Allogenic stem cells for Crohn's anal fistulas: Treating early improves the deep remission rate.

AIM: The aim of this study was to evaluate the real-life clinical and radiological efficacy of darvadstrocel injection into complex perianal fistulas in Crohn's disease. Secondary endpoints were to assess symptomatic efficacy, adverse effects and factors associated with complete combined clinical-radiological response (deep remission). METHODS: After marketing the product in France, all first patients treated consecutively were included. A complete clinical response was defined by a complete closure of all external openings with no discharge on pressure. A complete radiological response (MRI), evaluated at least after six months of follow-up, was defined by a completely fibrotic sequela without abscess. A deep remission was defined as the association of a complete clinical response with a complete radiological response. RESULTS: A total of 43 patients were included (M/F: 22/21, median age 37 [26-45] years). The fistulas were already drained with seton(s) and were on biologic treatment. After a median follow-up of 383 (359-505) days, 28 (65%) patients showed a clinical response (22 complete and 6 partial) and 16 (37%) achieved a deep remission. The Perineal Disease Activity Index decreased significantly after treatment: 39 (91%) patients reported symptomatic improvement in terms of discharge, pain, and induration, and 28 (65%) no longer had any perineal symptoms. No severe adverse events were reported. A short history of Crohn's disease <3 years was significantly associated with deep remission (OD 4.5 [1.0-19.1], p = 0.04). CONCLUSION: Darvadstrocel injection resulted in a clinical response for two thirds of patients and deep remission for one third. A shorter duration of Crohn's disease was associated with deep remission.

Ano-rectovaginal fistula after obstetrical anal sphincter injury: Diverting stoma does not improve the surgical results.

AIM: Ano-rectovaginal fistulas (ARVF) are challenging for the surgeon. Most of the series mix aetiologies, leading to confusion with respect to the conclusion. The aim of this study was to assess the factors associated with the success of ARVF management following obstetrical anal sphincter injury (OASIS). METHODS: This retrospective multicentric study included all the patients undergoing surgery for ARVF identified by the hospital codes. Patients for whom the aetiology of ARVF was not OASIS were excluded. The major outcome measure was the success of the procedure. RESULTS: Sixty patients with treated ARVF due to OASIS were identified. The success of overall management was 91.7%. Female patients underwent a mean of 2.5 (±1.7) procedures. A diverting stoma was formed in 29 patients (48.3%) of which 26 were closed at the end of the management period (89.7%). Of the 148 surgical procedures, only 55 were successful (37.2%). The order of the procedures (OR = 1.38; 95% CI: 0.75-2.51) or the diverting stoma (OR = 1.46; 95% CI: 0.31-6.91) were not significantly associated with the success of the surgery. However, Martius flap (OR = 4.13; 95% CI: 1.1-15.54) and Musset procedures (OR = 5.79; 95% CI: 1.77-18.87) produced better results than the endorectal advancement flap (ERAF). The other procedures did not show a significant correlation with management success. CONCLUSION: A diverting stoma is not mandatory in the management of ARVF due to OASIS to improve the success of the surgical procedure. While the Martius flap procedure offers better results, the ERAF procedure may be preferred as a primary intervention in the absence of sphincter injury as it is less invasive. In cases of residual sphincter injury, the Musset procedure is most likely to be the best option.

Comparison of anal cancer screening strategies including standard anoscopy, anal cytology, and HPV genotyping in HIV-positive men who have sex with men.

BACKGROUND: There is no consensus on screening strategy of high-grade intraepithelial neoplasia (HGAIN). Guidelines range from clinical examination with digital anorectal examination followed by standard anoscopy (SA), to anal cytology (Pap)+/- HPV genotyping. We compared screening strategy yields based on Pap, SA, and HPV-16 genotyping alone or in combination in HIV-MSM. METHODS: Pap, SA, and HPV-16 genotyping were performed in all HIV-MSM attending a first anal cancer screening consultation in Paris, France. High-resolution anoscopy, the gold standard to detect HGAIN, was performed in the case of HPV-16 positivity or abnormal cytology. Yield was defined as the number of patients with HGAIN relative to the total number of patients screened. RESULTS: On 212 patients, the complete strategy (SA + Pap + HPV genotyping) yield (12.7%) was significantly higher than that of SA (3.3%, p < 0.001) and HPV-16 alone (6.6%, p < 0.05). Although none of the other strategies were significantly different from the complete strategy, Pap + HPV-16 and Pap + SA had closer yields (about 11%), with OR = 0.83 (95% CI [0.44;1.57]) and 0.87 (95% CI [0.46;1.64]), respectively. CONCLUSIONS: Pap combined with HPV-16 genotyping or SA tended towards higher yields compared to Pap alone, and closer to that of the complete strategy.

SiLaT: A paradigm shift in the treatment of pilonidal disease?

BACKGROUND: Pilonidal disease (PD) is a common condition for which the global incidence is increasing. Surgery is the currently preferred approach to treatment but there is a growing interest in new minimally invasive techniques, such as sinus laser therapy (SiLaT). AIM: Our primary objective was to assess the efficacy of SiLaT for the treatment of pilonidal disease. The secondary objectives were to evaluate morbidity and patient satisfaction and identify predictive factors of success. METHODS: All adult patients, who underwent SiLaT in our department for a primary or recurrent pilonidal sinus from June 1, 2018, to December 31, 2020, were included in the study. Healing was defined as the closure of cutaneous orifices and the absence of seepage or abscesses. RESULTS: In total, 111 consecutive patients, for whom the male/female sex ratio was 2.1 and the mean age 28.8 (± 9.4) years, were included in this study. Eighteen (16.2%) patients had already undergone prior surgery for PD. The mean follow-up was 339.2 (± 221.4) days. A healing rate of 78.4% was observed, with a median time to healing of 20.0 days (15.0-30.0). The median time to return to usual activities was three days (1-7). The only postoperative complication was bleeding, which occurred for two patients (1.8%). Eighty-two patients (88.2%) reported being "very satisfied" with the treatment. Multivariate analysis showed no predictive factors for healing among the studied variables. CONCLUSION: SiLaT is an efficient and safe procedure for the treatment of PD, with a high level of patient satisfaction. It will now be necessary to position it within the therapeutic algorithm.

Hemorrhoidal disease: Epidemiological study and analysis of predictive factors for surgical management.

INTRODUCTION: There are very few French studies on hemorrhoidal disease and its management. PATIENTS AND METHODS: Prospective single-center study from July to December 2021 including 472 patients. RESULTS: Bleeding, prolapse and pain were the main reasons for consultation. Treatment modalities were medical (44%),±instrumental (72%), and surgical (17%). After treatment, the bleeding score and prolapse score decreased significantly (P=0.002 and P≤0.0001, respectively), but improvement was more marked in the surgery group with a better rate of "very good satisfaction" (73% vs. 54%, P=0.003). Factors associated with likelihood of surgical treatment were: age>44years, hypertrophic perianal skin tags, high scores (Bristol>5, bleeding>5, prolapse>2), severe impact on quality of life, smoking and reading during bowel movements. We have developed an online application, which aims to assess the risk of requiring hemorrhoidal surgery. CONCLUSION: Less than 20% of patients who present with hemorrhoidal disease require surgical treatment, but it is associated with better effectiveness despite more complex postoperative consequences that sometimes motivate patient refusal. We have highlighted factors associated with surgical management, which can guide the practitioner in their therapeutic choices.

Unraveling Emerging Anal Cancer Clinical Biomarkers from Current Immuno-Oncogenomics Advances.

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk human papillomavirus (HPV) and is currently one of the fastest-growing causes of cancer incidence and mortality in developed countries. Although next-generation sequencing technologies (NGS) have revolutionized cancer and immuno-genomic research in various tumor types, a limited amount of clinical research has been developed to investigate the expression and the functional characterization of genomic data in ASCC. Herein, we comprehensively assess recent advancements in "omics" research, including a systematic analysis of genome-based studies, aiming to identify the most relevant ASCC cancer driver gene expressions and their associated signaling pathways. We also highlight the most significant biomarkers associated with anal cancer progression, gene expression of potential diagnostic biomarkers, expression of therapeutic drug targets, and emerging treatment opportunities. This review stresses the urgent need for developing target-specific therapies in ASCC. By illuminating the molecular characteristics and drug-target expression in ASCC, this study aims to provide insights for the development of precision medicine in anal cancer.

Deep Learning and High-Resolution Anoscopy: Development of an Interoperable Algorithm for the Detection and Differentiation of Anal Squamous Cell Carcinoma Precursors-A Multicentric Study.

High-resolution anoscopy (HRA) plays a central role in the detection and treatment of precursors of anal squamous cell carcinoma (ASCC). Artificial intelligence (AI) algorithms have shown high levels of efficiency in detecting and differentiating HSIL from low-grade squamous intraepithelial lesions (LSIL) in HRA images. Our aim was to develop a deep learning system for the automatic detection and differentiation of HSIL versus LSIL using HRA images from both conventional and digital proctoscopes. A convolutional neural network (CNN) was developed based on 151 HRA exams performed at two volume centers using conventional and digital HRA systems. A total of 57,822 images were included, 28,874 images containing HSIL and 28,948 LSIL. Partial subanalyses were performed to evaluate the performance of the CNN in the subset of images acetic acid and lugol iodine staining and after treatment of the anal canal. The overall accuracy of the CNN in distinguishing HSIL from LSIL during the testing stage was 94.6%. The algorithm had an overall sensitivity and specificity of 93.6% and 95.7%, respectively (AUC 0.97). For staining with acetic acid, HSIL was differentiated from LSIL with an overall accuracy of 96.4%, while for lugol and after therapeutic manipulation, these values were 96.6% and 99.3%, respectively. The introduction of AI algorithms to HRA may enhance the early diagnosis of ASCC precursors, and this system was shown to perform adequately across conventional and digital HRA interfaces.

Deep Learning in High-Resolution Anoscopy: Assessing the Impact of Staining and Therapeutic Manipulation on Automated Detection of Anal Cancer Precursors.

INTRODUCTION: High-resolution anoscopy (HRA) is the gold standard for detecting anal squamous cell carcinoma (ASCC) precursors. Preliminary studies on the application of artificial intelligence (AI) models to this modality have revealed promising results. However, the impact of staining techniques and anal manipulation on the effectiveness of these algorithms has not been evaluated. We aimed to develop a deep learning system for automatic differentiation of high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion in HRA images in different subsets of patients (nonstained, acetic acid, lugol, and after manipulation). METHODS: A convolutional neural network was developed to detect and differentiate high-grade and low-grade anal squamous intraepithelial lesions based on 27,770 images from 103 HRA examinations performed in 88 patients. Subanalyses were performed to evaluate the algorithm's performance in subsets of images without staining, acetic acid, lugol, and after manipulation of the anal canal. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve were calculated. RESULTS: The convolutional neural network achieved an overall accuracy of 98.3%. The algorithm had a sensitivity and specificity of 97.4% and 99.2%, respectively. The accuracy of the algorithm for differentiating high-grade squamous intraepithelial lesion vs low-grade squamous intraepithelial lesion varied between 91.5% (postmanipulation) and 100% (lugol) for the categories at subanalysis. The area under the curve ranged between 0.95 and 1.00. DISCUSSION: The introduction of AI to HRA may provide an accurate detection and differentiation of ASCC precursors. Our algorithm showed excellent performance at different staining settings. This is extremely important because real-time AI models during HRA examinations can help guide local treatment or detect relapsing disease.

Guillaume Dupuytren: his life and surgical contributions.

Guillaume Dupuytren (1777-1835) was one of the most influential surgeons of the past. He described and popularized many conditions, including Dupuytren disease, which continues to carry his name. This article reviews Guillaume Dupuytren's life and his contributions in surgery.

[Anal verruciform xanthoma in a transplant background for primary hyperoxaluria. Anal verruciform xanthoma after a combined hepato-renal transplantation]. / Xanthome verruciforme anal chez une patiente transplantée hépatique et rénale.

We report a case of anal verruciform xanthoma in a patient who underwent a combined liver and kidney transplantation for primary hyperoxaluria. Verruciform xanthoma is a rare and benign lesion arising in oral cavity and genital mucosa. It is characterized pathologically by papillary epithelial hyperplasia and aggregates of foamy macrophages in connective tissue papillae. This condition, whose pathogenesis remains unclear, has been reported in immunosuppressive background or associated with underlying dermatosis. We report here the second case of anal verruciform xanthoma. To our knowledge, this is the first report of verruciform xanthoma in association with primary hyperoxaluria.

[Pilonidal disease: The revolution in minimally invasive surgery]. / Sinus pilonidal infecté : la révolution de la chirurgie mini-invasive.

PILONIDAL DISEASE: THE REVOLUTION IN MINIMALLY INVASIVE SURGERY. Pilonidal disease is a common suppurative condition and affects 0.7% of the population. Surgical excision is the standard treatment. In France, the most common procedure is lay-open excision with healing by secondary intention. This procedure has low recurrence rates, but involves daily nursing care, long healing time and long period of sick-leave. Excision and primary repair or flap-based procedures are good alternatives to reduce these negative aspects but they expose to higher recurrence rates than excision with healing by secondary intention. The goal of minimally invasive techniques is to eradicate the suppuration, obtain healing as quick as possible, and limit the morbidity as much as possible. Old minimally invasive approaches such as phenolization or pit-picking are associated with low morbidity but with higher recurrence rates. Currently, new minimally invasive techniques are being developed. Endoscopic and laser treatment of pilonidal disease have shown promising results, with failure rates of less than 10% at 1 year, few complications and low morbidity. Complications are rare and minor. However, these interesting results need to be confirmed by better quality studies with longer follow-up.

SINUS PILONIDAL INFECTÉ : LA RÉVOLUTION DE LA CHIRURGIE MINI-INVASIVE. Le sinus pilonidal infecté est une pathologie fréquente qui affecterait 0,7 % de la population. Son traitement est chirurgical. En France, la technique de référence est l'exérèse, avec une plaie laissée ouverte, puis une cicatrisation dirigée. Elle a l'avantage de réduire le risque de récidive, au prix cependant de soins infirmiers quotidiens, d'une durée de cicatrisation longue impliquant un arrêt d'activité prolongé. Les techniques chirurgicales de fermeture ou de plastie visant à réduire la durée des soins sont moins contraignantes pour les patients, mais elles exposent à davantage de récidives que la technique ouverte. L'objectif des techniques mini-invasives est de simplifier les suites opératoires tout en limitant le risque de récidive. Les techniques mini-invasives anciennes comme la phénolisation ou le « pit picking ¼ exposent à un taux de récidive élevé malgré des suites simples. Aujourd'hui, de nouvelles techniques se développent, faisant appel, entre autres, à l'endoscopie ou encore au laser également utilisés pour le traitement des fistules anales. Les premiers résultats sont prometteurs, avec un taux d'échec globalement inférieur à 10 % à un an. Les complications sont rares, le plus souvent mineures, et les suites postopératoires sont simples sans nécessité de soins infirmiers. Cependant, ces résultats intéressants nécessitent d'être confirmés par des études de meilleure qualité avec un suivi prolongé.

[Anal fistulas: Sparing the sphincter]. / Fistules anales, épargner le sphincter.

ANAL FISTULAS: SPARING THE SPHINCTER. Fistulotomy is the most used treatment for anal fistula. It is very effective with a cure rate of over 95% but carries a risk of incontinence. This has led to the development of various sphincter sparing techniques. The injection of biological glue or paste and the insertion of a plug have disappointing results and are expensive. The rectal advancement flap is still practised because of its cure rate of around 75% but it may result in some incontinence. Intersphincteric ligation of the fistula track and laser treatment are widely practised in France with cure rates between 60 and 70%. Video-assisted anal fistula treatment as well as injections of adipose tissue, stromal vascular fraction, platelet-enriched plasma and/or mesenchymal stem cells are emerging techniques for which even better results are expected.

FISTULES ANALES, ÉPARGNER LE SPHINCTER. La fistulotomie est le traitement le plus souvent utilisé dans la fistule anale. Elle est très efficace, avec un taux de guérison supérieur à 95 %, mais expose à un risque d'incontinence. Cela a conduit au développement de diverses techniques d'épargne sphinctérienne. L'injection de colle ou de pâte biologique ainsi que la mise en place d'un plug ont des résultats finalement décevants et un coût élevé. Le lambeau rectal d'avancement est encore pratiqué en raison de son taux de guérison aux alentours de 75 %, mais il peut se solder par quelques troubles séquellaires de la continence. La ligature intersphinctérienne du trajet fistuleux et le laser sont largement pratiqués en France, avec des taux de guérison oscillant entre 60 et 70 %. Le traitement vidéo-assisté du trajet fistuleux ainsi que les injections périfistuleuses de tissu adipeux, de fraction vasculaire stromale, de plasma enrichi en plaquettes et/ou de cellules souches mésenchymateuses sont des techniques émergentes dont on espère de meilleurs résultats encore.

[Management of secondary lesions in ano-perineal Crohn's disease]. / Prise en charge des lésions secondaires de la maladie de Crohn anopérinéale.

MANAGEMENT OF SECONDARY LESIONS IN ANO-PERINEAL CROHN'S DISEASE. Anoperineal involvement in Crohn's disease is common and affects around 1/3 of patients during their disease. It constitutes a pejorative factor with an increased risk of permanent colostomy and proctectomy and is associated with a major deterioration in quality of life. Secondary anal lesions in Crohn's disease are fistulas and abscesses. They are difficult to treat and often recurrent. A multidisciplinary medico-surgical management in several stages is essential. The classic sequence is based on a first phase of drainage of fistulas and abscesses, a second phase of medical treatment based primarily on anti-TNF alpha and finally a third phase of surgical closure of the fistula tract(s). Conventional closure techniques such as biologic glue, plug, advancement flap and intersphincteric ligation of the fistula tract have limited effectiveness, are not always feasible, require technical skills and some have an impact on anal continence. In recent years, we have witnessed a real enthusiasm generated by the arrival of cell therapy. This has not spared proctology since adipose-derived allogeneic mesenchymal stem cells have had Marketing Authorisation and have been reimbursed in France since 2020 in the treatment of complex anal fistulas in Crohn's disease after failure of at least one biologic therapy. This new treatment offers an additional alternative in patients often in a situation of therapeutic impasse. Preliminary results in real life are satisfactory with a good safety profile. However, it will be necessary to confirm these results in the longer term and to work to determine the profile of the patients who could benefit the most from this expensive therapy.

PRISE EN CHARGE DES LÉSIONS SECONDAIRES DE LA MALADIE DE CROHN ANOPÉRINÉALE. L'atteinte anopérinéale de la maladie de Crohn est fréquente ; elle affecte environ un tiers des patients durant leur maladie. Elle constitue un facteur péjoratif responsable d'une majoration du risque de colostomie définitive et de proctectomie, et est associée à une altération majeure de la qualité de vie. Les lésions anales secondaires de la maladie de Crohn sont des fistules et des abcès. Elles sont difficiles à traiter et souvent récidivantes. Une prise en charge multidisciplinaire médico-chirurgicale en plusieurs étapes s'impose. La séquence classique se fonde sur une phase de drainage des fistules et des abcès, une phase de traitement médical fondé en priorité sur les anti-TNF alpha et enfin une phase de fermeture chirurgicale du (ou des) trajet(s) fistuleux. Les techniques de fermeture classiques comme la colle biologique, le plug, le lambeau d'avancement et la ligature intersphinctérienne du trajet fistuleux ont une efficacité limitée, ne sont pas toujours réalisables, nécessitent des compétences techniques et ont, pour certaines, un impact sur la continence anale. Ces dernières années, l'arrivée de la thérapie cellulaire suscite un véritable enthousiasme. Cet engouement n'a pas épargné la proctologie, puisque les cellules souches mésenchymateuses (CSM) allogéniques d'origine adipocytaires ont obtenu une autorisation de mise sur le marché (AMM), sont commercialisées et remboursées en France depuis 2020 dans le traitement des fistules anales complexes de la maladie de Crohn en échec d'au moins une biothérapie. Cette thérapie offre une alternative supplémentaire à des patients souvent en situation d'impasse thérapeutique. Les résultats préliminaires en vraie vie sont satisfaisants, avec un bon profil d'innocuité. Toutefois, il faudra confirmer ces résultats à plus long terme et travailler à identifier le profil des patients qui pourraient bénéficier au mieux de cette thérapie onéreuse.