Factors preventing restoration of bowel continuity in patients with rectal cancer submitted to anterior rectal resection and protective ileostomy

Objective: to evaluate the factors associated with non-closure of protective ileostomy after anterior resection of the rectum with total mesorectum excision for rectal cancer, the morbidity associated with the closure of ileostomies and the rate of permanent ileostomy in patients with rectal adenocarcinoma. Methods: we conducted a retrospective study with 174 consecutive patients diagnosed with rectal tumors, of whom 92 underwent anterior resection of the rectum with coloanal or colorectal anastomosis and protective ileostomy, with curative intent. We carried out a multivariate analysis to determine the factors associated with definite permanence of the stoma, as well as studied the morbidity of patients who underwent bowel continuity restoration. Results: In the 84-month follow-up period, 54 of the 92 patients evaluated (58.7%) had the ileostomy closed and 38 (41.3%) remained with the stoma. Among the 62 patients who had the ileostomy closed, 11 (17.7%) presented some type of postoperative complication: three had ileal anastomosis dehiscence, five had intestinal obstruction, two had surgical wound infection, and one, pneumonia. Eight of these patients required a new stoma. Conclusion: according to the multivariate analysis, the factors associated with stoma permanence were anastomotic fistula, presence of metastases and closure of the ileostomy during chemotherapy.


INTRODUCTION
I n recent years, remarkable advances have been described in the treatment of rectal cancer.
In the late 1970s, the use of circular staplers facilitated the surgical technique, allowing anterior resection of the rectum with anastomoses near the sphincter.The acceptance and diffusion of the total mesorectum excision (TME) allowed 30% to 50% relapse rates, demonstrated in some series, to be reduced to 6% to 10%.It has also been shown that at least 1cm tumor-free distal margins are oncologically safe 1 .These factors allowed the routine performance of low coloanal or colorectal anastomoses.

Although
theoretically advantageous by avoiding a permanent colostomy of the abdominoperineal resection (APR) of the rectum, low coloanal and colorectal anastomoses are technically-difficult, high-morbidity procedures.
Fistula rates increase significantly with the proximity of the anastomosis with the anal border.Those located less than 8cm from the anal border show dehiscence rates of up to 24% 2 .Due to these high rates, most authors recommend perfuming a loop ileostomy for protection of these anastomoses 3 .
After anterior resection of the rectum and TME with protective ileostomy for treatment of rectal tumors, the goal is to reconstruct the intestinal transit in eight to 12 weeks.However,

Original Article
Factors preventing restoration of bowel continuity in patients with rectal cancer submitted to anterior rectal resection and protective ileostomy.
da-Fonseca Factors preventing restoration of bowel continuity in patients with rectal cancer submitted to anterior rectal resection and protective ileostomy.

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Rev Col Bras Cir 45 (6):e1998 some patients never have their bowel continuity restored, and the ileostomy, initially called "temporary", remains definitively.Several authors describe a prevalence between 12% and 43% for this state, due to several causes, including patients with benign and malignant diseases 4,5 .
In addition, those who undergo reconstruction of the intestinal transit also exhibit significant rates of postoperative complications and, sometimes, there is a need to build a new stoma.Morbidity after reversal of decompression stoma varies between 17% and 45%.The most common complications are wound infection, intestinal obstruction and anastomosis dehiscence, with mortality ranging from 0% to 3.5% 6,7 .
This study aims to assess the factors associated with the non-closure of the protective ileostomy after anterior resection of the rectum and TME due to rectal cancer, the morbidity associated with the ileostomy closure, and the rate of stoma permanence after a long followup period in a cohort of patients with rectal adenocarcinoma.

METHODS
We Similar to other studies, we considered an ileostomy definitive when the closure operation was not performed after 12 months of its manufacture and when there was no programming to perform restoration of bowel continuity 9,10 .We defined the tumor location in the rectum by rectal digital examination and rigid rectosigmoidoscopy.We considered an anastomotic fistula the presence of fever associated with purulent or fecal discharge in the pelvic drainage, drainage of purulent secretion from the rectum or vagina and/or radiological signs of air outside the colon or opening of the colic wall.We defined ileostomy time as the period in months between the ARR with TME and the operation restore bowel continuity.
We considered the follow-up period as Initially, we performed a univariate analysis of each independent variable with the response variable.We considered as candidates for the multivariate model all variables that had p-value ≤0.20.We started the multivariate analysis with all the candidate variables and carried out a stepwise exclusion of those with the highest p-value, until reaching the model where all were significant at the 0.05 level.
We calculated the estimated probability

RESULTS
The mean follow-up period was 29.7 months (standard deviation [SD]: ±22.8 months) and the total follow-up period was 84 months.
Of the 92 patients evaluated, 30 remained with the ileostomy, while 62 underwent restoration of bowel continuity.After ileostomy closure, eight patients had a reconstructed stoma.
The 92 patients had a mean age of 55.6 years (SD: ±13.6 years), and 71 (77.2%) were less da-Fonseca Factors preventing restoration of bowel continuity in patients with rectal cancer submitted to anterior rectal resection and protective ileostomy.showed disease progression, nine (30%) were on chemotherapy for more than 12 months, two (6.7%) had comorbidities that prevented closure and other two (6.7%) had complications of the first operation.

Ileostomy closure
Among the 62 patients who had the bowel continuity restored, 11 (17.7%)presented some type of postoperative complication: three had ileal anastomosis dehiscence, five had intestinal obstruction, two had wound infection and one had pneumonia.All patients with complications, except those with surgical wound infection and pneumonia, were reoperated and the stoma was reconstructed (eight patients).

da-Fonseca
Factors preventing restoration of bowel continuity in patients with rectal cancer submitted to anterior rectal resection and protective ileostomy.

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Rev Col Bras Cir 45( 6):e1998 At the end of the follow-up period (84 months), of the 92 patients evaluated, 54 (58.7%) had restoration of bowel continuity and 38 (41.3%) remained with some type of intestinal stoma.
Figure 2 shows the probability curve of non-restoration of bowel continuity over the 60-month period, according to the Kaplan-Meier method.The computed estimate for 60 months was 37%.

DISCUSSION
The risks related to the closure and permanence of a stoma after several types of colorectal resection were previously addressed by some authors 4,5,9.11-14 .However, research addressing the overall rate of ileostomy persistence after treatment for rectal cancer is rare in the Ileostomy is also associated with the various complications, such as dermatitis, parastomal hernia, stenosis, bleeding, prolapse, retraction and dehydration in 60% of patients.The incidence of these complications increases with the time for restoration of bowel continuity 18,19 .
The median time for ileostomy closure of the patients analyzed herein was eight months.It is worth noting that several authors recommend the closure in eight to 12 weeks 20,21 , though as the data reported here, most describe significantly longer periods for the restoration of bowel continuity [22][23][24] .
This suggests that, for many patients, the ideal time stipulation for stoma closure is unreal.From small series of patients to large multicenter studies, it is rare to find references to patients who were freed of the stoma in a time considered ideal, up to 12 weeks after the ARR.The periods described for restoration of bowel continuity after rectal cancer treatment vary between four and 12 months 7,9,11,12,20,25 .Factors related to the delay in the reconstruction of intestinal transit are adjuvant chemotherapy, elderly patients, advanced stages of neoplasia and presence of comorbidities 5,20,24 .------------------------ In the present study, 32.6% of the patients did not have the protective ileostomy closed after ARR.The reported prevalence of stomatal permanence after colorectal resections varies between 12% and 43% 4,5,9,11,15,20,22,24 .
This great difference occurs due to the diversity between the studies, which include different types of colorectal resections, as well as covering benign diseases and malignant neoplasias.The factors described as related to the non-closure of the stoma are similar between the different researches and similar to those we found.The following causes are reported: postoperative chemotherapy, advanced age, metastatic disease, previous comorbidities and operative complications during tumor resection 9,20,24,25 .
We should also note that in the present study, according to the multivariate analysis, the occurrence of anastomotic fistula and metastases are factors that increase the risk of not having the ileostomy closed after ARR with TME.
The manufacturing of a temporary ileostomy has been shown to be efficient in avoiding complications due to fistulas of low colorectal anastomosis 27,28 .This procedure practically does not increase ARR operative time and overall morbidity.However, proximal deviation of the intestinal transit through an ileostomy is not a procedure that can be considered risk-free.
The closure of the ileostomy in this cohort was associated with a complication rate of 17.7%, with 12.9% reoperations, but we observed no mortality.
A meta-analysis evaluated 48 studies involving 6017 patients and showed that restoration of bowel continuity is associated with a morbidity of 17%, a reoperation rate of 3.7%, and a mortality rate of 0.4% 29 .In the same review, the most common complications were intestinal obstruction, surgical wound infection and anastomotic fistula, similar to those found in the present study.It is also emphasized that these complications often require operative treatment and need reconstruction of new intestinal stoma.Other authors also reported similar results, in which complication rates ranged from 10% to 60% 6,7,12,13,21 .
The present study has some limitations.
the one from the date of the operation to treat the rectal tumor until the last date registered in the patient's medical record or death date, counted in months.Patients were evaluated every three months in the first two years after the operation for treatment of the tumor, then every six months till completing five years of the procedure, and then annually onwards.During the follow-up visits, we submitted the patients to anamnesis and physical examination.We requested CEA dosages in the first two years of follow-up every three months, then every six months up to the first five years.Computed tomography of the abdomen and thorax were performed annually in the first five years of follow-up.Colonoscopies were performed after the first year of operation, and every two or three years thereafter.In case of new symptoms or suspected relapse, we could advance such examinations or request specific tests, such as magnetic resonance imaging, positron emission tomography.We analyzed the categorical variables using the Chi-square test, and quantitative ones with the Student's t-test (mean and SD) for variables with normal distribution, and the Mann-Whitney test for non-normally distributed ones (median and interquartile range -IQR).
of non-closure of the ileostomy according to the Kaplan-Meier method.The level of significance considered in this study was 0.05.The software used to perform the statistical calculations was the Statistical Package for Social Sciences (SPSS) version 20.0.The project of this study, as well as the informed consent form, were approved by the Ethics in Research Committee of the Federal University of Minas Gerais, under CAAE register 0739.0.203.000-12.

Factors
related to non-closure of theileostomy after anterior resection of the rectum Of the 92 patients, 62 (67.4%) had the ileostomy closed in the median of eight months (IQR: 5.0-10.0months).Figure 1 shows the number of patients who had the ileostomy closed at each follow-up month after ARR with TME.Of the 30 patients who did not have ileostomy closed, 17 (56.6%)

literature 4 ,
[15][16][17] .The present study identified the occurrence of anastomotic fistula after ARR, systemic metastasis and closure of the ileostomy during adjuvant chemotherapeutic treatment as factors associated with the stoma permanence after all the different stages of treatment in a cohort of patients with rectal cancer submitted ARR with TME and protective ileostomy.

Figure 2 .
Figure 2. Probability of non-restoration of bowel continuity during the 60-month follow-up period, according to the Kaplan-Meier method.

Table 1
brings the patients' demographic and clinicopathological characteristics.

Table 2
anastomotic fistula, presence of lymph node and systemic metastasis, and tumor staging.

Table 3
shows the univariate analysis of the factors associated with non-closure of the ileostomy after anterior resection of the rectum with total mesorectum excision and protective ileostomy.The variables CEA values greaterFigure 1. Number of patients with closed ileostomy, at each month of follow-up after anterior rectal resection (ARR) with total mesorectum excision (TME) (n=62).5 Rev Col Bras Cir 45(6):e1998

Table 1 .
Demographic and clinicopathological characteristics of the study patients (n=92).Factors preventing restoration of bowel continuity in patients with rectal cancer submitted to anterior rectal resection and protective ileostomy.

Table 2 .
Comparison of factors related to ileostomy closure and persistence of ileostomy after anterior resection of the rectum due to rectal cancer (n=92).

Table 3 .
Univariate analysis of factors associated with non-closure of the ileostomy after anterior resection of the rectum with total mesorectum excision and protective ileostomy (n=92).

Table 4 .
Univariate analysis of the variables related to the permanence of a definite stoma in patients with rectal cancer submitted to anterior resection of the rectum with total mesorectum excision and protective ileostomy (n=92).