Introduction of the concept of total mesorectal excision (TME) led to the lowest rates of local recurrence and it has become the therapeutic gold standard for the rectal cancer resection. However, bowel function was significantly affected after TME. Patients experience loneliness due to being toilet-bound, and as a result of changes in their lives and activities outside their homes and the impact on their family life. The prevalence of LARS and its risk factors are awareness of deficiency noted by a significant number of colorectal surgeons. We found that the incidence of LARS following rectal cancer resection was 69.3% (28.6% with minor LARS and 40.7% with major LARS), which is similar to previous findings. Bolton et al. found that the incidence of LARS was 82.6%, of which 19.7% were minor LARS and 62.9% were minor LARS. A different study indicated that of the 100 patients who underwent total or partial mesorectal excision, 16 had minor LARS and 51 had major LARS. Anterior resection could impair motility patterns in the distal colon, reduce the pressure gradient between the rectum and the anal canal, neural dysfunction, reduction of rectal compliance, dysfunction of the neorectal reservoir and an increase in rectal sensibility[22,23].
The nomogram provides an individualized and easily used tool to identify high-risk patients, and can lead to effective preventive measures in a timely fashion. We developed a nomogram of major LARS based on follow-up data collected 7-9 months after surgery. The internal and external validation of the nomogram was good in measures of discrimination and calibration respectively, which indicated that this predictive model is convenient and highly accurate as a means of estimating the risk of major LARS after rectal cancer resection.
This study demonstrated that being female is an independent risk factor for major LARS. Van Heinsbergen et al. reported that females experienced major LARS significantly more often than males, but in another study, it was found that the male gender is predisposed to LARS. Several reasons have been proposed for the female predisposition to LARS and include weaker muscle fibers in females and damage to the levator ani muscle and the perineal muscle due to pregnancy and vaginal childbirth with subsequent pelvic floor dysfunction.
Among the current modalities, neoadjuvant chemoradiotherapy is preferred and has become a standard of care in locally advanced rectal cancer[27, 28]. Preoperative chemoradiation played a major role in this predictive model. Consistent findings were demonstrated in a recent study which showed that a neoadjuvant modality is associated with more severe LARS and diminished quality of life. Among the reasons for the more likely major LARS after preoperative radiotherapy are: neoadjuvant chemoradiotherapy may induce pathological features, including fibrosis, nerve injury, mucosal edema, ulcers, inflammatory cell infiltration and significant vascular lesions in the non-neoplastic mucosa. Furthermore, neoadjuvant chemo-radiotherapy can cause excessive tissue edema, leading to a loss of surgical planes, thereby posing complications and an increased surgical challenge.
This study also showed that the risk of major LARS was related to low tumor height. The American Society of Colon and Rectal Surgeons (ASCRS) 2020 Clinical Practice Guidelines recommended that for tumors located in the mid to lower third of the rectum, a 2 cm distal margin is deemed adequate and allows for a low colorectal anastomosis. A distal margin of at least 1 cm is acceptable for tumors located at or below the mesorectal margin. Surgical treatment for distal rectal cancer in terms of oncologic and functional outcomes is known to be a technically demanding procedure. The anal sphincters and peripheral nerves are more likely to be injured in surgical treatment of low-lying rectal cancer, and such injury results in impaired normal defecation reflex and rectal defecation function.The closer the tumor is to the anus, the smaller the size of the residual rectal volume, and the more obvious the foreign body sensation caused by the anastomotic material.
Our study also revealed that major LARS is more common in diverting ileostomy. The reason for the association between an ileostomy and major LARS may be that the temporary ileostomy is more likely to be used in lower resections and those patients are more likely to receive neoadjuvant therapy. These two factors have both been identified as a risk for development of major LARS. As a result of disuse, atrophy of pelvic floor muscles which are unused for the time of temporary ileostomy, causes bowel function to be possibly impaired. Enteral nutrient deprivation of distal intestinal gut and fecal stream diversion results in alterations to the microbiota composition and impaired intestinal renewal, which consequently has an impact on intestinal structure and function.
In this study, postoperative anastomotic leakage was significantly associated with an increased risk of major LARS. It has been demonstrated that anastomotic leakage is a significant factor in the occurrence of major LARS. This may due to an anastomotic leak leading to pelvic inflammation and resulting in pelvic autonomic nerve lesions and excessive fibrotic scarring around the anastomotic stoma. It may lead to a decrease in compliance and in the capacity of the neorectum, which can induce urgency or incontinence.