Background Allogenic adipocyte stem cells represent an unprecedented opportunity for regenerative therapy to treat Crohn anal fistulas. Apart from the results of one 8-year-old trial, scientific evidence remains scarce. Methods Data from consecutive patients treated with darvadstrocel for Crohn anal fistulas were reviewed at 6 first tertiary reference centers. The judgment criteria combined asymptomatic status plus clinical occlusion of the fistula tract and MRI-confirmed healing of the tract (no inflammation and/or disappearance of the tract). Both clinical and MRI-confirmed healing of the tract defined a deep remission. Clinical remission was defined by an absence of complaint, occlusion of all external openings, and no fistula discharge. Results A total of 116 patients were extracted (median follow-up after cell stem injection: 11 [6-14] months). No severe adverse events were reported after surgery except for subsequent anal surgery in 29 (25%) patients. Fifty-one (44%) patients had clinical remission defined by the absence of complaints, the occlusion of all external openings, and the presence of no fistula discharge. Deep remission was observed in 23 (29%) patients. Patients with clinical remission more often received combined therapy (immunosuppressant antitumor necrosis factors) than those with no improvement (31 of 51 [61%] vs 23 of 65 [35%]; P = .007). Regression analysis showed that high fistulas (odds ratio, 3.8 [1.1-12.5]; P = .03) and younger age (<38 years, odds ratio, 2.3 [1.0-58;4]; P = .02) were associated with a better outcome. Conclusions Allogeneic stem cell treatment of Crohn's anal fistulas results in complete remission in less than half of patients, with a significant reintervention rate.

BACKGROUND:French and International anal cancer screening recommendations for at-risk populations, published in 2024, are based on cytology and/or high-risk human papillomavirus (HPV) detection on anal smears. Biological markers to triage the patients most at-risk for anal cancer are crucial in prioritising patients needing high-resolution anoscopy consultations, which are frequently overwhelmed. METHODS:The AIN3 cohort is a French national multicenter study including patients with a history of high-grade anal lesions (AIN3). Patients were followed-up for at least 3 years, with anal smears and clinical examinations performed yearly. Levels of ZNF582 and ASCL1 gene methylation were quantified using real-time PCR on anal smears collected at the time of inclusion. FINDINGS:Overall, 514 anal smears were contributive for host-cell DNA methylation analysis. Patients' mean age was 50.8 years and 40% were women. Among the 41% who were living with HIV, 91% were men. Median follow-up duration was 48 months, and 22 patients (4%) developed anal cancer during follow-up. Higher methylation levels of ZNF582 and ASCL1 were significantly associated with high-grade squamous cell intraepithelial lesion (HSIL) cytology, p16-Ki67 dual-staining positivity, and high-risk HPV and HPV16 positivity on the same anal smear. Both methylation markers showed an AUC of 0.72 for discrimination between HSIL and non-HSIL cytology on the same anal smear. Higher methylation levels of both markers were significantly associated with evolution to anal cancer in univariate and multivariable analyses adjusted for age and HIV status (p < 0.001). When assessing the AUC over 1 and 3 years of follow-up, methylation markers demonstrated superior predictive value for anal cancer compared to other markers. INTERPRETATION:We have demonstrated the predictive value of host-cell DNA methylation marker levels in anal smears with regard to evolution to anal cancer in a very high-risk population. FUNDING:This study was funded by the Agence Nationale de Recherche sur le Sida et les hépatites virales (ANRS) I Maladies Infectieuses Emergentes.

In France, about 2000 new cases of anal cancer are diagnosed annually. Squamous cell carcinoma is the most common histological type, mostly occurring secondary to persistent HPV16 infection. Invasive cancer is preceded by precancerous lesions. In addition to patients with a personal history of precancerous lesions and anal cancer, three groups are at very high risk of anal cancer: (i) men who have sex with men and are living with HIV, (ii) women with a history of high-grade squamous intraepithelial lesions (HSILs) or vulvar HPV cancer, and (iii) women who received a solid organ transplant more than 10 years ago. The purpose of screening is to detect HSILs so that they can be treated, thereby reducing the risk of progression to cancer. All patients with symptoms should undergo a proctological examination including standard anoscopy. For asymptomatic patients at risk, an initial HPV16 test makes it possible to target patients at risk of HSILs likely to progress to cancer. Anal cytology is a sensitive test for HSIL detection. Its sensitivity is greater than 80% and exceeds that of proctological examination with standard anoscopy. It is indicated in the event of a positive HPV16 test. In the presence of cytological abnormalities and/or lesions and a suspicion of dysplasia on clinical examination, high-resolution anoscopy is indicated. Performance is superior to that of proctological examination with standard anoscopy. However, this technique is not widely available, which limits its use. If high-resolution anoscopy is not possible, screening by a standard proctological examination is an alternative. There is a need to develop high-resolution anoscopy and triage tests and to evaluate screening strategies.

The aim of this study was to evaluate the efficacy and safety of radiofrequency ablation (RFA) in the management of haemorrhoidal disease with 1 year’s follow-up. This prospective multicentre study assessed RFA (Rafaelo©) in outpatients with grade II–III haemorrhoids. RFA was performed in the operating room under locoregional or general anaesthesia. Primary endpoint was the evolution of a quality-of-life score adapted to the haemorrhoid pathology (HEMO-FISS-QoL) 3 months after surgery. Secondary endpoints were evolution of symptoms (prolapsus, bleeding, pain, itching, anal discomfort), complications, postoperative pain and medical leave. A total of 129 patients (69

Background The most effective treatment for anal fistula is fistulotomy, but it involves a risk of anal incontinence. To reduce this morbidity, sphincter-sparing treatments have been developed, but their success in real life is often less than 50%. The aim is to determine the clinical healing rate 6 months after radiofrequency treatment. Methods We planned to evaluate 50 patients from three French proctology centres. Treatment efficacy was evaluated at 6 and 12 months by means of clinical and magnetic resonance imaging examination. We evaluated morbidity and healing prognostic factors. Results Fifty patients with a mean age of 51 years (22-82) were included. Eleven patients had a low trans-sphincteric fistula (LTS), 21 patients had a high trans-sphincteric fistula (HTS), eight had a complex fistula and nine had Crohn's disease fistula. After 6 months, 17 patients (34.7%) had a clinically healed fistula, including five (45.5%) with LTS fistula, seven (33.3%) with HTS fistula, one (12.5%) with complex fistula, four (44.4%) with Crohn's disease, with no significant difference between these fistula types (p: 0.142). At 12 months, the healing rate was identical. MRI in 15 out of 17 clinically healed patients showed a deep remission of 73.3% at 12 months. Energy power was associated with the success of the treatment. There was an 8.2% incidence of post-surgical complications with 4.1% being abscesses (one required surgical management). Postoperative pain was minor. No new cases or deterioration of continence have been shown. Conclusion Radiofrequency is effective in 34.7% of the cases as an anal fistula treatment in this first prospective study, with low morbidity and no effect on continence. Clinical healing was deep (MRI) in three-quarters at 1 year. The increase in energy power during the procedure seems to be a key point to be analysed to optimise results.

The most effective treatment for anal fistula is fistulotomy, but it involves a risk of anal incontinence. To reduce this morbidity, sphincter-sparing treatments have been developed, but their success in real life is often less than 50%. The aim is to determine the clinical healing rate 6 months after radiofrequency treatment. We planned to evaluate 50 patients from three French proctology centres. Treatment efficacy was evaluated at 6 and 12 months by means of clinical and magnetic resonance imaging examination. We evaluated morbidity and healing prognostic factors. Fifty patients with a mean age of 51 years (22–82) were included. Eleven patients had a low trans-sphincteric fistula (LTS), 21 patients had a high trans-sphincteric fistula (HTS), eight had a complex fistula and nine had Crohn's disease fistula. After 6 months, 17 patients (34.7%) had a clinically healed fistula, including five (45.5%) with LTS fistula, seven (33.3%) with HTS fistula, one (12.5%) with complex fistula, four (44.4%) with Crohn's disease, with no significant difference between these fistula types ( p : 0.142). At 12 months, the healing rate was identical. MRI in 15 out of 17 clinically healed patients showed a deep remission of 73.3% at 12 months. Energy power was associated with the success of the treatment. There was an 8.2% incidence of post-surgical complications with 4.1% being abscesses (one required surgical management). Postoperative pain was minor. No new cases or deterioration of continence have been shown. Radiofrequency is effective in 34.7% of the cases as an anal fistula treatment in this first prospective study, with low morbidity and no effect on continence. Clinical healing was deep (MRI) in three-quarters at 1 year. The increase in energy power during the procedure seems to be a key point to be analysed to optimise results.

Since our last publication of algorithms for the management of perianal fistulas in patients with Crohn’s disease, researchers have proposed a treat to target strategy systematic combotherapy for anal lesions, and indications for stem cell injection. In the absence robust publications, the Société Nationale Française de Coloproctologie (French National Society of Coloproctology [SNFCP]) wished to establish a group consensus using the Delphi method. From October 2020 to January 2021, a scientific committee and panel of gastroenterologists and surgeons established answers which were submitted to the members of the SNFCP during a national conference in November 2020. Three questions were clarified and reformulated, and then submitted during a third and final round of consultation of members of the SNFCP. The target was defined as being the response obtained in every domain (symptoms, physical and radiological evaluation) which could be considered satisfactory, without the need to intensify therapeutic management. By consensus, the time required for clinical evaluation of the efficacy of treatment was 6 months. A response on magnetic resonance imaging (MRI) should include the absence of a collection of 10 mm or more in size at 6 months, and a frank decrease or complete disappearance of hyperintensity in T1 and T2 sequences of the main tract at 12 months. Systematic association of an immunosuppressant with tumor necrosis factor inhibitors did not reach the consensus level for adalimumab (50%), but just did for infliximab (70%). The majority of the respondents considered failure of one, or even two lines of different biotherapies to be potential indications for injection of stem cells. These findings reinforce the importance of composite targets including MRI evaluation, and underscore the need for precise timing of evaluation. Combotherapy is only recommended with infliximab. Injection of stem cells is a second- or third-line option.

Aim In patients with fistulizing perianal Crohn's disease (CD), the need for a secondary surgical step is not defined. The aim was to assess the efficacy of surgical closure compared to a single seton removal in patients with drained fistulizing perianal CD treated with adalimumab. Methods This was a multicentre, randomized controlled trial, comparing seton removal + surgical closure (closure group) to seton removal alone (control group) with a stratification according to the American Gastroenterological Association classification. The primary end-point was fistula closure at month 12 defined by the association of the following criteria: no seton, absence of a visible external opening, absence of discharge from the tract after finger compression, absence of an internal opening, absence of perianal pain/abscess and absence of fistula-related abnormalities. Results Among the 64 included patients (262 expected) (48 complex fistula, 75%), 33 were randomized to the closure group and 31 to the control group. In the closure group, 26 patients (78.8%) had glue. At month 12, overall fistula closure was achieved in 35 of the evaluable 58 patients (60%): 18/32 (56%) in the surgery group and 17/26 (65%) in the control group (P = 0.479). In the closure group, fistula closure was observed in 13/25 (52%) and 5/7 (71%) patients with complex and simple fistula respectively (P = 0.426), compared with 12/18 (67%) and 5/8 (63%), respectively in the control group (P = 1.000). Conclusions Seton removal alone seems to be no more effective than a secondary surgical step (in particular glue injection) in patients having fistulizing perianal CD controlled by an initial drainage combined with adalimumab. The results should be interpreted with caution.

BACKGROUND:Treatment of an anal fissure (AF) is based on medical treatment (nonoperative therapies) and surgical procedures. However, the choice of treatment and its role in therapeutic strategy vary from one country to another, and to date, no standard French recommendation is currently available. Our aim was to assess French practices in the treatment of AFs.METHODS:A national survey of members of the French National Society of Colo-Proctology (SNFCP) was carried out using an online questionnaire (1) to evaluate French practice and (2) to compare them with guidelines of other societies.RESULTS:Two hundred responses were obtained among the 300 registered members, representing a participation rate of 67%. Members of the SNFCP agree with all scientific societies on the importance of first-line medical treatment, with surgery proposed as a second-line treatment in the case of the failure of well-conducted medical treatment. However, calcium channel blockers and topical nitrates as first-line treatment are rarely prescribed in France. Priority is therefore given to "simple" topical healing products and oral analgesics on demand. Similarly, surgical management differs since LIS is the "gold standard" in most guidelines, whereas in France, despite the data in the literature, fissurectomy is the first-line treatment.CONCLUSIONS:Our study indicated the fissure treatment discrepancies of France with other countries concerning the usage of topical treatments and the choice of first-line surgical treatments that is currently considered a "French exception".

BACKGROUND:Crohn's disease (CD) is complicated by perianal fistulas in approximately 20% of patients. Achieving permanent fistula closure remains a challenge for physicians. An association between serum anti-tumor necrosis factor-α concentrations and clinical outcomes in patients with CD has been demonstrated; however, little information is available on serum adalimumab (ADA) concentrations and remission of perianal fistulas in such patients.AIM:To study the relationship between serum ADA concentrations and clinical remission of CD-associated perianal fistulas.METHODS:This cross-sectional study of patients with CD-associated perianal fistulas treated with ADA was performed at four French hospitals between December 2013 and March 2018. At the time of each serum ADA concentration measurement, we collected information about the patients and their fistulas. The primary study endpoint was clinical remission of fistulas defined as the absence of drainage (in accordance with Present's criteria), with a PDAI ≤ 4, absence of a seton and assessment of the overall evaluation as favorable by the proctologist at the relevant center. We also assessed fistula healing [defined as being in clinical and radiological (magnetic resonance imaging, MRI) remission] and adverse events.RESULTS:The study cohort comprised 34 patients who underwent 56 evaluations (patients had between one and four evaluations). Fifteen patients had clinical remissions (44%), four of whom had healed fistulas on MRI. Serum ADA concentrations were significantly higher at evaluations in which clinical remission was identified than at evaluations in which it was not [14 (10-16) vs 10 (2-15) μg/mL, P = 0.01]. Serum ADA concentrations were comparable at the times of evaluation of patients with and without healed fistulas [11 (7-14) vs 10 (4-16) μg/mL, P = 0.69]. The adverse event rate did not differ between different serum ADA concentrations.CONCLUSION:We found a significant association between high serum ADA concentrations and clinical remission of CD-associated perianal fistulas.

AIM:Over the past 10 years, several studies have focused on sexuality in patients with Crohn's disease. Very few of them specifically focused on perianal disease (PD). This study aimed to compare the prevalence of sexual dysfunction (SD) in Crohn's disease patients with active PD versus controls without active PD. METHOD:Patients from 14 French centres with active PD, defined by the presence of symptomatic ulceration, fistula or stenosis, were arbitrarily included. They were compared with controls from the existing SEXIA cohort. Men completed the International Index of Erectile Function (IIEF) and women the Female Sexual Function Index (FSFI). The primary end-point was SD defined by FSFI < 26.55 in women and IIEF < 42.9 in men. RESULTS:Ninety-seven patients (64 women, 33 men) and 238 controls (131 women, 107 men) were included. SD was found in 66% of the female patients versus 50% of the controls (P = 0.04). In the male population, SD was found in 30% of the cases versus 16% of the controls (P = 0.06). Erectile dysfunction affected 46% of the male patients and 43% of the controls (P = 0.8). On multivariate analysis, the predictive factor most strongly associated with SD in women was severely active anal PD defined by a perineal disease activity index > 4 [OR = 13.05 (2.32-73.44)]. CONCLUSION:Women with active PD had an increased prevalence of SD compared with controls without active PD. In the male population, the study was unable to determine whether there was a difference as it was underpowered.

Objectif : L’absence de standardisation des objectifs à atteindre par les traitements des fistules anopérinéales (FAP) de la maladie de Crohn limite les possibilités d’analyse et de comparaison des données issues des études disponibles. L’élaboration d’une liste standardisée d’objectifs à atteindre permettrait de résoudre ces problèmes. Cette étude valide la liste d’objectifs cruciaux (core outcome set [COS]) à atteindre pour le Crohn fistulisant. Méthode : Les objectifs susceptibles d’être retenus ont été définis par une revue de la littérature et des interviews de patients. La sélection consensuelle a été établie à l’issue d’un processus Delphi en trois étapes en évaluant sur une échelle de Likert en neuf points, l’importance que ces objectifs avaient pour définir la réussite d’un traitement. Des représentants de chacun des trois groupes impliqués dans ces traitements ont été recrutés à l’échelle nationale (chirurgiens et radiologistes, gastroentérologues et infirmières spécialisées en maladies inflammatoires intestinales, et enfin patients). Chaque intervenant a noté les différents objectifs possibles, puis a corrigé ses notes après avoir pris connaissance des autres notes données par les membres de son groupe (au deuxième tour) puis encore une fois après avoir pris connaissance des notations données par tous les participants (au troisième tour). Résultats : Au total, 295 objectifs potentiels ont été identifiés à partir d’une revue de la littérature et d’interviews, ils ont été catégorisés en 92 domaines. Cent quatre-vingt-sept participants (taux de réponse : 78,5 %) ont accordé la priorité à 49 objectifs à l’issue d’une méthode Delphi à trois cycles. Une réunion de consensus finale de 41 experts et patients s’est accordée sur un COS comprenant huit catégories d’objectifs. Ce COS comprenait trois catégories d’objectifs importants pour le patient (qualité de vie, incontinence et score combiné des priorités du patient) et cinq catégories d’objectifs retenus par les praticiens (activité de la maladie périanale, développement d’un nouvel abcès périanal, fistule nouvelle/récidivante, chirurgie non planifiée et dérivation fécale). Conclusion : Un COS sur les FAP de laMC a été élaboré par tous les acteurs clés de cette maladie. L’utilisation du COS diminuera l’hétérogénéité dans l’expression des résultats des traitements, ce qui rendra plus pertinente la comparaison des traitements entre eux, la synthèse des données et, en fin de compte, les soins rendus aux patients.

Fistulising ano-perineal (FAP) lesions occur in more than 20% of patients with Crohn's disease (CD). Despite advanced surgery techniques and anti-tumour necrosis factor (anti-TNF) agents use, relapse rate of FAP-CD remains 30%. The objective of the present study was to identify predictors of a subsequent ano-perineal abscess in patients with FAP-CD in remission. We conducted a retrospective study including all consecutive FAP-CD patients achieving clinical ano-perineal remission between 2007 and 2015 in one referral centre. Remission was defined by the absence of any draining fistula or abscess within 3 months after the last drainage surgery. Patient characteristics were collected at drainage, at 3 months – corresponding to the inclusion date - and during follow-up. Primary outcome was the occurrence of a subsequent ano-perineal abscess related to FAP-CD and confirmed by examination under anaesthesia and/or MRI. Predictive factors of subsequent abscess were determined in anti-TNF naïve and anti-TNF treated populations. One hundred and thirty-seven patients (57% female, median age 35 years) corresponding to 157 abscesses [120 (76.4%) treated by anti-TNF at inclusion] were included. Patients not treated by anti-TNF at inclusion were significantly older (40 years vs. 34 years, p = 0.005) and had more often simple fistulas [10 (29%) vs. 66 (58%), p = 0.004]. During the follow-up period [median duration of 43 (IQR 26–63) months], 35 (22%) experienced a subsequent abscess, which occurred within a median time of 1.8 years. Survival without abscess was 96.7% at 1 year, 78.4% at 3 years and 74.4% at 5 years. In the subgroup of 120 patients treated with anti-TNF agents (84 infliximab and 36 adalimumab) at inclusion, ileo-colonic (OR 5.19, p = 0.017) location, stricturing phenotype (OR 5.32, p = 0.013) and discontinuation of anti-TNF therapy during the follow-up period (OR 3.37, p = 0.049) were associated with a subsequent abscess in multi-variate analysis. Conversely, discontinuation of immunosuppressive therapy was associated with a reduced risk of a new abscess (OR 0.22, p = 0.29). Neither the type of anti-TNF agent nor combotherapy use were associated to FAP-CD relapse. In CD patients with fistulising ano-perineal disease achieving remission, survival without subsequent abscess was approximately 75% at 5 years. Colonic disease location, stricturing phenotype and discontinuation of anti-TNF therapy were associated with a higher risk of new abscess.

BACKGROUNDDespite an optimal medico-surgical management of perineal Crohn's disease (PCD), fistula relapse still occurs in 30% of patients. Our aim was to determine predictors of fistula relapse in patients in remission after treatment of a PCD lesion.METHODSConsecutive patients treated for fistulizing PCD have been included in a retrospective study when they achieved fistula remission within 3 months after the surgery. Remission was defined as the absence of any draining fistula at clinical examination. Primary outcome was the occurrence of a fistula relapse, defined as a subsequent perianal draining fistula or an abscess confirmed clinically and/or by pelvic MRI.RESULTSOne hundred and thirty-seven patients (57% female, median age: 35 years) corresponding to 157 abscess events, including 120 (76.4%) treated by anti-TNF after drainage, achieved fistula remission after surgery. During the follow-up period (median duration: 43 months [interquartile range 26 to 64]), 34 (22%) patients experienced a fistula relapse within a median time of 1.8 years. Survival without fistula was 96.7% at 1 year, 78.4% at 3 years, and 74.4% at 5 years. Fistula relapse rates were not different in patients receiving infliximab or adalimumab (P = 0.66). In patients treated by anti-TNF at inclusion, discontinuation of anti-TNF therapy (odds ratio 3.49, P = 0.04), colonic location (OR 6.25, P = 0.01), and stricturing phenotype (odds ratio 4.39, P = 0.01) were independently associated with fistula relapse in multivariate analysis.CONCLUSIONIn patients achieving fistula remission of PCD, relapse rates are low and are not different between infliximab and adalimumab. Discontinuation of anti-TNF therapy is associated with increased relapse rate.