The Anterior resection syndrome:

In Europe, colorectal cancer is the second most common cancer in women after breast cancer and third most common cancer in men following lung and prostate cancer. It accounts to 9.7% of all cancers worldwide with 1.8 million new cases diagnosed annually.  Around half of all colorectal cancer cases affect the rectum.¹Surgery is the main curative therapy for rectal cancer. This involves either an abdominal perineal resection (AP) or a sphincter-sparing resection. Improvements in pre-operative staging and surgical techniques have led to the advent of low and ultra-low anterior resection, both being sphincter sparing surgeries for patients who might have otherwise undergone an AP resection. Hence for patients in whom a negative distal margin can be achieved, low anterior resection is preferred as it maintains bowel continence and avoids a permanent colostomy. However, bowel functional disturbances constitute a major problem for many surviving rectal cancer patients following anterior resection. The wide spectrum of symptoms following resection and restitution of rectum is what constitutes low anterior resection syndrome (LARS).²

Studies have shown  that anterior resection syndrome may be attributed to sphincter injury, denervation during pelvic dissection associated with altered rectal sensation, low coloanal anastomosis as well as reduced capacity and compliance of rectal remnant.³Anterior resection syndrome constitutes fecal incontinence or urgency, frequent or fragmented bowel movements, emptying difficulties and increased intestinal gas. Although most of the functional impairments are clinically recovered following one year after surgery, long term studies report the presence of bowel dysfunction for years following resection.  This dysfunction varies in its symptoms and severity and may have significant impact on patient’s quality of life.^4-5 Hence, the aims of the study were to evaluate the incidence of anterior resection syndrome, identify correlation between anterior resection syndrome and clinical variables and  evaluate the impact of anterior resection syndrome on quality of life.

Materials and methods

All adult patients, under the care of all surgical firms at the national acute hospital in Malta, who had undergone anterior resection for rectal cancer between January 2014 and December 2016 were included. Approval from data protection unit at Mater Dei hospital was sought to obtain access to patient’s details and files for data collection. Approval from local research ethics committee and the patients’ caring consultants was obtained. The study was also registered with ClinicalTrials.gov.

Patients were recruited from data recorded in operation record sheets. Patients were excluded if they met the below criteria:

• colon cancer >15cm from anal verge
• permanent stoma
• known disseminated or recurrent disease
• patient without restitution of bowel continuity after one year

All patients were sent a letter by ordinary mail which contained an information sheet and a consent form describing the study aim and declaration of its confidentiality. It also contained 2 validated questionnaires: LARS scale questionnaire and  EORTC QLQ-30.^6-7

The LARS score is a validated five-score questionnaire focusing on bowel symptoms. According to the score patients are grouped into non-LARS (if score obtained is 0-20 points), minor LARS (21-29 points) and major LARS (30-42 points).⁶ Hence, it enables quantification of the severity of intestinal and defecatory dysfunction following anterior resection. The EORTC QLQ-30 is a validated 30-item questionnaire designed to assess quality of life in cancer patients. The higher the score was suggestive of better quality of life and better functioning level.⁷

Participants were asked to return the consent form and the questionnaire in a paid self-addressed envelope. Patients who failed to answer the questionnaire were contacted by phone and encouraged to participate to increase the response rate.

The following data on patients’ demographic (age, sex, comorbidities), tumour related factors (distance from anal verge, histological and MRI based TNM staging) and stoma related data (presence, type, time before closure) were collected. iSoft Clinical Manager (iCM) and electronic case summaries were used to collect clinical variables. The cancer staging was based on American Joint Commission on Cancer (AJCC) Tumor Node metastasis (TNM) classification system. Analysis was performed using IBM SPSS® Statistics. The relationship between possible risk factors and the severity of LARS as the dependent variable was analysed using ordinal logistic regression. Categorical variables were assessed using one-way ANOVA. Scheffe post-hoc test was used for analysis of variance. Statistical significance was set at p<0.05. The study has been reported in line with the STROCSS criteria.

Results

179 patients had anterior resection between January 2014 and December 2016; out of which 124 patients failed to fit the inclusion criteria hence, 57 patients were eligible to participate.  Only 1 patient failed to return the questionnaire and one questionnaire was invalid as several answers were selected simultaneously. Thus the study population was composed of 55 patients (Figure 1).

Figure 1

Flow chart of patient selection

Table 1 shows the demographic and therapeutic characteristics of the studied participants. Most of the participants were male (69%, n=38) and had an overall  mean age of 65 years. One quarter of the patients were diabetic (25%, n=14), 71% (n=39) received neoadjuvant therapy whilst 44% (n=44) had adjuvant therapy as decided by the multidisciplinary team.  In most patients rectal cancer was between 5-10cm from anal verge (60%, n=33). Most patients had T3 disease with no lymph node involvement. (Table 2). Sixty-four percent of procedures (n=35) were performed using an open technique, with laparoscopy being employed in one third of patients. Four percent of patients (n=2) required conversion to open with adhesion being the reasons for conversion. A defunctioning stoma was created in 51% of patients (n=28) with the majority of these having loop ileostomy. Stoma reversal was performed with a mean of 215 days after primary surgery.

LARS symptoms were identified in 51% of patients (n=27); classified as minor in 23% of patients (n=13) and major in 28% of patients (n=15) (Figure 2). The mean time from surgery to patients assessment of LARS though the questionnaire was 995 days.

Figure 2

Stratification of patients according to LARS symtoms

Association

Our logistic analysis showed a significant association of LARS with distance from anal verge (OR3.55, 95% CI 1.22-10.28; p=0.02), preoperative radiotherapy (OR 4.66, 95% CI 1.44-15.15; p=0.01) and presence of stoma (OR3.36, 95%CI 1.21-9.30; p=0.02). No significant association was found between gender, diabetes mellitus, tumour staging, surgical technique and interval from stoma reversal (Table 2). 

Quality of life

The larger difference in mean quality of life scores was between the Major LARS group and each of the other two groups as demonstrated in Figure 3. One-way ANOVA analysing quality of life by LARS showed that these differences in quality of life score are statistically significant.  The Scheffe post-hoc test ascertained that the significant difference lies between the No LARS and the Major LARS groups (p<0.0005; 95% CI 0.81 - 1.94) and between the Minor LARS and the Major LARS groups (p<0.01; 95% CI 0.39 - 1.64) (Figure 4).

Figure 3

Box plot demonstrating quality of life based on LARS score category

Figure 4

Scheffe post-hoc test demonstrating quality of life according to different LARS categories

Discussion

In our study, more than half the patients who underwent anterior resection for rectal cancer presented with anterior resection syndrome. Of these, 28% of these experienced major symptoms even after one year post operatively.  Although functional bowel changes are more severe in the initial 12 months postoperatively, after which stabilisation in symptoms is achieved, this study demonstrates that the symptoms experienced in LARS are not transient with its effects persisting following one year post operatively. This is comparable to other international studies.^4,8-10

Literature demonstrates multiple factors which may contribute to LARS. These include the patient’s age,³gender,^3,8,11 surgical techniques,^11-12 presence of stoma,^9,11,13-14 level of anastomosis^4,11,15 and radiotherapy.^9,11 Consistent with other literature, our study showed that  distance from anal verge (p=0.02), preoperative radiotherapy (p=0.01) and presence of stoma (p=0.02) are significantly associated with LARS.   Pre-operative radiotherapy and presence of stoma may not have a direct causal relationship to LARS but may be a co-variant of the distance from anal verge.  Patients who have a rectal tumour at low distance from anal verge are more likely to have a protective temporary stoma to secure anastomosis and receive neo-adjuvant therapy hence further contributing to LARS. Conversely, patients who have distal sited tumours  have a decrease in rectal capacity and reservoir following resection whilst radiotherapy is known to cause pelvic nerve damage, suggesting their independent aspect in contributing to LARS.  

LARS was noted to exert significant impact on patient’s quality of life. Our study showed that the perception of quality of life was significantly worse in patients who were classified to have major LARS compared to those who did not suffer from LARS or had minor LARS symptoms. This is consistent with the study by Juul et al. which assessed the effect of LARS across multiple European countries.¹⁶

The strengths of the study include the use of validated scores for classification of LARS and quality of life increasing the validity of the results. This study had a response rate of 96% suggesting adequate representation of the population studied.  As the study was performed by filling in an anonymous questionnaire, the patients were more likely to express their symptoms rather than by patient’s interview; hence being representative of the true incidence of LARS and its impact on quality of life. Nevertheless, the limitations of this study include its retrospective study design and the small study population.

This study adds to the understanding of the contributing factors leading to LARS, the long term effects of this syndrome post-operatively and its impact on quality of life.   Based on our study findings, the factors contributing to LARS are noted to be largely non-modifiable. Hence, adequate consideration should be given in the pre-operative counselling and post-operative identification of the syndrome and management of bowel dysfunction.

Conclusion

With the improved surgical techniques, colorectal procedures which achieve adequate surgical margin and total mesorectal excision are  the current surgical standard for rectal carcinoma. However restoration of bowel continuity does not mean satisfactory bowel function. More than half the patients who had anterior resection suffer from LARS at least one year after surgery. Given its impact on patient’s quality of life, pre-operative counselling  on bowel dysfunction is crucial in patients who are scheduled to undergo anterior resection. Additionally, patients should be adequately evaluated during postoperative follow-up to enable early identification of the syndrome and provide a patient-tailored management approach.

Summary box

Facts already known:

• In Europe, colorectal cancer is the second most common cancer in women and third most common in men.
• Around half of all colorectal cancer cases affect the rectum.
• Anterior resection is a sphincter sparing surgery for the treatment of rectal cancer.

New findings:

• The effects of low anterior resection syndrome (LARS) are not transient with its effects persisting 1 year post operatively.
• The distance from anal verge, preoperative radiotherapy and presence of stoma are significantly associated with LARS.
• Patients suffering from major LARS have a significant decrease in their quality of life

References

1. Macrae FA. Colorectal cancer: epidemiology, risk factors and protective factors [Internet]. USA:UpToDate; 2020 [cited 2020 September 28]. Available from: https://www.uptodate.com/contents/colorectal-cancer-epidemiology-risk-factors-and-protective-factors#H3
2. Bazzell A, Madsen LT, Dains J. Clinical Management of Bowel Dysfunction After Low Anterior Resection for Rectal Cancer. J Adv Pract Oncol. 2016;7(6): 618–629.
3. Dulskas A, Smolskas E, Kilius A, Cizauskaite A, Samalavicius N.E. Incidence of the anterior resection syndrome using low anterior resection score (LARS scale). Lithuanian Surgery. 2017;16(2):102-107.
4. Sturiale A, Martellucci J, Zurli L, Vaccaro C, Brusciano L, Limongelli P et al. Long-term functional follow-up after anterior rectal resection for cancer. Int J Colorectal Dis. 2017;32(1): 83-88.
5. Van Duijvendijk P, Slors JF, Taat CW, van Tienhoven G, Obertop H, Boeckxstaens GE. Prospective evaluation of anorectal function after total mesorectal excision for rectal carcinoma with or without preoperative radiotherapy. Am J Gastroenterol. 2002; 97(9):2282–2289.
6. European Society of Coloproctology: The LARS score. [Internet]. UK:European Society of Coloproctology; 2020 [cited 2020 June 25]. Available from: https://www.escp.eu.com/news/focus-on/beyond-colorectal-cancer/1579-lars-score
7. European Organisation for Research and Treatment of Cancer, Quality of Life. [Internet]. UK:European Organisation for Research and Treatment of Cancer;  2020 [cited 2020 June 25]. Available from: https://qol.eortc.org/form/#1
8. Carillo A, Enriquez-Navascues JM, Rodriguez A, Placer C, Mugica JA, Saralegui Y. et al.Incidence and characterisation of the Anterior Resection Syndrome through the use of the LARS scale (Low Anterior Resection Score). CIR ESP. 2016;94(3):137-143.
9. Ekkarat P, Boonpipattanapong T, Tantiphlachiva K, Sangkhathat, S. Factors determining low anterior resection syndrome after rectal cancer resection: a study in Thai patients. Asian Journal of Surgery. 2016;39:225-231.
10. Emmertsen KJ, Laurberg S and Rectal Cancer Function Study Group. Impact of bowel dysfunction on quality of life after sphincter-preserving resection for rectal cancer. Br J Surg. 2013;100(10):1377-1387.
11. Jimenez-Rodriguez RM, Segura-Sampedro JJ, Rivero-Belenchon I et al. Is the interval from surgery to ileostomy closure a risk factor for low anterior resection syndrome? Colorectal Disease. 2016;19: 485-490.
12. Ziv Y, Zbar A, Bar-Shavit Y, Igov I. Low anterior resection syndrome (LARS): cause and effect and reconstructive considerations. Tech Coloproctol. 2013;17:151-162.
13. Lee E, Kim K.S. Relationships between anxiety, depression, low anterior resection syndrome, and quality of life following lower anterior resection for rectal cancer. Perspect Nurs Sci. 2014;11: 74-85.
14. Coco C, Valentini V, Manno A, Rizzo G, Gambacorta MA, Mattana C et al. Functional results after radiochemotherapy and total mesorectal excision for rectal cancer. Int J Colorectal Dis.2007;22:903-910.
15. Denost Q, Laurent C, Capdepont M, Zerbib F, Rullier E. Risk factors for fecal incontinence after intersphincteric resection for rectal cancer. Dis Colon Rectum. 2011;54:963-968.
16. Juul T, Ahlberg M,  Biondo S, Espin E, Jimenez LM, Matzel KE et al. Low anterior resection syndrome and quality of life: an international multicenter study. Dis Colon Rectum. 2014;57(5):585-91.

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