Colorectal cancer (CRC) is one of the leading cancers worldwide as well as in Malaysia. Malaysia was the third highest overall CRC incidence (18.30 per 100,000) in South East Asia, after Singapore and Brunei [1]. Malaysia reported an 11.3% increase in new cancer cases from 103,507 in 2007–2011 to 115,238 in 2012–2016. It was the most common cancer in men and second in women in Malaysia according to Malaysian National Cancer Registry report 2012–2016. Chinese ethnicity has the highest incidence, followed by Malay and Indian [2]. Left-sided carcinoma is the commonest form and constitutes 81.8% of all notified cases [3].

Historically, low-lying rectal cancer was treated with abdominal perineal resection, which was considered the gold standard. During the past decades, the approach and treatment of rectal cancer have improved and advanced markedly with the introduction of neoadjuvant therapy and innovation and advent of better surgical techniques and equipment. Low anterior resection (LAR) and total mesorectal excision (TME) with or without diversion stoma has become the preferred surgical procedure in a patient with resectable rectal cancer, with the intention to preserve anal sphincter and avoid permanent stoma [4].

Oncological outcomes following rectal cancer surgery have improved significantly over recent decades with lower recurrences and longer over survival. However, these survival advantages have greatly overshadowed functional outcomes of surgery, which are poor for many patients and consistently under-reported [5]. Anatomical preservation in sphincter preserving surgery does not always mean a perfect restoration of anorectal function. Many of the patients experienced several bowel symptoms after surgery, which include flatus and fecal incontinence, frequent bowel opening, urgency, or sense of incomplete defecation. This combination of such symptoms after sphincter preserving surgery is referred to as LAR syndrome (LARS) and it can be associated with significant negative impact on quality of life [6].

A pragmatic definition of anterior resection syndrome is disordered bowel function after rectal resection, leading to detriment in quality of life. These symptoms usually improved a few months after surgery, and reach plateau within 2 years. Studies have shown the presence of adverse symptoms after surgery can be long term and up to 15 years after surgery, with the prevalence of obstructed defecation symptoms from 12% to 73% and fecal incontinence symptoms varying from 0% to 71% [5]. The term "low anterior resection syndrome" is more commonly used due to its association with lower resection and anastomosis [7].

LARS has a major impact on the quality of life depending on the severity of the symptoms. Many patients suffer from disability, describing social limitations, and developing psychiatric disorders [8]. The estimated prevalence of LARS was reported to be ranging from 19% to 52% in variety of studies [9]. The use of different assessment and collection tools that are not specific to LARS leads to such discrepancies in the data collection for prevalence. A validated scoring system specific to LAR was introduced by Emmertsen and Laurberg [10], taking into consideration of bowel dysfunction and its overall impact on patient quality of life. This allows the collection of comparable data as well as makes meta-analysis possible.

Despite LARS being a significant and rising concern among surgeons and patients, the exact pathophysiology was not fully understood. Recent studies have addressed possible factors contributing to LARS, such as age, surgical technique (total or partial mesorectal excision), type of anastomosis, adjuvant therapy, neoadjuvant therapy, and postoperative complications (anastomosis leakage or stricture) [11].

Since patients who undergo a sphincter-sparing rectal resection are at risk of developing LARS, perioperative efforts should be made to prevent LARS. The aim of this study was to identify the prevalence of LARS among patients who underwent sphincter preserving rectal surgery and clinical risk factors associated with the development of LARS in our populations.

With the advancement of neoadjuvant therapy and surgical technique, overall survival for rectal cancer has increased compared to previously. Apart from the oncological outcome, more attention is being paid to functional outcomes in patients who underwent sphincter preserving rectal cancer surgery. Severe bowel dysfunction has led to a negative impact on patients’ quality of life and affects their day-to-day activities. Thus, it is important to evaluate bowel symptoms during follow-up and risk factors associated with the development of LARS need to be studied. Studies have shown that functional disturbances are most prominent during the first 12 months before stabilizing into long-term dysfunction [6]. Evidence has also shown that LARS could be permanent changes rather than short-term rectal irritability as adverse effects still present after 15 years following surgery [15].

A meta-analysis conducted in 2018 [16] has shown bowel dysfunction assessment after surgery was inconsistent because the majority of the studies have used nonvalidated questionnaires. The introduction of LARS score allows the collection of comparable data and studies with higher-level evidence such as meta-analyses can be conducted. Our study showed a prevalence of major LARS of 32.8%, which is consistent with the majority of the studies. The meta-analysis by Croese et al. [16] reported prevalence ranged from 17.8% to 56%, and all primary studies included had assessed prevalence of LARS using LARS score and thus offered a more accurate representative of the prevalence.

LARS has gained more attention in recent years and substantial research was conducted to study the cause of LARS. However, the definite cause and pathophysiology for the development of LARS and its severity is not clearly understood yet. It is believed that symptoms of LARS are usually caused by multifactorial which include impaired anal sphincter function, neorectal reservoir dysfunction, and colonic dysmotility. An impaired anal sphincter can be the result from rectal mobilization and mesorectum dissection, mechanical tear during stapler insertion [17] or the effect of pelvic radiotherapy, and these can be manifested as urgency and incontinence [5]. Neorectal reservoir dysfunction can be the result of denervation during surgery dissection and pelvic radiotherapy leading to hyposensitivity due to impaired afferent nerve function [18]. It can also be due to reduced rectum capacity and compliance after surgery, thus smaller amount of feces is sufficient to stimulate defecation reflex causing stool frequency, urgency, frequent and incontinence. However, construction of neorectal reservoir such as colonic J-pouch only provide symptomatic improvement of less than 18 months, but no long-term benefit [19].

Various factors have been reported to be possibly associated with LARS in multiple studies conducted past decade, which include female sex, tumor height, level of anastomosis, neoadjuvant or adjuvant radiation therapy, presence of stoma, and postoperative complications. In our study, we found no significant differences in the development of LARS between sex and different age group. Only 1 study [20] reported that age of >70 years was associated with LARS (P=0.003), but the results were not significant in other studies.

This study investigated the possible factors that predispose to the development of major LARS using an international validated LARS score in 76 patients. Our results suggested that tumor height of less than 8 cm from anal verge was a significant factor in the development of major LARS (P=0.039). Tumor height and anastomosis height was one of the statistically significant variables affecting major LARS which was reported in a few other studies [10, 20, 21]. Lower tumor height will result in less rectum remnants after surgery in order to achieve oncological resection margin. A low rectal tumor will invariably require TME during resection of primary tumor. TME was also reported to be significant factor associated with the development of LARS in a study by Carrillo et al. [22]. Although height of the tumor and anastomosis height was not discussed in that particular study, TME was performed for middle and low rectal tumor.

The rectum functions as a reservoir for stools, more rectum has to be resected in the low-lying tumor, thus leaving behind a smaller neorectal reservoir. Conventional end-to-end colorectal or coloanal anastomosis was believed to contribute to symptoms of LARS such as incontinence and urgency. Various alternative configuration techniques have been introduced, these include side to end anastomosis, colonic pouch, or transverse coloplasty. Early data suggested that patients who received reconstructive neorectal reservoir had a better functional bowel outcome in 12 months compared to end-to-end anastomosis. However, the frequency in the end-to-end anastomosis group reduced to that of pouch group by 24 months after surgery [23, 24]. The effect of neorectal volume in relation to the functional outcome remain unclear and offer no long-term benefits in any of the reconstructive technique [19].

Among all, neoadjuvant or adjuvant radiotherapy was one of the most consistent factors assessed and has shown to be statistically significant in the majority of the studies. Radiotherapy plays a critical role in the treatment of rectal cancer either as neoadjuvant or adjuvant therapy in adjunct to surgical resection. Despite having better local recurrence outcome and increase overall survival [25], pelvic radiation is not without risk. Multiple studies including a meta-analysis have consistently reported neoadjuvant radiotherapy as an independent risk factor for the development of LARS [9, 16, 21, 26, 27]. This is probably related to pelvic floor nerve damage and neorectal hyposensitivity as a complication from pelvic radiation. However, our study failed to show a relationship between radiation and poor bowel function. This is probably due to some patients in our study refusing radiotherapy as part of their treatment, and the lack of radiotherapy services in one of our centers might contribute as well.

There is conflicting data on diversion stoma and duration of stoma in relation to poorer bowel function after anterior resection. Our study has not shown any association between the stoma and major LARS. A recent randomized controlled trial in 2017 [28] compared LARS score in patient treated with diversion stoma and without a stoma, had found no statistically different in major LARS when comparing both groups. However, few other studies have shown that the presence of diversion stoma is statistically associated with major LARS [9, 22]. Only 1 study [27] reported that stoma closure after 1 year had increased risk of major LARS. The association was believed due to confounding factor rather than diversion stoma itself. Usually diversion stoma is created for low-lying tumor with lower anastomosis, which is again combined with TME, which both are known to increase risk of LARS.

Common complications occur after anterior resection include anastomotic leak, pelvic abscess, ileus, and anastomotic stricture. Some studies have shown an increased risk of major LARS following anastomotic leak; however, the results were not consistent. The anastomotic leak can lead to adverse bowel symptoms manifested as increase frequency and incontinence, as well as impaired quality of life [29]. In the study, anastomotic leak and other complications like pelvic abscess, ileus, and anastomotic stricture were not associated with major LARS. The study also tried to evaluate the association between the approach of surgery and the development of major LARS. In our study, both laparotomy and laparoscopic approaches have not shown any statistically significant. This result is expected as we believe careful dissection during the surgery rather than the approach is more important to prevent denervation of pelvis nerve plexus.

There were certain limitations within this current study. Firstly, the questionnaire was delivered only to those patients who follow up in the colorectal clinic within the study period. However, we managed to get 76 patients to answer the questionnaire despite limited clinic consultation and a low turn-up rate of patients where the healthcare is burdened with COVID-19 during the study period. In order to achieve a large cohort of patients to study the association between various risk factors and LARS, retrospective data were collected from 2011 until 2019. Thus, the patient who underwent surgery earlier will have a longer duration before they answer the questionnaire. This might lead to an underestimation of the prevalence of LARS especially in the patient who had surgery earlier. The nature of anastomosis and chemotherapy agents was not assessed in this study due to their heterogenicity.

In conclusion, using an internationally validated questionnaire LARS score, our study reports that 1/3 of patients (32.8%) developed major LARS following sphincter preserving surgery for rectal cancer. This study identified low tumor height as a significant risk factor that has a negative impact on bowel function after surgery. The high prevalence of LARS emphasizes the need for study regarding risk factors and the importance of understanding the pathophysiology of LARS, in order for us to improve patient bowel function and quality of life after rectal cancer surgery.