Ligation of intersphincteric fistula tract (LIFT) for trans-sphincteric cryptoglandular anal fistula: long-term impact on faecal continence.

BACKGROUND: The ligation of intersphincteric fistula tract is a surgical technique designed to treat trans-sphincteric anal fistulas aiming to preserve sphincter integrity. Recent studies suggest its efficacy in short-term fistula healing with limited impact on continence. However, comprehensive prospective data on long-term outcomes, including recurrence and bowel continence, are limited. The present study aims to report on the long-term functional outcomes. METHODS: Patients who underwent the ligation of intersphincteric fistula tract procedure for trans-sphincteric cryptoglandular anal fistulas between July 2012 and October 2018 at two Dutch referral centres were retrospectively reviewed. The primary outcome of interest was the long-term bowel continence after the ligation of intersphincteric fistula tract procedure, using the faecal incontinence severity index. Short-term data (collected in 2018) and long-term data (collected in 2023) on bowel continence, healing rates and recurrences were obtained through electronic records and Rockwood questionnaires. Sankey diagrams were used to visually represent individual variations in continence status (preoperative versus follow-up). RESULTS: Among 110 patients included (50% female, median follow-up 92 months), 101 patients (92%) were treated with previous surgeries (median 2, range 0-6) and 80% had previous seton drainage. Preligation of intersphincteric fistula tract, 16% of the patients reported incontinence (mean(s.d.) faecal incontinence severity index: 2.4(7.5), increasing to 18% after ligation of intersphincteric fistula tract at short-term follow-up, including 11% newly induced cases. Long-term follow-up collected using Rockwood questionnaires (63% response rate) in 69 patients uncovered a 74% incontinency rate (mean(s.d.) faecal incontinence severity index: 9.22(9.5). In those patients without subsequent surgery 49% (17 of 35) reported incontinence at long-term follow-up. Primary fistula healing after ligation of intersphincteric fistula tract was 28%. Preoperative seton drainage significantly improved healing rates (33% versus 9%). Notably, 43% (34 of 79) of unhealed fistulas transitioned into intersphincteric tracts; in these patients, 19 were treated with subsequent fistulotomy achieving cure in 18 cases. CONCLUSIONS: Ligation of intersphincteric fistula tract healing rates fell below recent literature standards. Although the immediate impact on postoperative continence appears minimal, long-term incontinence rates are concerning. In recognizing the deterioration of individual continence, we advocate for a patient-centered approach and urge fellow researchers and clinicians to collect comprehensive prospective continence data.

Study on 3D High-Resolution Anorectal Manometry Interrater Agreement in the Evaluation of Dyssynergic Defecation Disorders.

Anorectal manometry measurements exhibit significant interrater variability. Newer techniques like 3D high-resolution anorectal manometry (3D-HRAM) have the potential to enhance diagnostic accuracy and our understanding of defecation disorders. However, the extent of interrater variability in 3D-HRAM is still unknown. Between January 2020 to April 2022, patients referred for pelvic floor physical therapy (PFPT) due to functional defecation complaints underwent 3D-HRAM testing. In a retrospective analysis, three expert raters independently evaluated the 3D-HRAM results in a blinded matter to assess interrater agreement. The evaluation also determined the level of agreement concerning dyssynergic patterns during simulated defecation. The 3D-HRAM results of 50 patients (37 females) were included. Twenty-nine patients had complaints of fecal incontinence, eleven patients had chronic constipation, and ten patients had several other complaints. There was a substantial agreement (kappa 0.612) between the raters concerning the 3D images on dyssynergic patterns during simulated defecation. Our study emphasizes the need for standardized guidelines in evaluating 3D-HRAM test results to reduce subjectivity and further improve agreement among raters. Implementing these guidelines could improve diagnostic consistency and enhance personalized treatment strategies, increasing the reliability and usefulness of 3D-HRAM testing in clinical practice.

Antibiotic Treatment foLlowing surgical drAinage of perianal abScess (ATLAS): protocol for a multicentre, double-blind, placebo-controlled, randomised trial.

INTRODUCTION: Perianal fistula is a burdening disease with an annual incidence of 6-12/100 000 in Western countries. More than 90% of crypto-glandular fistulas originate from perianal abscess. Despite adequate drainage, up to 83% recur or result in an anal fistula, the majority developing within 12 months. There is some evidence that gut-derived bacteria play a role in the development of perianal fistula. Up till now, it is not common practice to routinely administer prophylactic antibiotics to prevent anal fistula development. There is a need for a study to establish whether adding antibiotic treatment to surgical drainage of perianal abscess results in a reduction in perianal fistulas. METHODS AND ANALYSIS: This multicentre, double-blind, randomised, placebo-controlled trial investigates whether addition of antibiotics (ciprofloxacin and metronidazole) to surgical drainage of a perianal abscess is beneficial compared with surgical drainage alone. The primary outcome is the development of a perianal fistula within 1 year. Secondary outcomes include quality of life, treatment costs, need for repeated drainage, patient-reported outcomes and other clinical outcomes. Participants are recruited in one academic and seven peripheral Dutch clinics. To demonstrate a reduction of perianal fistula from 30% to 15% when treated with adjuvant antibiotics with a two-sided alpha of 0.05, a power of 80% and taking a 10% loss to follow-up percentage into account, the total sample size will be 298 participants. Data will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The study protocol has been approved by the Medical Ethics Review Committee of the Amsterdam University Medical Centers (nr. 2021_010). Written consent is obtained from each participant prior to randomisation into the study. The results of this trial will be submitted for publication in international peer-reviewed journals, presented at conferences and spread to coloproctological associations. TRIAL REGISTRATION NUMBERS: 2020-004449-35; NCT05385887.

D-2-hydroxyglutaric aciduria Type I: Functional analysis of D2HGDH missense variants.

D-2-hydroxyglutaric aciduria Type I (D-2-HGA Type I), a neurometabolic disorder with a broad clinical spectrum, is caused by recessive variants in the D2HGDH gene encoding D-2-hydroxyglutarate dehydrogenase (D-2-HGDH). We and others detected 42 potentially pathogenic variants in D2HGDH of which 31 were missense. We developed functional studies to investigate the effect of missense variants on D-2-HGDH catalytic activity. Site-directed mutagenesis was used to introduce 31 missense variants in the pCMV5-D2HGDH expression vector. The wild type and missense variants were overexpressed in HEK293 cells. D-2-HGDH enzyme activity was evaluated based on the conversion of [2 H4 ]D-2-HG to [2 H4 ]2-ketoglutarate, which was subsequently converted into [2 H4 ]L-glutamate and the latter quantified by LC-MS/MS. Eighteen variants resulted in almost complete ablation of D-2-HGDH activity and thus, should be considered pathogenic. The remaining 13 variants manifested residual activities ranging between 17% and 94% of control enzymatic activity. Our functional assay evaluating the effect of novel D2HGDH variants will be beneficial for the classification of missense variants and determination of pathogenicity.