Perianal Abscess Research Articles

EARLY TUMOR NECROSIS FACTOR ANTAGONIST TREATMENT PREVENTS PERIANAL FISTULA IN PEDIATRIC CROHN’S DISEASE

Abstract BACKGROUND Perianal fistulizing complications (PFCs) develop amongst approximately 1/3 of children with Crohn’s disease (CD), are difficult to treat, and commonly recur. Recent retrospective studies suggested PFCs may be preventable with early therapy. We aimed to evaluate PFC prevention in a prospective cohort. Based on prior work, we hypothesized early tumor necrosis antagonist (anti-TNF) treatment would be associated with reduced risk of PFC development. METHODS The RISK cohort prospectively enrolled children (<18 yr) newly diagnosed with CD from 28 sites in North America (2008-2012). We obtained data from the Crohn’s & Colitis Foundation’s IBD Plexus program. PFCs were defined as perianal fistula and/or abscess. Patients with PFCs at or before enrollment were excluded. Non-penetrating perianal lesions such as skin tags and fissures were collectively considered “perianal lesions”. We evaluated treatment from enrollment until 1mo prior to PFC development or end of enrollment. Treatment was categorized into 3 mutually exclusive groups: 1) No immunosuppression; 2) Immunomodulators (IM, thiopurines and/or methotrexate) but no anti-TNF; and 3) Anti-TNF (regardless of IM). Steroids were considered separately. We performed nearest neighbor propensity score trio matching, matching patients across treatment categories on gender, age at diagnosis, growth delay, deep endoscopic ulcers, small bowel involvement, and colonic involvement. Using matched samples, we evaluated the predicted probability of PFC development first by treatment group, then by time to follow up of the medication initiation after studying into 6-time intervals to maximum 3yr. Logistic regression analyses were used to estimate the odds ratios (OR) for PFC development. RESULTS In total, 889 patients without PFC at enrollment in RISK were included. Overall, 41% were female, 70% were >10 yr old. The study included a moderately ill population, including 21% with growth delay, 43% with deep ulcers, and 70% with weighted pediatric Crohn’s disease activity index (wPCDAI) >30. After propensity score matching, 621 remained, including 207 in each treatment group. Propensity score matching was well balanced except more anti-TNF users (76%) had growth delay (26%) than IM (16%) or neither (65%; p=0.002). Regression revealed anti-TNF therapy was associated with 79% reduced odds, and perianal lesions 3-fold increased odds of PFC development. No other characteristic or treatment were significant (Table). Predicted probability of PFC development by each treatment group is depicted in the Figure. CONCLUSIONS In a prospective inception cohort of children with CD who had not yet developed PFCs, only early anti-TNF therapy use was associated with reduced risk of PFC development. These findings corroborate other studies, and indicate early treatment prevents or delays PFC development. Table. Adjusted odds ratio estimates of perianal fistula complications (after propensity matching). Figure. Predicted probability of developing perianal fistulizing complication by treatment group.

P753 Early perianal abscess recurrence in patients with perianal Crohn's disease on biologic therapy predicts long-term permanent fecal diversion

Abstract Background Generally, it’s difficult to estimate the efficacy of biologics (Bio) for perianal lesions of Crohn’s disease (CD) and lack of evidence. Sometimes, we experience the recurrence of perianal abscess and need to perform re-drainage even after starting 1st Bio. When the 1st bio fails, choosing an accurate 2nd Bio is difficult. The most severe result of this situation is rectal amputation. We wonder if any relationships between recurrence timing and long-term outcomes exist. We reviewed and aimed to know our institute’s perianal CD (pCD) treatment. Methods We retrospectively investigated patients' medical charts with pCD from 1988 to 2022 at Kenseikai Nara Coloproctology Center. We excluded the patients without using Bio or starting Bio after rectal amputation. The cases with missing values are excluded, too. We defined "early" as within two years and compared two cohorts, the early recurrence group (ER) and the no or late recurrence group (non-ER). We use the Kaplan-Meier method for calculating the time to fecal diversion. Results Eighty patients were recruited. The mean current age is 37.5 years old, and the onset of CD is 22.6 years old. The Perianal lesion’s onset is 24.5 years old. The male is 66, and 19 smokers are included. In this part, perianal lesion means only perianal abscess and fistula. Montreal Classification is shown in TABLE1. The Median follow-up duration was 142.5 months. We performed perianal surveillance (PS) for these patients, including EUA, Abscess Drainage, and seton placement, 3.1 times for each person. After the surgical interventions, we treat them with four Bio. After starting Bio, we experienced 33 early recurrences. We observed eight transient stoma creations, nine rectal amputations, and one anorectal cancer. Among them, we calculate the relationships between early recurrence and rectal amputation and find that early recurrence is a risk factor for permanent fecal diversion (HR 6.84 95%CI 1.48-31.7, p=0.0047 FIGURE1). We needed to switch the Bio for 31 patients during the observational period. To know which way of switching is effective for pCD, we calculate the relationships between the practice of switching and any treatment failure. Same class switching and changing MOA are not different for any treatment failure, which means re-abscess drainage and creation of any stoma (HR 0.40 95%CI 0.10-1.57 p=0.19). Conclusion Perianal abscess recurrence as we need to re-incision and drainage within two years after starting Bio treatment are related to permanent fecal diversion. We must pay attention to such kinds of patients, but the types of Bio we change didn’t affect any treatment failure. Further studies are needed in this field.

P1189 Clinical features and surgical necessity rate of fistulising perianal disease in newly diagnosed patients with Crohn's disease: Interim analysis of inception cohort registry study of patients with Crohn's disease (iCREST-CD)

Abstract Background Fistulising perianal diseases (FPD) are common in patients with Crohn's disease (CD) in Asia, but the treatment pattern and the proportion of patients who develop new FPD after diagnosis are not clear. An interim analysis of a large registry study was performed to evaluate the difference in prognosis between patients with and without FPD at diagnosis of CD and the incidence and timing of onset of FPD in patients without FPD at diagnosis of CD. Methods iCREST-CD is a prospective, non-interventional, longitudinal, observational registry study conducted at 19 tertiary centres in Japan. Patients newly diagnosed with CD from June 2016 to June 2020 based on the diagnostic criteria of the Japanese Guidelines, aged ≥16 years at the time of informed consent with no prior exposure to biologics were enrolled. Patient demographics, clinical data, disease activity and medical treatment record up to June 2022 were used. FPD were defined as a perianal abscess and/ or perianal fistula. Results Of the 662 patients with newly diagnosed CD for whom with or without FPD were recorded, 236 patients [35.6%] had FPD at diagnosis (Group A). Of the 426 patients who did not have FPD at the time of diagnosis, 32 patients developed FPD during the observation period (Group B), and 394 patients did not develop it (Group C). The mean age [SD] at the time of CD diagnosis in Groups A, B, and C was 25.0 [8.6], 31.6 [15.5], and 31.7 [14.4] years, respectively. The proportion of female was 21.2%, 34.4% and 37.8%, respectively; L2 disease location was 14.6%, 23.3%, and 18.0%, respectively; and B2+B3 disease behaviour was 27.5%, 53.1%, and 40.6%, respectively. The mean CRP (mg/L [SD]) was 28.5 [33.8], 42.4 [43.6], and 27.1 [36.3], respectively. For disease activity based on HBI score, the proportion with moderate (8≦HBI≦16) and severe (16<HBI) activity was 17.6%, 36.8%, and 24.0%, respectively (Table). The rate of patients who developed FPD was 4.5% (19 patients) by 12 months and 6.5% (28 patients) by 24 months, respectively (Figure). In Group A with a mean observation period (month [SD]) of 27.9 [8.8], 12.3% and 17.3% of patients needed perianal surgery at 12 and 24 months, respectively. In Group B with a mean observation period of 29.7 [7.7], 7 FPD patients [21.9%] subsequently underwent perianal surgery, all within 12 months of FPD onset. Conclusion Patients who did not have a perianal abscess or fistula at the time of their CD diagnosis but later developed these problems tended to have numerically higher CD activity at the time of diagnosis and were more likely to require perianal surgery. These results suggest that patients with highly active CD are at risk of developing new FPD and should be carefully monitored.

P300 An Expert Delphi Consensus: Early Identification of Patients at Risk of Crohn's Disease in Perianal Fistulas and Abscesses (PREFAB) and Identification and Management of Isolated Perianal Crohn's Disease (ipCD) - Part A, PREFAB

Abstract Background In ± 10% of all Crohn’s disease (CD) patients a perianal abscess (PAA) or fistula (PAF) is the manifesting symptom. The delay in diagnosis of CD, from fistula or abscess onset, is very long and associated with worse outcomes. The aim of this Delphi study was to reach consensus on a clinical decision tool to help select patients with raised suspicion of CD in PAA/PAF patients, to identify underlying CD earlier and reduce the diagnostic delay. Methods A panel of international experts in the field of proctology and/or Inflammatory Bowel Disease (IBD), consisting of surgeons, gastroenterologists and radiologists were invited to participate in the PREFAB part of this Delphi study. The first round was an electronic survey and the second round a virtual consensus meeting. In the first round, participants were asked to anonymously provide their opinion probing 1) the relevance and use of clinical characteristics (“Red Flags”) suggestive of underlying CD, 2) the use of faecal calprotectin (FCP) as an adjunct for screening for CD and 3) on the diagnostic work-up for IBD in PAA/PAF patients with raised clinical suspicion. In the second round, statements were paired/revised based on the feedback from the first round and presented in a final set of statements. Consensus was predefined as ≥70% agreement. Results A total of 30 experts participated in the first round and 25 in the second round (83.3%). Final consensus was reached for 29% of all statements in the first Delphi round and, after adjustments/merging, for all 11 statements (100%) in the second round. Ninety-seven percent of participants agreed that shortening of the delay in diagnosis by using a clinical decision tool could improve outcomes in patients with perianal disease as a first symptom. Consensus was reached on the red flags to be included in the clinical decision tool, on screening of all patients with any perianal fistula (regardless of the complexity, biological behaviour and co-existent perianal symptoms) to identify CD in an early (sub)clinical phase, on referral criteria and on the diagnostic workup and follow up of patients with raised suspicion. Conclusion A clinical decision tool for early identification of CD in patients with PAA/PAF as a first symptom could shorten delay in diagnosis and improve outcomes. Global consensus for this tool, including a practical and relevant algorithm for finding or excluding CD in patients with PAA/PAF as a manifesting sign, was reached within two rounds. This clinical decision tool will be validated in 2024 in a large, prospective multicenter study.

P997 New Objective Assessment of perianal Crohn’s disease, Perianal Lesion Index; PLI

Abstract Background In the previous survey, decisions of biological treatment (Bio) success for perianal Crohn’s disease (pCD) were made by the patient’s subjective improvement and physician’s assessment, so it lacks objectivity. Moreover, physicians, surgeons, and proctologists are related to treating pCD. This aspect is the difficulty of the treatment of pCD. We need a common assessment for each area’s doctor. We aimed to develop a new objective assessment of pCD, including endoscopic findings, and assess the efficacy of the newly launched Bio except anti-TNFα agents for pCD. Methods Usually, perianal abscesses and fistula are derived from ulcers in the lower rectum and anal canal, so we adapted SES-CD to the location and checked discharge and needs of setons, and finally scored it (Table 1). We named this assessment Perianal Lesion Index; PLI. We retrospectively evaluated 20 pCD patients who received Ustekinumab (UST) and Vedolizumab (VDZ) from March 2017 to March 2023 at our institute. We checked each patient’s PLI, CRP, LRG, and CDAI and compared them before starting Bio and eight weeks after initiation of Bio using a paired T-test. Finally, we used the Pearson correlation coefficient to examine the correlation between PLI and conventional serum biomarkers and CDAI. Results The male-to-female ratio was 4.0, the average age at the treatment initiation was 35. Eighteen patient’s diseases were located in the small and large intestines, 10 patients were penetrating type, and 2 patients were stenotic type. We used UST for 16 patients and VDZ for 4 patients. Seven patients were naïve for Bio, 8 patients were treated by one Bio, and 5 patients were treated by two Bio.PLI was positively correlated with CRP (r=0.59, p<0.001) but not correlated with LRG (r=0.77, p=0.077) and CDAI (r=0.35, p=0.07). The pretreatment average PLI was 8.5 and significantly decreased to 3.9 (p<0.001) 8 weeks after Bio initiation. There was a significant change in CRP (3.1 to 0.9, p =0.03) but not CDAI (193 to 147, p=0.2). There were significant PLI changes in each treatment group; the UST group’s PLI change was 8.3 to 3.1 (p<0.001), and the VDZ group's PLI was 9.5 to 8.0 (p=0.02) (Figure 1). Conclusion PLI seems to be an objective assessment for pCD, and it was positively correlated to CRP. We could assess each drug’s efficacy for pCD. Further investigation is needed to establish PLI’s accuracy, and we hope this assessment will contribute to the choices of Bio for pCD and the evaluation of its efficacy

P519 Assessment of anal sphincter complex in pregnant patients with non-active perianal Crohns disease

Abstract Background Pregnant IBD patients are more likely to undergo Cesarean delivery (CS).. Active perianal Crohn’s disease (PCD) is the only Crohns - related indication for CS. The rationale for CS in this group is that active PCD damages the sphincters and therefore a vaginal delivery may exacerbate the damage to the point of fecal incontinence. Pregnant PCD patients with non-active PCD are commonly not offered CS. We suspect that lack of active PCD does not necessarily attest for the physiological function of the anal complex sphincter and that vaginal delivery may exacerbate their condition to the point of incontinence. Therefore, we conducted a prospective trial to examine, prior to delivery, the anatomy and physiology of the sphincter complex in our cohort and weather pregnant patients with non-active PCD suffer from sphincter damageMethods All consecutive pregnant patients with Non-active PCD were enlisted. Patients underwent physical examination, anal manometry and Trans Rectal Ultra Sound (TRUS) before conception or during pregnancy before delivery. Active PCD was defined as: Perianal abscess, fistulas with active drainage, severe fissures and stricture. Non active PCD was defined as history of prior PCD, history of surgery for perianal fistula or old scars from previous abscess drainage. Results There were 13 patients who were enlisted to our study. Table 1 describes the TRUS, Manometry and pregnancy details. There were 9 patients (69%) with evidence of sphincter damage in our cohort including external and/or internal sphincter of at least 30 degrees of the muscle radius. Of them, 6 had posterior damage and 4 had anterior damage. In Manometry all patients had either normal or satisfying results. Three patients were strongly recommended to choose CS due to the sphincter damage. Conclusion patients with non-active PCD and future intent to deliver should be assessed routinely regarding their sphincter complex status. This should include TRUS, manometry and clinical evaluation. We discuss with each patient the advantages and disadvantages of vaginal delivery versus CS, weighing the risk of repeated CS (mainly placenta previa and accreta) against the risk of incontinence. Maternal age, Obstetrical history and estimated fetal weight at delivery are the main factors to consider. Although it is still unclear if detected muscle injury affect clinical incontinence, it is our practice to recommend CS for patients with significant muscle damage. We emphasize our recommendation specifically in patients with anterior damage because potentially delivery damage would be to the same area

P974 Incidence of Perianal Complications in Clinical Trials for Therapies for Moderate to Severe Inflammatory Bowel Disease

Abstract Background Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) with distinct clinical consequences. Distinct from patients with UC is that nearly 25% of patients with CD patients have or will develop perianal disease. Predictors for the development of new perianal disease or complications from existing perianal disease are not well described but such occurrences are included as adverse events (AEs) in clinical trials for IBD. We performed a systematic review and meta-analysis of perianal AEs in pivotal trials of therapies for IBD. Methods We conducted a search of PubMed, EMBASE, MEDLINE, Medline Plus, and CDSR library databases for registry and pivotal Phase II-III clinical trials of therapies for IBD. Safety data from clinicaltrials.gov was reviewed to identify incidence of perianal AEs using the terms "abscess" and "fistula." Reported perianal AEs included the following: anal abscess, fissure, fistula; perianal abscess, fistula; perineal abscess; perirectal and rectal abscess; subcutaneous (gluteal) abscess. Results Perianal AE incidence across all trials reviewed was 0.47% (91/19,327 patients). Perianal AEs were more likely to occur in patients with CD (0.77%, 70/9,046) than UC (0.20%, 21/10,281). Perianal AEs occurred more frequently in populations of drug-exposed patients than in patients exposed to placebo. In drug-exposed patients with UC, 0.22% (16/7,415) of patients experienced a perianal AE vs 0.17% (5/2,935) of patients exposed to placebo. In drug-exposed patients with CD, 0.76% (55/7,271) of patients experienced a perianal AE vs 0.61% (15/2,465) of patients exposed to placebo. The results are summarized in Table 1. Conclusion We found that perianal AEs occur in pivotal UC and CD clinical trials. Expectedly, the frequency of perianal AEs was higher in trials of CD than those for UC. However, the development of perianal AEs in trials of UC suggests that these patients may have been misclassified and have CD. Available data do not allow distinction between development of a perianal AE in a patient with known perianal disease or progression of undiagnosed clinical or subclinical perianal disease, nor does it allow for distinction in a patient not responding to the experimental agent. The finding that perianal AEs occurred more frequently with drug exposure than placebo may be due to fistula healing with consequential abscess formation or unique mechanistic effects that worsen perianal disease. These results highlight a probable rate of misclassification of patients with UC in pivotal trials, and suggest the possibility of subclinical perianal disease in some patients. Further clarification and study of these AEs and their implications are warranted.

P419 Proximal Crohn’s disease location is associated with a more benign course of perianal Crohn’s disease (the PERIAPROX study)

Abstract Background Proximal Crohn’s disease (CD) location (L4 according to the Montreal Classification) is associated with a more severe course with higher risk of abdominal surgery. However, little is known about the relation with perianal disease. The aim of our study was to investigate the impact of L4 disease location on perianal disease incidence and clinical course. Methods A case-control study was conducted in the prospectively maintained ENEIDA database for all CD with and without L4 location between January 2005 and March 2023. Demographic data, disease characteristics, perianal disease diagnosis and evolution according to biologic therapy and surgery requirement were collected. Demographic data, CD characteristics, perianal disease diagnosis and course were analyzed. Cox proportional hazards and Kaplan-Meier methods were used for the analysis of perianal incidence, and biologic and surgery requirement. Results A cohort of 14022 CD patients were included in the analysis. The mean follow-up duration was 6.4 years (SD 4.9). L4 location showed a lower prevalence of perianal disease (18.0 vs 19.9%, p=0.018), with lower rate of fistulas (60.9 vs 66.1%, p=0.021) and perianal abscesses (33.5 vs 39.4%, p=0.013). Perianal disease and L4 were associated with male sex (OR 1.29, p<0.001), younger age (43 vs 44), and the structuring phenotype (OR 2.14, p<0.001). L4 location was associated with a lower incidence of perianal disease (HR 0.891, p=0.041), while proctitis was associated with a higher risk (HR=2.161, p<0.001). L4 location was also associated with a lower requirement for biologics (HR 0.712, p=0.023), along with advanced age (HR 0.988, p<0.001). Proctitis (HR 1.292) and a history of perianal surgery (3.373) were associated with a higher requirement for biologics. At univariate analysis, L4 location was associated with a lower requirement of surgery (HR 0.833), however at multivariate analysis this finding was not confirmed (p=0.525). Instead, a history of active smoking (HR 1.419), the use of biologics (HR 2.262), and CD penetrating pattern (HR 1.277) were associated with a higher requirement for perianal surgery. Conclusion L4 location is associated with a lower incidence of perianal disease and a more benign course with lower requirement for biologics and surgery.

DOP66 INSPIRE: Preliminary data from an observational post-marketing registry on the effectiveness and safety of darvadstrocel in patients with Crohn’s Disease and complex perianal fistulas

Abstract Background Darvadstrocel (DVS), a suspension of expanded allogeneic adipose-derived mesenchymal stem cells, is approved for the treatment of complex Crohn’s perianal fistulas (CPF). INSPIRE (EUPAS24267) is a European observational post-approval study evaluating real-world effectiveness and safety of DVS in patients with complex CPF for up to 36 months. Here we report preliminary clinical and safety outcomes from INSPIRE. Methods Patients with complex CPF who had received DVS according to local standard practice were eligible to enrol. Clinical response (closure of ≥50% of external openings [EOs]) and clinical remission (closure of all EOs) of DVS-treated fistulas that were draining at baseline, were evaluated in the all-treated (AT; received ≥1 dose of DVS with an evaluation for fistula response after 6 months) and per-protocol (PP; received DVS as per label-approved guidelines) cohorts. Treatment-emergent adverse events (TEAEs), serious TEAEs and AEs of special interest were reported for the safety cohort (all patients treated with DVS). Results As of April 2023, 652 patients had enrolled (Table 1). Complete data to evaluate 12-month clinical response and remission were available for 134 (AT cohort) and 124 (PP cohort) patients, of whom 79.9% (AT, n = 107) and 79.8% (PP, n = 99) had a clinical response and 76.1% (AT, n = 102) and 76.6% (PP, n = 95) had clinical remission (Figure 1). From baseline to Month 12, there was a decrease in the mean (standard deviation [SD]) Perianal Disease Activity Index score (–3.5 [3.3]; n/N = 96/302 and –3.7 [3.2]; n/N = 89/249) and a decrease in the mean (SD) Harvey–Bradshaw Index for Crohn’s disease activity (-0.3 [2.8]; n/N = 102/302 and -0.4 [2.9]; n/N = 95/249) in the AT and PP cohorts, respectively. Complete safety data were available for 619 patients (median [min–max] follow-up 480 [6–1595]) days. Overall, 26% (n = 162) had ≥1 TEAE and 10% (n = 63) ≥1 serious TEAE. The most frequent TEAEs were anal abscess (6.9%), COVID-19 (1.9%) and proctalgia (1.1%). No deaths were reported. One breast cancer lymph node metastasis and one ovarian epithelial cancer were reported; both events were confounded by immunosuppressant treatment and were not considered related to DVS treatment. Conclusion These preliminary data are consistent with the pivotal ADMIRE-CD study and demonstrate a single dose of DVS in patients with complex CPF is associated with positive clinical outcomes in up to 80% of patients, and a favourable safety profile, both of which are maintained after 12 months. The inherent limitations of registry-based studies mean these data should be interpreted with caution. However, the ongoing INSPIRE study will provide longer follow-up data to confirm these observations with respect to any study limitations.

P402 Early diagnosis of Crohn’s disease with perianal lesions as first clinical symptom: Development and validation of a new MR imaging-based model disease

Abstract Background Early diagnosis is crucial for the treatment and prognosis of Crohn's disease. Perianal fistulae or abscesses may present as the initial manifestation of Crohn's disease (CD) in patients. Despite magnetic resonance imaging (MRI) is the gold standard for the clinical assessment of perianal fistulae, there is shortage of MRI properties for clinical use in early perianal fistula diagnosis in CD. Methods Data from patients with a definitive diagnosis of PFCD and cryptoglandular disease (CGD) between September 2013 and December 2020 were examined retrospectively. The data was splited into training and test sets at a 7:3 ratio. The MRI characteristics were reviewed by two gastroenterology radiologists in consensus. The characteristics were then used to train a random forest classification model to predict a diagnosis of PFCD. The validity of the model was assessed using the area under the receiver operating characteristic curve (AUROC) and confusion matrix. Predictor importance was determined using the Shapley additive explanation (SHAP) framework. Results A total of 144 patients diagnosed with PFCD and 406 patients diagnosed with CGD were included. Utilizing the Boruta algorithm, 12 significant features which confirmed important for the diagnosis of PFCD, and a random forest classification model was developed. The model demonstrated an area under the receiver operating characteristic curve (AUROC) of 0.9294 (95% CI: 0.8706-0.9882), an accuracy of 0.9515 (95% CI: 0.9067-0.9788) and a kappa of 0.8779. SHAP values was utilized to estimate the variable importance, and the top five features were ulceration in rectal wall, thickened rectal wall, T2 hyperintensity, submucosal fistula and age. The model for predicting PFCD diagnosis based on MRI was dynamically visualised using a web display approach (https://doctoryang1971.shinyapps.io/forceplot/). Conclusion We have developed a multi-modal visual dynamic prediction model that can be effectively used to guide the early diagnosis of patients with Crohn's disease who present with perianal fistula at their first clinical visit. PFCD is likely to originate as transmural ulcers leading to submucosal inflammation or fistulae before penetrating the anal sphincter and developing into complex perianal fistulae.

P498 An expert Delphi consensus: Early identification of patients at risk of Crohn's disease in perianal fistulas and abscesses (PREFAB) and identification and management of isolated perianal Crohn's disease (ipCD) - Part B, ipCD

Abstract Background In clinical practice, some patients with ‘idiopathic’ perianal fistulae (iPAF) and no evidence of luminal IBD are labelled ‘isolated perianal Crohn’s disease’ (ipCD) and treated with IBD-directed therapies. However, there are no accepted criteria to guide which patients should be diagnosed as ipCD, or how they should be managed. This project aimed to provide a definition of ipCD, strategies for management, and a platform for building further understanding of this group. Methods An expert panel of IBD gastroenterologists, surgeons and radiologists took part in a Delphi consensus on ipCD. The first-round was an electronic survey, probing: 1) personal experience of ipCD; 2) how fistula histology may influence ipCD diagnosis; 3) patient and fistula features suggestive of ipCD; and 4) suggested management of patients with suspected-ipCD. Responses informed the creation of clinical criteria for ipCD, and statements on ipCD management, which were discussed, amended, and agreed-upon at a second-round virtual consensus meeting. Consensus was predefined as ≥70% ‘strongly agree’ or ‘agree with minor reservation’. Results >30 specialists participated. In round 1: 93% agreed ipCD is a separate Crohn’s phenotype; 83% reported having treated ipCD patients with IBD medical therapies; 73% agreed iPAF patients with fistula histology suggestive of ipCD could be labelled as histologically-confirmed ipCD; and 93% agreed histologically-confirmed ipCD with complex fistulation should be treated with IBD medical therapy (e.g., biologics). However, there was no consensus on the appropriateness of IBD medical therapy for simple fistulae. For iPAF patients without histological evidence of IBD, the panel agreed factors suggestive of ipCD. These included: family history of IBD, symptoms of IBD extraintestinal manifestations, co-existent/previous perianal lesions (fissures, anal stricture, tags), and certain fistula features. Factors were used to produce a criteria to diagnose ipCD and identify patients appropriate for a trial of medical therapy. If a trial of therapy is pursued, the panel agreed careful discussion of the risks of treatment, and known-unknowns, when treating ipCD. Optimised anti-TNF is preferred first-line (82% agreement) with a careful review of treatment response, and contemporaneous MRI, at 6-12 months (93% agree). Conclusion ipCD is a contentious label and standardisation of the diagnosis could help us better assess this group and their treatment outcomes. We present a suggested criteria for diagnosing this group, and a pragmatic approach to trialling biologic therapy. Key to managing this group is honest discussion regarding the known-unknowns of ipCD treatment, to manage patient expectations and support a joint decision-making approach.

P1200 Study of correlation between polymorphisms of vitamin D metabolism genes and perianal disease in Crohn's disease

Abstract Background Vitamin D (VD) is a fat-soluble vitamin essential for calcium homeostasis and that acts at the extraskeletal level. UVB skin exposure allows the synthesis of provitamin D. This undergoes a first hydroxylation in the leaver by the CYP2R1 enzyme and a second hydroxylation in the kidney by the CYP27B1 enzyme: active VD is obtained. VD is transported into the circulation by VDBP and exerts its activity in the target cells binding its VDR receptor. Finally, VD is inactivated by the renal enzyme CYP24A1. Perianal disease (pCD) is a severe phenotypic manifestation of CD that may present as perianal fistula, abscess, recto-vaginal fistula, or stenosis. Among the mechanisms involved in its pathogenesis we recognise local inflammation and intestinal microbiota alteration. Vitamin D (VD) seems to act on these elements. As there are currently no studies on this subject in the literature, the aim of this study is to evaluate the presence of an association between SNPs of genes coding for enzymes, transporters and receptors involved in the VD pathway and the occurrence of pCD in CD patients. Methods The study was carried out on the biological samples of 206 patients with CD, including 34 with pCD, who were followed up at the inflammatory bowel disease clinic in Turin, Italy. Through the use of Real-Time PCR, the genotype distribution of the following genes were assessed: VDR, CYP27B1, CYP24A1, and GC. For the association study, chi-square test was performed with calculation of p value and, when significant, logistic regression and calculation of OR with 95% CI was performed. Results Studying the association between SNPs and the presence of pCD, the following results were obtained: BsmI p=0.0470 and Apal p=0.0251. For BsmI heterozygous genotype there was an OR=2.5 (95% CI 1.2-5.3) of developing perianal disease and p value=0.02, while for ApaI heterozygous there was OR=2.91 (95% CI 1.3-6.6) of presenting pCD, with p value=0.01. Conclusion In the literature, there are several studies examining the association between the heterozygous Aa genotypes of ApaI and Bb genotypes of BsmI and increased inflammatory markers. In addition, some studies suggest that these two genotypes represent a risk factor for some diseases, including multiple myeloma, systemic lupus erythematosus, and mild cognitive disorder. This study demonstrates for the first time an impact of polymorphisms of genes associated with the VD pathway in predicting the onset of pCD. Specifically, the presence of the heterozygous genotype of BsmI and ApaI significantly increases the risk. Future studies need to be performed in different and larger cohorts of patients in order to confirm these data.

Restricted cubic spline model analysis of the association between anal fistula and anorectal abscess incidence and body mass index.

The epidemiological profile of anal fistula and anorectal abscess has not been well studied. Based on the results of a retrospective cross-sectional survey, we aimed to investigate the potential influential factors associated with anal fistula and anorectal abscess. We conducted a retrospective analysis of outpatients who visited the proctology department at China-Japan Friendship Hospital between January 2017 and May 2022. A comprehensive questionnaire was designed to collect potential influential factors, and according to formal anorectal examination and the corresponding diagnostic criteria, all the participants were divided into patients with anal fistula or perianal abscess and healthy control group. Multiple logistic regression was used to identify factors in significant association with anal fistula and perianal abscess. Additionally, we combined restricted cubic spline regression to examine the dose-response relationship between factors and the risk of developing anal fistula or anorectal abscess. The present study included 1,223 participants, including 1,018 males and 206 females, with 275 anal fistulas, 184 anorectal abscesses, and 765 healthy controls. We found no statistically significant differences between patients and controls in basic information and preoperative assessment of life factors, except for body mass index. It was indicated that people with overweight or obesity were more prone to anal fistula (OR overweight = 1.35, 95% CI: 1.00-1.82, P = 0.047; OR obesity = 3.44, 95% CI: 2.26-5.26, P < 0.001) or anorectal abscess (OR overweight = 1.41, 95% CI: 1.00-1.99, P = 0.05; OR obesity: 2.24, 95% CI: 1.37-3.67, P = 0.001) than normal-weight individuals. The dose-response research indicated the J-shaped trend between the ascending BMI levels and the higher risk of suffering from anal fistula and anorectal abscess. Our findings indicate that overweight and obesity are risk factors for anal fistula and anorectal abscess, which plays a role in the prevention of anorectal diseases. This provides some theoretical basis for clinicians to provide health education to their patients.

Causal relationship between obesity and anorectal abscess: a Mendelian randomization study.

Observational studies have indicated that obesity is a risk factor for anorectal abscess (ARB). However, it remains unclear whether a causal genetic relationship exists between obesity and ARB. Univariate and multivariate Mendelian randomization (MR) were conducted using data from a large, published genome-wide association study (GWAS) of European ancestry to infer a causal relationship between obesity and ARB. Inverse variance weighted (IVW) analysis served as the primary analysis method, with results reported as odds ratios (OR). MR analysis revealed that body mass index (BMI) positively affects ARB (OR 1.974, 95% confidence interval (CI) 1.548-2.519, p = 4.34 × 10-8). The weighted median method (OR = 1.879, 95% CI 1.248-2.829, p = 0.002) and Bayesian model averaging (BMA) (OR = 1.88, 95% CI 1.477-2.392, p = 2.85 × 10-7) also demonstrated consistent results. Subsequently, the impact of several obesity-related characteristics on ARB was assessed. Body fat percentage (BF), whole body fat mass (FM), waist circumference (WC), and hip circumference (HC) were found to be causally associated with an increased risk of ARB. However, these associations vanished after adjusting for BMI effects. The study confirms a positive causal effect of obesity on ARB, highlighting that reasonable weight control is an important strategy to reduce the incidence of ARB.

A case study on Manjalkaram (medicated alkaline lotion) in the management of Powthiram (fistula-in-ano)

Abstract Background: Abscesses around the lower rectum and anal canal are known as anorectal abscesses. These are crucial as they often culminate in fistula-in-ano. Anorectal abscess and fistulas are one of the most frequent results in the manifestation of simple or complex and extensive fistulous tracts. Karam (herbo-mineral preparation) therapy is a Siddha parasurgical technique commonly used to cure anal disease. Materials and Methods: Manjalkaram is a medicated alkaline lotion preparation that acts as herbal chemical cauterization agent to cure anal disease. A 60-year-old male patient, already treated with allopathy, experienced a recurrence of fistula-in-ano. The patient decided to get Siddha treatment and presented with the complaints of pain in the anal area, swelling, and discharge of pus with stool and mild irritation. The patient was diagnosed with fistula-in-ano. Purgatives were given the previous night to clean the bowel, and the following day, local cleaning was carried out by providing Triphala decoction as a herbal antiseptic lotion. A probe was inserted into the fistula, and a Manjalkaram-soaked medicated thread was inserted through the fistula and tied through an external opening to the internal opening with help of the probe. A Manjalkaram-soaked gauze (Manjalkaraseelai) was inserted and changed once in a week. Result: Even though fistula-in-ano is very difficult to treat, the patient got completely healed within 2 months with the effect of Manjalkaram application. Conclusion: Manjalkaram application is found to be an effective, time-saving, affordable, and acceptable treatment for fistula-in-ano.

Retroperitoneal Abscess as an Extension of Ischiorectal Abscess: A Rare Case Report

Infections of the retroperitoneum can result from primary haematogenous spread of microbes or secondary infections originating from the retroperitoneal area or nearby organs. These abscesses can be caused by a perforated retrocaecal appendix, diverticulitis, perforated duodenal ulcers, iatrogenic gastrointestinal tract perforations, pancreatic cancer, inflammatory bowel diseases, genitourinary extravasation due to obstruction, osteomyelitis, postoperative duodenal ulcer perforations, and infections related to pelvic and puerperal conditions, as well as trauma. However, the occurrence of a retroperitoneal abscess as an extension of an ischiorectal abscess is exceedingly rare. Hereby, the authors present a case report of 27-year-old male who presented with persistent lower right quadrant abdominal pain, high-grade fever, and pus discharge from the perianal region for the last five days. He experienced difficulty passing stools and flatus for three days. Contrast-enhanced Computed Tomography (CECT) revealed a perforated appendix with fluid collection in the preperitoneal space on the right-side. Surgery revealed a significant amount of purulent discharge below the rectus muscle, extending along the right abdomen to the psoas muscle and connecting with the ischiorectal fossa. Retroperitoneal abscesses can originate from the perianal or ischiorectal region through various anatomical spaces.

Clinical Background and the Effectiveness of Transanal Ultrasonography for Perianal Abscesses

Clinical Background and the Effectiveness of Transanal Ultrasonography for Perianal Abscesses

A rare complication of central fascial paralysis associated with quinolone

Quinolones, which are broad-spectrum antibiotics, are frequently preferred in the treatment of infections. In infections developing in immunosuppressed patients, side effects of quinolones, which are started empirically without determining the agent and etiology, are also quite common. In this article, central facial paralysis due to ciprofloxacin initiated for anal abscess in an immunosuppressed patient receiving chemotherapy for multiple myeloma is described, and we aim to draw attention to this rare side effect. To the best of our knowledge, this is the first case reported in the literature.

Incision and Drainage: Perianal Abscess.

Incision and Drainage: Perianal Abscess.

Management of acute perianal abscess: is surgeon specialization associated with improved outcomes?

Acute surgical units (ASU) are increasingly being adopted and in our system are staffed by colorectal and non-colorectal general surgeons. This study aims to evaluate whether surgeon specialization was associated with improved outcomes in perianal abscess. Patients with perianal abscess admitted to the ASU between 2016 and 2020 were identified from a prospective database and their medical records reviewed. Patients with IBD, treatment for fistula-in-ano within the preceding year, or perianal sepsis of non-cryptoglandular origin were excluded. Patients admitted under an ASU colorectal (CR) consultant were compared with those under a non-CR general surgeon in a retrospective cohort study. Primary outcome was perianal abscess recurrence. For those without initial fistula, hazard of recurrent abscess or fistula was analysed. Multivariable Cox PH regression analysis was performed. Four-hundred and eight patients were included (150 CR, 258 non-CR). The CR group more frequently had a fistula identified at index operation (34.0% versus 10.9%, P < 0.0001). However, Cox multivariable analysis found no difference in hazard of recurrent abscess between groups (HR 1.12, 95% CI 0.65-1.95, P = 0.681)). Abscess recurred in 18.7% CR and 15.5% non-CR. Subsequent fistula developed in 14.7% in both groups. For patients without initial fistula, there was no difference between groups in hazard of recurrent abscess or fistula (HR 1.18, 95% CI 0.69-2.01, P = 0.539). Surgeon specialization was not associated with improved outcomes for ASU patients with perianal abscess, albeit with potential selection bias. CR surgeons were more proactive identifying fistulas; this raises the possibility that drainage alone may be adequate treatment.