Aspects of low anterior resection syndrome : prevalence, risk factors and treatment

After sphincter sparing rectal cancer surgery an impaired bowel function, i.e. Low Anterior Resection Syndrome (LARS), is common. The symptoms included in LARS are incontinence for flatus and/or feces, urgency, fragmentation and frequent bowel movements. The cause is thought to be multifactorial and involves sphincter impairment, reduced compliance and capacity of the neorectum and altered motility, among others. With improved cancer survival the importance and focus on functional outcomes is increasing. The LARS-score is a validated questionnaire aimed to evaluate LARS and consists of five questions where each question has response alternatives with weighted scores. According to responses the total score is registered and depending on score a patient is classified into no, minor or major LARS group. The overall aim of this thesis was to gain knowledge about Low Anterior Resection Syndrome, in order to better understand and manage patients post rectal cancer surgery.

Study I was a longitudinal cohort study evaluating long-term LARS and quality of life (QoL) at two different time-points (mean 5 years apart). In total, 282 patients were included in the final analysis and results showed no significant difference in proportion major LARS, comparing the different time-points (p=0.455). At second follow-up 49% of patients still experienced major LARS and the major LARS group reported inferior QoL, compared to the no/minor LARS group, at both time-points. This was one of the first studies with long-term longitudinal data on LARS and concluded that difficulties with LARS and the impact on patients QoL persists over time.

Study II was a population-based cross-sectional study with the aim to measure the prevalence of LARS and impact of QoL in a, clearly defined, Swedish cohort. The prevalence of LARS was 77.4% and the proportion with major LARS was 53.1%. Major LARS was associated to worse QoL reported with the EORTC QLQ-C30 questionnaire as well as worse bowel related QoL (BQoL). The study confirmed that major LARS is common after rectal cancer surgery and associated to significantly impaired QoL. This was one of the first studies providing population-based prevalence data in a Swedish cohort. The conclusion was that after anterior resection for rectal cancer a majority of patients suffer from major LARS which have a negative impact on QoL.

In Study III we evaluated the role of a defunctioning stoma and the association to major LARS. The adjusted OR for major LARS (vs. no LARS) was 2.43 (95% CI 1.14-5.20) comparing defunctioning stoma to no stoma. The results failed to show any evident association between time to stoma reversal and major LARS. This was one of the largest studies regarding this topic and one of a few with defunctioning stoma and association to major LARS, as primary endpoint. The study concluded that the results indicates that the presence of a defunctioning stoma is associated with major LARS in a long-term perspective, while failing to show any clear association to time to stoma reversal.

In the last Study (IV) the aim was to evaluate transanal irrigation (TAI) as a treatment strategy in patients with major LARS. In this RCT patients were randomized to either intervention group (TAI) or control group (conservative treatment). Patients were followup for 12 months and the primary endpoint was differences in bowel function at end of follow-up. In addition to the LARS-score three more outcome measures were used: CCFFIS questionnaire, four study specific questions and the EORTC QLQ-C30 quality of life instrument. An interim analysis was performed after 40 included patients with complete follow-up and the results from this analysis was clearly in favor of TAI which resulted in termination of further inclusion. The final results included follow-up data from 16 patients in the intervention group and 23 in the control group. At end of follow-up, statistical significant differences were reported in a majority of the outcome measures in favor of TAI. In LARS-score there were no differences at baseline but at 12 month of follow-up there were a 9.3 points mean difference in LARS-score (p=0.002) and 2.8 points mean difference in CCFFIS (p=0.050). Also, statistical significant results in 2 out of 4 study specific questions and 7 of 15 subscales on EORTC QLQ-C30. This study was the first RCT evaluating TAI as treatment for major LARS and concluded that TAI reduces symptoms of LARS with improved QoL.

List of scientific papers

I. Low Anterior Resection Syndrome and Quality of Life After Sphincter- Sparing Rectal Cancer Surgery: A Long-term Longitudinal Follow-up. Pieniowski E, Palmer G, Juul T, Lagergren P, Johar A, Emmertsen K, Nordenvall C, Abraham-Nordling M. Dis Colon Rectum. 2019; 62 (1):14-20.
https://doi.org/10.1097/DCR.0000000000001228

II. Prevalence of low anterior resection syndrome and impact on quality of life after rectal cancer surgery: population-based study. Pieniowski E, Nordenvall C, Palmer G, Johar A, Tumlin Ekelund S, Lagergren P, Abraham-Nordling M. BJS Open. 2020; (4):935-942.
https://doi.org/10.1002/bjs5.50312

III. Defunctioning stoma and time to stoma reversal in rectal cancer surgery; risk factor for Low Anterior Resection Syndrome? Pieniowski E, Nordenvall C, Johar A, Palmer G, Tumlin Ekelund S, Lagergren P, Abraham-Nordling M. [Manuscript]

IV. A randomized controlled clinical trial of transanal irrigation versus conservative treatment in patients with Low Anterior Resection Syndrome after rectal cancer surgery. Pieniowski E, Bergström C, Nordenvall C, Westberg K, Johar A, Tumlin Ekelund S, Larsson K, Pekkari K, Palmer G, Lagergren P, Abraham-Nordling M. [Manuscript]