A systematic review and meta-analysis of the use of packing in the management of perianal abscesses.

BACKGROUND: Perianal abscesses are common presentations and reasons for emergency general surgery admissions. Management involves incision and drainage of the abscess and packing the cavity with internal wound dressings. This meta-analysis aimed to assess in adults if packing an abscess or leaving it unpacked leads to a significant difference in the outcomes of pain on wound dressing, time to healing, rate of fistulation and abscess recurrence. METHODS: Randomised controlled trials (RCTs) with participants aged 18 years or older that compared packing of perianal abscess cavities with no packing between 2002 and 2022 were searched for in December 2022 on OVID Medline and Embase, the CENTRAL register of trials, PubMed and Google Scholar. Risk of bias was assessed using the Cochrane Risk of Bias tool. Random effects meta-analysis was conducted on the data extracted. RESULTS: Three RCTs involving 490 patients were analysed for the outcomes of abscess recurrence and postoperative fistula formation; the data were not adequate to assess pain on dressing and time to healing. For unpacked versus packed, the pooled relative risk of abscess recurrence was 1.57 (95% confidence interval (CI) 0.764, 3.29, p=0.219) and for fistula formation 0.686 (95% CI 0.430, 1.09, p=0.114). These results suggest there is no significant benefit to packing abscess cavities. CONCLUSIONS: Analysis of the outcomes suggests there is no significant difference with regards to rates of abscess recurrence or fistula formation between the packed and unpacked groups; however, appropriately powered RCTs are required in this area to provide more primary evidence to inform best practice and clinical management.

Reconstruction of perianal skin defect using modified keystone flap after perianal tumor resection.

Purpose: The large resection area of perianal tumor makes the skin defect hard to reconstruct. The keystone flap has demonstrated a growing application in skin defects. Herein, we aimed to explore the efficacy of keystone flap in the repair of skin defect after perianal tumor resection. Methods: This study is a retrospective review of patients diagnosed with perianal tumor from January 2010 to November 2021. A standardized data collection template was used to collect variables. The detailed process of the reconstructive surgery is carefully described in this article. After surgery, the healing process was closely observed. Results: Twenty patients underwent keystone flap repair. The average wound size before closure measured 3.5 × 4.9 cm2. Primary wound healing was achieved, and the flap survived during the follow up period, which ranged from 6 to 24 months. No severe complications occurred; slight edema was noticed in one patient. Conclusion: The application of keystone flap is a promising way to repair skin defect after tumor removal, and the complications rate was low after surgery. It can be concluded that this method is an effective and reliable way to repair perianal skin defect.

Self-screening questionnaire for perianal fistulizing disease in patients with Crohn's disease.

Background/Aims: A poor prognostic factor for Crohn's disease (CD) includes perianal fistulizing disease, including perianal fistula and/or perianal abscess. Currently, a tool to assess perianal symptoms in patients with CD remains nonexistent. This study aimed to develop a perianal fistulizing disease self-screening questionnaire for patients with CD. Methods: This prospective pilot study was conducted at three tertiary referral centers between January 2019 and May 2020. We formulated questions on perianal symptoms, including tenesmus, anal discharge, bleeding, pain, and heat. A 4-point Likert scale was used to rate each question. Patients with CD completed a questionnaire and underwent pelvic magnetic resonance imaging (MRI). Results: Overall, 93 patients were enrolled, with 51 (54.8%) diagnosed with perianal fistulizing disease, as determined by pelvic MRI. The Spearman correlation findings demonstrated that anal pain (p = 0.450, p < 0.001) and anal discharge (p = 0.556, p < 0.001) were the symptoms that most significantly correlated with perianal disease. For anal pain and discharge, the area under the receiver operating characteristic curve of the scores was significantly higher than that of the combined score for all five symptoms (0.855 vs. 0.794, DeLong's test p = 0.04). For the two symptoms combined, the sensitivity, specificity, and positive predictive and negative predictive values were 88.2, 73.8, 80.4, and 83.8%, respectively, with 81.7% accuracy for detecting perianal fistulizing disease. Conclusions: This study indicates that simple questions regarding anal pain and discharge can help accurately identify the presence of perianal fistulizing disease in patients with CD.

Network Pharmacology Combined with Molecular Docking Approach to Investigate the Mechanism of ChuShiWeiLing Decoction Against Perianal Eczema.

BACKGROUND: ChuShiWeiLing Decoction (CSWLD) is a famous classical Chinese prescription for the treatment of eczema with desirable effect in clinical practice. It has gradually exerted good curative effects on perianal eczema (PE) in recent years, but its specific mechanism is not elucidated yet. OBJECTIVE: This research explores the underlying pharmacological mechanism of CSWLD in addressing PE through network pharmacology combined with molecular docking strategy. METHODS: The key chemical compounds and potential target genes of CSWLD were screened by bioinformatics. The major targets of CSWLD were discovered using network modules. Functional annotation of Gene Ontology (GO) was undertaken, as well as pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Molecular docking of core protein-ligand interactions was modeled using AutoDock software. Pymol software was used to perform a molecular dynamics simulation for the ideal core protein-ligand that was discovered by molecular docking. RESULTS: A total of 2,853 active compounds and 922 targets of CSWLD were collected. The target with a higher degree was identified through the PPI network, namely TNF, IL6, ALB, STAT3, EGFR, TLR4, CXCL8 and PTPRC. GO and KEGG analyses suggested that CSWLD treatment of PE mainly involves cellular activation, activation of leukocytes, and adhesion among leukocytes. The molecular docking results showed that wogonin, hederagenin and quercetin of CSWLD could bind to IL-6 and TNF, respectively. CONCLUSION: Our results indicated that the bioactives, potential targets, and molecular mechanism of CSWLD against PE.

Multicenter registry of pediatric inflammatory bowel disease from a developing country.

BACKGROUND: Despite the rising incidence of pediatric inflammatory bowel disease (PIBD) globally, multicenter collaborative studies of PIBD children among developing countries remain sparse. We therefore aimed to define the initial presentation and short-term outcomes of Thai children with PIBD from a multicenter registry. METHODS: Four teaching hospitals participated in this study. A diagnosis of PIBD requires gastrointestinal endoscopy and histopathology in children aged < 19 years. Besides demographics, we collected clinical information and treatment with the data at 1-year follow up. RESULTS: We included 35 Crohn's disease (CD), one IBD-unclassified, and 36 ulcerative colitis (UC) children (total n = 72 with 60.6% males). The mean age at diagnosis was 7.9 years (SD 4.1) with 38% being very early onset IBD (VEO-IBD). When compared with UC, the CD children were more likely to exhibit fever (42.3 vs. 13.9%), weight loss/failure to thrive (68.6 vs. 33.3%), and hypoalbuminemia (62.9 vs. 36.1%) but less likely to have bloody stools (51.4 vs. 91.7%) (all P < 0.05). No significant differences in demographics, clinical data and medications used with regards to VEO-IBD status. At 1 year after diagnosis (n = 62), 30.7% failed to enter clinical remission and 43.7% remained on systemic corticosteroids. Diarrhea (OR 9.32) and weight issues (OR 4.92) at presentation were independent predictors of failure to enter clinical remission; and females (OR 3.08) and CD (vs. UC) (OR 3.03) were predictors of corticosteroids use at 1-year follow-up. CONCLUSIONS: A high proportion of VEOIBD is noted, and CD was more likely to present with significant inflammatory burden. Diarrhea and weight issues at presentation were independent predictors of failure to enter clinical remission; and females and CD (vs. UC) were predictors of corticosteroids use at 1-year follow-up.

[Key microbial monitoring and clinical analysis of bloodstream infections and CRO colonization after hematopoietic stem cell transplantation in hematological patients].

Objective: To investigate the distribution and clinical characteristics of pathogenic bacteria following hematopoietic stem cell transplantation (HSCT), as well as to provide a preliminary research foundation for key microbial monitoring, and clinical diagnosis and treatment of infections after HSCT in hematological patients. Methods: We retrospectively analyzed the clinical data of 190 patients who tested positive for microbial testing [G-bacteria blood culture and/or carbapenem-resistant organism (CRO) screening of perianal swabs] at our center from January 2018 to December 2022. Patients were divided into blood culture positive, perianal swab positive, and double positive groups based on the testing results. The three patient groups underwent statistical analysis and comparison. Results: The top four pathogenic bacteria isolated from sixty-three patients with G-bacteria bloodstream infection (BSI) were Escherichia coli (28 strains, 43.75% ), Klebsiella pneumonia (26 strains, 40.63% ), Pseudomonas aeruginosa (3 strains, 4.69% ), and Enterobacter cloacae (3 strains, 4.69% ). The top three pathogenic bacteria isolated from 147 patients with CRO perianal colonization were carbapenem-resistant Klebsiella pneumoniae (58 strains, 32.58% ), carbapenem-resistant Escherichia coli (49 strains, 27.53% ), and carbapenem-resistant Enterobacter cloacae (20 strains, 11.24% ). The 3-year disease-free survival (DFS ) and overall survival (OS) of double positive group patients were significantly lower compared to those in the blood culture and perianal swab positive groups (DFS: 35.6% vs 53.7% vs 68.6%, P=0.001; OS: 44.4% vs 62.4% vs 76.9%, P<0.001), while non-relapse mortality (NRM) was significantly higher (50.0% vs 34.9% vs 10.6%, P<0.001). Failed engraftment of platelets and BSI are independent risk factors for NRM (P<0.001). Using polymyxin and/or ceftazidime-avibactam for more than 7 days is an independent protective factor for NRM (P=0.035) . Conclusion: This study suggests that the occurrence of BSI significantly increases the NRM after HSCT in patients with hematological diseases; CRO colonization into the bloodstream has a significant impact on the DFS and OS of HSCT patients.

The Cystic Sponge Anus.

Introduction: A peculiar spongy appearance of the perianal skin was observed in a patient who underwent wide excision surgery for inguinal and gluteal hidradenitis suppurativa (HS). Case Presentation: This peculiar appearance was observed in a 62-year-old male patient. It included multiple orifices and cavities forming the spongy aspect of the perianal skin with multiple cysts and giant comedones. The perianal lesions were asymptomatic and the patient had never received any perianal treatment for the comedones or cysts. Histopathology was performed and demonstrated dilated hair follicles with flaky keratin and loose hair shafts in the center. The spongy appearance was most likely the result of spontaneous shedding of the cystic contents. Conclusion: We suspect that the "cystic sponge anus" might be associated with HS, smoking, the male gender, and may yet be another expression of an occlusive follicular disease. Future studies will be needed to clarify the prevalence and comorbidities of the "cystic sponge anus."

TOpCLASS Expert Consensus Classification of Perianal Fistulizing Crohn's Disease: A Real-World Application in a Serial Fistula MRI Cohort.

BACKGROUND AND AIMS: Perianal fistulizing Crohn's disease (PFCD) is an aggressive phenotype of Crohn's disease defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by the TOpCLASS consortium that seeks to unify disease severity with patient-centered goals but has not yet been validated. We aimed to apply this to a real-world cohort and identify factors that predict transition between classes over time. METHODS: We identified all patients with PFCD and at least one baseline and one follow-up pelvic (pMRI). TOpCLASS classification, disease characteristics, and imaging indices were collected retrospectively at time periods corresponding with respective MRIs. RESULTS: We identified 100 patients with PFCD of which 96 were assigned TOpCLASS Classes 1 - 2c at baseline. Most patients (78.1%) started in Class 2b, but changes in classification were observed in 52.1% of all patients. Male sex (72.0%, 46.6%, 40.0%, p = 0.03) and prior perianal surgery (52.0% vs 44.6% vs 40.0%, p = 0.02) were more frequently observed in those with improved class. Baseline pMRI indices were not associated with changes in classification, however, greater improvements in mVAI, MODIFI-CD, and PEMPAC were seen among those who improved. Linear mixed effect modeling identified only male sex (-0.31, 95% CI -0.60 to -0.02) with improvement in class. CONCLUSION: The TOpCLASS classification highlights the dynamic nature of PFCD over time, however, our ability to predict transitions between classes remains limited and requires prospective assessment. Improvement in MRI index scores over time was associated with a transition to lower TOpCLASS classification.

Longitudinal evaluation of the cutaneous and rectal microbiota of German shepherd dogs with perianal fistulas undergoing therapy with ciclosporin and ketoconazole.

BACKGROUND: Perianal fistulas are painful ulcers or sinus tracts that disproportionately affect German shepherd dogs and are proposed as a spontaneous animal model of fistulising Crohn's disease. OBJECTIVES: To characterise the rectal and cutaneous microbiota in German shepherd dogs with perianal fistulas and to investigate longitudinal shifts with lesion resolution during immunomodulatory therapy. ANIMALS: Eleven German shepherd dogs with perianal fistulas and 15 healthy German shepherd dogs. MATERIALS AND METHODS: Affected dogs were evaluated and swabbed at three visits, 30 days apart, while undergoing treatment with ciclosporin and ketoconazole. Healthy German shepherd dogs were contemporaneously sampled. Sites included the rectum, perianal skin and axilla. The microbiome was evaluated following sequencing of the V4 hypervariable region of the 16S ribosomal RNA (rRNA) gene. RESULTS: Alpha diversity was not significantly different between healthy and affected dogs at each of the three body sites (p > 0.5), yet rectal and perianal beta diversities from affected dogs differed significantly from those of healthy dogs at Day 0 (p = 0.004). Rectal and perianal relative abundance of Prevotella spp. increased and perianal Staphylococcus spp. relative abundance decreased in affected dogs over time, coincident with lesion resolution. CONCLUSIONS AND CLINICAL RELEVANCE: Changes in lesional cutaneous and rectal microbiota occur in German shepherd dogs with perianal fistulas and shift over time with lesion resolution during immunomodulatory therapy. Further investigations of the role of cutaneous and enteric microbiota in the pathogenesis of perianal fistulas, and whether manipulation of microbial populations may ameliorate disease, are needed.

Anorectal Infections in Neutropenic Leukemia Patients: A Common Clinical Challenge.

Anorectal infections in neutropenic leukemia patients are a significant and potentially life-threatening complication. The pathogenesis of this condition is not entirely understood and believed to be multifactorial, including mucosal injury as a result of cytotoxic drugs, profound neutropenia and impaired host defense. Establishing an early diagnosis is key and often made clinically on the basis of signs and symptoms, but also from imaging studies demonstrating perianal inflammation or fluid collection. The management of anorectal infections in neutropenic leukemia patients is not straightforward, as there are no well-conducted studies on this entity. This review seeks to provide a framework into the pathophysiology and clinical presentation of anorectal infections in neutropenic leukemia patients, propose a diagnostic approach and to discuss controversies in the management of this condition.

Perianal disease: Updates and controversies in closing the gaps.

Perianal complications are common and morbid in children with Crohn's disease. In this review, we describe the epidemiology, the presentation and diagnosis, evaluation and management. We focus on updates such as the increasing frequency of biologic medications and MRI for evaluation. We also highlight controversies on the timing and approaches to surgical techniques. Finally, perianal disease requires the coordination of multidisciplinary care with nursing, radiology, gastroenterology, and surgery to optimize outcomes - both medical and patient-centered.

Vaginal delivery in women with perianal Crohn's disease: why not?

BACKGROUND: Pregnant women with active perianal Crohn's disease indicate a cesarean delivery according to the current European Crohn's and Colitis Organisation guidelines. This advice is based on the assumption that vaginal delivery leads to exacerbation of perianal disease and worsening of fecal continence. However, there is no strong evidence to support this. OBJECTIVE: This study aims to examine the effects of the delivery method on perianal disease progression and fecal incontinence in women with perianal Crohn's disease. STUDY DESIGN: In this retrospective cohort study, 102 women were selected from the 1000 inflammatory bowel disease cohort of a tertiary hospital in the Netherlands. All women are aged >18 years, have perianal Crohn's disease, and have given birth. In addition, all women completed a questionnaire. Fecal continence was scored using the Vaizey score. Using SPSS, descriptive analysis and linear regression analysis were performed, and P values <.05 were considered statistically significant. RESULTS: The cesarean delivery rate within our cohort was 19.5%. Within the group of women who delivered at least one child vaginally (n=84), 25.5% reported alteration of fecal continence, compared with 13.1% in women who only had cesarean delivery (n=18). After a mean follow-up of 15 years, the median Vaizey score within the cesarean delivery group was 5, compared with 7 in the vaginal delivery group. Within the vaginal delivery group, 18.8% reported perianal disease progression, compared with 22.2% in the cesarean delivery group. No significant relation between mode of delivery and fecal continence or perianal disease progression was found (B, 0,97 [-1,19 to 3,14], P=.38). CONCLUSION: Fecal incontinence and perianal disease progression after vaginal delivery in Crohn's disease women with active perianal fistula is not significantly increased in this retrospective cohort. This study opens the discussion for more tailored obstetric advice in women with perianal Crohn's disease.

Insights into treatment of complex Crohn's perianal fistulas.

Complex perianal fistula is a common complication of Crohn's disease (CD) which leads to negative impact on patient's quality of life. Successful management of the disease requires a multidisciplinary approach, including a gastroenterologist and a colorectal surgeon, applying combined surgical and medical therapy. One of frequently practiced surgical procedures is seton placement in the fistula tract, which is used to control perianal sepsis and drain the fistula, while preventing recurrent abscess formation.Darvadstrocel, a suspension of expanded, allogeneic, adipose-derived, mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Following approval of darvadstrocel, the INSPIRE registry is being conducted in order to evaluate long-term safety and effectiveness of the drug on a large, heterogenous population.An online expert meeting was held from March 20 to March 30, 2023, which provided relevant insights into the decision-making process regarding seton use and obtained feedback on the first experiences with darvadstrocel. The aim of this article is to present the perspectives from gastroenterologists and colorectal surgeons practicing in Czechia, Hungary, Israel, Lithuania, Serbia, and Slovenia in topics such as diagnosis and treatment options for patients with complex Crohn's perianal fistulas (CPF), specifically focusing on the use of setons and darvadstrocel.During this virtual session, unavailability of comprehensive data on safety and efficacy of available treatment procedures was emphasized as an important obstacle towards development of standardized recommendations and improvement of outcomes in treatment of (CPF). Furthermore, achieving consensus in seton use, duration of its placement, and frequency of change is recognized as one of CPF treatments major challenges. Despite these issues, it is important to promote better understanding and treatment of complex perianal fistulas in order to improve the quality of life of those affected by this condition.

Very Early Onset of Fistulizing Inflammatory Bowel Disease With RIPK1 Mutation: A Case Report.

Infantile inflammatory bowel disease (IBD) is a very rare subgroup of IBD that develops in children younger than two years with genetic susceptibility, especially in those with monogenic defects. This type, when compared with IBD in older children, is more resistant to conventional medical treatment and presents with more complications that require more surgical interventions. Our patient is a male with first-degree consanguineous parents. He was 16 months old when he presented with multiple perianal fistulas, fissures, abscesses, diarrhea, fever, and failure to thrive. He underwent a protective double-barrel ileostomy and surgical repair of the perianal disease. Crohn's disease was confirmed after endoscopy and biopsy. A genetic workup was done and revealed receptor-interacting protein kinase 1 (RIPK1) mutations. Conventional pediatric IBD treatment was initiated after surgery, including tumor necrosis factor antagonist adalimumab 40 mg subcutaneously weekly for five months. Despite treatment, he presented with dysuria and a colovesical fistula. The patient underwent secondary surgical repair.

Current update on the role of endoanal ultrasound: a primer for radiologists.

Endoanal ultrasound (EAUS) is a valuable imaging modality for the evaluation of anal and perianal pathologies. It provides detailed information about the anatomy and physiology of the anorectal region and has been used in pre-and post-operative settings of anorectal pathologies. EAUS is not only useful in the evaluation of benign pathologies but also in loco-regional staging of anal and rectal tumors. EAUS has several advantages over MRI, including reduced cost, better patient tolerance, and improved scope of application in patients with contraindications to MRI. Despite its benefits, EAUS is not widely performed in many centers across the globe. This article aims to educate radiologists, trainees, and surgeons about the indications, contraindications, patient preparation, imaging technique, and findings of EAUS. We will also highlight the technical difficulties, diagnostic challenges, and procedural complications encountered during EAUS, along with a comparative analysis of EAUS with other imaging approaches.

Perianal Injury Prevention in Patients With Leukemia.

BACKGROUND: Perianal injuries in adults with hematologic malignancies can result in sepsis or death. Patients on a 36-bed acute care oncology unit experienced increased perianal injuries from 2018 to 2021 based on a chart review, which revealed that 24 patients with leukemia, all of whom had received cytarabine, developed perianal injuries. OBJECTIVES: This study examined whether a nurse-led educational intervention would decrease perianal injuries. METHODS: A survey examined baseline nurse knowledge on perianal injuries. Nurses received a 10-minute in-service education session about perianal injuries, their predisposing factors, and prevention strategies followed by a survey to test their knowledge. Twenty nurses completed the pre- and postintervention surveys. FINDINGS: After the intervention, staff knowledge increased by 33%. One year postintervention, perianal injuries had decreased by more than 50%. Nurse and patient education are vital to decrease perianal injuries in patients with leukemia.

Which magnetic resonance imaging feature is associated with treatment response in perianal fistulizing Crohn's disease?

PURPOSE: Perianal fistulae are disabling complications of Crohn's Disease. Magnetic resonance imaging features could predict treatment response. This study aimed to determine which magnetic resonance imaging features were predictive of long-term clinical outcome in real life. METHODS: Consecutive patients with magnetic resonance imaging performed in a tertiary center were retrospectively analyzed. Clinical outcome was defined as a need for surgical drainage of perianal fistulae or hospitalization. Clinical data and magnetic resonance imaging features (MAGNIFI-CD and Van Assche indices, degree of fibrosis) were studied. RESULTS: Fifty-two patients were included between 2016 and 2019 with a mean follow-up of 38 months [29;48]. A higher MAGNIFI-CD index (17/25 versus 11/25; p < 0.01) was associated with an unfavorable long-term clinical outcome. The MAGNIFI-CD index showed an area under the curve of 0.74 (p = 0.006) to predict the clinical outcome of perianal Crohn's disease, compared to 0.67 (p < 0.05) for the Van Assche index. At a threshold of 13 for the MAGNIFI-CD index, sensitivity was 75% (CI95% [59%; 86%]) and specificity was 69% (CI95% [44%; 86%]). No association was found between the degree of fibrosis and clinical outcome, but the association of a high degree of fibrosis (≥ 80%) and of a low MAGNIFI-CD index (≤ 13) was predictive of clinical outcome (p < 0.01). CONCLUSION: The MAGNIFI-CD index could be used to predict clinical outcome in perianal Crohn's disease. In combination with a high degree of fibrosis, a low MAGNIFI-CD index, may help to identify patients with the best prognosis.

Leukocyte Dysfunction and reduced CTLA-4 Expression are Associated with Perianal Crohn's Disease.

Although perianal Crohn's disease (PCD) is highly associated with the exacerbated inflammation, the molecular basis and immunological signature that distinguish patients who present history of perianal lesions are still unclear. This paper aims to define immunological characteristics related to PCD. In this cross-sectional observational study, we enrolled 20 healthy controls and 39 CD patients. Blood samples were obtained for detection of plasma cytokines and LPS. PBMC were phenotyped by flow cytometry. Leukocytes were stimulated with LPS or anti-CD3/anti-CD28 antibodies. Our results show that CD patients had augmented plasma IL-6 and LPS. However, their PBMC was characterized by decreased IL-6 production, while patients with history of PCD produced higher IL-6, IL-8 and IFN-γ, along with decreased TNF. CD patients had augmented FoxP3 and CTLA-4 regulatory markers, though the PCD subjects presented a significant reduction in CTLA-4 expression. CTLA-4, as well as IL-6 and TNF responses were able to distinguish the PCD patients from those who did not present perianal complications. In conclusion, IL-6, TNF, and CTLA-4 exhibit a distinct expression pattern in CD patients with a history of PCD, regardless of disease activity. These findings clarify some mechanisms involved in the development of the perianal manifestations and may have a great impact in the disease management.

Does combined medical and surgical treatment improve perianal fistula outcomes in patients with Crohn's disease? A systematic review and meta-analysis.

BACKGROUND: The optimal treatment of perianal fistulizing Crohn's disease (PFCD) is unknown. We performed a systematic review with meta-analysis to compare combined surgical intervention and anti-TNF therapy (combined therapy) vs. either therapy alone. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched systematically through December 2023. Surgical intervention was defined as an exam under anesthesia ± setons. We calculated weighted risk ratios (RR) with 95% confidence intervals (CI) for our co-primary outcomes: fistula response and healing, defined clinically as a reduction in fistula drainage or number of draining fistulas and fistula closure respectively. RESULTS: Thirteen studies were analysed: 515 patients treated with combined therapy, 330 patients with surgical intervention and 406 patients with anti-TNF therapy with follow-up between 10 weeks and 3 years. Fistula response (RR 1.10; 95% CI, 0.93-1.30, p=0.28) and healing (RR 1.06; 95% CI, 0.86-1.31, p=0.58) was not significantly different when comparing combined therapy with anti-TNF therapy alone. In contrast, combined therapy was associated with significantly higher rates of fistula response (1.25; 95% CI, 1.10-1.41, p<0.001) and healing (RR 1.17; 95% CI, 1.00-1.36, p=0.05) compared with surgical intervention alone. Our results remained stable when limiting to studies that assessed outcomes within 1 year and studies where <10% of patients underwent fistula closure procedures. CONCLUSION: Combined surgery and anti-TNF therapy was not associated with improved PFCD outcomes compared with anti-TNF therapy alone. Due to an inability to control for confounding and small study sizes, future, controlled trials are warranted to confirm these findings.