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HOME > Ann Coloproctol > Volume 37(5); 2021 > Article
Original Article
 The Effect of Anastomotic Leakage on the Incidence and Severity of Low Anterior Resection Syndrome in Patients Undergoing Proctectomy: A Propensity Score Matching Analysis
Sungjin Kim, Sung Il Kangorcid, So Hyun Kim, Jae-Hwang Kim
Annals of Coloproctology 2021;37(5):281-290.
DOI: https://doi.org/10.3393/ac.2021.03.15
Published online: June 7, 2021

Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea

Correspondence to: Sung Il Kang, M.D. Department of Surgery, Yeungnam University Medical Center, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Korea Tel: +82-53-620-3580, Fax: +82-31-787-4055 E-mail: sungiry@naver.com
• Received: December 31, 2020   • Revised: March 9, 2021   • Accepted: March 15, 2021

Copyright © 2021 The Korean Society of Coloproctology

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Purpose
    Proctectomy for the treatment of rectal cancer results in inevitable changes to bowel habits. Symptoms such as fecal incontinence, constipation, and tenesmus are collectively referred to as low anterior resection syndrome (LARS). Among the several risk factors that cause LARS, anastomotic leakage (AL) is a strong risk factor for permanent stoma formation. Therefore, the purpose of this study was to investigate the relationship between the severity of LARS and AL in patients with rectal cancer based on the LARS score and the Memorial Sloan Kettering Cancer Center (MSKCC) defecation symptom questionnaires.
  • Methods
    We retrospectively analyzed patients who underwent low anterior resection for rectal cancer since January 2010. Patients who completed the questionnaire were classified into the AL group and control group based on medical and imaging records. Major LARS and MSKCC scores were analyzed as primary endpoints.
  • Results
    Among the 179 patients included in this study, 37 were classified into the AL group. After propensity score matching, there were significant differences in the ratio of major LARS and MSKCC scores of the control group and AL group (ratio of major LARS: 11.1% and 37.8%, P < 0.001; MSKCC score: 67.29±10.4 and 56.49±7.2, respectively, P < 0.001). Univariate and multivariate analyses revealed that AL was an independent factor for major LARS occurrence and MSKCC score.
  • Conclusion
    This study showed that AL was a significant factor in the occurrence of major LARS and defecation symptoms after proctectomy.
  • Keywords: Proctectomy; Anastomotic leakage; Low anterior resection syndrome; Rectal neoplasms
Surgical resection is the basic principle of rectal cancer treatment. With advances in surgical techniques, such as total mesorectal excision, chemotherapy, and radiation therapy, survival rates for rectal cancer have gradually increased, with a 5-year survival rate exceeding 70% in Korea [1].
However, proctectomy involves inevitable changes in bowel habits, which can impede quality of life. After rectal resection, a series of symptoms occur, including fecal incontinence, constipation, tenesmus, urgency, feeling of incomplete emptying, and frequent bowel movement that are collectively referred to as low anterior resection syndrome (LARS) [2, 3]. The incidence of LARS varies across studies but is commonly reported in more than half of the patients with rectal resection. According to a cohort study of 961 patients who underwent rectal resection in Denmark, LARS occurs in 64% of patients with rectal resection; of which, 41% complained of severe symptoms [4]. LARS symptoms were alleviated 6 months to 1 year postoperatively [2, 5]. However, there are reports that about 50% of patients complain of symptoms, even 15 years postoperatively [6, 7]. As such, LARS can affect the quality of life over a long period of time.
Various factors affect the incidence and severity of LARS. Representative risk factors include preoperative radiotherapy, anastomosis near the anal verge, end-to-end anastomosis without a pouch, and anastomotic leakage (AL) [3]. Of these, AL is a complication reported in about 20% of patients who underwent endto-end anastomosis after rectal resection [8, 9] and is a strong risk factor for permanent stoma formation [10]. Nevertheless, due to patients’ rejection of permanent stoma or a burden on the operator, the operator maintains the continuity of the intestinal tract, except in inevitable cases, such as sepsis due to AL. However, from a long-term perspective, this can worsen the quality of life of patients.
Several studies have been conducted on AL associated with LAR, and methods to prevent this have also been demonstrated [9, 11]. However, few studies have investigated the association between AL and LARS, and especially in Korea, even though the incidence of LARS has not been properly investigated [12]. There are no clinical studies that prove inflammatory reactions, such as fibrotic scar or chronic sinus, induced by AL cause deterioration of the remnant rectum and lead to LARS. If the association between LARS and AL is proven through research, the rationale for this would be that preventing AL can prevent the occurrence of LARS. Therefore, the purpose of this study was to investigate the relationship between AL and the severity of LARS in patients with rectal cancer.
Patients who underwent low anterior resection for rectal cancer from January 2010 to September 2019 at Yeungnam University Medical Center in Daegu, Korea were reviewed retrospectively. Low anterior resection was performed by an experienced colorectal surgeon. At the time of investigation, the study was performed on patients who underwent surgery more than 1 year before. The exclusion criteria were (1) permanent or temporary ostomy at the time of investigation, (2) patients who underwent colon resection or small bowel resection of > 100 cm or gastrectomy in addition to low anterior resection, (3) patients with cognitive or mental disabilities who lack the ability to understand the questionnaire and respond properly, and (4) patients who disagree with the study or have lost contact with the study investigators. If patients did not visit the hospital after follow-up was completed, the researchers explained the study details through telephonic conversations, and if patients agreed, they could visit the hospital at the desired time and complete the questionnaire.
The Korean version of the LARS score questionnaire [13] was used, and the scores were converted according to each item. The sum of the scores of each item was classified as follows: 0 to 20, no LARS; 21 to 29, minor LARS; 30 to 42, major LARS. The items of the Memorial Sloan Kettering Cancer Center (MSKCC) [14] questionnaire were translated to Korean. The scores of the 1st, 4th, 5th, 7th, 11th, and 12th items were recalculated because a higher score represents a more severe defecation problem. We evaluated the defecation symptom as the sum of the scores for each item, indicating that the higher the score, the better the defecation function.
In this study, AL is defined as defects in the intestinal wall of the anastomosis site, and determined based on medical and imaging records and classified as follows based on the classification system commonly used in clinical practice [15]: grade A leakage requires no therapeutic intervention, and does not affect a patient’s management; grade B leakage requires active therapeutic intervention, but is manageable without reoperation; and grade C leakage requires reoperation. Clinically, AL signs were defined as fever, abdominal pain, fecal discharge from a drain, peritoneal irritation sign, and pelvic abscess postoperatively. All clinically diagnosed ALs were confirmed by digital rectal examination or computed tomography. The medical records of patients who completed the questionnaire were analyzed retrospectively and classified into the AL group (grade B, C) and control group (no AL, grade A).
To minimize the effect of confounders on selection bias, propensity score and nearest-neighbor matching (PSM) analyses were performed. Patients in the AL group were matched on a 1:2 propensity score with patients in the control group according to age, sex, body mass index, tumor location, neoadjuvant treatment, surgical approach, operative method, anastomosis type, and fecal diversion.
Baseline demographics were compared between the AL and control groups. The Student t-test or Mann-Whitney U-test was used for continuous variables; and for categorical variables, a chi-square test or Fisher exact test was used. Univariate analyses were performed to identify factors associated with the LARS and MSKCC total scores by using logistic regression and linear regression analyses. Variables with P-values of < 0.05 in univariate analyses were included in the multivariate analyses. All statistical analyses were considered significant at P < 0.05. Statistical analysis was performed using IBM SPSS Statistics ver. 22.0 (IBM Corp., Armonk, NY, USA).
This study was approved by the Institutional Review Board of Yeungnam University Medical Center (No. YUMC 2020-03-117-007) with the written informed consent from the patients.
A survey including the LARS score and MSKCC defecation symptom questionnaires was conducted between November 2019 and September 2020. A total of 208 patients met the selection criteria. Patients who were scheduled to visit our institution for the treatment or follow-up of rectal cancer answered the questionnaire after the explanation of the researcher. Of the 208 patients, 179 answered the questionnaire (Fig. 1).
Among the 179 patients, 23 patients (12.8%) had grade B leakage and 14 (7.8%) had grade C leakage. A total of 37 patients with grade B and C leakage were classified into the AL group and the remaining 142 patients were classified into the control group.
There was no difference in baseline characteristics between the 2 groups (Table 1). By performing PSM, 74 out of 142 patients in the control group were matched. There was no difference between the 2 groups except for the time to surgery factor after PSM. Before and after PSM, the LARS and MSKCC scores were significantly different between the control group and AL group (LARS score [before matching]: 14.60 ± 12.6 and 28.30 ± 6.4, P < 0.001; LARS score [after matching]: 15.62 ± 13.0 and 28.30 ± 6.4, P < 0.001; MSKCC score [before matching]: 66.88 ± 9.1 and 55.24 ± 7.0, P < 0.001; MSKCC score [after matching]: 66.63 ± 8.5 and 55.24 ± 7.0, P < 0.001). Moreover, the ratio of major LARS was significantly higher in the AL group (control group and AL group; before matching: 12.7% and 37.8%, P < 0.001; after matching: 13.5% and 37.8%, P < 0.001).
Before PSM, univariate analysis showed that major LARS was associated with neoadjuvant therapy, tumor stage, and grade B and C AL. After PSM, neoadjuvant therapy, fecal diversion, tumor stage, and grade B and C AL were significant factors with major LARS in the univariate analysis (Table 2). Multivariate analysis demonstrated that grade B and C AL and neoadjuvant therapy were independent factors for major LARS (Table 3).
The same analysis was conducted to identify the independent factor for the MSKCC score. Before PSM, grade B and C AL were independent factors for MSKCC score in univariate analysis. Sex, tumor location, and grade B and C AL were independent factors for MSKCC in the univariate analysis after PSM (Table 4). The multivariate analysis showed that sex, tumor location, and grade B and C AL were significantly associated with MSKCC score (Table 5).
The LARS score and MSKCC scores have an inverse relation, which forms a significant (P < 0.001) correlation graph (Fig. 2). And the LARS and MSKCC scores were the same in both fecal diversion device (FDD) and loop ileostomy groups (Table 6).
Our study findings showed that AL and neoadjuvant chemoradiotherapy affected LARS and defecation symptoms in patients with rectal cancer who underwent LAR. These results are comparable to those of previous studies that also evaluated the factor which affect LARS and defecation symptoms [4, 16, 17].
The exact diagnosis and approach to LARS depend on asking appropriate questions about the patient’s symptoms. According to a recent meta-analysis, due to the lack of a LARS definition, long-term bowel function was not evaluated, and in 65% of studies, a validated questionnaire was not used [18]. The surveys for investigating the quality of life that have been published are very diverse and complex; therefore, it takes a long time to complete and analyze them. It has also been reported that they represent specific symptoms and are not suitable for collecting complex symptoms associated with bowel movements and reflecting the quality of life associated with bowel movements [19].
According to several studies, there are a number of factors that worsen LARS, such as radiotherapy, the extent of rectal excision, the creation of a colonic pouch, and AL. In this study, we focused on AL, a deteriorating factor of LARS. Since there are many factors that affect LARS among the risk factors of AL, such as low-lying tumor and preoperative chemoradiation, correction between the leak group and the no-leak group was performed through PSM. Regarding the impact of postoperative AL on defecation symptoms, there are not much available data and a somewhat heterogeneous investigation of symptoms. There are also few studies on the histological approach of AL. Daams et al. [20] showed that the healing of gastrointestinal anastomosis in an experimental model occurred by the formation of a fibrotic cap at the serosal portion, which formed a matrix for fibroblasts. Based on this result, AL occurrence is considered a negative event for bowel function because of the inflammatory change and excessive fibrotic scarring that may develop thereafter in the pelvic cavity. This can alter compliance and the capacity of the neorectum, which can induce urgency or incontinence.
If neoadjuvant therapy was performed, surgery was performed 6 weeks after the end of neoadjuvant therapy. Therefore, it can be seen that LARS is worsened by ischemia and fibrosis caused by progressive obliterating endarteritis and the late toxicity of radiotherapy. Gastrointestinal tract ulceration causes symptoms such as perforation, fistulization, and peritonitis, and is associated with an extensive area of fibrosis [21]. Anal sphincter damage is also induced by radiotherapy, which is due to the damage to the myenteric plexus and smooth-muscle hypertrophy [22]. The length of the residual rectum on magnetic resonance imaging affects LARS severity, and it is reported that LARS severity is high when the length of the residual rectum is less than 4 cm [23].
Reduced neorectal reservoir volume is considered a major cause of urgency or incontinence. According to several studies, low-lying tumors or anastomoses of < 5 cm from the anal verge are independent risk factors for deteriorated defecation symptoms [17,23]. Damage to the internal anal sphincter during rectal mobilization causes passive incontinence [24], and damage to the pelvic floor innervations leads to fecal incontinence and urgency [25]. Moreover, a decrease in the length of the urethral rectum leads to a decrease in neorectal capacity, which leads to a worsening of bowel dysfunction [26].
In our study, female patients showed better bowel function than male patients. To date, there have been no studies that have studied the relationship between bowel dysfunction after low anterior resection and sex difference. The result of our study is expected to be due to the anatomical difference of the pelvis, which is related to the difficulty of surgery. Females had a significantly longer pelvic inlet and outlet, while males had a greater pelvic depth [27]. Therefore, female patients will experience less nerve damage during surgery, and bowel function postoperatively is expected to be better than that of male patients. However, a larger study is needed to confirm this.
In addition to loop ileostomy, which is the traditional method of fecal diversion, patients who performed fecal diversion using the FDD [28], which is being clinically tested at our hospital, are included. In the clinical trial at that time, it was concluded that the ratio of AL between the patient group who underwent ileostomy and the patient group using FDD was the same; hence, it was decided to include patients who used FDD in this study. As was mentioned in the results section, there was no significant difference in LARS score and MSKCC score between the FDD group and the loop ileostomy groups. Therefore, FDD and loop ileostomy were considered as the same fecal diversion method when performing univariate and multivariate analyses.
This study has several limitations. First, it is a nonrandomized study design. Operators must do their best to prevent AL occurrence, and there cannot be a study design that randomizes AL occurrence. Since patients were classified into 2 groups according to the presence or absence of AL, selection bias may occur regarding factors that may cause AL. Thus, the author implemented the PSM method to compensate for the selection bias. For more effective matching, the number of patients should be greater than in this study. Therefore, prospective multicenter research is needed. Second, this is a study based on a survey; since the questionnaire survey is conducted based on the subjective symptoms of the patient, it may be difficult to use it as an objective indicator, and as the survey is mainly conducted on elderly patients, it is difficult to expect accurate memories. Third, the time of the questionnaire survey from surgery was different for each patient. Since LARS shows a trend of improvement from 1 year postoperatively, studies were conducted on patients who underwent operation for more than 1 year, but many studies have shown that symptoms persist for up to 2 years postoperatively. Therefore, it is necessary to investigate defecation symptoms or LARS at several time points, not at 1-time point postoperatively.
In conclusion, this study showed that AL is a risk factor for major LARS and changes in defecation function after low anterior resection and neoadjuvant chemoradiotherapy. Further prospective multicenter studies are needed to confirm the negative prognostic factors of AL and the relationship with major LARS.

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

Fig. 1.
Flow chart of study patients. LAR, low anterior resection; uLAR, ultra low anterior resection; AL, anastomotic leakage.
ac-2021-03-15f1.jpg
Fig. 2.
Graph of correlation between low anterior resection syndrome (LARS) score and Memorial Sloan Kettering Cancer Center (MSKCC) score. (A) Before propensity score matching (PSM). (B) After PSM.
ac-2021-03-15f2.jpg
Table 1.
Comparison of characteristics before and after propensity score matching
Characteristic Before matching
 After matching
AL group (n = 37) Control group (n = 142) P-value AL group (n = 37) Control group (n = 74) P-value
Age (yr) 0.343 0.308
 ≥ 70 9 (24.3) 46 (32.4) 9 (24.3) 25 (33.8)
 < 70 28 (75.7) 96 (67.6) 28 (75.7) 49 (66.2)
Sex 0.693 0.272
 Male 25 (67.6) 91 (64.1) 25 (67.6) 42 (56.8)
 Female 12 (32.4) 51 (35.9) 12 (32.4) 32 (43.2)
BMI (kg/m2) 0.429 0.069
 ≤ 25 28 (75.7) 98 (69.0) 28 (75.7) 43 (58.1)
 > 25 9 (24.3) 44 (31.0) 9 (24.3) 31 (41.9)
Time after surgery (yr) 0.089 0.003
 ≤2 9 (24.3) 56 (39.4) 9 (24.3) 40 (54.1)
 > 2 28 (75.7) 86 (60.6) 28 (75.7) 34 (45.9)
Tumor location 0.737 0.608
 Upper rectum 11 (29.7) 52 (36.6) 11 (29.7) 29 (39.2)
 Mid rectum 15 (40.5) 52 (36.6) 15 (40.5) 27 (36.5)
 Lower rectum 11 (29.7) 38 (26.8) 11 (29.7) 18 (24.3)
Neoadjuvant therapy 0.553 0.476
 No 32 (86.5) 117 (82.4) 32 (86.5) 60 (81.1)
 Yes 5 (13.5) 25 (17.6) 5 (13.5) 14 (18.9)
Surgical approach 0.414 0.419
 Open 6 (16.2) 16 (11.3) 6 (16.2) 8 (10.8)
 Laparoscopic 31 (83.8) 126 (88.7) 31 (83.8) 66 (89.2)
Operative method 0.932 0.722
 LAR 30 (81.1) 116 (81.7) 30 (81.1) 62 (83.8)
 uLAR 7 (18.9) 26 (18.3) 7 (18.9) 12 (16.2)
Anastomotic type 0.942 1.000
 Stapled end to end 34 (91.9) 131 (92.3) 34 (91.9) 68 (91.9)
 Handsewn end to end 3 (8.1) 11 (7.7) 3 (8.1) 6 (8.1)
Fecal diversion 0.936 0.967
 No 13 (35.1) 50 (35.2) 13 (35.1) 30 (40.5)
 FDD 11 (31.8) 46 (32.4) 11 (31.8) 23 (31.1)
 Loop ileostomy 13 (35.2) 46 (32.4) 13 (35.1) 21 (28.4)
IMA ligation 0.697 0.773
 High 26 (70.3) 95 (66.9) 26 (70.3) 50 (67.6)
 Low 11 (29.7) 47 (33.1) 11 (29.7) 24 (32.4)
Tumor stage 0.678 0.490
 I 7 (18.9) 34 (23.9) 7 (18.9) 20 (27.0)
 II 10 (27.0) 33 (23.2) 10 (27.0) 12 (16.2)
 III 17 (45.9) 54 (38.0) 17 (45.9) 31 (41.9)
 IV 3 (8.1) 21 (14.8) 3 (8.1) 11 (14.9)
LARS score 28.30 ± 6.4 14.60 ± 12.6 < 0.001 28.30 ± 6.4 15.62 ± 13.0 < 0.001
LARS classification < 0.001 < 0.001
 No 2 (5.4) 86 (60.6) 2 (5.4) 42 (56.8)
 Mild 21 (56.8) 38 (26.8) 21 (56.8) 22 (29.7)
 Major 14 (37.8) 18 (12.7) 14 (37.8) 10 (13.5)
MSKCC score 55.24 ± 7.0 66.88 ± 9.1 < 0.001 55.24 ± 7.0 66.63 ± 8.5 < 0.001

Values are expressed as mean±standard deviation or number (%).

AL, anastomotic leakage; BMI, body mass index; LAR, low anterior resection; uLAR, ultra low anterior resection; FDD, fecal diversion device; IMA, inferior mesenteric artery; LARS, low anterior resection syndrome; MSKCC, Memorial Sloan Kettering Cancer Center.

Table 2.
Univariate analysis of risk factors for major LARS
Factor Incidence of major LARS (%) Before matching
 Incidence of major LARS (%) After matching
P-value Odds ratio 95% CI P-value Odds ratio 95% CI
Age (yr)
  ≤ 70 19.4 1 23.4 1
> 70 16.4 0.725 0.859 0.369–2.002 20.6 0.746 0.850 0.317–2.275
Sex
Male 17.2 1 23.9 1
Female 20.6 0.763 1.129 0.511–2.494 20.5 0.673 0.820 0.326–2.063
BMI (kg/m2)
< 25 16.7 1 21.1 1
≥ 25 22.6 0.515 1.310 0.581–2.951 25.0 0.639 1.244 0.499–3.107
Time from surgery (yr)
≤2 15.4 1 18.4 1
>2 20.2 0.512 1.315 0.580–2.982 25.8 0.353 1.546 0.616–3.879
Tumor location
Upper rectum 14.3 1 12.5 1
Mid & lower rectum 20.7 0.357 1.484 0.640–3.439 28.2 0.064 2.745 0.941–8.005
Neoadjuvant therapy
No 14.1 1 17.4 1
Yes 40.0 0.005 3.529 1.472–8.459 47.4 0.007 4.275 1.497–12.211
Surgical approach
Open 27.3 1 42.9 1
Laparoscopic 17.2 0.225 0.529 0.189–1.480 19.6 0.060 0.325 0.101–1.048
Operative method
LAR 17.1 1 19.6 1
uLAR 24.2 0.581 1.303 0.509–3.333 36.8 0.107 2.398 0.827–6.957
Anastomotic type
Stapled end to end 17.6 1 20.6 1
Handsewn end to end 28.6 0.284 1.957 0.573–6.687 44.4 0.115 3.068 0.761–12.509
Fecal diversion
No 12.7 1 9.3 1
Yes 21.6 0.187 1.793 0.754–4.268 30.9 0.012 4.356 1.379–13.764
IMA ligation
High 20.7 1 25.0 1
Low 13.8 0.326 0.647 0.271–1.543 17.1 0.360 0.621 0.224–1.723
Tumor stage
I & II 11.9 1 12.2 1
III & IV 24.2 0.037 2.364 1.051–5.315 30.6 0.025 3.167 1.153–8.699
Anastomotic leakage
No & grade A 12.7 1 13.5 1
Grade B, C 40.5 0.001 4.193 1.832–9.598 40.5 0.002 4.364 1.713–11.119

LARS, low anterior resection syndrome; CI, confidence interval; BMI, body mass index; LAR, low anterior resection; uLAR, ultra low anterior resection; IMA, inferior mesenteric artery.

Table 3.
Multivariate analysis of risk factors for major LARS
Factor Before matching
 After matching
P-value Odds ratio 95% CI P-value Odds ratio 95% CI
Neoadjuvant therapy
 No 1 1
 Yes 0.001 4.960 1.886–13.042 0.026 4.235 1.189–15.087
Fecal diversion
 No NA NA NA 1
 Yes NA NA NA 0.077 3.096 0.884–10.837
Tumor stage
 I & II 1 1
 III & IV 0.079 2.195 0.914–5.270 0.053 3.048 0.986–9.422
Anastomotic leakage
 No & grade A 1 1
 Grade B, C < 0.001 6.129 2.471–15.200 0.001 6.396 2.110–19.389

LARS, low anterior resection syndrome; CI, confidence interval; NA, not applicable.

Table 4.
Univariate analysis of risk factors for MSKCC score
Factor Before matching
 After matching
B (β) P-value 95% CI for B B (β) P-value 95% CI for B
Age (yr)
  ≤ 70
> 70 –0.856 (–0.040) 0.596 –4.035 to 2.323 –0.290 (–0.014) 0.885 –4.240 to 3.661
Sex
Male
Female 2.831 (0.137) 0.068 –0.214 to 5.876 4.023 (0.205) 0.031 0.379 to 7.666
BMI (kg/m2)
< 25
≥ 25 –1.184 (–0.055) 0.468 –4.394 to 2.026 0.163 (0.008) 0.932 –3.630 to 3.956
Time from surgery (yr)
≤2
>2 –1.815 (–0.088) 0.240 –4.855 to 1.225 –3.258 (–0.169) 0.077 –6.873 to 0.357
Tumor location
Upper rectum
Mid & lower rectum –2.807 (–0.135) 0.071 –5.852 to 0.239 –4.208 (–0.211) 0.027 –7.916 to –0.500
Neoadjuvant therapy
No
Yes –1.512 (–0.057) 0.448 –5.435 to 2.412 0.423 (0.017) 0.863 –4.411 to 5.258
Surgical approach
Laparoscopic
Open 1.268 (0.084) 0.263 –0.959 to 3.496 1.560 (0.108) 0.259 –1.167 to 4.287
Operative method
LAR
uLAR –0.991 (–0.039) 0.606 –4.773 to 2.791 –2.910 (–0.114) 0.232 –7.714 to 1.893
Anastomotic type
Stapled end to end
Handsewn end to end –2.995 (–0.081) 0.280 –8.443 to 2.454 –4.655 (–0.132) 0.166 –11.268 to 1.958
Fecal diversion
No
Yes 1.713 (0.083) 0.271 –1.350 to 4.775 1.019 (0.052) 0.590 –2.715 to 4.752
IMA ligation
High
Low 1.695 (0.080) 0.286 –1.431 to 4.821 2.622 (0.127) 0.184 –1.266 to 0.650
Tumor stage
I & II
III & IV –0.541 (–0.027) 0.717 –3.481 to 2.399 1.510 (0.078) 0.415 –2.146 to 5.167
Anastomotic leakage
No & grade A
Grade B, C –11.637 (–0.476) < 0.001 –14.824 to –8.450 –11.385 (–0.559) < 0.001 –14.587 to –8.183

MSKCC, Memorial Sloan Kettering Cancer Center; CI, confidence interval; BMI, body mass index; LAR, low anterior resection; uLAR, ultra low anterior resection; IMA, inferior mesenteric artery.

B=unstandardized coefficients, β=standardized β-coefficient.

Table 5.
Multivariate analysis of risk factors for MSKCC score
Factor Before matching
 After matching
B (β) P-value 95% CI for B B (β) P-value 95% CI for B
Sex
 Male NA NA NA 0.459 to 6.540
 Female NA NA NA 3.500 (0.178) 0.024
Tumor location
 Upper rectum NA NA NA
 Mid & lower rectum NA NA NA –3.764 (–0.188) 0.018 –6.858 to –0.670
Anastomotic leakage
 No & grade A Reference
 Grade B, C –11.637 (–0.476) < 0.001 –14.824 to –8.450 –10.651 (–0.523) < 0.001 –13.784 to –7.517

MSKCC, Memorial Sloan Kettering Cancer Center; CI, confidence interval; NA, not applicable.

B=unstandardized coefficients, β=standardized β-coefficient.

Table 6.
Comparison of LARS score and MSKCC score according to fecal diversion method
Factor Before matching
 After matching
Loop ileostomy (n = 59) FDD (n = 57) P-value Loop ileostomy (n = 34) FDD (n = 34) P-value
LARS score 18.00 ± 12.84 17.75 ± 12.67 0.918 22.65 ± 11.56 19.82 ± 13.29 0.353
MSKCC score 64.43 ± 10.18 65.74 ± 9.04 0.464 61.86 ± 9.30 64.59 ± 9.17 0.229

Values are presented as mean±standard deviation.

LARS, low anterior resection syndrome; MSKCC, Memorial Sloan Kettering Cancer Center; FDD, fecal diversion device.

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Figure & Data

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      The Effect of Anastomotic Leakage on the Incidence and Severity of Low Anterior Resection Syndrome in Patients Undergoing Proctectomy: A Propensity Score Matching Analysis
      Ann Coloproctol. 2021;37(5):281-290.   Published online June 7, 2021
      DOI: https://doi.org/10.3393/ac.2021.03.15
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    The Effect of Anastomotic Leakage on the Incidence and Severity of Low Anterior Resection Syndrome in Patients Undergoing Proctectomy: A Propensity Score Matching Analysis
    Image Image
    Fig. 1. Flow chart of study patients. LAR, low anterior resection; uLAR, ultra low anterior resection; AL, anastomotic leakage.
    Fig. 2. Graph of correlation between low anterior resection syndrome (LARS) score and Memorial Sloan Kettering Cancer Center (MSKCC) score. (A) Before propensity score matching (PSM). (B) After PSM.

    Fig. 1.

    Fig. 2.

    The Effect of Anastomotic Leakage on the Incidence and Severity of Low Anterior Resection Syndrome in Patients Undergoing Proctectomy: A Propensity Score Matching Analysis
    Characteristic Before matching
    		 After matching
    AL group (n = 37) Control group (n = 142) P-value AL group (n = 37) Control group (n = 74) P-value
    Age (yr) 0.343 0.308
     ≥ 70 9 (24.3) 46 (32.4) 9 (24.3) 25 (33.8)
     < 70 28 (75.7) 96 (67.6) 28 (75.7) 49 (66.2)
    Sex 0.693 0.272
     Male 25 (67.6) 91 (64.1) 25 (67.6) 42 (56.8)
     Female 12 (32.4) 51 (35.9) 12 (32.4) 32 (43.2)
    BMI (kg/m2) 0.429 0.069
     ≤ 25 28 (75.7) 98 (69.0) 28 (75.7) 43 (58.1)
     > 25 9 (24.3) 44 (31.0) 9 (24.3) 31 (41.9)
    Time after surgery (yr) 0.089 0.003
     ≤2 9 (24.3) 56 (39.4) 9 (24.3) 40 (54.1)
     > 2 28 (75.7) 86 (60.6) 28 (75.7) 34 (45.9)
    Tumor location 0.737 0.608
     Upper rectum 11 (29.7) 52 (36.6) 11 (29.7) 29 (39.2)
     Mid rectum 15 (40.5) 52 (36.6) 15 (40.5) 27 (36.5)
     Lower rectum 11 (29.7) 38 (26.8) 11 (29.7) 18 (24.3)
    Neoadjuvant therapy 0.553 0.476
     No 32 (86.5) 117 (82.4) 32 (86.5) 60 (81.1)
     Yes 5 (13.5) 25 (17.6) 5 (13.5) 14 (18.9)
    Surgical approach 0.414 0.419
     Open 6 (16.2) 16 (11.3) 6 (16.2) 8 (10.8)
     Laparoscopic 31 (83.8) 126 (88.7) 31 (83.8) 66 (89.2)
    Operative method 0.932 0.722
     LAR 30 (81.1) 116 (81.7) 30 (81.1) 62 (83.8)
     uLAR 7 (18.9) 26 (18.3) 7 (18.9) 12 (16.2)
    Anastomotic type 0.942 1.000
     Stapled end to end 34 (91.9) 131 (92.3) 34 (91.9) 68 (91.9)
     Handsewn end to end 3 (8.1) 11 (7.7) 3 (8.1) 6 (8.1)
    Fecal diversion 0.936 0.967
     No 13 (35.1) 50 (35.2) 13 (35.1) 30 (40.5)
     FDD 11 (31.8) 46 (32.4) 11 (31.8) 23 (31.1)
     Loop ileostomy 13 (35.2) 46 (32.4) 13 (35.1) 21 (28.4)
    IMA ligation 0.697 0.773
     High 26 (70.3) 95 (66.9) 26 (70.3) 50 (67.6)
     Low 11 (29.7) 47 (33.1) 11 (29.7) 24 (32.4)
    Tumor stage 0.678 0.490
     I 7 (18.9) 34 (23.9) 7 (18.9) 20 (27.0)
     II 10 (27.0) 33 (23.2) 10 (27.0) 12 (16.2)
     III 17 (45.9) 54 (38.0) 17 (45.9) 31 (41.9)
     IV 3 (8.1) 21 (14.8) 3 (8.1) 11 (14.9)
    LARS score 28.30 ± 6.4 14.60 ± 12.6 < 0.001 28.30 ± 6.4 15.62 ± 13.0 < 0.001
    LARS classification < 0.001 < 0.001
     No 2 (5.4) 86 (60.6) 2 (5.4) 42 (56.8)
     Mild 21 (56.8) 38 (26.8) 21 (56.8) 22 (29.7)
     Major 14 (37.8) 18 (12.7) 14 (37.8) 10 (13.5)
    MSKCC score 55.24 ± 7.0 66.88 ± 9.1 < 0.001 55.24 ± 7.0 66.63 ± 8.5 < 0.001
    Factor Incidence of major LARS (%) Before matching
    		 Incidence of major LARS (%) After matching
    P-value Odds ratio 95% CI P-value Odds ratio 95% CI
    Age (yr)
      ≤ 70 19.4 1 23.4 1
    > 70 16.4 0.725 0.859 0.369–2.002 20.6 0.746 0.850 0.317–2.275
    Sex
    Male 17.2 1 23.9 1
    Female 20.6 0.763 1.129 0.511–2.494 20.5 0.673 0.820 0.326–2.063
    BMI (kg/m2)
    < 25 16.7 1 21.1 1
    ≥ 25 22.6 0.515 1.310 0.581–2.951 25.0 0.639 1.244 0.499–3.107
    Time from surgery (yr)
    ≤2 15.4 1 18.4 1
    >2 20.2 0.512 1.315 0.580–2.982 25.8 0.353 1.546 0.616–3.879
    Tumor location
    Upper rectum 14.3 1 12.5 1
    Mid & lower rectum 20.7 0.357 1.484 0.640–3.439 28.2 0.064 2.745 0.941–8.005
    Neoadjuvant therapy
    No 14.1 1 17.4 1
    Yes 40.0 0.005 3.529 1.472–8.459 47.4 0.007 4.275 1.497–12.211
    Surgical approach
    Open 27.3 1 42.9 1
    Laparoscopic 17.2 0.225 0.529 0.189–1.480 19.6 0.060 0.325 0.101–1.048
    Operative method
    LAR 17.1 1 19.6 1
    uLAR 24.2 0.581 1.303 0.509–3.333 36.8 0.107 2.398 0.827–6.957
    Anastomotic type
    Stapled end to end 17.6 1 20.6 1
    Handsewn end to end 28.6 0.284 1.957 0.573–6.687 44.4 0.115 3.068 0.761–12.509
    Fecal diversion
    No 12.7 1 9.3 1
    Yes 21.6 0.187 1.793 0.754–4.268 30.9 0.012 4.356 1.379–13.764
    IMA ligation
    High 20.7 1 25.0 1
    Low 13.8 0.326 0.647 0.271–1.543 17.1 0.360 0.621 0.224–1.723
    Tumor stage
    I & II 11.9 1 12.2 1
    III & IV 24.2 0.037 2.364 1.051–5.315 30.6 0.025 3.167 1.153–8.699
    Anastomotic leakage
    No & grade A 12.7 1 13.5 1
    Grade B, C 40.5 0.001 4.193 1.832–9.598 40.5 0.002 4.364 1.713–11.119
    Factor Before matching
    		 After matching
    P-value Odds ratio 95% CI P-value Odds ratio 95% CI
    Neoadjuvant therapy
     No 1 1
     Yes 0.001 4.960 1.886–13.042 0.026 4.235 1.189–15.087
    Fecal diversion
     No NA NA NA 1
     Yes NA NA NA 0.077 3.096 0.884–10.837
    Tumor stage
     I & II 1 1
     III & IV 0.079 2.195 0.914–5.270 0.053 3.048 0.986–9.422
    Anastomotic leakage
     No & grade A 1 1
     Grade B, C < 0.001 6.129 2.471–15.200 0.001 6.396 2.110–19.389
    Factor Before matching
    		 After matching
    B (β) P-value 95% CI for B B (β) P-value 95% CI for B
    Age (yr)
      ≤ 70
    > 70 –0.856 (–0.040) 0.596 –4.035 to 2.323 –0.290 (–0.014) 0.885 –4.240 to 3.661
    Sex
    Male
    Female 2.831 (0.137) 0.068 –0.214 to 5.876 4.023 (0.205) 0.031 0.379 to 7.666
    BMI (kg/m2)
    < 25
    ≥ 25 –1.184 (–0.055) 0.468 –4.394 to 2.026 0.163 (0.008) 0.932 –3.630 to 3.956
    Time from surgery (yr)
    ≤2
    >2 –1.815 (–0.088) 0.240 –4.855 to 1.225 –3.258 (–0.169) 0.077 –6.873 to 0.357
    Tumor location
    Upper rectum
    Mid & lower rectum –2.807 (–0.135) 0.071 –5.852 to 0.239 –4.208 (–0.211) 0.027 –7.916 to –0.500
    Neoadjuvant therapy
    No
    Yes –1.512 (–0.057) 0.448 –5.435 to 2.412 0.423 (0.017) 0.863 –4.411 to 5.258
    Surgical approach
    Laparoscopic
    Open 1.268 (0.084) 0.263 –0.959 to 3.496 1.560 (0.108) 0.259 –1.167 to 4.287
    Operative method
    LAR
    uLAR –0.991 (–0.039) 0.606 –4.773 to 2.791 –2.910 (–0.114) 0.232 –7.714 to 1.893
    Anastomotic type
    Stapled end to end
    Handsewn end to end –2.995 (–0.081) 0.280 –8.443 to 2.454 –4.655 (–0.132) 0.166 –11.268 to 1.958
    Fecal diversion
    No
    Yes 1.713 (0.083) 0.271 –1.350 to 4.775 1.019 (0.052) 0.590 –2.715 to 4.752
    IMA ligation
    High
    Low 1.695 (0.080) 0.286 –1.431 to 4.821 2.622 (0.127) 0.184 –1.266 to 0.650
    Tumor stage
    I & II
    III & IV –0.541 (–0.027) 0.717 –3.481 to 2.399 1.510 (0.078) 0.415 –2.146 to 5.167
    Anastomotic leakage
    No & grade A
    Grade B, C –11.637 (–0.476) < 0.001 –14.824 to –8.450 –11.385 (–0.559) < 0.001 –14.587 to –8.183
    Factor Before matching
    		 After matching
    B (β) P-value 95% CI for B B (β) P-value 95% CI for B
    Sex
     Male NA NA NA 0.459 to 6.540
     Female NA NA NA 3.500 (0.178) 0.024
    Tumor location
     Upper rectum NA NA NA
     Mid & lower rectum NA NA NA –3.764 (–0.188) 0.018 –6.858 to –0.670
    Anastomotic leakage
     No & grade A Reference
     Grade B, C –11.637 (–0.476) < 0.001 –14.824 to –8.450 –10.651 (–0.523) < 0.001 –13.784 to –7.517
    Factor Before matching
    		 After matching
    Loop ileostomy (n = 59) FDD (n = 57) P-value Loop ileostomy (n = 34) FDD (n = 34) P-value
    LARS score 18.00 ± 12.84 17.75 ± 12.67 0.918 22.65 ± 11.56 19.82 ± 13.29 0.353
    MSKCC score 64.43 ± 10.18 65.74 ± 9.04 0.464 61.86 ± 9.30 64.59 ± 9.17 0.229
    Table 1. Comparison of characteristics before and after propensity score matching

    Values are expressed as mean±standard deviation or number (%).

    AL, anastomotic leakage; BMI, body mass index; LAR, low anterior resection; uLAR, ultra low anterior resection; FDD, fecal diversion device; IMA, inferior mesenteric artery; LARS, low anterior resection syndrome; MSKCC, Memorial Sloan Kettering Cancer Center.

    Table 2. Univariate analysis of risk factors for major LARS

    LARS, low anterior resection syndrome; CI, confidence interval; BMI, body mass index; LAR, low anterior resection; uLAR, ultra low anterior resection; IMA, inferior mesenteric artery.

    Table 3. Multivariate analysis of risk factors for major LARS

    LARS, low anterior resection syndrome; CI, confidence interval; NA, not applicable.

    Table 4. Univariate analysis of risk factors for MSKCC score

    MSKCC, Memorial Sloan Kettering Cancer Center; CI, confidence interval; BMI, body mass index; LAR, low anterior resection; uLAR, ultra low anterior resection; IMA, inferior mesenteric artery.

    B=unstandardized coefficients, β=standardized β-coefficient.

    Table 5. Multivariate analysis of risk factors for MSKCC score

    MSKCC, Memorial Sloan Kettering Cancer Center; CI, confidence interval; NA, not applicable.

    B=unstandardized coefficients, β=standardized β-coefficient.

    Table 6. Comparison of LARS score and MSKCC score according to fecal diversion method

    Values are presented as mean±standard deviation.

    LARS, low anterior resection syndrome; MSKCC, Memorial Sloan Kettering Cancer Center; FDD, fecal diversion device.

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