). No difference was observed in DFS (p = .525). The rate of CD grade III-IV was 27% in patients ≤74 years and 21% in patients ≥75 years (p = .495). The in-hospital mortality rate was 1.3% in patients ≤74 and none in patients ≥75 years. Reoperation rates were similar between groups.

CONCLUSION: These results indicate that age above 74 should not automatically exclude patients from undergoing CRS-HIPEC. Careful selection ensures favorable survival without an increase in postoperative morbidity.

Introduction: A defunctioning ileostomy lowers the risk of anastomotic leakage after anterior resection for rectal cancer, but may cause kidney injury. This study investigated short- and long-term kidney injuries in patients undergoing low anterior resection, comparing those with and without a stoma.

Method: All rectal cancer patients with tumors ≤12 centimetres from the anal verge, operated in Sweden 2007–2021, were identified through the Colorectal Cancer Database Sweden. The primary outcome was end-stage kidney disease, defined as kidney transplantation or maintenance dialysis initiation. Secondary outcomes included chronic kidney disease, acute kidney injury, and dehydration. The impact of stoma reversal and potential mediation effects through anastomotic leakage were also examined. Cox regression was used, weighted by propensity scores based on clinical and socioeconomic predictors for receiving a defunctioning ileostomy.

Result: Some 5,291 patients remained after exclusions; 4,625 (87%) received a defunctioning ileostomy and 666 (13%) did not. Stoma placement was not significantly associated with end-stage kidney disease (HR 1.69, 95% CI: 0.19–15.23) or chronic kidney disease (HR 1.65, 95% CI: 0.91–3.00), but was associated with acute kidney injury (HR 3.03, 95% CI: 1.62–5.68) and dehydration (HR 4.02, 95% CI: 2.33–6.95). Risks of chronic kidney disease, acute kidney injury, and dehydration declined following stoma reversal. Stomas reduced anastomotic leakage with a minor attenuating mediation effect on acute kidney injury.

Discussion: Long-term kidney damage from ileostomy placement during low anterior resection for rectal cancer was not observed. However, short-term effects were demonstrated. Stoma reversal appeared to have an alleviating effect, suggesting its potential role in mitigating kidney damage.

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.

AIM: This study aimed to estimate the impact of socioeconomic status on the probability of receiving open (OPEN) or minimally invasive surgery (MIS) for curative abdominal rectal cancer resection.

METHODS: All patients diagnosed with rectal cancer clinical Stage I-III during the period 2010-2021 who underwent curative abdominal resection surgery, MIS or OPEN, were included. Patients were identified in the Colorectal Cancer Database, a register-linkage based on the Swedish Colorectal Cancer Register and linked to several national Swedish health-related and demographic registers. Socioeconomic factors, sex, patient and tumour characteristics, number of previous surgical procedures and category of hospital were collected. Exposures were level of education (categorized as 6-9, 10-12, >12 years), household income (quartiles 1-4) and country of birth (Sweden, Nordic countries outside Sweden, Europe outside the Nordic countries, outside Europe), and outcome was MIS or OPEN. Multivariable logistic regression models were fitted for each exposure, adjusted for age, sex, cT and cN, level of tumour, and number of previous abdominal surgical procedures.

RESULTS: A total of 13 778 patients were included of whom 43.6% underwent MIS (n = 6007) and 56.4% OPEN (n = 7771). Highest level of education (OR for highest vs. lowest level of education 1.15; 95% CI 1.03-1.29) and highest household income quartile (OR for highest vs. lowest household income quartile 1.27; 95% CI 1.12-1.44) increased the likelihood of receiving MIS.

CONCLUSION: Despite the tax-financed healthcare system in Sweden, rectal cancer patients with the highest level of education and the highest household income had an increased probability of receiving MIS.

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.

Introduction: Anastomotic leakage after anterior resection for rectal cancer is a common and potentially dangerous complication, resulting in morbidity and sometimes mortality. The rate of failure to rescue (FTR), or death after leakage, has previously been reported at 6-7% within 90 days. The aim of this study was to investigate the incidence of and predictive factors for FTR in a modern population-based cohort.

Method: This retrospective, nationwide registry-based study included patients from the Colorectal Cancer Database Sweden (CRCBaSe) who had undergone anterior resection for rectal cancer between 2007 to 2021. Patients without a registered leakage were excluded. Predictive factors were investigated in a multiple logistic regression model and included age, American Society of Anaesthesiologists’ classification, sex, obesity, cardiovascular disease, diabetes, education, hospital volume and defunctioning stoma use. The primary endpoint was FTR within 90 days of surgery.

Result: A total of 637 patients with leakage were identified, of whom 19 (2.8%) died within 90 days. High age was predictive of FTR (odds ratio (OR): 1.14; 95% CI: 1.06–1.23). Male sex (OR: 1.76; 95% CI: 0.52–5.90) and cardiovascular disease (OR 2.59; 95% CI: 0.90–7.47) were also related to FTR, but not statistically significantly.

Discussion: The FTR within 90 days after anterior resection for rectal cancer is low in routine Swedish healthcare. The only strong predictor for FTR was high age, while ASA classification unexpectedly did not confer any predictive value in presence of other covariates.