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Comparison of surgical outcomes between video-assisted anal fistula treatment and fistulotomy plus seton for complex anal fistula: A propensity score matching analysis - Retrospective cohort study
International Journal of Surgery 75 (2020) 99–104
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International Journal of Surgery journal homepage: www.elsevier.com/locate/ijsu
Comparative Study
Comparison of surgical outcomes between video-assisted anal fistula treatment and fistulotomy plus seton for complex anal fistula: A propensity score matching analysis - Retrospective cohort study
T
Hailong Liua,1, Xuan Tanga,b,1, Yi Changa, Ajian Lia, Zhen Lia, Yihua Xiaoa, Yong Zhanga, Zhihui Pana, Liang Lva, Moubin Lina,b, Lu Yinc,∗∗, Huihong Jianga,b,∗ a b c
Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
A R T I C LE I N FO
A B S T R A C T
Keywords: Complex anal fistula VAAFT Seton Surgical outcome Recurrence
Background: Video-assisted anal fistula treatment (VAAFT) is a new minimally invasive technique for treating complex anal fistula (CAF). This study aimed to compare the efficacy and safety of VAAFT with fistulotomy plus seton (FPS) for treatment of CAF. Materials and methods: We included 148 patients with CAF receiving surgical treatment at our hospital between January 2017 and December 2018. Propensity score matching (PSM) analysis was conducted with patients’ baseline characteristics, and surgical outcomes were compared between the matched groups. Logistic analysis was performed to identify the risk factors for fistula recurrence after VAAFT. Results: Among the study population, 68 and 80 patients underwent VAAFT and FPS, respectively. After PSM, 64 matched pairs of patients were created with no significant differences in baseline characteristics. Compared with FPS, VAAFT had greater efficiency of locating internal openings (90.6% vs. 100%), less intraoperative blood loss (26 ± 15 vs. 12 ± 5 mL), lower incidence of postoperative bleeding (10.9% vs. 1.5%), shorter postoperative hospital stay (6.8 ± 5.1 vs. 5.0 ± 3.3 days), reduced postoperative pain, and decreased wound secretion (all P < 0.05). VAAFT showed a significantly lower Wexner incontinence score than FPS (0.9 ± 1.7 vs. 1.9 ± 2.6, P = 0.003) at 3 months postoperatively, but no significant difference in the healing rate was observed either at 3-month or 1-year (P = 1.000) follow-up. A total of 12 patients (17.6%) developed fistula recurrence after VAAFT, and logistic analysis revealed that multiple fistula tracts, prolonged operating time and severe postoperative wound secretion were independent risk factors (odds risk = 2.18, 3.25 and 3.04, respectively, all adjusted P < 0.05). Conclusion: Compared with FPS, VAAFT offers some advantages for treatment of CAF, including minimal damage, less pain, rapid recovery, fewer complications and better sphincter preservation.
1. Introduction
recurrent, or has multiple tracts [3]. Management of complex anal fistula (CAF) has always been a difficult and frustrating challenge for clinicians. Fistulotomy plus seton (FPS) as a traditional surgical procedure, has been used for centuries and is still common today; but the high risk of recurrence and incontinence remains a distressing problem [4,5]. Over the last decade, various minimally invasive techniques have been developed for treating CAF, including fibrin glue, fistula plug, fistula laser closure (FiLaC), and ligation of intersphincteric fistula tract
Anal fistula is a pathological connection between the anorectal canal and perianal skin, which results in persistent purulent drainage or intermittent perianal swelling and tenderness followed by spontaneous discharge, with a prevalence rate of 86 cases per 1 million population [1,2]. It is termed complex when the fistula involves greater than 30%–50% of the sphincter mechanism, is anterior in a female, is
∗
Corresponding author. Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, 450 Tengyue Road, Shanghai, 200090, China. Corresponding author. Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China. E-mail addresses: [email protected] (L. Yin), [email protected] (H. Jiang). 1 Co-first authors: Hailong Liu and Xuan Tang. ∗∗
https://doi.org/10.1016/j.ijsu.2020.01.137 Received 15 July 2019; Received in revised form 20 January 2020; Accepted 23 January 2020 Available online 01 February 2020 1743-9191/ © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
International Journal of Surgery 75 (2020) 99–104
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correctly locate the internal opening and possible secondary tracts or abscess cavities. The fistuloscope was introduced from the external opening with 1% glycine-mannitol solution running, and was then advanced gently until reaching the end of the fistula tract. In most cases, the fistuloscope exited through the internal opening. Sometimes the internal opening was narrow and its location could only be identified by observing the fistuloscope light behind the rectal mucosa. Two or three sutures were placed at the margin of the internal opening to isolate it but not to close it. The purpose of the treatment phase was complete destruction of the fistula tracts and closure of the internal opening. The obturator in the fistuloscope was replaced by an electrode, which fulgurated the tract wall from inside out under continuous direct vision. Care was taken not to overlook any secondary tracts or abscess cavities. An endobrush or forceps was inserted instead of the electrode to remove the necrotic material. Continuous injection of irrigation solution ensured that all exfoliated necrotic material was washed into the rectum through the internal opening. The internal opening was completely closed using absorbable sutures. Finally, a thin rubber pipe was placed in the fistula tract from the external opening to guarantee adequate drainage. The pipe was removed at 3–5 days postoperatively without special status. Patients in both groups were administered ciprofloxacin and metronidazole as perioperative antibiotics for 3 days. Postoperative analgesics were not routinely provided unless necessary. If no abnormalities were found, the patient began a fluid diet 6 h after surgery and gradually increased to a semifluid diet. Avoidance of dry and hard stools contributed to the healing of the surgical incision. A warm sitz bath after defecation was recommended to each patient.
(LIFT) [6]. However, the outcomes are still not fully satisfactory, with a widely reported healing rate from 14% to 83% [7–10]. It has been suggested that omission of the internal opening or secondary tracts in surgery is the major factor in fistula recurrence [11]. With the advance of endoscopic techniques, a novel sphinctersparing technique, video-assisted anal fistula treatment (VAAFT), has been recently introduced [12]. The major advantage of VAAFT is that it allows direct visualization of the fistula from inside, so that all internal openings and extensions can be identified and eradicated. An increasing number of studies have been published describing this procedure, with encouraging results [13–16]. However, so far, no study has directly compared the efficacy and safety of VAAFT with FPS in the treatment of CAF. Here, we presented our preliminary comparison of VAAFT with FPS in an effort to provide a basis for the selection of surgical approach. To minimize the possible biases and confounding factors, propensity score-matching (PSM) analysis was applied in this study. 2. Materials and methods 2.1. Study population This study was a retrospective analysis of prospectively collected data of 148 consecutive patients with CAF who received surgical treatment at our hospital. 80 CAF patients undergoing FPS between January and December 2017 served as the control group, and 68 CAF patients undergoing VAAFT between January and December 2018 were designated as the study group. An anal fistula was termed complex when the tract crossed more than 30%–50% of the external sphincter (high trans-, supra- or extra-sphincteric fistula), was located anteriorly in women, was recurrent, or had multiple tracts [3]. All patients were evaluated with a series of standardized clinical tests to determine the fistula tracts and primary openings, including digital rectal examination, pelvic ultrasound and magnetic resonance imaging (MRI). A colonoscopy was also performed to exclude cases of inflammatory bowel disease. Any active inflammation or abscess was ruled out before surgery. Written consent was obtained from all patients and their information was stored in the hospital database and used for research. The study protocol was conducted in accordance with the Declaration of Helsinki [17], and approved by the Research Ethics Committee of our hospital (LL-2019-SCI-002). The trial was registered at Chinese Clinical Trial Registry (ChiCTR1900024492), and the work has been reported in line with the STROCSS criteria [18].
2.3. Data collection and follow-up Clinical data were abstracted from patients' medical records, including demographics (e.g., age, sex and diabetes history), fistula characteristics (e.g., fistula surgery history, tracts, location and type), operative variables (e.g., location of internal opening, operating time and intraoperative blood loss) and postoperative outcomes (e.g. postoperative pain, wound secretion, complications and hospital stay). The fistula tracts were identified by imaging examination and confirmed by surgery. Anal fistula was categorized into low or high type depending on whether the tract crossed the upper part of the deep external sphincter [1]. Anal fistula was also defined as inter-, trans‐, supra‐ or extra‐sphincteric according to the Park's Classification System [1]. Intraoperative blood loss was evaluated by measuring the weight change of surgical swabs and the volume in the suction reservoir. The severity of postoperative pain was assessed by a visual analog scale (VAS) score 0 (no pain) to 10 (worst pain) at 1 and 3 days after operation [19]. Postoperative wound secretion was measured on postoperative days 1 and 3 using a self-administered scale, scored 1 (≤1 piece of gauze was soaked within 12 h), 2 (2 or 3 pieces of gauze were soaked within 12 h) and 3 (> 3 pieces of gauze were soaked within 12 h). Each piece of gauze was about 5 × 5 cm2 in area and 0.4 cm thick. Postoperative complications mainly included urinary retention and bleeding that required hemostasis. All patients received two follow-up visits. The first follow-up was scheduled 3 months after surgery at the outpatient clinic. The treatment was considered a failure if the symptoms of anal fistula persisted or there was recurrence during follow-up, and the severity of incontinence was assessed using the Wexner score questionnaire [20]. The second assessment was taken in January 2020 by telephone to investigate the fistula recurrence rate within 1 year after surgery, and the patients reporting recurrence were asked to return to our outpatient clinic for further evaluation.
2.2. Surgical procedures and postoperative care All operations were performed by the same experienced surgical team using standardized techniques. All patients underwent mechanical bowel preparation before surgery. A saddle block (spinal anesthesia) was given, and the patient was positioned in a lithotomy or prone jackknife position depending on the location of the fistula. In the FPS, the internal opening was identified by digital rectal examination and injection of methylene blue through the external opening. A probe was then gently inserted and passed between the two openings. The portion of the fistula tract outside the sphincter complex and any lateral secondary tracts were laid open over the probe, and the granulation tissue was removed using a curette. Hemostasis was achieved. For the portion of the tract inside the sphincter complex, a rubber band seton was passed through and tied over the perianal skin to effect drainage of perianal sepsis. Multiple setons might be inserted at one time if multiple fistula tracts were present. The tightening of the seton was not started until the suppurative process was complete. The tightening was repeated every week until the sphincter muscle was cut through. The equipment required for VAAFT was manufactured by Karl Storz GmbH (Tuttlingen, Germany), including a fistuloscope, obturator, unipolar electrode, endobrush, and forceps. VAAFT comprised diagnostic and treatment phases. The aim of the diagnostic phase was to
2.4. Statistical analysis All statistical analyses were performed with SPSS version 22.0 (IBM, 100
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Armonk, NY, USA) and Empower Stats software (www.empowerstats. com, X&Y solutions, Inc. Boston, MA, USA). In order to reduce the bias from confounding variables, PSM analysis was performed to adjust the baseline differences in this study. PSs were calculated for each patient by logistic regression model according to the following covariates: age, sex, fistula history, fistula tract, fistula location and Park's type. VAAFT patients were matched to FPS patients on the basis of their PSs using nearest-neighbor matching (1:1) with a caliper of 0.20 of the standard deviation of the logit of the PS. After the matching process, both groups were compared according to the baseline characteristics in order to reevaluate the comparability of both groups. Finally, the matched groups were well balanced in terms of the different variables of interest of this study [21]. Continuous variables were expressed as mean ± standard deviation, and category variables were presented as number and percentage. Comparison between groups was made using Student's t-test and χ2 or Fisher's exact test. Logistic regression analysis was performed to control for confounding factors and identify independent risk factors for fistula recurrence after VAAFT. Risk factors with a univariate association of P < 0.1 were eligible for inclusion in the multivariate logistic regression model. The results were presented as odds risk (OR) and 95% confidence interval (CI). P < 0.05 was considered statistically significant.
Table 2 Comparison of surgical outcomes between the propensity-matched VAAFT and FPS groups. Variable
VAAFT (n = 64)
Detection of internal opening No 0 (0%) Yes 64 (100%) Operating time (min) 54 ± 34 Intraoperative blood loss (mL) 12 ± 5 Postoperative pain (1 day) 2.9 ± 1.4 Postoperative pain (3 days) 1.5 ± 1.2 Postoperative wound secretion (1 day) 1 40 (62.5%) 2 18 (28.1%) 3 6 (9.4%) Postoperative wound secretion (3 days) 1 54 (84.4%) 2 10 (15.6%) 3 0 (0%) Postoperative urinary retention No 63 (98.4%) Yes 1 (1.6%) Postoperative bleeding No 63 (98.5%) Yes 1 (1.5%) Postoperative hospital stay (day) 5.0 ± 3.3 Curative effect (3 months) Healing 54 (84.4%) Recurrence 10 (15.6%) Curative effect (1 year) Healing 54 (84.4%) Recurrence 10 (15.6%) Wexner score (3 months) 0.9 ± 1.7
3. Results 3.1. Baseline characteristics of the study population A total of 148 patients with CAF were enrolled in this study, and the baseline characteristics are summarized in Table 1. There were 115 (77.7%) men and 33 (22.3%) women, with a median age of 50 years (range 20–86 years). Of these, 68 (45.9%) and 80 (54.1%) patients were treated by VAAFT and FPS, respectively. There were no significant differences between the two groups in age (P = 0.510), previous fistula surgery (P = 0.410), fistula tract (P = 0.715), fistula location (P = 0.582) and Park's type (P = 0.231); however, the male/female ratio was higher in the VAAFT group (P = 0.048). PSM was subsequently performed to balance the difference between the two groups. After matching, a total of 64 patient pairs (1:1) were extracted, with no significant differences in baseline characteristics between the patients undergoing either VAAFT or FPS (all P > 0.05).
FPS (n = 64)
P value
6 (9.4%) 58 (90.6%) 46 ± 28 26 ± 15 4.4 ± 1.5 2.8 ± 1.4
0.028 0.058 < 0.001 < 0.001 < 0.001
10 (15.6%) 38 (59.4%) 16 (25.0%)
< 0.001
40 (62.5%) 19 (29.7%) 5 (7.8%)
0.005
64 (100%) 0 (0%)
1.000
56 (89.1%) 8 (10.9%) 6.8 ± 5.1
0.033 0.009
55 (85.9%) 9 (14.1%)
1.000
53 (82.8%) 11 (17.2%) 1.9 ± 2.6
1.000 0.003
VAAFT, video-assisted anal fistula treatment. FPS, fistulectomy plus seton.
3.2. Comparison of surgical outcomes between propensity-matched groups Operative data and postoperative outcomes of the propensity-matched cohort are presented in Table 2. Compared with FPS, VAAFT had a higher efficiency of locating internal opening (90.6% vs. 100%, P = 0.028), less intraoperative blood loss (26 ± 15 vs. 12 ± 5 mL, P < 0.001), lower incidence of postoperative bleeding (10.9% vs. 1.5%, P = 0.033) and shorter postoperative hospital stay (6.8 ± 5.1 vs. 5.0 ± 3.3 days, P = 0.009). We also performed VAS pain and
Table 1 Comparison of baseline characteristics between patients undergoing VAAFT and FPS. Variable
Age (year) < 50 ≥50 Sex Male Female Previous fistula surgery No Yes Fistula tract Single Multiple Fistula location Low type High type Park's type Inter-sphincteric Trans-sphincteric Supra-sphincteric Extra-sphincteric
Overall cohort
Propensity-matched cohort
VAAFT (n = 68)
FPS (n = 80)
P value
VAAFT (n = 64)
FPS (n = 64)
P value
36 (52.9%) 32 (47.1%)
37 (46.3%) 43 (53.7%)
0.510
35 (54.7%) 29 (45.3%)
34 (53.1%) 30 (46.9%)
1.000
58 (85.3%) 10 (14.7%)
57 (71.3%) 23 (28.7%)
0.048
54 (84.4%) 10 (15.6%)
52 (81.2%) 12 (18.8%)
0.815
32 (47.1%) 36 (52.9%)
44 (55.0%) 36 (45.0%)
0.410
31 (48.4%) 33 (51.6%)
32 (50.0%) 32 (50.0%)
1.000
48 (70.6%) 20 (29.4%)
59 (73.7%) 21 (26.3%)
0.715
47 (73.4%) 17 (26.6%)
20 (31.2%) 44 (68.8%)
1.000
17 (25.0%) 51 (75.0%)
24 (30.0%) 56 (70.0%)
0.582
17 (26.6%) 47 (73.4%)
20 (31.2%) 44 (68.8%)
0.697
11 (16.2%) 39 (57.4%) 12 (17.6%) 6 (8.8%)
20 (25.0%) 42 (52.5%) 16 (20.0%) 2 (2.5%)
0.231
11 (17.2%) 38 (59.3%) 12 (18.8%) 3 (4.7%)
17 (26.6%) 32 (50.0%) 13 (20.3%) 2 (3.1%)
0.576
VAAFT, video-assisted anal fistula treatment. FPS, fistulectomy plus seton. 101
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4. Discussion
wound secretion assessments on postoperative days 1 and 3, respectively, and VAAFT showed significantly reduced postoperative pain (both P < 0.001) and decreased wound secretion (P < 0.001 and P = 0.005, respectively). Nine (14.1%) patients in the FPS group and one (1.6%) in the VAAFT group required analgesics on postoperative day 1. No significant differences were found in operating time (P = 0.058) or incidence of postoperative urinary retention (P = 1.000). The first follow-up was performed at 3 months after surgery, and fistula recurrence was observed in 10 (15.6%) and nine (14.1%) patients undergoing VAAFT and FPS, respectively, with no significant difference (P = 1.000). However, the VAAFT group experienced less postoperative incontinence, with a significantly lower Wexner score than the FPS group had (0.9 ± 1.7 vs. 1.9 ± 2.6, P = 0.003). The second follow-up was to compare the fistula recurrence rate within 1 year after surgery, and no significant difference was found between the groups (15.6% vs. 17.2%, P = 1.000), as at first follow-up.
CAF is a common and often frustrating anorectal disease, leading to impaired quality of life and work performance [2]. Unfortunately, the treatment of this condition is always complicated and technically challenging. The main principles of management include: identification of the tracts and internal opening, eradication of sepsis, and preservation of sphincter function [1]. FPS has been commonly used to treat CAF for hundreds of years. The function of the seton is to provide drainage, induce chronic fibrosis, and cut the fistulous tract with preservation of the sphincter [22]. Compared with fistulotomy alone, FPS significantly reduces the risk of postoperative incontinence and anus deformity [23]. However, due to the blindness of the probe pass, the secondary tracts and internal opening can probably be omitted or mistaken, thus resulting in fistula recurrence. Additionally, a grooved scar may be left after seton insertion, causing incontinence and an anal foreign body sensation. In recent years, the development of minimally invasive techniques has brought new insights for the treatment of CAF [6]. Fibrin glue and fistula plug are both simple and repeatable methods, but the postoperative recurrence rate reached > 50% [7,8]. FiLaC and LIFT are two other promising sphincter-sparing techniques, with a reported healing rate of 71%–83% [9,10]. However, like FPS, they are essentially blind procedures, and the outcomes depend more on surgeons’ experience at the time of surgery. Hence, how to minimize failure while maintaining continence has always been an urgent task for colorectal surgeons. In 2011, Meinero and Mori [12] first described VAAFT, which was presented as both a diagnostic and therapeutic tool. The introduction of VAAFT has dramatically changed the treatment strategy for CAF. Methylene blue staining and probe were the classical methods for fistula detection, but with a risk of false detection in CAF. As the fistula tracts were often tortuous and full of secretions, it was difficult to obtain enough pressure to burst from the external to internal opening [24]. By contrast, with the visualization and continuous injection of irrigation solution, VAAFT allowed detection of possible fistula branches. Many studies have shown the high accuracy and effectiveness of VAAFT in locating internal openings [12–14,25]. In the present study, the internal opening was identified in all patients using VAAFT, which was a significant advantage over methylene blue staining or probe. In addition, the unipolar electrode and endobrush eradicated sepsis under direct vision, which avoided blind probing and residue, and reduced damage to the sphincter complex. Using PSM analysis, our data showed that, compared with FPS, VAAFT offered significant advantages in reduced surgical trauma, less bleeding, decreased pain, shorter hospital stay and faster recovery. Furthermore, the follow-up results revealed that although the two surgical procedures achieved similar healing rates both at 3‐month and 1‐year visits, VAAFT provided better preservation of sphincter function than FPS did, with a significantly lower Wexner incontinence score. According to previous studies, the recurrence rate after VAAFT was reported to be 7.5%–33.3% [15,16,26,27]. A comparable result was observed in our study, 12 of 68 (17.6%) patients undergoing VAAFT suffered fistula recurrence during follow-up. An interesting point was that the fistula recurrence rates within 3 months and 1 year after VAAFT were the same, with no more recurrence between the interval. From our experience, we suggest that 3 months after VAAFT is an appropriate time point for follow-up. We further performed a risk analysis and found that operating time was significantly correlated with fistula recurrence after VAAFT. Previous studies have indicated that fistula irrigation under pressure might cause the spread of infected granulation tissue into normal tissue [28]. The prolonged operating time increases the risk of infection spreading, resulting in delayed healing, or recurrence. Severe wound secretion on postoperative day 3 was another independent risk factor, suggesting the importance of postoperative drainage management [27]. Moreover, our results showed that although VAAFT provides direct visualization of the fistula tracts, which
3.3. Recurrence-associated factors after VAAFT Of the 68 patients undergoing VAAFT, 12 (17.6%) developed fistula recurrence within 3 months after surgery. The second follow-up showed that the fistula recurrence rate (17.6%) at 1 year postoperatively was the same as at the first follow-up, with no more recurrence observed between 3 months and 1 year after surgery. Univariate analysis revealed that fistula tract (P = 0.004), Park's type (P = 0.010), operating time (P = 0.004) and wound secretion on postoperative day 3 (P = 0.008) might be associated with fistula recurrence after VAAFT. Further multivariate logistic analysis identified that multiple fistula tracts and operating time ≥60 min were independent risk factors, with an OR of 2.18 (95% CI: 1.15–11.91, adjusted P = 0.028) and 3.25 (95% CI: 1.26–15.31, adjusted P = 0.021), respectively. Wound secretion on postoperative day 3 was another significant predictor of VAAFT outcome. Compared with score 0, score 1 or 2 showed a 3.04-fold (95% CI: 1.08–19.35, adjusted P = 0.040) increased risk of fistula recurrence (see Table 3).
Table 3 Logistic analysis of risk factors for fistula recurrence after VAAFT. Variable
Univariate
Multivariate
OR (95% CI)
P value
2.67 (0.72–9.90)
0.143
0.48 (0.05–4.15)
0.501
3.22 (0.79–13.17)
0.103
7.33 (1.88–28.56)
0.004
4.40 (0.52–36.94)
0.172
5.73 (1.53–21.52)
7.31 (1.89–28.24) Postoperative wound secretion (3 days) 1 vs. 2-3 7.29 (1.68–31.69)
Age (year) < 50 vs. ≥50 Sex Male vs. Female Previous fistula surgery No vs. Yes Fistula tract Single vs. Multiple Fistula location Low vs. High Park's type Inter/trans- vs. Supra/ extra-sphincteric Operating time (min) < 60 vs. ≥60
OR (95% CI)
P value
2.18 (1.15–11.91)
0.028
0.010
1.62 (0.81–11.40)
0.182
0.004
3.25 (1.26–15.31)
0.021
0.008
3.04 (1.08–19.35)
0.040
VAAFT, video-assisted anal fistula treatment. OR, odds risk. CI, confidence interval. 102
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Guarantor
contributed significantly to the detection and destruction of secondary tracts, multiple fistula tracts remain to be a major risk factor of recurrence after VAAFT. Non-identification of internal openings is also considered to be an important predictor of fistula recurrence after surgery [29], but it was not included in our analysis as all internal openings in the VAAFT group were successfully identified. Other potential risk factors reported in the literature, such as male sex [16] and previous fistula surgery [30], did not prove significant in this study. The reasons for these differences remain to be determined and may contribute to better management and improved prognosis. Based on previous reports and our experience, some points should be considered when performing VAAFT. Firstly, as the fistuloscope is a rigid scope 4 mm in diameter and 18 cm in length, it would be hard to pass through or deal with the lesion when the fistula tracts are too narrow or crooked. Our suggestion is adding a secondary minimal incision to reposition the fistuloscope, and being gentle when operating the fistuloscope, and a rotatory or vertical movement might be helpful. A similar view was taken by Chivate et al. [28]. Secondly, closure of the internal opening is a critical step in VAAFT. Although many methods have been developed, mainly including stapling, mucosal advancement flap and suturing, there is currently limited evidence to suggest which is most favorable [31]. Mendes et al. [32] suggested that in cases of severe fibrosis, stapling or suturing might not be easy to achieve complete closure or might lead to early dehiscence, and mucosal advancement flap would be a better choice. Thirdly, adequate drainage is another critical step in the cure of CAF. In this study, after closing the internal opening, we placed a thin rubber pipe in the fistula tract to facilitate postoperative drainage. We found that it was not necessary to inject fibrin glue after closure of the internal opening, as it might impair drainage of the tract. Seow-En et al. [27] also indicated that fibrin glue injection did not assure complete internal opening closure. Some limitations of this study should be noted. First, as a retrospective study, selection bias was inevitable, although we attempted to minimize the impact by performing PSM analysis. Second, our data were obtained from a single center and might not reflect the experiences of other institutions. Last, other potential risk factors not included in the study could not be examined for confounding effects. Hence, further validation of our findings is warranted.
Hailong Liu and Huihong Jiang. Availability of data The authors confirm that the data supporting the findings of this study are available within the article. Provenance and peer review Not commissioned, externally peer-reviewed. CRediT authorship contribution statement Hailong Liu: Conceptualization, Methodology, Writing - original draft. Xuan Tang: Methodology, Formal analysis, Data curation. Yi Chang: Investigation, Software. Ajian Li: Investigation, Software. Zhen Li: Investigation, Resources. Yihua Xiao: Investigation, Resources. Yong Zhang: Investigation, Resources. Zhihui Pan: Investigation, Resources. Liang Lv: Investigation, Resources. Moubin Lin: Investigation, Resources. Lu Yin: Conceptualization, Data curation, Project administration. Huihong Jiang: Conceptualization, Writing review & editing, Supervision. Declaration of competing interest The authors have no conflicts of interest to declare. Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.ijsu.2020.01.137. References [1] J.A. Simpson, A. Banerjea, J.H. Scholefield, Management of anal fistula, BMJ 345 (2012) e6705, , https://doi.org/10.1136/bmj.e6705. [2] P. Sainio, Fistula-in-ano in a defined population. Incidence and epidemiological aspects, Ann. Chir. Gynaecol. 73 (1984) 219–224 PubMed PMID: 6508203. [3] M.H. Whiteford, J. Kilkenny 3rd, N. Hyman, W.D. Buie, J. Cohen, C. Orsay, G. Dunn, W.B. Perry, C.N. Ellis, J. Rakinic, S. Gregorcyk, P. Shellito, R. Nelson, J.J. Tjandra, G. Newstead, Practice parameters for the treatment of perianal abscess and fistula-in-ano (revised), Dis. Colon Rectum 48 (2005) 1337–1342, https://doi. org/10.1007/s10350-005-0055-3. [4] J. Garcia-Aguilar, C. Belmonte, D.W. Wong, S.M. Goldberg, R.D. Madoff, Cutting seton versus two-stage seton fistulotomy in the surgical management of high anal fistula, Br. J. Surg. 85 (1998) 243–245, https://doi.org/10.1046/j.1365-2168.1998. 02877.x. [5] V. Durgun, A. Perek, M. Kapan, S. Kapan, S. Perek, Partial fistulotomy and modified cutting seton procedure in the treatment of high extrasphincteric perianal fistulae, Dig. Surg. 19 (2002) 56–58, https://doi.org/10.1159/000052007. [6] E. Limura, P. Giordano, Modern management of anal fistula, World J. Gastroenterol. 21 (2015) 12–20, https://doi.org/10.3748/wjg.v21.i1.12. [7] G.N. Buchanan, C.I. Bartram, R.K. Phillips, S.W. Gould, S. Halligan, T.A. Rockall, P. Sibbons, R.G. Cohen, Efficacy of fibrin sealant in the management of complex anal fistula: a prospective trial, Dis. Colon Rectum 46 (2003) 1167–1174, https:// doi.org/10.1097/01.Dcr.0000084408.85802.A2. [8] D.K. Thekkinkattil, I. Botterill, N.S. Ambrose, L. Lundby, P.M. Sagar, S. Buntzen, P.J. Finan, Efficacy of the anal fistula plug in complex anorectal fistulae, Colorectal Dis. 11 (2009) 584–587, https://doi.org/10.1111/j.1463-1318.2008.01627.x. [9] P. Giamundo, M. Geraci, L. Tibaldi, M. Valente, Closure of fistula-in-ano with laser– FiLaC: an effective novel sphincter-saving procedure for complex disease, Colorectal Dis. 16 (2014) 110–115, https://doi.org/10.1111/codi.12440. [10] P. Sileri, L. Franceschilli, G.P. Angelucci, S. D'Ugo, G. Milito, F. Cadeddu, I. Selvaggio, S. Lazzaro, A.L. Gaspari, Ligation of the intersphincteric fistula tract (LIFT) to treat anal fistula: early results from a prospective observational study, Tech. Coloproctol. 15 (2011) 413–416, https://doi.org/10.1007/s10151-0110779-0. [11] Y.P. Sangwan, L. Rosen, R.D. Riether, J.J. Stasik, J.A. Sheets, I.T. Khubchandani, Is simple fistula-in-ano simple? Dis. Colon Rectum 37 (1994) 885–889 PubMed PMID: 8076487. [12] P. Meinero, L. Mori, Video-assisted anal fistula treatment (VAAFT): a novel sphincter-saving procedure for treating complex anal fistulas, Tech. Coloproctol. 15 (2011) 417–422, https://doi.org/10.1007/s10151-011-0769-2.
5. Conclusions Our study suggests that, compared to FPS, VAAFT possesses significant advantages for treatment of CAF, including minimal damage, less pain, rapid recovery, fewer complications and better sphincter preservation. Moreover, fistula recurrence after VAAFT may be related to multiple fistula tracts, prolonged operating time and severe postoperative wound secretion. With improvement of this technique and surgical experience, a better result is expected. Ethical approval This study has been approved by the Research Ethics Committee of Yangpu Hospital, Tongji University School of Medicine (LL-2019-SCI002). Sources of funding This study was supported by the projects of Shanghai Municipal Commission of Health and Family Planning (201740146) and Wu Jieping Medical Foundation (320.2710.1839). Research registration unique identifying number (UIN) The trial was registered at Chinese Clinical Trial Registry (ChiCTR1900024492). http://www.chictr.org.cn/edit.aspx?pid= 41115&htm=4. 103
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[24] S. Eisenhammer, The final evaluation and classification of the surgical treatment of the primary anorectal cryptoglandular intermuscular (intersphincteric) fistulous abscess and fistula, Dis. Colon Rectum 21 (1978) 237–254 1978, PubMed PMID: 657933. [25] G. Kochhar, S. Saha, M. Andley, A. Kumar, G. Saurabh, R. Pusuluri, V. Bhise, A. Kumar, Video-assisted anal fistula treatment, J. Soc. Laparoendosc. Surg. 18 (2014), https://doi.org/10.4293/jsls.2014.00127 e2014.00127. [26] A. Pini Prato, C. Zanaboni, M. Mosconi, C. Mazzola, L. Muller, P.C. Meinero, M.G. Faticato, L. Leonelli, G. Montobbio, N. Disma, G. Mattioli, Preliminary results of video-assisted anal fistula treatment (VAAFT) in children, Tech. Coloproctol. 20 (2016) 279–285, https://doi.org/10.1007/s10151-016-1447-1. [27] I. Seow-En, F. Seow-Choen, P.K. Koh, An experience with video-assisted anal fistula treatment (VAAFT) with new insights into the treatment of anal fistulae, Tech. Coloproctol. 20 (2016) 389–393, https://doi.org/10.1007/s10151-016-1450-6. [28] S.D. Chivate, Comment on Meinero and Mori: video-assisted anal fistula treatment (VAAFT): a novel sphincter-saving procedure to repair complex anal fistulas, Tech. Coloproctol. 16 (2012) 465–466, https://doi.org/10.1007/s10151-012-0873-y. [29] J. Jordan, J.V. Roig, J. Garcia-Armengol, E. Garcia-Granero, A. Solana, S. Lledo, Risk factors for recurrence and incontinence after anal fistula surgery, Colorectal Dis. 12 (2010) 254–260, https://doi.org/10.1111/j.1463-1318.2009.01806.x. [30] J. Garcia-Aguilar, C. Belmonte, W.D. Wong, S.M. Goldberg, R.D. Madoff, Anal fistula surgery. Factors associated with recurrence and incontinence, Dis. Colon Rectum 39 (1996) 723–729 PubMed PMID: 8674361. [31] S.O. Adegbola, K. Sahnan, G. Pellino, P.J. Tozer, A. Hart, R.K.S. Phillips, J. Warusavitarne, O.D. Faiz, Short-term efficacy and safety of three novel sphinctersparing techniques for anal fistulae: a systematic review, Tech. Coloproctol. 21 (2017) 775–782, https://doi.org/10.1007/s10151-017-1699-4. [32] C.R. Mendes, L.S. Ferreira, R.A. Sapucaia, M.A. Lima, S.E. Araujo, Video-assisted anal fistula treatment: technical considerations and preliminary results of the first Brazilian experience, ABCD. Arq. Bras. Cir. Dig. (São Paulo) 27 (2014) 7–81, https://doi.org/10.1590/S0102-67202014000100018.
[13] P.K. Chowbey, R. Khullar, A. Sharma, V. Soni, K. Najma, M. Baijal, Minimally invasive anal fistula treatment (MAFT)-An appraisal of early results in 416 patients, Indian J. Surg. 77 (2015) 716–721, https://doi.org/10.1007/s12262-013-0977-2. [14] H.H. Jiang, H.L. Liu, Z. Li, Y.H. Xiao, A.J. Li, Y. Chang, Y. Zhang, L. Lv, M.B. Lin, Video-assisted anal fistula treatment (VAAFT) for complex anal fistula: a preliminary evaluation in China, Med. Sci. Mon. Int. Med. J. Exp. Clin. Res. 23 (2017) 2065–2071, https://doi.org/10.12659/msm.904055. [15] M. Zarin, M.I. Khan, M. Ahmad, M. Ibrahim, M.A. Khan, VAAFT: video assisted anal fistula treatment; bringing revolution in fistula treatment, Pakistan J. Med. Sci. 31 (2015) 1233–1235, https://doi.org/10.12669/pjms.315.6836. [16] S.H. Emile, H. Elfeki, M. Shalaby, A. Sakr, A Systematic review and meta-analysis of the efficacy and safety of video-assisted anal fistula treatment (VAAFT), Surg. Endosc. 32 (2018) 2084–2093, https://doi.org/10.1007/s00464-017-5905-2. [17] General Assembly of the World Medical Association, World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects, J. Am. Coll. Dent. 81 (2014) 14–18 PubMed PMID: 25951678. [18] R. Agha, A. Abdall-Razak, E. Crossley, N. Dowlut, C. Iosifidis, G. Mathew, For the STROCSS Group, STROCSS 2019 Guideline: strengthening the reporting of cohort studies in surgery, Int. J. Surg. 72 (2019) 156–165, https://doi.org/10.1016/j.ijsu. 2019.11.002. [19] P.L. Ritter, V.M. Gonzalez, D.D. Laurent, K.R. Lorig, Measurement of pain using the visual numeric scale, J. Rheumatol. 33 (2006) 574–580 2006; 33(3): 574-580, PubMed PMID: 16511926. [20] J.M. Jorge, S.D. Wexner, Etiology and management of fecal incontinence, Dis. Colon Rectum 36 (1993) 77–97 PubMed PMID: 8416784. [21] R.B. D'Agostino Jr., Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group, Stat. Med. 17 (1998) 2265–2281 PubMed PMID: 9802183. [22] A. Theerapol, B.Y. So, S.S. Ngoi, Routine use of setons for the treatment of anal fistulae, Singap. Med. J. 43 (2002) 305–307 PubMed PMID: 12380728. [23] A. Cariati, Fistulotomy or seton in anal fistula: a decisional algorithm, Updates Surg. 65 (2013) 201–205, https://doi.org/10.1007/s13304-013-0216-1.
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International Journal of Surgery journal homepage: www.elsevier.com/locate/ijsu
Comparative Study
Comparison of surgical outcomes between video-assisted anal fistula treatment and fistulotomy plus seton for complex anal fistula: A propensity score matching analysis - Retrospective cohort study
T
Hailong Liua,1, Xuan Tanga,b,1, Yi Changa, Ajian Lia, Zhen Lia, Yihua Xiaoa, Yong Zhanga, Zhihui Pana, Liang Lva, Moubin Lina,b, Lu Yinc,∗∗, Huihong Jianga,b,∗ a b c
Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai, China Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
A R T I C LE I N FO
A B S T R A C T
Keywords: Complex anal fistula VAAFT Seton Surgical outcome Recurrence
Background: Video-assisted anal fistula treatment (VAAFT) is a new minimally invasive technique for treating complex anal fistula (CAF). This study aimed to compare the efficacy and safety of VAAFT with fistulotomy plus seton (FPS) for treatment of CAF. Materials and methods: We included 148 patients with CAF receiving surgical treatment at our hospital between January 2017 and December 2018. Propensity score matching (PSM) analysis was conducted with patients’ baseline characteristics, and surgical outcomes were compared between the matched groups. Logistic analysis was performed to identify the risk factors for fistula recurrence after VAAFT. Results: Among the study population, 68 and 80 patients underwent VAAFT and FPS, respectively. After PSM, 64 matched pairs of patients were created with no significant differences in baseline characteristics. Compared with FPS, VAAFT had greater efficiency of locating internal openings (90.6% vs. 100%), less intraoperative blood loss (26 ± 15 vs. 12 ± 5 mL), lower incidence of postoperative bleeding (10.9% vs. 1.5%), shorter postoperative hospital stay (6.8 ± 5.1 vs. 5.0 ± 3.3 days), reduced postoperative pain, and decreased wound secretion (all P < 0.05). VAAFT showed a significantly lower Wexner incontinence score than FPS (0.9 ± 1.7 vs. 1.9 ± 2.6, P = 0.003) at 3 months postoperatively, but no significant difference in the healing rate was observed either at 3-month or 1-year (P = 1.000) follow-up. A total of 12 patients (17.6%) developed fistula recurrence after VAAFT, and logistic analysis revealed that multiple fistula tracts, prolonged operating time and severe postoperative wound secretion were independent risk factors (odds risk = 2.18, 3.25 and 3.04, respectively, all adjusted P < 0.05). Conclusion: Compared with FPS, VAAFT offers some advantages for treatment of CAF, including minimal damage, less pain, rapid recovery, fewer complications and better sphincter preservation.
1. Introduction
recurrent, or has multiple tracts [3]. Management of complex anal fistula (CAF) has always been a difficult and frustrating challenge for clinicians. Fistulotomy plus seton (FPS) as a traditional surgical procedure, has been used for centuries and is still common today; but the high risk of recurrence and incontinence remains a distressing problem [4,5]. Over the last decade, various minimally invasive techniques have been developed for treating CAF, including fibrin glue, fistula plug, fistula laser closure (FiLaC), and ligation of intersphincteric fistula tract
Anal fistula is a pathological connection between the anorectal canal and perianal skin, which results in persistent purulent drainage or intermittent perianal swelling and tenderness followed by spontaneous discharge, with a prevalence rate of 86 cases per 1 million population [1,2]. It is termed complex when the fistula involves greater than 30%–50% of the sphincter mechanism, is anterior in a female, is
∗
Corresponding author. Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, 450 Tengyue Road, Shanghai, 200090, China. Corresponding author. Department of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, China. E-mail addresses: [email protected] (L. Yin), [email protected] (H. Jiang). 1 Co-first authors: Hailong Liu and Xuan Tang. ∗∗
https://doi.org/10.1016/j.ijsu.2020.01.137 Received 15 July 2019; Received in revised form 20 January 2020; Accepted 23 January 2020 Available online 01 February 2020 1743-9191/ © 2020 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
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correctly locate the internal opening and possible secondary tracts or abscess cavities. The fistuloscope was introduced from the external opening with 1% glycine-mannitol solution running, and was then advanced gently until reaching the end of the fistula tract. In most cases, the fistuloscope exited through the internal opening. Sometimes the internal opening was narrow and its location could only be identified by observing the fistuloscope light behind the rectal mucosa. Two or three sutures were placed at the margin of the internal opening to isolate it but not to close it. The purpose of the treatment phase was complete destruction of the fistula tracts and closure of the internal opening. The obturator in the fistuloscope was replaced by an electrode, which fulgurated the tract wall from inside out under continuous direct vision. Care was taken not to overlook any secondary tracts or abscess cavities. An endobrush or forceps was inserted instead of the electrode to remove the necrotic material. Continuous injection of irrigation solution ensured that all exfoliated necrotic material was washed into the rectum through the internal opening. The internal opening was completely closed using absorbable sutures. Finally, a thin rubber pipe was placed in the fistula tract from the external opening to guarantee adequate drainage. The pipe was removed at 3–5 days postoperatively without special status. Patients in both groups were administered ciprofloxacin and metronidazole as perioperative antibiotics for 3 days. Postoperative analgesics were not routinely provided unless necessary. If no abnormalities were found, the patient began a fluid diet 6 h after surgery and gradually increased to a semifluid diet. Avoidance of dry and hard stools contributed to the healing of the surgical incision. A warm sitz bath after defecation was recommended to each patient.
(LIFT) [6]. However, the outcomes are still not fully satisfactory, with a widely reported healing rate from 14% to 83% [7–10]. It has been suggested that omission of the internal opening or secondary tracts in surgery is the major factor in fistula recurrence [11]. With the advance of endoscopic techniques, a novel sphinctersparing technique, video-assisted anal fistula treatment (VAAFT), has been recently introduced [12]. The major advantage of VAAFT is that it allows direct visualization of the fistula from inside, so that all internal openings and extensions can be identified and eradicated. An increasing number of studies have been published describing this procedure, with encouraging results [13–16]. However, so far, no study has directly compared the efficacy and safety of VAAFT with FPS in the treatment of CAF. Here, we presented our preliminary comparison of VAAFT with FPS in an effort to provide a basis for the selection of surgical approach. To minimize the possible biases and confounding factors, propensity score-matching (PSM) analysis was applied in this study. 2. Materials and methods 2.1. Study population This study was a retrospective analysis of prospectively collected data of 148 consecutive patients with CAF who received surgical treatment at our hospital. 80 CAF patients undergoing FPS between January and December 2017 served as the control group, and 68 CAF patients undergoing VAAFT between January and December 2018 were designated as the study group. An anal fistula was termed complex when the tract crossed more than 30%–50% of the external sphincter (high trans-, supra- or extra-sphincteric fistula), was located anteriorly in women, was recurrent, or had multiple tracts [3]. All patients were evaluated with a series of standardized clinical tests to determine the fistula tracts and primary openings, including digital rectal examination, pelvic ultrasound and magnetic resonance imaging (MRI). A colonoscopy was also performed to exclude cases of inflammatory bowel disease. Any active inflammation or abscess was ruled out before surgery. Written consent was obtained from all patients and their information was stored in the hospital database and used for research. The study protocol was conducted in accordance with the Declaration of Helsinki [17], and approved by the Research Ethics Committee of our hospital (LL-2019-SCI-002). The trial was registered at Chinese Clinical Trial Registry (ChiCTR1900024492), and the work has been reported in line with the STROCSS criteria [18].
2.3. Data collection and follow-up Clinical data were abstracted from patients' medical records, including demographics (e.g., age, sex and diabetes history), fistula characteristics (e.g., fistula surgery history, tracts, location and type), operative variables (e.g., location of internal opening, operating time and intraoperative blood loss) and postoperative outcomes (e.g. postoperative pain, wound secretion, complications and hospital stay). The fistula tracts were identified by imaging examination and confirmed by surgery. Anal fistula was categorized into low or high type depending on whether the tract crossed the upper part of the deep external sphincter [1]. Anal fistula was also defined as inter-, trans‐, supra‐ or extra‐sphincteric according to the Park's Classification System [1]. Intraoperative blood loss was evaluated by measuring the weight change of surgical swabs and the volume in the suction reservoir. The severity of postoperative pain was assessed by a visual analog scale (VAS) score 0 (no pain) to 10 (worst pain) at 1 and 3 days after operation [19]. Postoperative wound secretion was measured on postoperative days 1 and 3 using a self-administered scale, scored 1 (≤1 piece of gauze was soaked within 12 h), 2 (2 or 3 pieces of gauze were soaked within 12 h) and 3 (> 3 pieces of gauze were soaked within 12 h). Each piece of gauze was about 5 × 5 cm2 in area and 0.4 cm thick. Postoperative complications mainly included urinary retention and bleeding that required hemostasis. All patients received two follow-up visits. The first follow-up was scheduled 3 months after surgery at the outpatient clinic. The treatment was considered a failure if the symptoms of anal fistula persisted or there was recurrence during follow-up, and the severity of incontinence was assessed using the Wexner score questionnaire [20]. The second assessment was taken in January 2020 by telephone to investigate the fistula recurrence rate within 1 year after surgery, and the patients reporting recurrence were asked to return to our outpatient clinic for further evaluation.
2.2. Surgical procedures and postoperative care All operations were performed by the same experienced surgical team using standardized techniques. All patients underwent mechanical bowel preparation before surgery. A saddle block (spinal anesthesia) was given, and the patient was positioned in a lithotomy or prone jackknife position depending on the location of the fistula. In the FPS, the internal opening was identified by digital rectal examination and injection of methylene blue through the external opening. A probe was then gently inserted and passed between the two openings. The portion of the fistula tract outside the sphincter complex and any lateral secondary tracts were laid open over the probe, and the granulation tissue was removed using a curette. Hemostasis was achieved. For the portion of the tract inside the sphincter complex, a rubber band seton was passed through and tied over the perianal skin to effect drainage of perianal sepsis. Multiple setons might be inserted at one time if multiple fistula tracts were present. The tightening of the seton was not started until the suppurative process was complete. The tightening was repeated every week until the sphincter muscle was cut through. The equipment required for VAAFT was manufactured by Karl Storz GmbH (Tuttlingen, Germany), including a fistuloscope, obturator, unipolar electrode, endobrush, and forceps. VAAFT comprised diagnostic and treatment phases. The aim of the diagnostic phase was to
2.4. Statistical analysis All statistical analyses were performed with SPSS version 22.0 (IBM, 100
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Armonk, NY, USA) and Empower Stats software (www.empowerstats. com, X&Y solutions, Inc. Boston, MA, USA). In order to reduce the bias from confounding variables, PSM analysis was performed to adjust the baseline differences in this study. PSs were calculated for each patient by logistic regression model according to the following covariates: age, sex, fistula history, fistula tract, fistula location and Park's type. VAAFT patients were matched to FPS patients on the basis of their PSs using nearest-neighbor matching (1:1) with a caliper of 0.20 of the standard deviation of the logit of the PS. After the matching process, both groups were compared according to the baseline characteristics in order to reevaluate the comparability of both groups. Finally, the matched groups were well balanced in terms of the different variables of interest of this study [21]. Continuous variables were expressed as mean ± standard deviation, and category variables were presented as number and percentage. Comparison between groups was made using Student's t-test and χ2 or Fisher's exact test. Logistic regression analysis was performed to control for confounding factors and identify independent risk factors for fistula recurrence after VAAFT. Risk factors with a univariate association of P < 0.1 were eligible for inclusion in the multivariate logistic regression model. The results were presented as odds risk (OR) and 95% confidence interval (CI). P < 0.05 was considered statistically significant.
Table 2 Comparison of surgical outcomes between the propensity-matched VAAFT and FPS groups. Variable
VAAFT (n = 64)
Detection of internal opening No 0 (0%) Yes 64 (100%) Operating time (min) 54 ± 34 Intraoperative blood loss (mL) 12 ± 5 Postoperative pain (1 day) 2.9 ± 1.4 Postoperative pain (3 days) 1.5 ± 1.2 Postoperative wound secretion (1 day) 1 40 (62.5%) 2 18 (28.1%) 3 6 (9.4%) Postoperative wound secretion (3 days) 1 54 (84.4%) 2 10 (15.6%) 3 0 (0%) Postoperative urinary retention No 63 (98.4%) Yes 1 (1.6%) Postoperative bleeding No 63 (98.5%) Yes 1 (1.5%) Postoperative hospital stay (day) 5.0 ± 3.3 Curative effect (3 months) Healing 54 (84.4%) Recurrence 10 (15.6%) Curative effect (1 year) Healing 54 (84.4%) Recurrence 10 (15.6%) Wexner score (3 months) 0.9 ± 1.7
3. Results 3.1. Baseline characteristics of the study population A total of 148 patients with CAF were enrolled in this study, and the baseline characteristics are summarized in Table 1. There were 115 (77.7%) men and 33 (22.3%) women, with a median age of 50 years (range 20–86 years). Of these, 68 (45.9%) and 80 (54.1%) patients were treated by VAAFT and FPS, respectively. There were no significant differences between the two groups in age (P = 0.510), previous fistula surgery (P = 0.410), fistula tract (P = 0.715), fistula location (P = 0.582) and Park's type (P = 0.231); however, the male/female ratio was higher in the VAAFT group (P = 0.048). PSM was subsequently performed to balance the difference between the two groups. After matching, a total of 64 patient pairs (1:1) were extracted, with no significant differences in baseline characteristics between the patients undergoing either VAAFT or FPS (all P > 0.05).
FPS (n = 64)
P value
6 (9.4%) 58 (90.6%) 46 ± 28 26 ± 15 4.4 ± 1.5 2.8 ± 1.4
0.028 0.058 < 0.001 < 0.001 < 0.001
10 (15.6%) 38 (59.4%) 16 (25.0%)
< 0.001
40 (62.5%) 19 (29.7%) 5 (7.8%)
0.005
64 (100%) 0 (0%)
1.000
56 (89.1%) 8 (10.9%) 6.8 ± 5.1
0.033 0.009
55 (85.9%) 9 (14.1%)
1.000
53 (82.8%) 11 (17.2%) 1.9 ± 2.6
1.000 0.003
VAAFT, video-assisted anal fistula treatment. FPS, fistulectomy plus seton.
3.2. Comparison of surgical outcomes between propensity-matched groups Operative data and postoperative outcomes of the propensity-matched cohort are presented in Table 2. Compared with FPS, VAAFT had a higher efficiency of locating internal opening (90.6% vs. 100%, P = 0.028), less intraoperative blood loss (26 ± 15 vs. 12 ± 5 mL, P < 0.001), lower incidence of postoperative bleeding (10.9% vs. 1.5%, P = 0.033) and shorter postoperative hospital stay (6.8 ± 5.1 vs. 5.0 ± 3.3 days, P = 0.009). We also performed VAS pain and
Table 1 Comparison of baseline characteristics between patients undergoing VAAFT and FPS. Variable
Age (year) < 50 ≥50 Sex Male Female Previous fistula surgery No Yes Fistula tract Single Multiple Fistula location Low type High type Park's type Inter-sphincteric Trans-sphincteric Supra-sphincteric Extra-sphincteric
Overall cohort
Propensity-matched cohort
VAAFT (n = 68)
FPS (n = 80)
P value
VAAFT (n = 64)
FPS (n = 64)
P value
36 (52.9%) 32 (47.1%)
37 (46.3%) 43 (53.7%)
0.510
35 (54.7%) 29 (45.3%)
34 (53.1%) 30 (46.9%)
1.000
58 (85.3%) 10 (14.7%)
57 (71.3%) 23 (28.7%)
0.048
54 (84.4%) 10 (15.6%)
52 (81.2%) 12 (18.8%)
0.815
32 (47.1%) 36 (52.9%)
44 (55.0%) 36 (45.0%)
0.410
31 (48.4%) 33 (51.6%)
32 (50.0%) 32 (50.0%)
1.000
48 (70.6%) 20 (29.4%)
59 (73.7%) 21 (26.3%)
0.715
47 (73.4%) 17 (26.6%)
20 (31.2%) 44 (68.8%)
1.000
17 (25.0%) 51 (75.0%)
24 (30.0%) 56 (70.0%)
0.582
17 (26.6%) 47 (73.4%)
20 (31.2%) 44 (68.8%)
0.697
11 (16.2%) 39 (57.4%) 12 (17.6%) 6 (8.8%)
20 (25.0%) 42 (52.5%) 16 (20.0%) 2 (2.5%)
0.231
11 (17.2%) 38 (59.3%) 12 (18.8%) 3 (4.7%)
17 (26.6%) 32 (50.0%) 13 (20.3%) 2 (3.1%)
0.576
VAAFT, video-assisted anal fistula treatment. FPS, fistulectomy plus seton. 101
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4. Discussion
wound secretion assessments on postoperative days 1 and 3, respectively, and VAAFT showed significantly reduced postoperative pain (both P < 0.001) and decreased wound secretion (P < 0.001 and P = 0.005, respectively). Nine (14.1%) patients in the FPS group and one (1.6%) in the VAAFT group required analgesics on postoperative day 1. No significant differences were found in operating time (P = 0.058) or incidence of postoperative urinary retention (P = 1.000). The first follow-up was performed at 3 months after surgery, and fistula recurrence was observed in 10 (15.6%) and nine (14.1%) patients undergoing VAAFT and FPS, respectively, with no significant difference (P = 1.000). However, the VAAFT group experienced less postoperative incontinence, with a significantly lower Wexner score than the FPS group had (0.9 ± 1.7 vs. 1.9 ± 2.6, P = 0.003). The second follow-up was to compare the fistula recurrence rate within 1 year after surgery, and no significant difference was found between the groups (15.6% vs. 17.2%, P = 1.000), as at first follow-up.
CAF is a common and often frustrating anorectal disease, leading to impaired quality of life and work performance [2]. Unfortunately, the treatment of this condition is always complicated and technically challenging. The main principles of management include: identification of the tracts and internal opening, eradication of sepsis, and preservation of sphincter function [1]. FPS has been commonly used to treat CAF for hundreds of years. The function of the seton is to provide drainage, induce chronic fibrosis, and cut the fistulous tract with preservation of the sphincter [22]. Compared with fistulotomy alone, FPS significantly reduces the risk of postoperative incontinence and anus deformity [23]. However, due to the blindness of the probe pass, the secondary tracts and internal opening can probably be omitted or mistaken, thus resulting in fistula recurrence. Additionally, a grooved scar may be left after seton insertion, causing incontinence and an anal foreign body sensation. In recent years, the development of minimally invasive techniques has brought new insights for the treatment of CAF [6]. Fibrin glue and fistula plug are both simple and repeatable methods, but the postoperative recurrence rate reached > 50% [7,8]. FiLaC and LIFT are two other promising sphincter-sparing techniques, with a reported healing rate of 71%–83% [9,10]. However, like FPS, they are essentially blind procedures, and the outcomes depend more on surgeons’ experience at the time of surgery. Hence, how to minimize failure while maintaining continence has always been an urgent task for colorectal surgeons. In 2011, Meinero and Mori [12] first described VAAFT, which was presented as both a diagnostic and therapeutic tool. The introduction of VAAFT has dramatically changed the treatment strategy for CAF. Methylene blue staining and probe were the classical methods for fistula detection, but with a risk of false detection in CAF. As the fistula tracts were often tortuous and full of secretions, it was difficult to obtain enough pressure to burst from the external to internal opening [24]. By contrast, with the visualization and continuous injection of irrigation solution, VAAFT allowed detection of possible fistula branches. Many studies have shown the high accuracy and effectiveness of VAAFT in locating internal openings [12–14,25]. In the present study, the internal opening was identified in all patients using VAAFT, which was a significant advantage over methylene blue staining or probe. In addition, the unipolar electrode and endobrush eradicated sepsis under direct vision, which avoided blind probing and residue, and reduced damage to the sphincter complex. Using PSM analysis, our data showed that, compared with FPS, VAAFT offered significant advantages in reduced surgical trauma, less bleeding, decreased pain, shorter hospital stay and faster recovery. Furthermore, the follow-up results revealed that although the two surgical procedures achieved similar healing rates both at 3‐month and 1‐year visits, VAAFT provided better preservation of sphincter function than FPS did, with a significantly lower Wexner incontinence score. According to previous studies, the recurrence rate after VAAFT was reported to be 7.5%–33.3% [15,16,26,27]. A comparable result was observed in our study, 12 of 68 (17.6%) patients undergoing VAAFT suffered fistula recurrence during follow-up. An interesting point was that the fistula recurrence rates within 3 months and 1 year after VAAFT were the same, with no more recurrence between the interval. From our experience, we suggest that 3 months after VAAFT is an appropriate time point for follow-up. We further performed a risk analysis and found that operating time was significantly correlated with fistula recurrence after VAAFT. Previous studies have indicated that fistula irrigation under pressure might cause the spread of infected granulation tissue into normal tissue [28]. The prolonged operating time increases the risk of infection spreading, resulting in delayed healing, or recurrence. Severe wound secretion on postoperative day 3 was another independent risk factor, suggesting the importance of postoperative drainage management [27]. Moreover, our results showed that although VAAFT provides direct visualization of the fistula tracts, which
3.3. Recurrence-associated factors after VAAFT Of the 68 patients undergoing VAAFT, 12 (17.6%) developed fistula recurrence within 3 months after surgery. The second follow-up showed that the fistula recurrence rate (17.6%) at 1 year postoperatively was the same as at the first follow-up, with no more recurrence observed between 3 months and 1 year after surgery. Univariate analysis revealed that fistula tract (P = 0.004), Park's type (P = 0.010), operating time (P = 0.004) and wound secretion on postoperative day 3 (P = 0.008) might be associated with fistula recurrence after VAAFT. Further multivariate logistic analysis identified that multiple fistula tracts and operating time ≥60 min were independent risk factors, with an OR of 2.18 (95% CI: 1.15–11.91, adjusted P = 0.028) and 3.25 (95% CI: 1.26–15.31, adjusted P = 0.021), respectively. Wound secretion on postoperative day 3 was another significant predictor of VAAFT outcome. Compared with score 0, score 1 or 2 showed a 3.04-fold (95% CI: 1.08–19.35, adjusted P = 0.040) increased risk of fistula recurrence (see Table 3).
Table 3 Logistic analysis of risk factors for fistula recurrence after VAAFT. Variable
Univariate
Multivariate
OR (95% CI)
P value
2.67 (0.72–9.90)
0.143
0.48 (0.05–4.15)
0.501
3.22 (0.79–13.17)
0.103
7.33 (1.88–28.56)
0.004
4.40 (0.52–36.94)
0.172
5.73 (1.53–21.52)
7.31 (1.89–28.24) Postoperative wound secretion (3 days) 1 vs. 2-3 7.29 (1.68–31.69)
Age (year) < 50 vs. ≥50 Sex Male vs. Female Previous fistula surgery No vs. Yes Fistula tract Single vs. Multiple Fistula location Low vs. High Park's type Inter/trans- vs. Supra/ extra-sphincteric Operating time (min) < 60 vs. ≥60
OR (95% CI)
P value
2.18 (1.15–11.91)
0.028
0.010
1.62 (0.81–11.40)
0.182
0.004
3.25 (1.26–15.31)
0.021
0.008
3.04 (1.08–19.35)
0.040
VAAFT, video-assisted anal fistula treatment. OR, odds risk. CI, confidence interval. 102
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Guarantor
contributed significantly to the detection and destruction of secondary tracts, multiple fistula tracts remain to be a major risk factor of recurrence after VAAFT. Non-identification of internal openings is also considered to be an important predictor of fistula recurrence after surgery [29], but it was not included in our analysis as all internal openings in the VAAFT group were successfully identified. Other potential risk factors reported in the literature, such as male sex [16] and previous fistula surgery [30], did not prove significant in this study. The reasons for these differences remain to be determined and may contribute to better management and improved prognosis. Based on previous reports and our experience, some points should be considered when performing VAAFT. Firstly, as the fistuloscope is a rigid scope 4 mm in diameter and 18 cm in length, it would be hard to pass through or deal with the lesion when the fistula tracts are too narrow or crooked. Our suggestion is adding a secondary minimal incision to reposition the fistuloscope, and being gentle when operating the fistuloscope, and a rotatory or vertical movement might be helpful. A similar view was taken by Chivate et al. [28]. Secondly, closure of the internal opening is a critical step in VAAFT. Although many methods have been developed, mainly including stapling, mucosal advancement flap and suturing, there is currently limited evidence to suggest which is most favorable [31]. Mendes et al. [32] suggested that in cases of severe fibrosis, stapling or suturing might not be easy to achieve complete closure or might lead to early dehiscence, and mucosal advancement flap would be a better choice. Thirdly, adequate drainage is another critical step in the cure of CAF. In this study, after closing the internal opening, we placed a thin rubber pipe in the fistula tract to facilitate postoperative drainage. We found that it was not necessary to inject fibrin glue after closure of the internal opening, as it might impair drainage of the tract. Seow-En et al. [27] also indicated that fibrin glue injection did not assure complete internal opening closure. Some limitations of this study should be noted. First, as a retrospective study, selection bias was inevitable, although we attempted to minimize the impact by performing PSM analysis. Second, our data were obtained from a single center and might not reflect the experiences of other institutions. Last, other potential risk factors not included in the study could not be examined for confounding effects. Hence, further validation of our findings is warranted.
Hailong Liu and Huihong Jiang. Availability of data The authors confirm that the data supporting the findings of this study are available within the article. Provenance and peer review Not commissioned, externally peer-reviewed. CRediT authorship contribution statement Hailong Liu: Conceptualization, Methodology, Writing - original draft. Xuan Tang: Methodology, Formal analysis, Data curation. Yi Chang: Investigation, Software. Ajian Li: Investigation, Software. Zhen Li: Investigation, Resources. Yihua Xiao: Investigation, Resources. Yong Zhang: Investigation, Resources. Zhihui Pan: Investigation, Resources. Liang Lv: Investigation, Resources. Moubin Lin: Investigation, Resources. Lu Yin: Conceptualization, Data curation, Project administration. Huihong Jiang: Conceptualization, Writing review & editing, Supervision. Declaration of competing interest The authors have no conflicts of interest to declare. Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.ijsu.2020.01.137. References [1] J.A. Simpson, A. Banerjea, J.H. Scholefield, Management of anal fistula, BMJ 345 (2012) e6705, , https://doi.org/10.1136/bmj.e6705. [2] P. Sainio, Fistula-in-ano in a defined population. Incidence and epidemiological aspects, Ann. Chir. Gynaecol. 73 (1984) 219–224 PubMed PMID: 6508203. [3] M.H. Whiteford, J. Kilkenny 3rd, N. Hyman, W.D. Buie, J. Cohen, C. Orsay, G. Dunn, W.B. Perry, C.N. Ellis, J. Rakinic, S. Gregorcyk, P. Shellito, R. Nelson, J.J. Tjandra, G. Newstead, Practice parameters for the treatment of perianal abscess and fistula-in-ano (revised), Dis. Colon Rectum 48 (2005) 1337–1342, https://doi. org/10.1007/s10350-005-0055-3. [4] J. Garcia-Aguilar, C. Belmonte, D.W. Wong, S.M. Goldberg, R.D. Madoff, Cutting seton versus two-stage seton fistulotomy in the surgical management of high anal fistula, Br. J. Surg. 85 (1998) 243–245, https://doi.org/10.1046/j.1365-2168.1998. 02877.x. [5] V. Durgun, A. Perek, M. Kapan, S. Kapan, S. Perek, Partial fistulotomy and modified cutting seton procedure in the treatment of high extrasphincteric perianal fistulae, Dig. Surg. 19 (2002) 56–58, https://doi.org/10.1159/000052007. [6] E. Limura, P. Giordano, Modern management of anal fistula, World J. Gastroenterol. 21 (2015) 12–20, https://doi.org/10.3748/wjg.v21.i1.12. [7] G.N. Buchanan, C.I. Bartram, R.K. Phillips, S.W. Gould, S. Halligan, T.A. Rockall, P. Sibbons, R.G. Cohen, Efficacy of fibrin sealant in the management of complex anal fistula: a prospective trial, Dis. Colon Rectum 46 (2003) 1167–1174, https:// doi.org/10.1097/01.Dcr.0000084408.85802.A2. [8] D.K. Thekkinkattil, I. Botterill, N.S. Ambrose, L. Lundby, P.M. Sagar, S. Buntzen, P.J. Finan, Efficacy of the anal fistula plug in complex anorectal fistulae, Colorectal Dis. 11 (2009) 584–587, https://doi.org/10.1111/j.1463-1318.2008.01627.x. [9] P. Giamundo, M. Geraci, L. Tibaldi, M. Valente, Closure of fistula-in-ano with laser– FiLaC: an effective novel sphincter-saving procedure for complex disease, Colorectal Dis. 16 (2014) 110–115, https://doi.org/10.1111/codi.12440. [10] P. Sileri, L. Franceschilli, G.P. Angelucci, S. D'Ugo, G. Milito, F. Cadeddu, I. Selvaggio, S. Lazzaro, A.L. Gaspari, Ligation of the intersphincteric fistula tract (LIFT) to treat anal fistula: early results from a prospective observational study, Tech. Coloproctol. 15 (2011) 413–416, https://doi.org/10.1007/s10151-0110779-0. [11] Y.P. Sangwan, L. Rosen, R.D. Riether, J.J. Stasik, J.A. Sheets, I.T. Khubchandani, Is simple fistula-in-ano simple? Dis. Colon Rectum 37 (1994) 885–889 PubMed PMID: 8076487. [12] P. Meinero, L. Mori, Video-assisted anal fistula treatment (VAAFT): a novel sphincter-saving procedure for treating complex anal fistulas, Tech. Coloproctol. 15 (2011) 417–422, https://doi.org/10.1007/s10151-011-0769-2.
5. Conclusions Our study suggests that, compared to FPS, VAAFT possesses significant advantages for treatment of CAF, including minimal damage, less pain, rapid recovery, fewer complications and better sphincter preservation. Moreover, fistula recurrence after VAAFT may be related to multiple fistula tracts, prolonged operating time and severe postoperative wound secretion. With improvement of this technique and surgical experience, a better result is expected. Ethical approval This study has been approved by the Research Ethics Committee of Yangpu Hospital, Tongji University School of Medicine (LL-2019-SCI002). Sources of funding This study was supported by the projects of Shanghai Municipal Commission of Health and Family Planning (201740146) and Wu Jieping Medical Foundation (320.2710.1839). Research registration unique identifying number (UIN) The trial was registered at Chinese Clinical Trial Registry (ChiCTR1900024492). http://www.chictr.org.cn/edit.aspx?pid= 41115&htm=4. 103
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[24] S. Eisenhammer, The final evaluation and classification of the surgical treatment of the primary anorectal cryptoglandular intermuscular (intersphincteric) fistulous abscess and fistula, Dis. Colon Rectum 21 (1978) 237–254 1978, PubMed PMID: 657933. [25] G. Kochhar, S. Saha, M. Andley, A. Kumar, G. Saurabh, R. Pusuluri, V. Bhise, A. Kumar, Video-assisted anal fistula treatment, J. Soc. Laparoendosc. Surg. 18 (2014), https://doi.org/10.4293/jsls.2014.00127 e2014.00127. [26] A. Pini Prato, C. Zanaboni, M. Mosconi, C. Mazzola, L. Muller, P.C. Meinero, M.G. Faticato, L. Leonelli, G. Montobbio, N. Disma, G. Mattioli, Preliminary results of video-assisted anal fistula treatment (VAAFT) in children, Tech. Coloproctol. 20 (2016) 279–285, https://doi.org/10.1007/s10151-016-1447-1. [27] I. Seow-En, F. Seow-Choen, P.K. Koh, An experience with video-assisted anal fistula treatment (VAAFT) with new insights into the treatment of anal fistulae, Tech. Coloproctol. 20 (2016) 389–393, https://doi.org/10.1007/s10151-016-1450-6. [28] S.D. Chivate, Comment on Meinero and Mori: video-assisted anal fistula treatment (VAAFT): a novel sphincter-saving procedure to repair complex anal fistulas, Tech. Coloproctol. 16 (2012) 465–466, https://doi.org/10.1007/s10151-012-0873-y. [29] J. Jordan, J.V. Roig, J. Garcia-Armengol, E. Garcia-Granero, A. Solana, S. Lledo, Risk factors for recurrence and incontinence after anal fistula surgery, Colorectal Dis. 12 (2010) 254–260, https://doi.org/10.1111/j.1463-1318.2009.01806.x. [30] J. Garcia-Aguilar, C. Belmonte, W.D. Wong, S.M. Goldberg, R.D. Madoff, Anal fistula surgery. Factors associated with recurrence and incontinence, Dis. Colon Rectum 39 (1996) 723–729 PubMed PMID: 8674361. [31] S.O. Adegbola, K. Sahnan, G. Pellino, P.J. Tozer, A. Hart, R.K.S. Phillips, J. Warusavitarne, O.D. Faiz, Short-term efficacy and safety of three novel sphinctersparing techniques for anal fistulae: a systematic review, Tech. Coloproctol. 21 (2017) 775–782, https://doi.org/10.1007/s10151-017-1699-4. [32] C.R. Mendes, L.S. Ferreira, R.A. Sapucaia, M.A. Lima, S.E. Araujo, Video-assisted anal fistula treatment: technical considerations and preliminary results of the first Brazilian experience, ABCD. Arq. Bras. Cir. Dig. (São Paulo) 27 (2014) 7–81, https://doi.org/10.1590/S0102-67202014000100018.
[13] P.K. Chowbey, R. Khullar, A. Sharma, V. Soni, K. Najma, M. Baijal, Minimally invasive anal fistula treatment (MAFT)-An appraisal of early results in 416 patients, Indian J. Surg. 77 (2015) 716–721, https://doi.org/10.1007/s12262-013-0977-2. [14] H.H. Jiang, H.L. Liu, Z. Li, Y.H. Xiao, A.J. Li, Y. Chang, Y. Zhang, L. Lv, M.B. Lin, Video-assisted anal fistula treatment (VAAFT) for complex anal fistula: a preliminary evaluation in China, Med. Sci. Mon. Int. Med. J. Exp. Clin. Res. 23 (2017) 2065–2071, https://doi.org/10.12659/msm.904055. [15] M. Zarin, M.I. Khan, M. Ahmad, M. Ibrahim, M.A. Khan, VAAFT: video assisted anal fistula treatment; bringing revolution in fistula treatment, Pakistan J. Med. Sci. 31 (2015) 1233–1235, https://doi.org/10.12669/pjms.315.6836. [16] S.H. Emile, H. Elfeki, M. Shalaby, A. Sakr, A Systematic review and meta-analysis of the efficacy and safety of video-assisted anal fistula treatment (VAAFT), Surg. Endosc. 32 (2018) 2084–2093, https://doi.org/10.1007/s00464-017-5905-2. [17] General Assembly of the World Medical Association, World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects, J. Am. Coll. Dent. 81 (2014) 14–18 PubMed PMID: 25951678. [18] R. Agha, A. Abdall-Razak, E. Crossley, N. Dowlut, C. Iosifidis, G. Mathew, For the STROCSS Group, STROCSS 2019 Guideline: strengthening the reporting of cohort studies in surgery, Int. J. Surg. 72 (2019) 156–165, https://doi.org/10.1016/j.ijsu. 2019.11.002. [19] P.L. Ritter, V.M. Gonzalez, D.D. Laurent, K.R. Lorig, Measurement of pain using the visual numeric scale, J. Rheumatol. 33 (2006) 574–580 2006; 33(3): 574-580, PubMed PMID: 16511926. [20] J.M. Jorge, S.D. Wexner, Etiology and management of fecal incontinence, Dis. Colon Rectum 36 (1993) 77–97 PubMed PMID: 8416784. [21] R.B. D'Agostino Jr., Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group, Stat. Med. 17 (1998) 2265–2281 PubMed PMID: 9802183. [22] A. Theerapol, B.Y. So, S.S. Ngoi, Routine use of setons for the treatment of anal fistulae, Singap. Med. J. 43 (2002) 305–307 PubMed PMID: 12380728. [23] A. Cariati, Fistulotomy or seton in anal fistula: a decisional algorithm, Updates Surg. 65 (2013) 201–205, https://doi.org/10.1007/s13304-013-0216-1.
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