Analysis of the clinical factors associated with anal function after intersphincteric resection for very low rectal cancer

Over the last two decades, surgical treatment for patients with very low rectal cancer has radically evolved, allowing permanent colostomy to be avoided in these patients. Reappraisal of the distal margin has allowed increased potency of sphincter-preserving resections. Moreover, total mesorectal excision (TME)[1], coupled with techniques such as end-anal stapling and coloanal anastomosis using the double-stapling technique (DST)[2], can be used to preserve the sphincter without compromising on the oncological results[3‐5].

However, when the tumor is located close to the dentate line, conventional anterior resection using the interperitoneal approach with DST may not allow a secure distal resection margin. To resolve this problem, partial or total internal sphincteric resection (ISR) and coloanal anastomosis per anus can be used for safe surgical resection of the tumor[6‐11]. ISR has been proposed to achieve distal clearance in selected patients with very low rectal tumors extending to the upper part of the internal sphincter muscle. Furthermore, it has been proposed to restore the anal structure, preserve fecal continence, and reduce the numbers of patients requiring a permanent stoma.

ISR has been widely recognized to achieve a safe distal resection margin, which can be as small as 1 to 2 cm[12, 13]. However, with this procedure, which involves dividing the rectum between the internal sphincter and the external sphincter or the levator ani, it remains unclear whether a secure circumferential resection margin (CRM) of the tumor can be obtained. Further, partial or total ISR procedures have been shown to possibly interfere with fecal continence[7, 8, 14‐16].

Anal incontinence is considered to influence various factors in patients receiving ISR, including preoperative radiation therapy[17, 18], reconstruction methods[9], extent of sphincter preservation[19], tumor level, and height of the anastomosis[20]. Moreover, fecal incontinence-related quality of life (QOL) scores were poorer in ISR patients than the patients with low anterior resection[16]. Although ISR was proposed as an alternative procedure to avoid abdominoperineal resection (APR), a colostomy is a viable option for patients who suffer from fecal incontinence, which offers a definitive cure along with an improved quality of life[21].

To evaluate the feasibility of ISR in very low rectal cancer patients, it is necessary to clarify the oncologic results and functional outcomes related to this procedure. The aims of this study were to evaluate the surgical safety of the procedure, to assess its oncologic and functional outcomes, and to identify factors predictive of anal dysfunction in the absence of radiotherapy.

Patients and tumor characteristics are shown in Table1.

During the study period, ISR covered 144 patients (26.3%) who underwent surgery for lower-third rectal cancer, located below the peritoneal reflex, 49 patients of conventional anterior resection with DST, 35 patients of abdominoperineal resection, and 20 patients of local excision. The study population was made up of 30 patients (16 men and 14 women) with a median age of 58.9 years (range, 31 to 75 years); 1 patient (3.3%) had a pTis of a large villous tumor, 8 patients had a pT1 tumor (26.7%), 10 patients had a pT2 tumor (33.3%) and 11 patients had a pT3 tumor (36.7%). According to the UICC TNM classification system, the tumors were classified as stage 0 in 1 patient, stage I in 16 patients, stage IIA in 5 patients, stage IIIB in 5 patients, and stage IVA in 1 patient.

Surgical and histopathological findings are shown in Table2.

In this study, partial ISR, subtotal ISR, and total ISR were performed in 12, 4, and 14 patients, respectively. Furthermore, 4 of 11 patients (36.4%) with T3 tumors intraoperatively decided to undergo additional partial ESR. The mean distance between the distal edge of the tumor and the dentate line was 8.9 ± 8.0 mm (range, -3 to 25 mm) in all the patients. Tumor location was significantly different for each ISR procedure (partial ISR, 16.0 ± 4.6 mm; subtotal ISR, 5.0 ± 4.1 mm; total ISR, 3.5 ± 5.1 mm).

Assessment of the fixed surgical specimens revealed that the median distal edge of the tumor was 7 mm (range, 3 to 22 mm), and it was negative in all cases. The median circumferential margin of the tumor was 3 mm (range, 0.5 to 9 mm). The circumferential resection margin was positive (<1 mm) in two patients with T3 tumor without partial ESR. Reconstruction of the colonic J-pouch was performed in 26 patients, and straight coloanal anastomosis was performed in 4 patients due to narrow pelvis or bulky mesocolic fat tissue.

Although ISR is the sphincter-preserving procedure for very low rectal cancer, there are concerns regarding local control and defecatory function. In this study, we report the outcomes of ISR of very low rectal cancer, less than 2.5 cm from the dentate line, with a median follow-up period of 56 months. Our data show that this operation is feasible, with no postoperative mortality found in the study group. Moreover, it is associated with favorable oncological outcomes for Tis-T2 tumors. With regard to the Wexner score, total ISR did not produce worse outcomes than partial ISR did, with the exception that permanent stoma were necessitated by unfavorable anastomosis. However, anastomotic stricture, which occurred as a postoperative complication, was found to negatively affect anal function.

From an oncological point of view, local control of the disease remains the most important objective in rectal cancer surgery. The local recurrence rate of very low rectal cancer for ISR varied widely, ranging between 0%[23] to 31%[25]. With ISR, the rate of secure distal resection margin was in the range of 95%[23] to 100%[18], and our results showed a median distance of 7 mm, and a definite negative distal margin in all patients. Therefore, ISR was found to provide an optimal distal resection margin, which is difficult to attain by using only the abdominal approach for very low rectal cancer. Rate of positive CRM of the rectal cancer also influenced factor of local recurrence. In our study group, 6.7% of all patients had a CRM ≤1 mm, and similar results were reported in the range of 0% to 13.3%[18, 26]. Preoperative CRT was considered useful for preventing local recurrence in low rectal cancer patients requiring ISR[14, 23]. Kuo et al.[26] reported a positive CRM rate of 13.3%, but a local recurrence rate of 7.7% in their ISR series of 26 patients; 88.5% of these patients had undergone preoperative CRT. Paradoxically, Hohenberger and colleagues[27] reported that in ISR patients with lower-third rectal cancer without radiotherapy, the local recurrence rate was high, at 46.5%. In our study, local recurrence was significantly higher in patients with T3 tumors than in those with Tis-T2 tumors. Akasu et al.[28] reported that both T3 tumors and a positive microscopic resection margin in patients who underwent ISR were significantly associated with local recurrence. Because ISR involves dissection of the rectum between the internal sphincter muscle and the external sphincter muscle, in patients with T3 tumors with expanding microscopic tumor cells near the levator ani or the external sphincter muscles, during surgical resection, there is a considerable risk of cutting into the tumor or achieving a very short distance of a few millimeters to the CRM. Thus, for a group of patients with T3 tumors, ISR was applied to attain good responses to neoadjuvant CRT, leading to secure CRM.

Partial or total resection of the internal sphincter muscle resulted in defecatory dysfunction with frequent defecation, urgency, and fecal incontinence[16, 18, 29]. Moreover, preoperative radiotherapy against T3 tumors or lymph node involvement was found to have a negative impact on anal function after ISR[17, 18, 26]. In the study by Ito et al.[17], of all the patients who underwent ISR, 40% received radiotherapy and were found to have a mean Wexner score of 10 at 12 months. Moreover, Denost et al.[20] reported a median Wexner score of 11 in most of the patients who received radiotherapy.

It has been shown that colonic J-pouch reconstruction in conjunction with ISR can minimize the anal dysfunction-related side effects of a sphincteric resection[9]. Hida et al.[30] reported the long-term benefits of colonic J-pouch reconstruction suggesting that it improves reservoir function to a greater extent than straight anastomosis does, especially in patients in whom the anastomosis is less than 4 cm from the anal verge. In addition, Dennett et al.[31] reported that colonic J-pouch is effective in very low rectal cancer surgery, causing apparent reduction in the incidence of anastomotic leaks and in bowel frequency. In our study, the mean Wexner score was 11.5 in most patients with colonic J-pouch reconstruction, and none of the patients had received radiation therapy. In previous studies, total ISR was performed in 8.9%[29] to 33.7%[20] of all the ISR patients. A possible reason for the poorer outcomes about Wexner score in our study was that the number of patients who required total ISR accounted for approximately half the ISR patients (42.1%), because coloanal anastomosis using conventional DST was technically possible in a few patients who required partial ISR during our study period.

The outcome for continence is reported to be worse after total ISR than after subtotal or partial ISR[19, 20]. In our results for Wexner scores, anal function between total or subtotal ISR and partial ISR were not different, but patients of partial ISR had earlier recovery than those of subtotal or total ISR. Our functional results are limited because of the differences in stoma closure rates between partial ISR and subtotal/total ISR patients. The rates of stoma closure in patients with subtotal or total ISR were lower than those in patients undergoing partial ISR. This result in itself indicates poor anal function outcomes for subtotal/total ISR. Especially with respect to the three patients with total ISR, stoma closure was not possible because of the high risk of major incontinence.

Postoperative complication rates varied between reported series from 18% to 64%[15]. Common complications included leakage, anastomotic stricture, fistula, pelvic sepsis, and prolapse. In a previous literature review, anastomotic leakage rates of 5% to 48%[32] were reportedly associated with ISR, and they varied depending on whether asymptomatic leaks were radiologically detected. Also, Tilney and Tekkis[9] reviewed 21 studies and reported an overall anastomotic leak rate of 10.5% and anastomotic stricture rate of 5.8%. Similar rates were reported in the current series: anastomotic leakage occurred in 7 of 30 patients (23.3%) and anastomotic stricture in 12% of the patients. Anastomotic leakage is an important feature since it has been found to lead to postoperative anastomotic stricture[33] and poor postoperative anorectal function[34]. However, in our study, there were no independent factors associated with anal dysfunction in the multivariate analysis, but patients with anastomotic stricture showed worse outcomes (frequency, urgency, and fragmentation) than patients without anastomotic stricture. In addition, symptoms related to anal function were not reduced in these patients. In our study, anastomotic stricture or occlusion occurred in five of seven patients with anastomotic leakage; thus, stricture formation could be attributed to leakage caused by ischemia or infection of the anastomotic site. Therefore, it is necessary to fully explain the possibility of fecal incontinence or of a permanent stoma to the patients before obtaining informed consent. Fecal QOL in our patients who had an anastomotic stricture was worse, and they might have little benefit from preserving the anal continuity with ISR.

Our study has some limitations: it was a retrospective study and the sample size was relatively small. There could be potential bias due to possible difference between those who were ambitious of receiving the anal sphincter preserving surgery and those who did not, which could affect the self-evaluation for gastrointestinal questionnaire. With regard to the additional partial ESR performed only in one patient with stoma closure, this was not taken into consideration while estimating anal function.

In summary, ISR is an oncologically safe procedure for pTis or pT2 tumors among very low rectal cancer patients. Also, total ISR, that is, complete removal of the internal sphincter muscles, carried risks of worse anal function or possibility of a permanent stoma. The complications associated with anastomosis, especially stenosis, resulted in poorer anal function. Larger studies are needed to evaluate functional results in ISR patients who suffer from anastomotic stricture.