A Disposable Nitinol Memory Alloy Anal Fistula Clip (AFC) for the Treatment of Cryptoglandular Fistula-In-Ano: a Prospective, Randomized, Controlled Study With Short-Term Follow-Up

Fifty-one patients with cryptoglandular fistula-in-ano were enrolled between January 2019 and January 2020 in the National Colorectal Disease Center of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. The patients were randomly assigned for management with either AFC or ERAF (Fig. 2). The primary endpoint was fistula healing after proctology clip placement assessed by clinical examination (at weeks 6 and 12 and month 6) and endorectal ultrasonography (ERUS) (at week 6). The secondary endpoints included reduced pain score (Visual Analog Scale, VAS) and incontinence (Wexner) score at followup. Safety evaluation based on adverse events was also monitored.


Introduction
Surgical treatment of fistula-in-ano is an ongoing challenge and has led to the design of the disposable shape memory nitinol anal fistula clip (AFC) (Fig. 1). We conducted a prospective clinical study to evaluate the efficacy and safety of the AFC for cryptoglandular fistula-inano treatment compared with the endorectal advancement flap (ERAF).

Methods
Fifty-one patients with cryptoglandular fistula-in-ano were enrolled between January 2019 and January 2020 in the National Colorectal Disease Center of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. The patients were randomly assigned for management with either AFC or ERAF ( Fig. 2). The primary endpoint was fistula healing after proctology clip placement assessed by clinical examination (at weeks 6 and 12 and month 6) and endorectal ultrasonography (ERUS) (at week 6). The secondary endpoints included reduced pain score (Visual Analog Scale, VAS) and incontinence (Wexner) score at followup. Safety evaluation based on adverse events was also monitored.

Results
Of the 51 patients, 25 were included in the AFC group and 26 in the ERAF group. There were no significant differences in selected features between the two groups at baseline.

Discussion
Although ERAF does not destroy the anal sphincter and has a moderate success rate, postoperative recurrence and incontinence represent challenges. 1,2 The AFC exerts constant pressure on the internal opening resulting in permanent and dynamic closure.
In the AFC group, one clip fell off on its own on day 10, while the rest were removed by cutting the lateral hinges of the clip with the special AFC clip cutter at about 3.8 weeks (range, 3-4 weeks) without complaint. Six clips needed to be removed under abnormal circumstances. In the ERAF group, eight patients still complained of persistent secretions around the anus at week 12, and five received a second operation. In this study, six cases in the two groups retained a narrow tract without secretion while the internal opening was closed. The key to success was the capture of sufficient tissue volume. If sufficient external drainage cannot be guaranteed, inflammatory complications are inevitable.
The main limitations of this study were the small sample size and the short follow-up time. Nevertheless, the study provides evidence for the safety and efficacy of AFC in the treatment of cryptoglandular fistula-in-ano. AFC is an innovative contribution to minimally invasive sphincter-preserving technology. Fig. 1 The clip is 14 mm in diameter and is made of a super-elastic shape memory alloy (nitinol). The clip system consists of the applicator and a special fistula brush

Data Availability
The datasets used and/or analyzed during the current study are available from the corresponding author upon request. After the completion of the trial, all data will be uploaded to China's clinical trial registration center.

Declarations
Ethics Approval and Consent to Participate All methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were approved by the ethics committee of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine (Nanjing, China). Written informed consent was obtained from all study subjects.

Consent for Publication
Consent for publication was obtained from all study subjects and their guardians by signing an informed consent form during screening. All the authors consent to publish the paper.

Competing Interests
The authors declare no competing interests.
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