RARE DISEASE
Anal fistula
Anal fistula
Anal fistula
Drug discovery
4
drugs
With orphan designations
Overview
An anal fistula is an abnormal tunnel between the anal canal and perianal skin, typically arising from cryptoglandular infections (70-90% of cases) or Crohn's disease [1][4][15]. Symptoms include pain, purulent discharge, swelling, and recurrent abscesses [1][6]. Diagnosis combines physical exam with imaging (MRI/endoscopic ultrasound) to map fistula tracts [1][3]. Surgical intervention remains cornerstone treatment, prioritizing fistula eradication while preserving sphincter integrity [1][16].
Therapies
Surgical: Fistulotomy (95% success for simple cases) [5], LIFT procedure (40-95% healing) [3], advancement flaps (75-95% efficacy) [3]
Medical: Biologics (anti-TNFα) for Crohn's-related fistulas (49-73% response) [8][17]
Emerging: Stem cell therapy (53-71% remission) [4][8], FiLaC laser ablation [3][13]
Categories: rare abdominal surgical diseases, rare gastroenterological diseases
Research Papers
1,474 drug discovery papers about Anal fistula, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,474 drug discovery papers about Anal fistula, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-06-29 | Cyanoacrylate Glue Insertion Versus Seton Placement in the Management of Trans-sphincteric Anal Fistula: A Prospective Comparative Study.
Anal fistula is a common perianal condition associated with significant morbidity, recurrence, and risk of incontinence. Traditional surgical techniques such as seton placement are effective but are often associated with pain, prolonged healing time, and extended hospitalisation. Cyanoacrylate glue has emerged as a minimally invasive sphincter-preserving alternative. This prospective comparative study was conducted at Sri Ramachandra Institute of Higher Education and Research, Chennai, India, between June 1, 2023, and December 31, 2024. Fifty patients with uncomplicated trans-sphincteric fistula (St James University Hospital classification grade 3) were randomly allocated to receive either seton placement (n=25) or cyanoacrylate glue insertion (n=25). Primary outcomes included postoperative pain measured by visual analogue scale (VAS), duration of hospital stay, healing time, healing rate, and anal incontinence assessed by the Wexner continence score. The mean age was 45.3 years (SD 8.2) in the seton group and 39.1 years (SD 7.6) in the glue group. Both groups were comparable in demographic characteristics. VAS pain scores were significantly lower in the glue group compared with the seton group (mean 2.0 (SD 0.8) vs 3.4 (SD 1.1); p<0.001). Hospital stay was shorter in the glue group (2.6 days (SD 1.2) vs 5.3 days (SD 1.8); p<0.001). Healing time was significantly reduced with cyanoacrylate glue (2.75 weeks (SD 1.1) vs 5.79 weeks (SD 2.3); p<0.001). Healing rates were 96% (24 of 25) in the seton group versus 80% (20 of 25) in the glue group (p=0.189). No anal incontinence was observed in either group at three-month follow-up. Cyanoacrylate glue insertion offers a safe, minimally invasive alternative to seton placement for carefully selected patients with uncomplicated trans-sphincteric anal fistula, with significant advantages in pain reduction, shorter hospital stay, and faster healing. Although healing rates were lower with glue (80% vs 96%), this difference was not statistically significant, and the study was underpowered to detect this difference in healing rate as a secondary endpoint. All treatment failures were successfully managed with salvage fistulotomy or repeat glue application without morbidity. Larger randomised controlled trials adequately powered for healing rate as a co-primary endpoint are warranted to confirm long-term efficacy.
2026-06-16 | COMPREHENSIVE CLINICAL REVIEW: MODERN AND AYURVEDIC PERSPECTIVES ON ANAL FISTULA AND FISSURE-IN-ANO
Anorectal disorders, specifically fistula-in-ano (Bhagandara) and fissure-in-ano (Parikartika), represent a significant portion of colorectal clinical practice. A fistula-in-ano is characterized by an abnormal epithelialized tract connecting the perianal skin to the anal canal, often arising from chronic anorectal abscesses. In contrast, a fissure-in-ano is a longitudinal tear in the distal anal canal mucosa. This review article explores the etiology, pathophysiology, and diagnostic frameworks for these conditions. Special emphasis is placed on the comparative analysis of modern surgical interventions—such as fistulotomy, fistulectomy, and LIFT (Ligation of Intersphincteric Fistula Tract)—against traditional Ayurvedic parasurgical procedures, specifically Kshar Sutra therapy. The objective is to provide a holistic management protocol that minimizes recurrence and preserves sphincter function. The review concludes that while modern diagnostics (MRI) are essential for mapping, the integration of Ayurvedic herbal management and Kshar Sutra offers a viable, minimally invasive alternative with low recurrence rates for complex cases.
2026-06-12 | Anterior Horseshoe Anal Fistula Treated With IFTAK (Interception of Fistulous Track With Application of Ksharasutra) Technique: A Case Study.
Anterior horseshoe anal fistula is a challenging variant of complex anorectal infections. Classical surgeries, including ksharasutra therapy in these cases may result in extensive postsurgical scarring and anal incontinence. On the other hand, interception of fistulous track with application of ksharasutra (IFTAK) technique has emerged as a novel way of managing anal fistulas because of its nature of minimal invasiveness, ability to cut and heal tissues with controlled fibrosis, and continence preservation. Here, we explain a detailed case study of a 40-year-old gentleman who presented with a recurrent anterior horseshoe fistula effectively managed with IFTAK. The digital rectal examination (DRE), proctoscopy, methylene blue test, and probing were done to delineate tracts and confirm the diagnosis. Fistula healed completely and showed no recurrence at 8 months of follow-up. Compared to traditional methods, the technique results in a shorter hospital stay and a shorter treatment duration.
2026-05-08 | A case report of postoperative poor drainage of perianal abscess in an obese diabetic patient treated with comprehensive therapy.
Postoperative inadequate drainage of perianal abscess is prevalent in obese patients with diabetes, caused by obesity-related high tissue pressure and diabetes-induced impaired immunity/microcirculation. We report a 25-year-old obese male (BMI 37.9 kg/m2) with newly diagnosed type 2 diabetes who developed recurrent abscess on postoperative Day 3 after surgery for perianal abscess, anal fistula, and mixed hemorrhoids. He was treated with active catheter drainage, ceftriaxone-based targeted anti-infection (guided by Klebsiella pneumoniae culture), and metformin + liraglutide for glucose control. The patient fully recovered with normalized inflammatory markers and blood glucose, without recurrence or anal fistula formation at 1-year follow-up. This validates the efficacy of the comprehensive strategy for high-risk patients with long-term clinical outcomes.
2026-03-29 | Management of a Complex Y-Shaped Anal Fistula with Periscrotal Extension: The Role of FiLaC in a Sphincter-Preserving Strategy
Branching complex anal fistulas with anterior or periscrotal extension are uncommon and represent a therapeutic challenge, as eradication of sepsis must be balanced against preservation of anal continence. A 34-year-old man with no previous proctologic history presented with chronic perineal suppuration evolving over several months, associated with intermittent local pain. Clinical examination suggested a complex Y-shaped anal fistula with a single internal opening, multiple external openings, and a long anterior tract extending toward the periscrotal region, associated with a subcutaneous cavity. No clinical features suggestive of inflammatory bowel disease were identified. Operative exploration confirmed the fistulous anatomy. Fistulectomy of accessible tract segments was performed, followed by placement of two draining setons in order to control sepsis while preserving the sphincter complex. Concomitant hemorrhoidal disease, considered incidental, was treated separately during the same surgical session. Early postoperative outcome was favorable. Complex Y-shaped anal fistula with periscrotal extension is a rare anatomical presentation. A staged therapeutic strategy based on initial sepsis control with draining setons followed by definitive sphincter-preserving treatment may optimize outcomes while minimizing the risk of continence impairment. In this setting, FiLaC may represent a valuable option among definitive treatment modalities.
antibodies
2026-06-30 | Association between intestinal functional disorders and anal fistula: evidence from a retrospective case-control study.
Clinical observations indicate that some individuals experience bowel dysfunction, such as diarrhea or constipation, prior to the diagnosis of anal fistula (AF). These observations suggest a potential association between pre-existing intestinal dysfunction and the occurrence of AF. However, systematic clinical evidence remains limited. This study aimed to evaluate the association between pre-diagnostic bowel dysfunction and AF and to explore whether such associations differ across AF anatomical subtypes. We conducted a retrospective hospital-based case-control study including 251 patients with newly diagnosed AF between July 2024 and July 2025. During the same period, 251 age- and sex-matched individuals without AF were selected as controls (1:1 matching; age ± 3 years). Demographic characteristics, lifestyle factors, and bowel function within 1 year before the index date were collected from medical records and supplementary interviews where applicable. Conditional logistic regression, accounting for the matched-pair design, was used to assess the association between bowel dysfunction and AF. Both crude (unadjusted) and adjusted analyses were performed. Stratified analyses were performed to explore heterogeneity across AF subtypes. Pre-existing bowel dysfunction was associated with a higher likelihood of developing AF (p < 0.05). Diarrhea showed a significant association with AF (OR ≈ 2.2), whereas constipation was not significantly associated. Smoking, alcohol consumption, prolonged sedentary or standing occupations, and higher body mass index (BMI) were also associated with AF. In exploratory analyses of AF subtypes, diarrhea showed modest heterogeneity across anatomical classifications, whereas constipation showed no significant variation across subtypes. This retrospective case-control study indicates that pre-existing intestinal functional disorders, particularly chronic diarrhea, are associated with a higher likelihood of AF, with the association appearing more pronounced among low anal fistulas. No consistent subtype-specific pattern was observed overall, although diarrhea showed modest heterogeneity across anatomical classifications in exploratory analyses. Given the retrospective observational design, these findings support association rather than causation and warrant confirmation in multicenter prospective studies. Clinically, these results suggest that earlier identification and risk assessment of patients with chronic diarrhea and other intestinal functional disturbances may provide valuable insights, but further research is needed to confirm these findings.
2026-05-05 | Characteristics of Anal Fistula Cancer in Patients Who Underwent Surgery: A Nationwide Observational Study Using Diagnosis Procedure Combination Data
ABSTRACT Aim Anal fistula cancer is a rare disease that occurs in < 1% of patients with anal fistulas. The clinical characteristics of anal fistula cancer are not fully understood. This study aimed to identify the characteristics of patients with anal fistula cancer by comparing them with those of patients with anal canal or rectal cancer. Methods This was a nationwide observational study using the Diagnosis Procedure Combination data. Patients who underwent abdominoperineal resection or total pelvic exenteration for anal fistula, anal canal, or rectal cancer were included in this study. Patient background, surgical outcomes, postoperative complications, and medical costs were compared among the three types of cancer. Results This study included 206 patients with anal fistula cancer, 1207 patients with anal canal cancer, and 18 254 patients with rectal cancer. Patients with anal fistula cancer were more likely to be male, younger, or smokers. In patients with anal fistula cancer, the proportion of open surgeries was significantly higher, and the length of hospital stay was significantly longer than in those with anal canal and rectal cancer. Anal fistula cancer tended to be more locally advanced than other cancers, whereas lymph node and distant metastases were less common. The incidence of incisional wound infection and wound dehiscence was significantly higher, and medical costs were the highest in patients with anal fistula cancer. Conclusion Anal fistula cancer is characterized by aggressive local progression, resulting in a higher frequency of open surgery, a higher incidence of wound‐related complications, and higher medical costs.
2025-12-30 | Anatomical Reappraisal of the Intersphincteric Space: A Histology-Based Reinterpretation of the Parks Classification of Anal Fistulas
Background: Anal fistula pathways have been traditionally described using the Parks classification; however, the microscopic nature of the “intersphincteric” space has never been characterized completely. Furthermore, the longitudinal muscle between the internal and external anal sphincters has a more complex structure than traditionally assumed. Objective: To clarify the layer-specific microanatomy of the anal sphincter region and reassess how the fistula pathways described by the Parks classification correspond to actual histological structures. Design: Descriptive histological analysis of cadaveric specimens. Settings: Department of Clinical Anatomy at Institute of Science Tokyo. Patients: Eleven adult, human donors who had consented to whole-body donation. Interventions: Tissue blocks containing the lateral anal canal were collected and processed for histological and immunohistochemical analyses in the transverse and coronal planes. Main Outcome Measures: Identification of the sphincter muscles, longitudinal muscles, levator ani muscles, interbundle gaps, and connective tissue compartments as well as their spatial relationships. Results: The longitudinal muscles exhibited a mosaic structure with dense and loose regions. The dense region ended near the mid-height of the internal sphincter, whereas the loose region expanded inferiorly to form a wide compartment of sparse fibers and loose connective tissue. From this compartment, the loose fibers branched laterally and inferiorly, passing through natural gaps within the external sphincter muscle. Two overlapping layers of the levator ani muscle were also identified. The loose compartment beneath the longitudinal muscle corresponded to the site identified by Parks classification as the origin of abscess formation. Limitations: Specimens were obtained from formalin-fixed cadavers of elderly donors, only the lateral anal canal wall was assessed, and correlations with clinical fistulas were inferential. Conclusions: The region between the sphincter muscles is not a simple plane, and instead, a heterogeneous compartment; its structural features provide a basis for the initiation and propagation patterns described in the Parks classification of anal fistulas.
2025-12-16 | [Transformation and evidence-based progress of diagnosis and treatment mode for complex anal fistula].
Complex anal fistula remains a particularly challenging clinical condition, the primary difficulty in its management lies in the risk of damage to the anal sphincters, which is associated with a high incidence of treatment failure, recurrence and impairment of anal function, potentially leading to varying degrees of fecal incontinence in severe cases. Currently, there is no established gold-standard for the treatment of complex anal fistula, and efforts to identify effective therapeutic approaches continue. With advancements in medical science, the diagnosis and management of complex anal fistula have gradually transitioned from empirical medicine to evidence-based medicine, with continuous emergence of new theories and clinical evidence. This article reviews the relevant literature and systematically summarizes recent evidence-based medical findings on complex anal fistula, explores the driving factors in the evolution of diagnostic and therapeutic paradigms, and analyzes current clinical controversies and focal points. Furthermore,it elaborates on evidence-based diagnosis and treatment strategies, including preoperative precise assessment and selection of surgical techniques, with the aim of providing clinical practical guidance and promoting the advancement of diagnostic and therapeutic standards for complex anal fistula.
2025-09-03 | Gut microbiota and perianal abscess and anal fistula: A bidirectional Mendelian randomization study.
Perianal abscess and anal fistula are debilitating surgical conditions characterized by severe pain, persistent pus discharge, and prolonged recovery periods with high recurrence rates, collectively imposing profound burdens on patients' quality of life, social functioning, and work productivity. Research has indicated potential distinction regarding the composition of gut microbiota in patients suffering from perianal abscess and anal fistula. The causal effect is yet unclear. The MiBioGen consortium was utilized to acquire data pertaining to gut microbiota, while the outcome data was provided by another project called the MRC Integrative Epidemiology Unit Open Genome-wide Association Studies (IEU Open GWAS) project. We performed bidirectional two-sample Mendelian randomization (MR) using inverse variance weighted (IVW) as the primary method, selected for its robustness to balanced pleiotropy when valid instrumental variables are used. Additionally, sensitivity analyses were conducted to examine the robustness of the results. Four gut microbiota taxa showed causal associations with perianal abscess risk: Eubacterium brachy group (OR = 1.41, P = .004), Ruminococcaceae UCG003 (OR = 0.61, P = .007), Erysipelatoclostridium (OR = 0.68, P = .009), and Butyrivibrio (OR = 0.81, P = .016). For anal fistula, 8 taxa were significant: Catenibacterium (OR = 1.22, P = .042) and Eubacterium ruminantium group (OR = 1.17, P = .013) increased risk, while Haemophilus (OR = 0.79, P = .005), Alloprevotella (OR = 0.78, P = .001), Ruminiclostridium5 (OR = 0.79, P = .019), Erysipelotrichaceae UCG003 (OR = 0.82, P = .034), Butyrivibrio (OR = 0.88, P = .006), and Escherichia-Shigella (OR = 0.82, P = .039) conferred protection. Furthermore, the findings from the sensitivity analyses demonstrate robust stability in these conclusions. Reverse MR analyses did not suggest reverse causality. This is the first MR investigation into the causal relationships between the onset of perianal infections and particular taxa of the gut microbiota. It enhances our comprehension of the correlation.
proteins
2025-07-09 | Single-cell RNA sequencing reveals the therapeutic mechanism of Calvatia lilacina in promoting wound healing of anal fistula
Background: Anal fistula is one of the most common and frequently occurring diseases in the anorectal department. Calvatia lilacina spore (CLS) has been applied for wound treatment with a long history as a traditional Chinese medicine (TCM). However, the mechanism of CLS to treat postoperative wound of anal fistula remains unclear. The present study aims to investigate the efficacy and mechanism of CLS in promoting anal fistula wound healing from the perspective of regulating the interaction between macrophages and fibroblasts. Methods: Twenty patients who received anal surgery were recruited in Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. We presented a single-cell atlas of granulation tissue, comparing samples with and without CLS treatment, utilizing single-cell RNA sequencing. The pharmacological effects and mechanism of CLS on anal fistula wound were assessed using elisa, IHC staining, western blot, IF staining, flow cytometry assays and cell co-culture. Results: The CLS had a uniform particle size and contained components mainly including proteins, steroids, polysaccharides and polyphenols. CLS reduced the expression level of TNF-α and increased the expression levels of VEGF, Collagen I in the granulation tissue. The single-cell sequencing revealed that the expression level of IL-6 and CXCL-8 was increased in the IL-6+ macrophages that promoted the expression of WASF3 in fibroblasts and further recruited ACTR2, ACTR3. Finally, CLS increased intercellular communication between macrophages and fibroblasts, enhancing MSF migration ability by activating JAK2/STAT3 signaling pathway. Conclusion: Our study objectively demonstrated the pharmacological effects of CLS in promoting the wound healing of anal fistula and investigated its mechanisms in terms of regulating the immune inflammatory process of macrophages increases signal communication with fibroblasts while promoting fibroblast transformation.
2025-01-15 | Curing cryptoglandular anal fistulas-Is it possible without surgery?
Empirical reviews suggested that cryptoglandular anal fistulas require surgical resolution. However, some reports have indicated the possibility of nonsurgical and conservative treatment, which is discussed in this review. This review explores the potential of nonsurgical approaches for curing anal fistulas through bacterial inhibition and immunomodulation. The longstanding cryptoglandular theory has been a subject of controversy, prompting the reevaluation of conventional surgical interventions for anal fistulas. The review was conducted through database searches, including Medline, EMBASE, PubMed, and the Cochrane Library. Emerging evidence suggests that targeting the anaerobic environments present in anal fistulas and perianal abscesses and eradicating bacteria and their by-products may be critical for successful treatment. Immunomodulatory strategies show promise as a potential avenue for the nonsurgical management of anal fistulas. Ongoing developments in pharmacological research offer opportunities for alternative treatment options, shedding light on the prospects of noninvasive anal fistula management.
2024-10-21 | [Treatment of chronic sinus tract leakage at rectal anastomosis with anal fistula endoscopy].
Objective: To introduce the method of using anal fistula endoscope to treat chronic sinus tract leakage at rectal anastomosis site. Methods: We used anal fistula endoscopy to treat a patient with chronic sinus tract leakage after radical resection of rectal cancer, mainly including the following 5 steps: (1) establishing a water injection circulation system through the anus; (2) scraping off purulent coating and mucosa on the surface of the sinus tract with the brush; (3) hemostasis and removal of necrotic tissue with electrocoagulation rods; (4) filling the sinus tract with bioprotein gel; (5) compressing the sinus tract with transanal drainage tube. Results: The patient is a 70 year old male with rectal cancer. After undergoing 3D laparoscopic assisted radical resection of rectal cancer via abdominal anterior resection (Dixon's procedure) and diverting ileostomy surgery for more than 3 months, leakage of the rectal anastomosis was found through colonoscopy and anal iodine water contrast imaging .The patient started eating and flowing juice 6 hours after surgery, got out of bed 24 hours after surgery, and was discharged 48 hours after the removal of the anal canal. Three months after surgery, colonoscopy and transanal iodine hydrography showed that the sinus repair was intact. The diverting ileostomy was reduced 4 months after surgery. Conclusion: Anal fistula endoscope is safe and feasible for the treatment of chronic sinus tract anastomotic leakage in selected patients.
2024-05-06 | Use of Anal Fistula Plug for Treatment of Fistula-in-ano: A Novel Technique?
Abstract Background: Fistula-in-ano is a chronic phase of anorectal suppuration characterized by purulent discharge. The conventional gold standard fistulotomy opens the entire track to heal with secondary intention. Anal fistula plug (AFP) is one of the newer modalities where the track is debrided from within and plugged with a biodegradable material made of porcine small intestinal submucosa. Materials and Methods: A total of 100 patients were enrolled in a randomized prospective study into two groups: conventional fistulotomy (CF) group and AFP group with 50 patients in each arm. The demography and surgical outcomes were assessed for postoperative pain, discharge and recovery, and failure. Results: All 100 patients included in the study had a history of anorectal suppuration which led to the residual anal fistula. Postoperative pain and analgesic requirements were equal in the two groups. The recovery period and return to work were shorter in the AFP group, and this difference was statistically significant. The success rate was 100% in the CF group as compared to 76% in the AFP group. There was no significant complication, failure, or recurrence in the CF group as against allergy (1), extrusion of plug (2), and failure/recurrence (9) in the AFP group. Conclusion: Our study shows that the application of bioprosthetic plugs may be an alternative option in a select group of patients. AFP has also shown to have a faster recovery with less morbidity and comparable success rates.
2023-11-15 | Treatment Approaches for the Effective Management of Anal Fistula in the Modern Era
A complication of incision drainage or abscess ulceration around the anus and rectum is anal fistula which manifests as the creation of irregular channels linking the rectum and anal canal with the skin circumambient to the anus. It mostly affects the male population having a yearly frequency of two cases per ten thousand individuals. Histologically in anal fistula chronic inflammatory cells and fibrous tissues are surrounded by epithelialization of variable degree, which are categorized as squamous, columnar, or transitional zone epithelium. Anal fistula influences the psychological condition of the patients, which leads to depression or anxiety symptoms, in addition to severely impacting their standards of living. In general, anal fistula cannot be treated without medical intervention and the most efficient treatment for anal fistula is surgery. The optimal treatment in the modern era includes the elimination of the infected lesion, adequate drainage, and fistula closure while minimizing injury to the anal sphincter which includes treatment with fibrin glue, fistula plug, LIFT, etc.
cell therapies
2026-07-11 | Autologous concentrated growth factors promote M2 macrophage polarization to accelerate wound healing after anal fistula surgery by activating the AKT/mTOR pathway.
Delayed healing of post-operative anal fistula wounds is driven by a hostile inflammatory microenvironment. While autologous concentrated growth factors (ACGF) show regenerative potential, the underlying immunomolecular mechanisms remain unclear. This study investigates if ACGF accelerates contaminated wound healing by modulating macrophage polarization via the AKT/mTOR pathway. In vitro, RAW264.7 macrophages were treated with ACGF to assess phenotypic switching and AKT/mTOR activation. The paracrine effects of ACGF-primed macrophages on fibroblasts were evaluated using a co-culture system with AKT-siRNA validation. In vivo, a rat fecal-contaminated wound model was established. Therapeutic efficacy, with or without the AKT inhibitor Triciribine, was assessed via laser speckle imaging, histology, and immunofluorescence. ACGF effectively reprogrammed macrophages from a pro-inflammatory M1 phenotype toward a reparative M2 phenotype, significantly upregulating CD206 and Arg-1 expression while activating AKT/mTOR signaling. Mechanistically, ACGF-primed macrophages significantly boosted RSF proliferation, migration, and collagen synthesis, effects that were substantially abrogated by AKT silencing. In vivo, ACGF treatment markedly accelerated wound closure, enhanced microvascular perfusion, and increased the density of CD31 + and Ki67 + cells. These regenerative benefits were accompanied by a significant shift toward M2 infiltration and a reduction in pro-inflammatory cytokines, all of which were reversed by pharmacological inhibition of AKT. ACGF promotes the healing of contaminated wounds by orchestrating an AKT/mTOR-dependent macrophage M2 polarization. This shift initiates a beneficial paracrine relay that enhances fibroblast activity and neoangiogenesis, effectively restoring the regenerative niche. Our findings establish ACGF as a potent immunomodulatory biomaterial and offer a promising therapeutic strategy for complex perianal wounds and chronic recalcitrant defects.
2026-06-23 | Use of microfragmented autologous adipose tissue (LIPOGEMS®) as a sphincter-saving therapy for complex anal fistulas: a single-center retrospective study.
Complex anal fistulas remain a therapeutic challenge due to high recurrence rates and the risk of incontinence associated with conventional treatments. Microfragmented autologous adipose tissue has emerged as a sphincter-sparing option with potential regenerative and anti-inflammatory properties. This study aimed to evaluate the safety and efficacy of its injection into the fistula tract combined with closure of the internal opening. A single-center, retrospective, observational study was conducted between June 2019 and May 2025. All patients with complex anal fistulas treated with microfragmented adipose tissue processed with LIPOGEMS® system were included. Demographic data, fistula characteristics, surgical history, perioperative variables, postoperative morbidity, healing rate, and hospital stay were analyzed. Follow-up visits were performed weekly in the first month, and at 3, 6 and 12 months thereafter. A total of 28 patients with complex fistula were included. Mean patient age was 51.2 years (SD: 15.3), with predominance of males (69.7%). Most fistulas were medium or high transsphincteric (85.7%) and the main location was posterior (57.1%). 75% of patients had undergone previous curative-intent procedures. Median operative time was 71 minutes, and median processed adipose volume was 14 ml. Two postoperative complications were recorded (one abdominal hematoma-CD I and one perianal abscess-CD IIIa). After a median follow-up of 11.2 months, the overall healing rate was 46.4%, higher in primary (57.1%) and posterior fistulas (56.3%). Median hospital stay was one day, and median clinical closure occurred at 2.7 months. LIPOGEMS® therapy appeared safe, feasible, and associated with encouraging healing outcomes, offering advantages in functional preservation and recovery. Larger prospective studies are needed to confirm these results and refine its role in fistula management.
2026-06-20 | Comparison of incision and drainage procedure with drainage and ligation of the intersphincteric fistula tract in the treatment of deep perianal abscess.
Patients with deep perianal abscess (DPA) and transsphincteric fistula typically require incision and drainage as emergency treatment. However, recurrent abscesses and fistulas are common. This study aimed to evaluate the impact of simultaneous ligation of the intersphincteric fistula tract (LIFT) on abscess recurrence, incontinence, and fistula healing. This study is a retrospective analysis of an institutional protocol and includes 111 patients divided into two groups: Group I (incision and drainage alone, n = 57) and Group II (incision and drainage combined with the LIFT procedure, n = 54). The primary endpoint was persistent fistula at 6 months, confirmed by clinical examination and magnetic resonance imaging (MRI). Secondary endpoints included abscess recurrence, Wexner incontinence score changes, and complications. Firth's penalized logistic regression, inverse probability of treatment weighting (IPTW), and log-rank analyses were performed to assess outcomes. At the 3rd month, the number of patients with persistent fistula was 16 (28.1%) in Group I, while it was 3 patients (5.6%) in Group II (P = 0.002). At the 6th month, persistent fistula was observed in 21 of 55 patients (38.2%) in Group I and 3 of 53 patients (5.7%) in Group II (P < 0.001). Firth's penalized logistic regression showed that the LIFT procedure was significantly associated with reduced fistula persistence (OR = 0.079, 95% CI 0.019-0.327, P < 0.001). A sensitivity analysis restricted to patients with MRI-confirmed transsphincteric fistula (Group I: n = 34; Group II: n = 54) confirmed these findings (59.4% vs. 5.7%, P < 0.001). IPTW-adjusted analysis yielded consistent results (weighted OR = 0.063). This study demonstrates that the LIFT procedure, when applied together with drainage, reduces the incidence of persistent fistula and shows a non-significant reduction in abscess recurrence in patients with DPA and complex anal fistula. These findings should be interpreted with caution due to the non-randomized design and require confirmation through prospective randomized controlled trials.
2026-06-08 | Autologous platelet-rich fibrin matrix (Obsidian RFT) as a sphincter-preserving treatment for anal fistula: a retrospective cohort study and subgroup analysis.
The treatment of anal fistula remains a delicate balance between achieving healing and preserving anal continence. Sphincter-preserving strategies, such as autologous platelet-rich plasma/fibrin (PRP/PRF) matrices, offer a regenerative approach with minimal morbidity. This study aims to evaluate the efficacy and safety of a specific autologous fibrin matrix system (Obsidian RFT) in the management of anal fistula and to identify predictors of treatment success. We conducted a retrospective analysis of patients treated with the Obsidian RFT system for anal fistula at a single institution between January 2020 and September 2025. The primary endpoint was fistula healing, defined as the complete cessation of drainage and closure of the external opening. Secondary endpoints included secondary healing (after a simple adjunctive procedure), overall final healing (after any reintervention), and postoperative fecal incontinence (Wexner score). A subgroup analysis was performed to evaluate outcomes in "ideal candidates" (single-tract, non-supralevator fistulas, no associated abscess). A total of 86 patients were included (mean age 52.4 ± 14.4 years; 64% male). The majority of fistulas were transsphincteric (96.5%). The median follow-up was 8.7 months. Primary healing was achieved in 45.3% of patients (39/86) after the first application. With the addition of a simple secondary procedure (repeat matrix application or limited fistulotomy), the secondary healing rate increased to 58.1% (50/86). Overall final healing, including patients requiring complex reinterventions, reached 64.0% (55/86). Persistence accounted for most failures, while true late recurrence was uncommon. Postoperative fecal incontinence was rare, occurring in only 2.3% of patients. In the "ideal patient" subgroup, primary healing was significantly higher (51.4%) compared to non-ideal candidates (18.8%; p = 0.018), rising to 65.7% with reintervention (p = 0.003). The Obsidian RFT system is a safe, sphincter-preserving option associated with minimal morbidity and negligible impact on continence. While primary healing rates are modest, the cumulative success rate significantly increases with a sequential approach, validating its use as a "staged" strategy. This modality serves as a valuable first-line treatment in a stepped-care algorithm to minimize incontinence risk before escalating to more invasive procedures.
2026-05-18 | Efficacy and safety of freshly collected autologous adipose tissue for complex anal fistulas in non-IBD patients: a prospective cohort study.
Complex cryptoglandular anal fistulas present a treatment challenge, with many surgical options associated with recurrence, variable healing rates, and risk of incontinence. Freshly collected autologous adipose tissue (FCAAT) has been proposed as a minimally invasive, one-step alternative. This study aimed to assess clinical healing and clinical improvement and to evaluate the safety of the procedure. This prospective cohort study included 31 patients without inflammatory bowel disease (IBD) with complex single-tract cryptoglandular anal fistulas treated with FCAAT between May 2019 and December 2023 and followed until August 2024. The surgical procedure involved liposuction, processing of adipose tissue, closure of the internal opening, and local injection along the fistula tract in a one-step procedure. Primary outcomes were clinical healing and clinical improvement; secondary outcomes were adverse events. The patient cohort presented with advanced disease. Median disease duration was 20 months, and one-third of patients had undergone previous attempts at surgical closure. Clinical healing was achieved in 23 patients (74%), with an additional four patients (13%) demonstrating clinical improvement. Five of 27 responders (19%) healed more than 3 months post-procedure. Common adverse events included proctalgia in 8 patients (22%), donor site pain 5 (14%), and minor graft site hematomas in 4 (11%). One Clavien-Dindo IIIa event (graft site bleeding) was managed with a single suture; all other complications were minor and resolved conservatively. FCAAT is a safe and effective one-step treatment for complex anal fistulas in non-IBD patients, offering a high healing rate with predominantly minor complications. A delayed effect was observed in some patients.
small molecules
2026-06-29 | Cyanoacrylate Glue Insertion Versus Seton Placement in the Management of Trans-sphincteric Anal Fistula: A Prospective Comparative Study.
Anal fistula is a common perianal condition associated with significant morbidity, recurrence, and risk of incontinence. Traditional surgical techniques such as seton placement are effective but are often associated with pain, prolonged healing time, and extended hospitalisation. Cyanoacrylate glue has emerged as a minimally invasive sphincter-preserving alternative. This prospective comparative study was conducted at Sri Ramachandra Institute of Higher Education and Research, Chennai, India, between June 1, 2023, and December 31, 2024. Fifty patients with uncomplicated trans-sphincteric fistula (St James University Hospital classification grade 3) were randomly allocated to receive either seton placement (n=25) or cyanoacrylate glue insertion (n=25). Primary outcomes included postoperative pain measured by visual analogue scale (VAS), duration of hospital stay, healing time, healing rate, and anal incontinence assessed by the Wexner continence score. The mean age was 45.3 years (SD 8.2) in the seton group and 39.1 years (SD 7.6) in the glue group. Both groups were comparable in demographic characteristics. VAS pain scores were significantly lower in the glue group compared with the seton group (mean 2.0 (SD 0.8) vs 3.4 (SD 1.1); p<0.001). Hospital stay was shorter in the glue group (2.6 days (SD 1.2) vs 5.3 days (SD 1.8); p<0.001). Healing time was significantly reduced with cyanoacrylate glue (2.75 weeks (SD 1.1) vs 5.79 weeks (SD 2.3); p<0.001). Healing rates were 96% (24 of 25) in the seton group versus 80% (20 of 25) in the glue group (p=0.189). No anal incontinence was observed in either group at three-month follow-up. Cyanoacrylate glue insertion offers a safe, minimally invasive alternative to seton placement for carefully selected patients with uncomplicated trans-sphincteric anal fistula, with significant advantages in pain reduction, shorter hospital stay, and faster healing. Although healing rates were lower with glue (80% vs 96%), this difference was not statistically significant, and the study was underpowered to detect this difference in healing rate as a secondary endpoint. All treatment failures were successfully managed with salvage fistulotomy or repeat glue application without morbidity. Larger randomised controlled trials adequately powered for healing rate as a co-primary endpoint are warranted to confirm long-term efficacy.
2026-06-16 | COMPREHENSIVE CLINICAL REVIEW: MODERN AND AYURVEDIC PERSPECTIVES ON ANAL FISTULA AND FISSURE-IN-ANO
Anorectal disorders, specifically fistula-in-ano (Bhagandara) and fissure-in-ano (Parikartika), represent a significant portion of colorectal clinical practice. A fistula-in-ano is characterized by an abnormal epithelialized tract connecting the perianal skin to the anal canal, often arising from chronic anorectal abscesses. In contrast, a fissure-in-ano is a longitudinal tear in the distal anal canal mucosa. This review article explores the etiology, pathophysiology, and diagnostic frameworks for these conditions. Special emphasis is placed on the comparative analysis of modern surgical interventions—such as fistulotomy, fistulectomy, and LIFT (Ligation of Intersphincteric Fistula Tract)—against traditional Ayurvedic parasurgical procedures, specifically Kshar Sutra therapy. The objective is to provide a holistic management protocol that minimizes recurrence and preserves sphincter function. The review concludes that while modern diagnostics (MRI) are essential for mapping, the integration of Ayurvedic herbal management and Kshar Sutra offers a viable, minimally invasive alternative with low recurrence rates for complex cases.
2026-06-12 | Anterior Horseshoe Anal Fistula Treated With IFTAK (Interception of Fistulous Track With Application of Ksharasutra) Technique: A Case Study.
Anterior horseshoe anal fistula is a challenging variant of complex anorectal infections. Classical surgeries, including ksharasutra therapy in these cases may result in extensive postsurgical scarring and anal incontinence. On the other hand, interception of fistulous track with application of ksharasutra (IFTAK) technique has emerged as a novel way of managing anal fistulas because of its nature of minimal invasiveness, ability to cut and heal tissues with controlled fibrosis, and continence preservation. Here, we explain a detailed case study of a 40-year-old gentleman who presented with a recurrent anterior horseshoe fistula effectively managed with IFTAK. The digital rectal examination (DRE), proctoscopy, methylene blue test, and probing were done to delineate tracts and confirm the diagnosis. Fistula healed completely and showed no recurrence at 8 months of follow-up. Compared to traditional methods, the technique results in a shorter hospital stay and a shorter treatment duration.
2026-05-08 | A case report of postoperative poor drainage of perianal abscess in an obese diabetic patient treated with comprehensive therapy.
Postoperative inadequate drainage of perianal abscess is prevalent in obese patients with diabetes, caused by obesity-related high tissue pressure and diabetes-induced impaired immunity/microcirculation. We report a 25-year-old obese male (BMI 37.9 kg/m2) with newly diagnosed type 2 diabetes who developed recurrent abscess on postoperative Day 3 after surgery for perianal abscess, anal fistula, and mixed hemorrhoids. He was treated with active catheter drainage, ceftriaxone-based targeted anti-infection (guided by Klebsiella pneumoniae culture), and metformin + liraglutide for glucose control. The patient fully recovered with normalized inflammatory markers and blood glucose, without recurrence or anal fistula formation at 1-year follow-up. This validates the efficacy of the comprehensive strategy for high-risk patients with long-term clinical outcomes.
2026-03-29 | Management of a Complex Y-Shaped Anal Fistula with Periscrotal Extension: The Role of FiLaC in a Sphincter-Preserving Strategy
Branching complex anal fistulas with anterior or periscrotal extension are uncommon and represent a therapeutic challenge, as eradication of sepsis must be balanced against preservation of anal continence. A 34-year-old man with no previous proctologic history presented with chronic perineal suppuration evolving over several months, associated with intermittent local pain. Clinical examination suggested a complex Y-shaped anal fistula with a single internal opening, multiple external openings, and a long anterior tract extending toward the periscrotal region, associated with a subcutaneous cavity. No clinical features suggestive of inflammatory bowel disease were identified. Operative exploration confirmed the fistulous anatomy. Fistulectomy of accessible tract segments was performed, followed by placement of two draining setons in order to control sepsis while preserving the sphincter complex. Concomitant hemorrhoidal disease, considered incidental, was treated separately during the same surgical session. Early postoperative outcome was favorable. Complex Y-shaped anal fistula with periscrotal extension is a rare anatomical presentation. A staged therapeutic strategy based on initial sepsis control with draining setons followed by definitive sphincter-preserving treatment may optimize outcomes while minimizing the risk of continence impairment. In this setting, FiLaC may represent a valuable option among definitive treatment modalities.
antibodies
2026-06-30 | Association between intestinal functional disorders and anal fistula: evidence from a retrospective case-control study.
Clinical observations indicate that some individuals experience bowel dysfunction, such as diarrhea or constipation, prior to the diagnosis of anal fistula (AF). These observations suggest a potential association between pre-existing intestinal dysfunction and the occurrence of AF. However, systematic clinical evidence remains limited. This study aimed to evaluate the association between pre-diagnostic bowel dysfunction and AF and to explore whether such associations differ across AF anatomical subtypes. We conducted a retrospective hospital-based case-control study including 251 patients with newly diagnosed AF between July 2024 and July 2025. During the same period, 251 age- and sex-matched individuals without AF were selected as controls (1:1 matching; age ± 3 years). Demographic characteristics, lifestyle factors, and bowel function within 1 year before the index date were collected from medical records and supplementary interviews where applicable. Conditional logistic regression, accounting for the matched-pair design, was used to assess the association between bowel dysfunction and AF. Both crude (unadjusted) and adjusted analyses were performed. Stratified analyses were performed to explore heterogeneity across AF subtypes. Pre-existing bowel dysfunction was associated with a higher likelihood of developing AF (p < 0.05). Diarrhea showed a significant association with AF (OR ≈ 2.2), whereas constipation was not significantly associated. Smoking, alcohol consumption, prolonged sedentary or standing occupations, and higher body mass index (BMI) were also associated with AF. In exploratory analyses of AF subtypes, diarrhea showed modest heterogeneity across anatomical classifications, whereas constipation showed no significant variation across subtypes. This retrospective case-control study indicates that pre-existing intestinal functional disorders, particularly chronic diarrhea, are associated with a higher likelihood of AF, with the association appearing more pronounced among low anal fistulas. No consistent subtype-specific pattern was observed overall, although diarrhea showed modest heterogeneity across anatomical classifications in exploratory analyses. Given the retrospective observational design, these findings support association rather than causation and warrant confirmation in multicenter prospective studies. Clinically, these results suggest that earlier identification and risk assessment of patients with chronic diarrhea and other intestinal functional disturbances may provide valuable insights, but further research is needed to confirm these findings.
2026-05-05 | Characteristics of Anal Fistula Cancer in Patients Who Underwent Surgery: A Nationwide Observational Study Using Diagnosis Procedure Combination Data
ABSTRACT Aim Anal fistula cancer is a rare disease that occurs in < 1% of patients with anal fistulas. The clinical characteristics of anal fistula cancer are not fully understood. This study aimed to identify the characteristics of patients with anal fistula cancer by comparing them with those of patients with anal canal or rectal cancer. Methods This was a nationwide observational study using the Diagnosis Procedure Combination data. Patients who underwent abdominoperineal resection or total pelvic exenteration for anal fistula, anal canal, or rectal cancer were included in this study. Patient background, surgical outcomes, postoperative complications, and medical costs were compared among the three types of cancer. Results This study included 206 patients with anal fistula cancer, 1207 patients with anal canal cancer, and 18 254 patients with rectal cancer. Patients with anal fistula cancer were more likely to be male, younger, or smokers. In patients with anal fistula cancer, the proportion of open surgeries was significantly higher, and the length of hospital stay was significantly longer than in those with anal canal and rectal cancer. Anal fistula cancer tended to be more locally advanced than other cancers, whereas lymph node and distant metastases were less common. The incidence of incisional wound infection and wound dehiscence was significantly higher, and medical costs were the highest in patients with anal fistula cancer. Conclusion Anal fistula cancer is characterized by aggressive local progression, resulting in a higher frequency of open surgery, a higher incidence of wound‐related complications, and higher medical costs.
2025-12-30 | Anatomical Reappraisal of the Intersphincteric Space: A Histology-Based Reinterpretation of the Parks Classification of Anal Fistulas
Background: Anal fistula pathways have been traditionally described using the Parks classification; however, the microscopic nature of the “intersphincteric” space has never been characterized completely. Furthermore, the longitudinal muscle between the internal and external anal sphincters has a more complex structure than traditionally assumed. Objective: To clarify the layer-specific microanatomy of the anal sphincter region and reassess how the fistula pathways described by the Parks classification correspond to actual histological structures. Design: Descriptive histological analysis of cadaveric specimens. Settings: Department of Clinical Anatomy at Institute of Science Tokyo. Patients: Eleven adult, human donors who had consented to whole-body donation. Interventions: Tissue blocks containing the lateral anal canal were collected and processed for histological and immunohistochemical analyses in the transverse and coronal planes. Main Outcome Measures: Identification of the sphincter muscles, longitudinal muscles, levator ani muscles, interbundle gaps, and connective tissue compartments as well as their spatial relationships. Results: The longitudinal muscles exhibited a mosaic structure with dense and loose regions. The dense region ended near the mid-height of the internal sphincter, whereas the loose region expanded inferiorly to form a wide compartment of sparse fibers and loose connective tissue. From this compartment, the loose fibers branched laterally and inferiorly, passing through natural gaps within the external sphincter muscle. Two overlapping layers of the levator ani muscle were also identified. The loose compartment beneath the longitudinal muscle corresponded to the site identified by Parks classification as the origin of abscess formation. Limitations: Specimens were obtained from formalin-fixed cadavers of elderly donors, only the lateral anal canal wall was assessed, and correlations with clinical fistulas were inferential. Conclusions: The region between the sphincter muscles is not a simple plane, and instead, a heterogeneous compartment; its structural features provide a basis for the initiation and propagation patterns described in the Parks classification of anal fistulas.
2025-12-16 | [Transformation and evidence-based progress of diagnosis and treatment mode for complex anal fistula].
Complex anal fistula remains a particularly challenging clinical condition, the primary difficulty in its management lies in the risk of damage to the anal sphincters, which is associated with a high incidence of treatment failure, recurrence and impairment of anal function, potentially leading to varying degrees of fecal incontinence in severe cases. Currently, there is no established gold-standard for the treatment of complex anal fistula, and efforts to identify effective therapeutic approaches continue. With advancements in medical science, the diagnosis and management of complex anal fistula have gradually transitioned from empirical medicine to evidence-based medicine, with continuous emergence of new theories and clinical evidence. This article reviews the relevant literature and systematically summarizes recent evidence-based medical findings on complex anal fistula, explores the driving factors in the evolution of diagnostic and therapeutic paradigms, and analyzes current clinical controversies and focal points. Furthermore,it elaborates on evidence-based diagnosis and treatment strategies, including preoperative precise assessment and selection of surgical techniques, with the aim of providing clinical practical guidance and promoting the advancement of diagnostic and therapeutic standards for complex anal fistula.
2025-09-03 | Gut microbiota and perianal abscess and anal fistula: A bidirectional Mendelian randomization study.
Perianal abscess and anal fistula are debilitating surgical conditions characterized by severe pain, persistent pus discharge, and prolonged recovery periods with high recurrence rates, collectively imposing profound burdens on patients' quality of life, social functioning, and work productivity. Research has indicated potential distinction regarding the composition of gut microbiota in patients suffering from perianal abscess and anal fistula. The causal effect is yet unclear. The MiBioGen consortium was utilized to acquire data pertaining to gut microbiota, while the outcome data was provided by another project called the MRC Integrative Epidemiology Unit Open Genome-wide Association Studies (IEU Open GWAS) project. We performed bidirectional two-sample Mendelian randomization (MR) using inverse variance weighted (IVW) as the primary method, selected for its robustness to balanced pleiotropy when valid instrumental variables are used. Additionally, sensitivity analyses were conducted to examine the robustness of the results. Four gut microbiota taxa showed causal associations with perianal abscess risk: Eubacterium brachy group (OR = 1.41, P = .004), Ruminococcaceae UCG003 (OR = 0.61, P = .007), Erysipelatoclostridium (OR = 0.68, P = .009), and Butyrivibrio (OR = 0.81, P = .016). For anal fistula, 8 taxa were significant: Catenibacterium (OR = 1.22, P = .042) and Eubacterium ruminantium group (OR = 1.17, P = .013) increased risk, while Haemophilus (OR = 0.79, P = .005), Alloprevotella (OR = 0.78, P = .001), Ruminiclostridium5 (OR = 0.79, P = .019), Erysipelotrichaceae UCG003 (OR = 0.82, P = .034), Butyrivibrio (OR = 0.88, P = .006), and Escherichia-Shigella (OR = 0.82, P = .039) conferred protection. Furthermore, the findings from the sensitivity analyses demonstrate robust stability in these conclusions. Reverse MR analyses did not suggest reverse causality. This is the first MR investigation into the causal relationships between the onset of perianal infections and particular taxa of the gut microbiota. It enhances our comprehension of the correlation.
proteins
2025-07-09 | Single-cell RNA sequencing reveals the therapeutic mechanism of Calvatia lilacina in promoting wound healing of anal fistula
Background: Anal fistula is one of the most common and frequently occurring diseases in the anorectal department. Calvatia lilacina spore (CLS) has been applied for wound treatment with a long history as a traditional Chinese medicine (TCM). However, the mechanism of CLS to treat postoperative wound of anal fistula remains unclear. The present study aims to investigate the efficacy and mechanism of CLS in promoting anal fistula wound healing from the perspective of regulating the interaction between macrophages and fibroblasts. Methods: Twenty patients who received anal surgery were recruited in Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. We presented a single-cell atlas of granulation tissue, comparing samples with and without CLS treatment, utilizing single-cell RNA sequencing. The pharmacological effects and mechanism of CLS on anal fistula wound were assessed using elisa, IHC staining, western blot, IF staining, flow cytometry assays and cell co-culture. Results: The CLS had a uniform particle size and contained components mainly including proteins, steroids, polysaccharides and polyphenols. CLS reduced the expression level of TNF-α and increased the expression levels of VEGF, Collagen I in the granulation tissue. The single-cell sequencing revealed that the expression level of IL-6 and CXCL-8 was increased in the IL-6+ macrophages that promoted the expression of WASF3 in fibroblasts and further recruited ACTR2, ACTR3. Finally, CLS increased intercellular communication between macrophages and fibroblasts, enhancing MSF migration ability by activating JAK2/STAT3 signaling pathway. Conclusion: Our study objectively demonstrated the pharmacological effects of CLS in promoting the wound healing of anal fistula and investigated its mechanisms in terms of regulating the immune inflammatory process of macrophages increases signal communication with fibroblasts while promoting fibroblast transformation.
2025-01-15 | Curing cryptoglandular anal fistulas-Is it possible without surgery?
Empirical reviews suggested that cryptoglandular anal fistulas require surgical resolution. However, some reports have indicated the possibility of nonsurgical and conservative treatment, which is discussed in this review. This review explores the potential of nonsurgical approaches for curing anal fistulas through bacterial inhibition and immunomodulation. The longstanding cryptoglandular theory has been a subject of controversy, prompting the reevaluation of conventional surgical interventions for anal fistulas. The review was conducted through database searches, including Medline, EMBASE, PubMed, and the Cochrane Library. Emerging evidence suggests that targeting the anaerobic environments present in anal fistulas and perianal abscesses and eradicating bacteria and their by-products may be critical for successful treatment. Immunomodulatory strategies show promise as a potential avenue for the nonsurgical management of anal fistulas. Ongoing developments in pharmacological research offer opportunities for alternative treatment options, shedding light on the prospects of noninvasive anal fistula management.
2024-10-21 | [Treatment of chronic sinus tract leakage at rectal anastomosis with anal fistula endoscopy].
Objective: To introduce the method of using anal fistula endoscope to treat chronic sinus tract leakage at rectal anastomosis site. Methods: We used anal fistula endoscopy to treat a patient with chronic sinus tract leakage after radical resection of rectal cancer, mainly including the following 5 steps: (1) establishing a water injection circulation system through the anus; (2) scraping off purulent coating and mucosa on the surface of the sinus tract with the brush; (3) hemostasis and removal of necrotic tissue with electrocoagulation rods; (4) filling the sinus tract with bioprotein gel; (5) compressing the sinus tract with transanal drainage tube. Results: The patient is a 70 year old male with rectal cancer. After undergoing 3D laparoscopic assisted radical resection of rectal cancer via abdominal anterior resection (Dixon's procedure) and diverting ileostomy surgery for more than 3 months, leakage of the rectal anastomosis was found through colonoscopy and anal iodine water contrast imaging .The patient started eating and flowing juice 6 hours after surgery, got out of bed 24 hours after surgery, and was discharged 48 hours after the removal of the anal canal. Three months after surgery, colonoscopy and transanal iodine hydrography showed that the sinus repair was intact. The diverting ileostomy was reduced 4 months after surgery. Conclusion: Anal fistula endoscope is safe and feasible for the treatment of chronic sinus tract anastomotic leakage in selected patients.
2024-05-06 | Use of Anal Fistula Plug for Treatment of Fistula-in-ano: A Novel Technique?
Abstract Background: Fistula-in-ano is a chronic phase of anorectal suppuration characterized by purulent discharge. The conventional gold standard fistulotomy opens the entire track to heal with secondary intention. Anal fistula plug (AFP) is one of the newer modalities where the track is debrided from within and plugged with a biodegradable material made of porcine small intestinal submucosa. Materials and Methods: A total of 100 patients were enrolled in a randomized prospective study into two groups: conventional fistulotomy (CF) group and AFP group with 50 patients in each arm. The demography and surgical outcomes were assessed for postoperative pain, discharge and recovery, and failure. Results: All 100 patients included in the study had a history of anorectal suppuration which led to the residual anal fistula. Postoperative pain and analgesic requirements were equal in the two groups. The recovery period and return to work were shorter in the AFP group, and this difference was statistically significant. The success rate was 100% in the CF group as compared to 76% in the AFP group. There was no significant complication, failure, or recurrence in the CF group as against allergy (1), extrusion of plug (2), and failure/recurrence (9) in the AFP group. Conclusion: Our study shows that the application of bioprosthetic plugs may be an alternative option in a select group of patients. AFP has also shown to have a faster recovery with less morbidity and comparable success rates.
2023-11-15 | Treatment Approaches for the Effective Management of Anal Fistula in the Modern Era
A complication of incision drainage or abscess ulceration around the anus and rectum is anal fistula which manifests as the creation of irregular channels linking the rectum and anal canal with the skin circumambient to the anus. It mostly affects the male population having a yearly frequency of two cases per ten thousand individuals. Histologically in anal fistula chronic inflammatory cells and fibrous tissues are surrounded by epithelialization of variable degree, which are categorized as squamous, columnar, or transitional zone epithelium. Anal fistula influences the psychological condition of the patients, which leads to depression or anxiety symptoms, in addition to severely impacting their standards of living. In general, anal fistula cannot be treated without medical intervention and the most efficient treatment for anal fistula is surgery. The optimal treatment in the modern era includes the elimination of the infected lesion, adequate drainage, and fistula closure while minimizing injury to the anal sphincter which includes treatment with fibrin glue, fistula plug, LIFT, etc.
cell therapies
2026-07-11 | Autologous concentrated growth factors promote M2 macrophage polarization to accelerate wound healing after anal fistula surgery by activating the AKT/mTOR pathway.
Delayed healing of post-operative anal fistula wounds is driven by a hostile inflammatory microenvironment. While autologous concentrated growth factors (ACGF) show regenerative potential, the underlying immunomolecular mechanisms remain unclear. This study investigates if ACGF accelerates contaminated wound healing by modulating macrophage polarization via the AKT/mTOR pathway. In vitro, RAW264.7 macrophages were treated with ACGF to assess phenotypic switching and AKT/mTOR activation. The paracrine effects of ACGF-primed macrophages on fibroblasts were evaluated using a co-culture system with AKT-siRNA validation. In vivo, a rat fecal-contaminated wound model was established. Therapeutic efficacy, with or without the AKT inhibitor Triciribine, was assessed via laser speckle imaging, histology, and immunofluorescence. ACGF effectively reprogrammed macrophages from a pro-inflammatory M1 phenotype toward a reparative M2 phenotype, significantly upregulating CD206 and Arg-1 expression while activating AKT/mTOR signaling. Mechanistically, ACGF-primed macrophages significantly boosted RSF proliferation, migration, and collagen synthesis, effects that were substantially abrogated by AKT silencing. In vivo, ACGF treatment markedly accelerated wound closure, enhanced microvascular perfusion, and increased the density of CD31 + and Ki67 + cells. These regenerative benefits were accompanied by a significant shift toward M2 infiltration and a reduction in pro-inflammatory cytokines, all of which were reversed by pharmacological inhibition of AKT. ACGF promotes the healing of contaminated wounds by orchestrating an AKT/mTOR-dependent macrophage M2 polarization. This shift initiates a beneficial paracrine relay that enhances fibroblast activity and neoangiogenesis, effectively restoring the regenerative niche. Our findings establish ACGF as a potent immunomodulatory biomaterial and offer a promising therapeutic strategy for complex perianal wounds and chronic recalcitrant defects.
2026-06-23 | Use of microfragmented autologous adipose tissue (LIPOGEMS®) as a sphincter-saving therapy for complex anal fistulas: a single-center retrospective study.
Complex anal fistulas remain a therapeutic challenge due to high recurrence rates and the risk of incontinence associated with conventional treatments. Microfragmented autologous adipose tissue has emerged as a sphincter-sparing option with potential regenerative and anti-inflammatory properties. This study aimed to evaluate the safety and efficacy of its injection into the fistula tract combined with closure of the internal opening. A single-center, retrospective, observational study was conducted between June 2019 and May 2025. All patients with complex anal fistulas treated with microfragmented adipose tissue processed with LIPOGEMS® system were included. Demographic data, fistula characteristics, surgical history, perioperative variables, postoperative morbidity, healing rate, and hospital stay were analyzed. Follow-up visits were performed weekly in the first month, and at 3, 6 and 12 months thereafter. A total of 28 patients with complex fistula were included. Mean patient age was 51.2 years (SD: 15.3), with predominance of males (69.7%). Most fistulas were medium or high transsphincteric (85.7%) and the main location was posterior (57.1%). 75% of patients had undergone previous curative-intent procedures. Median operative time was 71 minutes, and median processed adipose volume was 14 ml. Two postoperative complications were recorded (one abdominal hematoma-CD I and one perianal abscess-CD IIIa). After a median follow-up of 11.2 months, the overall healing rate was 46.4%, higher in primary (57.1%) and posterior fistulas (56.3%). Median hospital stay was one day, and median clinical closure occurred at 2.7 months. LIPOGEMS® therapy appeared safe, feasible, and associated with encouraging healing outcomes, offering advantages in functional preservation and recovery. Larger prospective studies are needed to confirm these results and refine its role in fistula management.
2026-06-20 | Comparison of incision and drainage procedure with drainage and ligation of the intersphincteric fistula tract in the treatment of deep perianal abscess.
Patients with deep perianal abscess (DPA) and transsphincteric fistula typically require incision and drainage as emergency treatment. However, recurrent abscesses and fistulas are common. This study aimed to evaluate the impact of simultaneous ligation of the intersphincteric fistula tract (LIFT) on abscess recurrence, incontinence, and fistula healing. This study is a retrospective analysis of an institutional protocol and includes 111 patients divided into two groups: Group I (incision and drainage alone, n = 57) and Group II (incision and drainage combined with the LIFT procedure, n = 54). The primary endpoint was persistent fistula at 6 months, confirmed by clinical examination and magnetic resonance imaging (MRI). Secondary endpoints included abscess recurrence, Wexner incontinence score changes, and complications. Firth's penalized logistic regression, inverse probability of treatment weighting (IPTW), and log-rank analyses were performed to assess outcomes. At the 3rd month, the number of patients with persistent fistula was 16 (28.1%) in Group I, while it was 3 patients (5.6%) in Group II (P = 0.002). At the 6th month, persistent fistula was observed in 21 of 55 patients (38.2%) in Group I and 3 of 53 patients (5.7%) in Group II (P < 0.001). Firth's penalized logistic regression showed that the LIFT procedure was significantly associated with reduced fistula persistence (OR = 0.079, 95% CI 0.019-0.327, P < 0.001). A sensitivity analysis restricted to patients with MRI-confirmed transsphincteric fistula (Group I: n = 34; Group II: n = 54) confirmed these findings (59.4% vs. 5.7%, P < 0.001). IPTW-adjusted analysis yielded consistent results (weighted OR = 0.063). This study demonstrates that the LIFT procedure, when applied together with drainage, reduces the incidence of persistent fistula and shows a non-significant reduction in abscess recurrence in patients with DPA and complex anal fistula. These findings should be interpreted with caution due to the non-randomized design and require confirmation through prospective randomized controlled trials.
2026-06-08 | Autologous platelet-rich fibrin matrix (Obsidian RFT) as a sphincter-preserving treatment for anal fistula: a retrospective cohort study and subgroup analysis.
The treatment of anal fistula remains a delicate balance between achieving healing and preserving anal continence. Sphincter-preserving strategies, such as autologous platelet-rich plasma/fibrin (PRP/PRF) matrices, offer a regenerative approach with minimal morbidity. This study aims to evaluate the efficacy and safety of a specific autologous fibrin matrix system (Obsidian RFT) in the management of anal fistula and to identify predictors of treatment success. We conducted a retrospective analysis of patients treated with the Obsidian RFT system for anal fistula at a single institution between January 2020 and September 2025. The primary endpoint was fistula healing, defined as the complete cessation of drainage and closure of the external opening. Secondary endpoints included secondary healing (after a simple adjunctive procedure), overall final healing (after any reintervention), and postoperative fecal incontinence (Wexner score). A subgroup analysis was performed to evaluate outcomes in "ideal candidates" (single-tract, non-supralevator fistulas, no associated abscess). A total of 86 patients were included (mean age 52.4 ± 14.4 years; 64% male). The majority of fistulas were transsphincteric (96.5%). The median follow-up was 8.7 months. Primary healing was achieved in 45.3% of patients (39/86) after the first application. With the addition of a simple secondary procedure (repeat matrix application or limited fistulotomy), the secondary healing rate increased to 58.1% (50/86). Overall final healing, including patients requiring complex reinterventions, reached 64.0% (55/86). Persistence accounted for most failures, while true late recurrence was uncommon. Postoperative fecal incontinence was rare, occurring in only 2.3% of patients. In the "ideal patient" subgroup, primary healing was significantly higher (51.4%) compared to non-ideal candidates (18.8%; p = 0.018), rising to 65.7% with reintervention (p = 0.003). The Obsidian RFT system is a safe, sphincter-preserving option associated with minimal morbidity and negligible impact on continence. While primary healing rates are modest, the cumulative success rate significantly increases with a sequential approach, validating its use as a "staged" strategy. This modality serves as a valuable first-line treatment in a stepped-care algorithm to minimize incontinence risk before escalating to more invasive procedures.
2026-05-18 | Efficacy and safety of freshly collected autologous adipose tissue for complex anal fistulas in non-IBD patients: a prospective cohort study.
Complex cryptoglandular anal fistulas present a treatment challenge, with many surgical options associated with recurrence, variable healing rates, and risk of incontinence. Freshly collected autologous adipose tissue (FCAAT) has been proposed as a minimally invasive, one-step alternative. This study aimed to assess clinical healing and clinical improvement and to evaluate the safety of the procedure. This prospective cohort study included 31 patients without inflammatory bowel disease (IBD) with complex single-tract cryptoglandular anal fistulas treated with FCAAT between May 2019 and December 2023 and followed until August 2024. The surgical procedure involved liposuction, processing of adipose tissue, closure of the internal opening, and local injection along the fistula tract in a one-step procedure. Primary outcomes were clinical healing and clinical improvement; secondary outcomes were adverse events. The patient cohort presented with advanced disease. Median disease duration was 20 months, and one-third of patients had undergone previous attempts at surgical closure. Clinical healing was achieved in 23 patients (74%), with an additional four patients (13%) demonstrating clinical improvement. Five of 27 responders (19%) healed more than 3 months post-procedure. Common adverse events included proctalgia in 8 patients (22%), donor site pain 5 (14%), and minor graft site hematomas in 4 (11%). One Clavien-Dindo IIIa event (graft site bleeding) was managed with a single suture; all other complications were minor and resolved conservatively. FCAAT is a safe and effective one-step treatment for complex anal fistulas in non-IBD patients, offering a high healing rate with predominantly minor complications. A delayed effect was observed in some patients.
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Drug Discovery Landscape
4 orphan drug designations for Anal fistula, including 1 approved therapy.
4 orphan drug designations for Anal fistula, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
darvadstrocel | cell therapies | FDA | 2022-02-22 | — | Takeda Development Center Americas, Inc. |
expanded human allogeneic mesenchymal adult stem cells extracted from adipose tissue | cell therapies | FDA | 2017-10-18 | — | Takeda Development Center Americas, Inc. |
Darvadstrocel [Alofisel] | cell therapies | EMA | 2009-10-08 | 2018-03-27 | Takeda Pharma A/S |
Autologous adipose-derived mesenchymal stem cells expanded [Ontaril] | cell therapies | EMA | 2005-08-26 | — | Tigenix S.A. |
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