The risk factors for failure and recurrence of LIFT procedure for fistula in ano
肛門瘺管 LIFT 手術失敗和復發的危險因素

Introduction  介紹

Fistula in ano (FIA) is common in surgical practices. The generally accepted pathogenesis is chronic infection of the anal gland developing between the anal mucosa and skin. However, the treatment for FIA is difficult due to the risk of incontinence. Treatments for FIA are sphincter sacrifice procedure and sphincter saving procedure. Examples of sphincter sacrifice are fistulotomy, fistulectomy, and seton with staged fistulotomy (1). Examples of sphincter saving are core-out fistulectomy, advancement flap, anal fistula plug, fibrin sealing, ligation of intersphincteric tract (LIFT), and video-assisted anal fistula treatment (VAAFT). Ligation intersphincteric fistula tract (LIFT) is one of the sphincter saving procedures with promising results in success rate and postoperative continence (1-3). This study aimed to examine the recurrence group after LIFT to identify risk factors and patterns of recurrence.
肛瘺 （FIA） 在外科實踐中很常見。普遍接受的發病機制是在肛門粘膜和皮膚之間發生的肛門腺慢性感染。然而，由於存在尿失禁的風險，FIA 的治療很困難。FIA 的治療方法是括約肌犧牲手術和括約肌保留手術。括約肌犧牲的例子是瘺管切開術、瘺管切除術和掛線分期瘺管切開術 （1）。保留括約肌的例子包括核心瘺切除術、前移皮瓣、肛瘺栓、纖維蛋白封閉、括約肌間束結紮術 （LIFT） 和電視輔助肛瘺治療 （VAAFT）。結紮括約肌間瘺束 （LIFT） 是括約肌保留手術之一，在成功率和術後節制方面具有可喜的結果 （1-3）。 本研究旨在檢查 LIFT 后復發組，以確定復發的危險因素和模式。

Patients and Methods  患者和方法

A retrospective study in medical records was conducted from Januar1, 2015 to January 30, 2020. The ethics committee of Rajavithi Hospital had reviewed and approved this study, with the study number 64020. Inclusion criteria were patients who underwent LIFT operation in Rajavithi Hospital, aged between 18-70 years, and had an imaging study of fistula in pre-operative and follow up time for at least three months. Exclusion criteria were underlying colorectal cancer or pelvic organ cancer, concomitant with inflammatory bowel disease (IBD), and previous pelvic radiation. Definitions of suspect recurrence in this study are non-healing external opening after 12 weeks and the occurrence of new external opening caused by the original internal opening. The fistula in ano classification in this study is based on Park’s anal fistula classification regarding high and low transsphincteric types, in which low transsphincteric is classified by how the tract involves one-third or less of the sphincter complex.
2015 年 1 月 1 日至 2020 年 1 月 30 日對病歷進行了回顧性研究。Rajavithi 醫院倫理委員會審查並批准了這項研究，研究編號為 64020。納入標準是在 Rajavithi 醫院接受 LIFT 手術的患者，年齡在 18-70 歲之間，並在術前和隨訪時間內進行了至少三個月的瘺管影像學研究。排除標準是潛在的結直腸癌或盆腔器官癌，伴有炎症性腸病 （IBD），以及既往盆腔放療。本研究中疑似復發的定義是 12 周後未癒合的外部開口以及由原始內部開口引起的新的外部開口的發生。本研究中的肛瘺分類基於關於高低經括約肌類型的 Park 肛瘺分類，其中低經括約肌根據束如何涉及三分之一或更少的括約肌複合體進行分類。

All data were collected and analyzed with SPSS (version 20.0). Mann-Whitney U test and Chi-square test were used to make comparisons between the groups. Univariate relationships between each independent variable and fistula formation were tested using binary logistic regression. Odds ratio (OR) with 95% confidence intervals (CI) of each variable was determined, and significant variables in the univariate analysis were included in a multivariate model of logistic regression. p-value of less than 0.05 was considered statistically significant.
所有數據均使用 SPSS （20.0 版） 收集和分析。採用 Mann-Whitney U 檢驗和卡方檢驗進行組間比較。使用二元 logistic 回歸檢驗每個自變數與瘺管形成之間的單變數關係。確定每個變數的比值比 （OR） 和 95% 置信區間 （CI），並將單變數分析中的顯著變數包含在 logistic 回歸的多變數模型中。小於 0.05 的 p 值被認為具有統計學意義。

Results  結果

There were 250 cases of fistula in ano operations in total. The cases were divided into 148 LIFT patients, 51 fistulotomy patients, 10 advancement flap patients, 15 seton and stage fistulotomy patients, 14 core-out fistulectomy patients, and 12 examinations under anesthesia patients.
肛門手術共有 250 例瘺管。病例分為 LIFT 患者 148 例，瘺管切開術 51 例，前移皮瓣患者 10 例，掛線和分期瘺管切開患者 15 例，挖芯瘺切除術患者 14 例，麻醉下檢查患者 12 例。

The recurrence percentage after LIFT procedure was 22.97% (34 patients). Seventy patients who underwent LIFT operation had a preoperative imaging study with MRI or endoanal ultrasonography. The average time for diagnosing recurrence was 99.12 ± 30.08 days (mean ± SD) (ranged between 60-200 days) and the average time to conduct operation after the recurrence diagnosis was 64.68 ± 25.76 days (mean ± SD) (ranged from 30-120 days.) Comparative demographic data between failure and success of LIFT procedure is shown in Table 1. Comparative operative data is shown in Table 2. In summary, univariable analysis factors associated with recurrence after LIFT are the type of FIA, presence of collection, tract diameter that is greater than five millimeters, and more than one attempt to ligate the tract. Subgroup analysis of collection shows the presence of collection in both ischiorectal and deep post anal space, which have a high risk of recurrence. Multivariable analysis of factors associated with recurrence is shown in Table 3.
LIFT 手術后復發率為 22.97% （34 例患者）。70 例接受 LIFT 手術的患者進行了術前 MRI 或肛門內超聲影像學檢查。診斷復發的平均時間為 99.12 ± 30.08 天 （平均 ± SD） （範圍為 60-200 天），復發診斷後進行手術的平均時間為 64.68 ± 25.76 天 （平均 ± SD） （範圍為 30-120 天）。LIFT 手術失敗和成功的比較人口統計數據如表 1 所示。比較手術數據如表 2 所示。總之，與 LIFT 后復發相關的單變數分析因素是 FIA 的類型、收集的存在、束直徑大於 5 毫米以及不止一次嘗試結紮束。收集的亞組分析顯示，坐骨直腸和肛門后深部間隙均存在收集，復發風險高。與復發相關的因素的多變數分析見表 3。

Recurrence patterns after LIFT are shown in Table 4. The most common pattern of recurrence was type 2: The remaining internal opening with a new external opening at the intersphincteric wound, which is shown in Figure 1. In this pattern, there were two cases occurred in “complex” due to multiple external openings at the first time of diagnosis. The operations for correction were as follows: Type 1 cases underwent LIFT 4 (36.4%), advancement flap 3 (27.3%), drainage seton with subsequent fistulotomy seton 1 (9.1%), and LIFT with placed drain 3 (27.3%). Type 2 cases underwent fistulotomy 15 (88.2%), LIFT 1 (5.9%), and drainage seton with subsequent fistulotomy 1 (5.9%). Type 3 cases underwent LIFT 1 (50%) and fistulectomy 1 (50%) and type IV cases underwent curettage sinus tract 1 (25%) and observation 3 (75%). Mean follow-up period in all patients was 115.42 ± 115.96 days. Recurrence after the second operation occurred in four cases, two cases after LIFT, 1 after anal advancement flap, and 1 after LIFT with placed drain. All four cases also underwent drainage seton.
LIFT 后的復發模式如 表 4 所示。最常見的復發模式是 2 型：剩餘的內部開口在括約肌間傷口處有新的外部開口，如圖 1 所示。在這種模式中，由於首次診斷時有多個外部開口，有 2 例發生在 「複雜」 中。矯正手術如下： 1 型病例行 LIFT 4 （36.4%） 、前移皮瓣 3 （27.3%）、引流掛線聯合隨後的瘺管切開掛線 1 （9.1%） 和放置引流管 3 的 LIFT （27.3%）。2 型病例接受了瘺管切開術 15 （88.2%） 、 LIFT 1 （5.9%） 和引流掛線術以及隨後的瘺管切開術 1 （5.9%）。3 型病例接受了 LIFT 1 （50%） 和瘺管切除術 1 （50%），IV 型病例接受了刮除竇道 1 （25%） 和觀察 3 （75%）。所有患者的平均隨訪時間為 115.42±115.96 天。第二次手術后復發 4 例，其中 2 例在 LIFT 后，1 例在肛門前移皮瓣后，1 例在 LIFT 放置引流管后。所有 4 例患者均接受了引流固定。

Discussion  討論

LIFT is one of the sphincter saving operative procedures for treating fistula in ano. An average success rate is 60-94% (4,5), with up to eight weeks of wound-healing time. Recurrence after LIFT procedure does not have a specific definition; however, the most used definition is non-healing of external wound or an external opening after eight weeks.
LIFT 是治療肛門瘺管的保留括約肌的手術程式之一。平均成功率為 60-94% （4,5），傷口癒合時間長達 8 周。LIFT 手術后復發沒有具體定義;然而，最常用的定義是 8 周後外部傷口不癒合或外部開口。

Risks of recurrence can be divided into three factors: patients, diseases, and surgeons’ experience. First, as for surgeons, this study does not show different results among the group of colorectal surgeons. The learning curve of surgeons in each procedure is the most important factor for an entrusted achievement of the result. However, the learning curve in LIFT does not define it. Nonetheless, Rojanasakul’s study reported the high success rate of LIFT (2). Thus, LIFT procedure has been adopted in training and practice of general surgery in Thailand, as well as in this study. A surgeon who has more than 20 years of experience and has self-studied LIFT can perform the operation without any difference in result when compared to other surgeons who have learned the procedure under proctorship. Therefore, it can be assumed that the LIFT procedure is not a difficult procedure, nor does it require a steep learning curve for colorectal surgeons. Regarding the difference from laparoscopic colorectal procedure (6,7), studies show a discrimination of results in rectal cancer in comparison between general surgeons and colorectal surgeons (8). Studies also show the significance of training and the result of surgery by specialists (9,10).
復發風險可分為三個因素：患者、疾病和外科醫生的經驗。首先，對於外科醫生，這項研究並沒有顯示結直腸外科醫生組之間的不同結果。外科醫生在每項手術中的學習曲線是獲得委託結果的最重要因素。但是，LIFT 中的學習曲線並未定義它。儘管如此，Rojanasakul 的研究報告了 LIFT 的高成功率 （2）。因此，LIFT 程式已被泰國普通外科的培訓和實踐以及本研究採用。與其他在監考下學習 LIFT 的外科醫生相比，擁有 20 多年經驗並自學 LIFT 的外科醫生可以進行手術，結果沒有任何差異。因此，可以假設 LIFT 手術不是一個困難的手術，也不需要結直腸外科醫生陡峭的學習曲線。關於與腹腔鏡結直腸手術的差異 （6,7），研究表明 ，與普通外科醫生和結直腸外科醫生相比，直腸癌的結果存在差異 （8）。研究還顯示了專家培訓和手術結果的重要性 （9,10）。

The factor regarding patients, as the previous studies’ report has stated, are immunocompromised host (11), Crohn’s disease (12), smoking (13), diabetic mellitus (14), obesity (1), and concurrent with rectal cancer (15). These all indicate risks of failure after LIFT procedure. In the postoperative period, the study has reported that regular examination, careful attention, and wound cleansing are helpful for an early diagnosis of recurrence and complications (16).
正如之前的研究報告所指出的，與患者有關的因素是免疫功能低下的宿主 （11）、克羅恩病 （12）、吸煙 （13）、糖尿病 （14）、肥胖 （1） 和併發直腸癌 （15）。這些都表明 LIFT 手術後存在失敗的風險。在術后期間，該研究報告稱，定期檢查、仔細關注和清潔傷口有助於復發和併發症的早期診斷 （16）。

The disease factor, based on Park’s classification (17), indicates that the supra-sphincteric and extra-sphincteric fistulae were at risk of recurrence (4,5,18,19). This study shows that the most common (recurrence) is the transsphincteric type. Possible explanations are an incidence that occurs more than other types, and transsphincteric which includes semi horseshoe and horseshoe. Horseshoe is a factor related to LIFT failure (18); however. the multivariable analysis did not show any significance. The presence of collection in one or both sides of ischiorectal or deep post anal space indicates failure of clearance infection in concordance to previous study result (20), which shows that horseshoe fistula has risks of recurrence and needs multiple surgeries to correct. A previous study shows types of clearance infection, such as curettage from original LIFT (2) or LIFT’s modification to remove tract, which do not imply an improvement of the cure rate (1). Nevertheless, drainage placement is not strong evidence to show an improved cure rate.
基於 Park 分類 （17） 的疾病因素表明括約肌上和括約肌外瘺有復發的風險 （4,5,18,19）。 這項研究表明，最常見的 （復發） 是經括約肌類型。可能的解釋是發病率比其他類型發生得更多，以及包括半馬蹄形和馬蹄形在內的跨括約肌。馬蹄鐵是與 LIFT 失敗相關的一個因素 （18）;然而。多變數分析未顯示任何顯著性。在坐骨直腸或肛后深部間隙的一側或兩側存在積液表明清除感染失敗，這與之前的研究結果一致 （20），這表明馬蹄形瘺有復發的風險，需要多次手術來糾正。先前的研究顯示了清除感染的類型，例如原始 LIFT 的刮宮術 （2） 或 LIFT 的修改以去除道，這並不意味著治癒率的提高 （1）。然而，引流放置並不是顯示治癒率提高的有力證據。

Early closure of external wound or an opening is one of the factors leading to failure since it has not achieved adequate sources to control in concordance with the previous study, which demonstrates the result of simple fistula surgery (21). This study shows the significance of presence of collection in univariable analysis; however, it does not show statistical significance regarding the type of collection in multivariable analysis. The other risk factor in this study was more than one intraoperative attempt to ligate the tract. The possible explanations may be a difficulty of identifying the tract in narrow intersphincteric space, high tract level, or occurrence of iatrogenic in transection tract, which leads to a poor or improper closure of the internal opening. A previous study has shown the importance of imaging study, which is the success rates of internal opening identifications and preoperative imaging studies. The success rates of rectal endoscopic anal ultrasonography (EAUS) and pelvic MRI in locating internal openings are 70-95% and 90-96%, respectively (22-24). The failure of locating internal opening is the report of the risks of operative failure, which is 20 times relative to the risk score (25). In this study, it showed similar correlation with univariable analysis. This study also showed that an intraoperative fistula tract with a diameter of more than five millimeters is a risk factor of recurrence. Technically, the closure of fistula tract via ligation or suture ligation are at risk of knot sliding, leading to an unaccomplished optimal tension of closure of fistula tract opening. Indirect comparative studies are those regarding fistula laser closure (FiLaC) and laser ablation of fistula tract (LAFT) in fistula tract size that is greater than five millimeters. Results indicate that the shrinkage of the tract is poor (26). Thus, the author suggests that suture buttress at internal sphincter on anal site and buttress on external sphincter on external site may be helpful to improve closure. However, further studies are still in need.
外傷口的早期閉合或開口是導致失敗的因素之一，因為它沒有獲得足夠的控制來源，這與之前的研究一致，這證明瞭簡單瘺管手術的結果 （21）。本研究顯示了集合在單變數分析中存在的重要性;但是，在多變數分析中，它不會顯示有關集合類型的統計顯著性。本研究中的另一個風險因素是術中不止一次嘗試結紮該道。可能的解釋可能是在狹窄的括約肌間隙中難以識別束、高束水準或在橫斷道中發生醫源性，從而導致內部開口閉合不良或不正確。先前的一項研究表明影像學研究的重要性，即內部開口識別和術前影像學研究的成功率。直腸內窺鏡肛門超聲檢查 （EAUS） 和盆腔 MRI 定位內部開口的成功率分別為 70-95% 和 90-96% （22-24）。 定位內部開口失敗是手術失敗風險的報告，相對於風險評分 （25） 是 20 倍。在這項研究中，它與單變數分析顯示出相似的相關性。這項研究還表明，直徑超過 5 毫米的術中瘺管是復發的危險因素。從技術上講，通過結紮或縫合結紮閉合瘺管有打結滑動的風險，導致瘺管開口閉合的最佳張力未完成。 間接比較研究是關於瘺管尺寸大於 5 毫米的瘺管鐳射閉合 （FiLaC） 和瘺管鐳射消融術 （LAFT） 的研究。結果表明，該束的收縮很差 （26）。因此，作者建議肛門部位內括約肌的縫合支撐和外部括約肌外側的縫合支撐可能有助於改善閉合。然而，仍需要進一步的研究。

There are three reported patterns of recurrence (27): complete failure, partial failure, and localized failure. Later reports in patterns of recurrence regarding new occurrence of fistula character are intersphincteric fistula, remaining or original fistula, and remaining external tract (28). This study shows two points of concern. First, in comparison with previous studies, the complexity of intersphincteric or partial failure is related to multiple external openings or the presence of collection in the first diagnosis. As a result, the fistulomy in the previous recommendation may not be sufficient for correction. Therefore, the author suggests adding C in order to define the complexity of recurrence pattern. The second concern is the new pattern of recurrence, in which a new external opening occurs at the other site, out of intersphincteric wound, making it different from previous studies. The cause may be failure to close the internal opening, which leads to a new onset of infection of the new tract. However, this cannot lead to a conclusion that it is a new type of recurrence pattern since this study was conducted in a small sample group. Thus, further studies are still needed.
有三種報告的復發模式 （27）：完全失敗、部分失敗和局部失敗。關於新出現的瘺管特徵的復發模式的後期報告是括約肌間瘺、剩餘或原始瘺管以及剩餘外束 （28）。這項研究顯示了兩個令人擔憂的點。首先，與以前的研究相比，括約肌間或部分衰竭的複雜性與首次診斷中多個外部開口或存在積液有關。因此，先前建議中的瘺管可能不足以進行糾正。因此，作者建議添加 C 來定義遞歸模式的複雜性。第二個問題是新的復發模式，其中在括約肌間傷口的另一個部位出現新的外部開口，使其與以前的研究不同。原因可能是未能關閉內部開口，從而導致新陰道感染的新發作。然而，這不能得出這是一種新型復發模式的結論，因為這項研究是在一個小樣本組中進行的。因此，仍需進一步研究。

The limitation of this study was the variable in imaging study due to surgeon’s preference and the feasibility of imaging during the study period. In addition, the operation to correct re-recurrence depended on the anatomy of the fistula as well.
本研究的局限性是由於外科醫生的偏好和研究期間影像學檢查的可行性而引起的影像學研究的變數。此外，糾正復發的手術也取決於瘺管的解剖結構。

Conclusion  結論

Fistula in ano is a disease with a lot of myths in curative outcomes depending on diseases, patients, and surgeons. LIFT is one of the operations that has an advantage in sphincter saving, with an ability to perform a reoperation when a recurrence occurs, down stage of fistula in ano. The pattern of recurrence is still undergoing examination and studies; thus, it needs a larger database to demonstrate the number of patterns. Furthermore, there is still a chance to improve the procedure of current techniques. In the future, LIFT may potentially play a fundamental role in fistula surgery.
肛瘺是一種在治療結果方面有很多神話的疾病，具體取決於疾病、患者和外科醫生。LIFT 是具有保留括約肌優勢的手術之一，能夠在復發時進行再次手術，即肛門瘺管的下期。復發模式仍在檢查和研究中;因此，它需要一個更大的資料庫來演示模式的數量。此外，仍有機會改進當前技術的程式。未來，LIFT 可能會在瘺管手術中發揮重要作用。