Unusual intra-rectal "laterally spreading tumour" in immunosuppressed patient with ulcerative colitis.

Condyloma acuminatum (CA) is a manifestation of Human Papillomavirus (HPV) infection which usually occurs in genital and perianal regions. We report a 46-year-old man with an ulcerative proctitis diagnosed four years earlier, asymptomatic for a long time under azathioprine but without any follow-up for three years. A colonoscopy was performed prior to potential immunosuppressive treatment discontinuation and showed a circumferential "laterally spreading tumour" in the rectum. Surprisingly biopsies revealed a CA with a very focally high-grade intra-epithelial lesion. Azathioprine was stopped and a transanal surgical resection was performed. At guided anamnesis, patient confirmed to be a former active "men who have sex with men". No recurrence of proctitis occurred despite azathioprine discontinuation. A retrospective review of the histological sections suggests that it was, in fact, an intestinal spirochetosis misdiagnosed as inflammatory bowel disease. Involvement of the rectal mucosa by HPV is a rare condition and this may have been promoted by inappropriate immunosuppressive treatment.

Belgian consensus guideline on the management of hemorrhoidal disease.

Introduction: Hemorrhoidal disease is a common problem that arises when hemorrhoidal structures become engorged and/or prolapse through the anal canal. Both conservative and invasive treatment options are diverse and guidance to their implementation is lacking. Methods: A Delphi consensus process was used to review current literature and draft relevant statements. These were reconciliated until sufficient agreement was reached. The grade of evidence was determined. These guidelines were based on the published literature up to June 2020. Results: Hemorrhoids are normal structures within the anorectal region. When they become engorged or slide down the anal canal, symptoms can arise. Every treatment for symptomatic hemorrhoids should be tailored to patient profile and expectations. For low-grade hemorrhoids, conservative treatment should consist of fiber supplements and can include a short course of venotropics. Instrumental treatment can be added case by case : infrared coagulation or rubber band ligation when prolapse is more prominent. For prolapsing hemorrhoids, surgery can be indicated for refractory cases. Conventional hemorrhoidectomy is the most efficacious intervention for all grades of hemorrhoids and is the only choice for non-reducible prolapsing hemorrhoids. Conclusions: The current guidelines for the management of hemorrhoidal disease include recommendations for the clinical evaluation of hemorrhoidal disorders, and their conservative, instrumental and surgical management.

Ustekinumab in bio-naïve and bio-failure Crohn's disease patients: Results from a « real-life ¼ monocentric cohort.

BACKGROUND: The pivotal clinical trials have largely demonstrated the efficacy and safety of ustekinumab in Crohn's disease. Real-life cohorts published so far only include very few bio-naïve patients. This study assesses effectiveness and safety of ustekinumab in bio-naïve and bio-failure patients treated with ustekinumab in routine practice and look for predictors of response. METHODS: We performed a retrospective monocentric study. Initial response was assessed by maintenance therapy beyond week 16. Sustained response was assessed by the continuation or cessation of therapy over time for another reason than stopping in sustained remission. Treatment persistence was assessed by Kaplan Meier curves and predictors of treatment persistence were studied by univariate and multivariate Cox model. RESULTS: Out of 156 recorded patients, three patients were still in their induction phase at time of analysis and 5 patients were lost to follow-up, leaving 148 patients for clinical effectiveness analyses, including 35 bio-naïve when starting ustekinumab. A maintenance therapy was initiated in 79.7%. At one year, the probability to be still treated with ustekinumab was 73.8%. Treatment cessation increased with smoking in multivariate analysis. Previous biologic failure (as a whole), CRP and fecal calprotectin baseline levels did not influence initial response and treatment persistence. CONCLUSION: A large proportion of CD patients initially respond to ustekinumab and continue this treatment beyond one year. Treatment persistence is as high in bio-failure as in bio-naïve patients.

[Increased neoplastic risks in ulcerative colitis associated with primary sclerosing cholangitis]. / Risques néoplasiques majorés dans la rectocolite ulcéro-hémorragique associée à la cholangite sclérosante primitive.

Ulcerative ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by the presence of continuous, uniform, gapless lesions of healthy mucous membrane extending integrally from the anus over a variable portion of the colon. It is a multisystemic pathology for which we will describe one of its hepatic manifestations, primary sclerosing cholangitis (PSC). We present here the story of a patient, a carrier of the Breast Cancer type 1 gene mutation (BRCA1), who initially presented with epigastric and peri-umbilical abdominal pain associated with several episodes of bloody diarrhea. The initial assessment made it possible to diagnose BRCA1 and the fortuitous discovery of biliary tract stenosis of an undetermined nature. Further investigations led to the conclusion that there was a strong presumption of UC associated with PSC or even cholangiocarcinoma (CCA). In the course of treatment, cancer of the gallbladder was also detected. This clinical case makes it possible to review, in the light of recent publications, the pathophysiological link existing between UC and PSC. This article also presents an in-depth analysis of this entity with malignant potential that can affect different sites of the digestive tract, and its own management, which is the subject of new recommendations.

La rectocolite ulcéro-hémorragique (RCUH) est une maladie inflammatoire chronique de l'intestin, caractérisée par la présence de lésions continues, uniformes et sans intervalle de muqueuse saine, s'étendant d'un seul tenant à partir de l'anus sur une portion variable du côlon. Il s'agit d'une pathologie multisystémique pour laquelle nous décrirons une de ses manifestations hépatiques, la cholangite sclérosante primitive (CSP). Nous exposons ici l'histoire d'un patient, porteur de la mutation du gène Breast Cancer de type 1 (BRCA1), s'étant initialement présenté pour douleurs abdominales épigastriques et péri-ombilicales, associées à plusieurs épisodes de diarrhées sanglantes. Le bilan initialement réalisé a permis de poser le diagnostic de RCUH ainsi que la mise en évidence fortuite d'une sténose des voies biliaires de nature indéterminée. Les explorations complémentaires ont permis de conclure à une forte présomption de RCUH associée à une CSP, voire un cholangiocarcinome (CCA). Dans le décours de la prise en charge, un cancer de la vésicule biliaire a également été mis en évidence. Ce cas clinique permet de revoir, à la lumière des publications récentes, le lien physiopathologique existant entre la RCUH et la CSP. L'article présente une analyse approfondie de cette entité qui possède un potentiel malin important, touchant plusieurs organes du tractus digestif, et qui requiert une prise en charge propre faisant l'objet de recommandations nouvelles.

[How I explore Crohn's disease by various imaging modalities]. / Comment j'explore la maladie de Crohn par imagerie.

Crohn's disease is a chronic inflammatory condition characterized by recurrent and/or chronic lesions, leading to cumulative structural bowel damage. It is established that the correlation between symptoms and intestinal lesions is weak. Therefore, monitoring by frequent cross-sectional imaging is proposed to assess the disease activity. There is no consensus about the preferred imaging option. Priority is given to non-radiating modalities, such as ultrasonography and MRI. Tomodensitometry will be reserved for emergency cases. Ultrasonography can be useful, in emergency as well as for the monitoring of lesions of known topography. Entero-MRI is henceforth considered the standard imaging technique for the diagnosis and follow-up of Crohn's disease. Its high contrast resolution allows an accurate assessment of disease activity, therapeutic efficacy, cumulative structural bowel damage and complications.

La maladie de Crohn est une maladie inflammatoire intestinale dont les manifestations récurrentes ou chroniques entraînent des dommages tissulaires cumulatifs. Il est avéré que la corrélation entre la symptomatologie clinique et les lésions intestinales est faible. Par conséquent, des examens d'imagerie fréquents sont nécessaires pour déterminer l'activité de la maladie. Il n'existe pas de consensus quant à l'utilisation de l'une ou l'autre technique. La priorité sera donnée à des examens peu irradiants comme l'échographie et l'IRM. La tomodensitométrie sera réservée aux situations d'urgence ou en cas de contre-indication à l'IRM. L'échographie est un outil à ne pas négliger, tant en urgence que pour le suivi de lésions de topographie connue. L'entéro-IRM est dorénavant l'examen de choix pour le diagnostic et le suivi de la maladie de Crohn. Son excellente résolution en contraste permet d'évaluer l'activité de la maladie, l'efficacité thérapeutique, les dommages tissulaires cumulés et la présence de complications.

[Current management of marginal zone lymphomas]. / Prise en charge actueLe du lymphome de la zone marginale.

Marginal zone lymphomas (MZL) encompass three sub-types: MALT (Mucosae Associated Lymphoid Tissue) MZL, nodal MZL and splenic MZL. Immunophenotyping is essential for accurate diagnosis. Helicobacter Pylori is frequently associated with gastric localizations and its eradication can be sufficient for cure. Treatment of nodal MZL is similar to that of follicular lymphoma. Eradication of hepatitis C virus, frequently associated with splenic MZL development, can be sufficient. Without HCV infection, splenectomy constitutes first line therapy. As other indolent lymphomas, disseminated MZL are incurable and treatment should be started only in symptomatic patients.

Persisting signs of disease activity at Magnetic Resonance Enterocolonography predict clinical relapse and disease progression in quiescent Crohn's disease.

INTRODUCTION: Deep remission including clinical remission and tissue healing has been advocated as the therapeutic target in Crohn's disease. Yet, the definition of deep remission remains unclear. The aim of this study was to assess the persisting lesions at magnetic resonance enterocolonography (MREC) in clinically quiescent Crohn's disease as well as their relapse predictive value. METHODS: we performed a prospective monocentre cohort study. We included patients with clinical remission. At baseline, these patients had blood tests, the measurement of fecal calprotectin and underwent a MREC. They were then followed up clinically for a minimum of 1 year. A relapse was defined by a HBI > 4 with an increase of at least 3 points. Correlations between clinical, demographic, biological parameters and MREC signs were assessed as well as the time-to-relapse predictive value of the studied variables. RESULTS: Twenty seven patients were recruited. Fourteen out of 27 had persisting disease activity at MREC. MREC signs only partly correlated with biomarkers. Ten out of 27 patients relapsed over a median follow up of 25 months. In univariate analysis, relative contrast enhancement of the most affected segment (HR: 2.56; P = 0.046), ulcers (HR: 12.5; P = 0.039), fistulas (HR: 14.1; P = 0.009) and target sign (HR: 3.63; P = 0.049) were associated with relapse. In multivariate analysis, fistula was the only one. CONCLUSIONS: Half of the patients with clinically quiescent Crohn's disease had persisting signs of disease activity at MREC. These signs predicted time-to-relapse.

[FROM EVIDENCE-BASED MEDICINE TO PERSONALIZED MEDICINE IN CROHN'S DISEASE]. / DE L'"EVIDENCE-BASED MEDICINE" À LA MÉDECINE PERSONNALISÉE DANS LA MALADIE DE CROHN.

The therapeutic armamentarium in Crohn's disease includes mesalazine, steroids (including topical drugs), anti-metabolites (purines, methotrexate), anti-TNFα antibodies and, more recently, selective inhibitors of lymphocytes homing (vedolizumab). The efficacy of these drugs has been shown in pivotal phase 3 placebo-controlled trials and meta-analyses. However, the use of these drugs in routine practice still remains ill-defined. Those are rather the cohort studies, natural history data and therapeutic strategy trials that help the clinician to determine, for each individual patient, the treatment leading to an optimal benefit/risk profile, aiming at moving from evidence-based medicine towards personalized medicine.

[Vedolizumab (Entyvio®) for the treatment of inflammatory bowel diseases]. / LE MÉDICAMENT DU MOIS. Vedolizumab (Entyvio®), nouveau traitement des maladies inflammatoires intestinales.

Anti-TNF agents are highly effective in treating inflammatory bowel diseases, but loss of response and side-effects leading to drug interruption are often reported. New molecules are needed to treat these patients. Vedolizumab is a fully humanized anti-body inhibiting the migration of circulating lymphocytes to the gut by binding the integrin α4ß7. In ulcerative colitis, clinical response, remission and mucosal healing were observed at 6 weeks in 47%, 17% and 40% of the patients, respectively. The maintenance study demonstrated 42% and 52% of clinical remission and response at week 52. In Crohn's disease, clinical response and remission were respectively observed in 15% and 31% of the patients at 6 weeks. Clinical remission at week 52 was 39%. The time to clinical response was longer in patients who had failed anti-TNF. The safety profile is excellent with the same proportion of side-effects in the placebo and in the treated groups. The most frequently reported adverse events were pharyngitis and headaches.

[Constipation and fecal incontinence in the elderly]. / Constipation et troubles de la continence fécale chez le sujet âgé.

Alterations of anorectal functions (constipation and fecal incontinence) are very frequent in the elderly. The patient's global evaluation with his past medical history, comorbidities, medications, as well as social environment and physical dependence, is more than ever necessary in this high risk population to guide the explorations and the medical care of these disorders.

Depth of remission in Crohn's disease patients seen in a referral centre : associated factors and impact on disease outcome.

INTRODUCTION: Our goals were to assess the prevalence of biological and tissue remission in routine practice in Crohn's disease, and to evaluate the correlation between biological or tissue remission and clinical or demographic characteristics as well as their impact on disease outcome. METHODS: We performed a retrospective monocenter study. Biological remission was defined by a CRP < 5 mg/I. Tissue remission was defined by the absence of ulcer at endoscopy and/or absence of signs of acute inflammation at MRI. Association with demographic, clinical and laboratory markers was studied by logistic regression models and rates of relapses, hospitalizations and surgeries were compared using the logrank test. RESULTS: Among the 263 patients included, 147 were in clinical remission; 102/147 (69%) were in biological remission. Fifty-six patients also had morphological evaluation: 37 (66%) were in tissue remission. Biological remission was associated with older age, higher hemoglobin and lower BMI. Tissue remission was associated with older age, lower platelets count, absence of previous surgery, and the use of immunosuppressant. Time-to-relapse was significantly longer in patients with biological remission and in patients with tissue remission as compared to patients without biological or tissue remission. CONCLUSIONS: Among the patients in clinical remission seen as outpatients, two thirds were either in biological and/or tissue remission. Biological and/or tissue remission was associated with a better outcome than clinical remission alone.

[Genetics and environment in chronic inflammatory bowel diseases]. / Génétique et environnement dans les maladies inflammatoires chroniques de l'intestin.

Inflammatory bowel diseases are both environmental and genetic illnesses. More than one hundred genes or loci involved in the regulation of innate or acquired immune response as well as intestinal mucosa homeostasis have been identified. Environmental studies have been less numerous up to now and only smoking and appendectomy have been validated, as protector for ulcerative colitis, while smoking is clearly associated with an increased risk and more severe forms of Crohn's disease. An important role is also currently suspected for the intestinal flora and the dysbiosis described in inflammatory bowel disease could contribute to the triggering or the persistence of the inflammation. New therapeutic strategies are currently studied, particularly aiming at targeting immune, inflammatory or homeostatic pathways corresponding to the predisposing gene variants.

[Fifteen years of use of anti-TNF antibodies in moderate to severe Crohn's disease: how to make the best of this experience]. / Quinze ans d'anti-TNF dans la maladie de Crohn: comment tirer le meilleur de cette révolution thérapeutique?

After fifteen years of use, the anti-TNF antibodies have become the corner stone of the treatment of moderate and severe Crohn's disease. The skill acquired over the years through experimental trials and clinical experience leads to increased therapeutic efficacy and minimized risks. These antibodies are introduced increasingly earlier in Crohn's disease as well as in a broader range of patients, aiming at changing the natural history of the diseases by avoiding the development of intestinal tissue damage and complications.

Sexually transmitted diseases and anorectum.

Sexually transmitted diseases (STD) are a major public health problem because their incidence is increasing worldwide despite prevention campaigns and because they raise the risk of HIV infection. Anorectal localisations of STD are common among men who have sex with men (MSM) but can also be seen among heterosexuals (men or women). Transmission of such infections is due to anal sex or to other sexual behaviours like "fisting". Although some pathogens (like Human Papillomavirus-HPV) are common in gastroenterologist/proctologist consultations, others are not so well-known. Furthermore during the last years, sexual risky behaviours have led to resurgence of old affections (like syphilis) or to emergence of unknown diseases (like lymphogranuloma venereum) in our countries. This presentation tends to focus on clinical manifestation, diagnosis and treatment of different STD: HPV, Herpes Simplex Virus, Neisseria gonorrhoeae, Chlamydia trachomatis (in particularly lymphogranuloma venereum) and Treponema pallidum.

Medical treatment of chronic anal fissure. where do we stand on reversible chemical sphincterotomy?

Anal fissure is a common problem which can evolve to chronicity. Chronic anal fissure is thought to be an ischemic ulceration related to sphincter hypertonia. Lateral internal sphincterotomy, the most common treatment for chronic anal fissure, may cause permanent injury to anal sphincter leading to fecal incontinence. To avoid such side effect were developed medications producing a temporary or reversible sphincterotomy reducing the sphincter pressure only until the fissure has healed: nitrates, calcium channel antagonists and botulinum toxin. Authors aimed to summary the state of research on such treatments (efficacy, side effects, recurrence risk) and to clarify the role of these different medical options in the current treatment of chronic anal fissure.

Negative association between smoking and anti-saccharomyces cerevisiae antibodies in Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a polygenic multifactorial heterogeneous disease. Anti-Saccharomyces Cerevisiae antibodies (ASCA) correlate highly with CD and are present in 50-80% of patients. The reason for ASCA positivity or negativity in CD is unknown. The aim of our work was to analyse clinical, epidemiological and genetic characteristics in ASCA+ or ASCA- CD patients. METHODS: 113 patients with CD were tested for ASCA (IgA and IgG) by using a commercial kit (Medipan Diagnostica). Age, gender, systemic manifestations, familial form of disease, age at diagnosis, location and behaviour of the disease, smoking habit as well as genotyping for -308 TNF gene polymorphisms were determined. RESULTS: 38.9% CD patients were negative for both IgA and IgG ASCA while 61.1% were ASCA positive (respectively IgA and IgG: 31.9%; IgA only: 9.7%; IgG only: 19.5%). The only significant difference between ASCA+ and ASCA- patients was for smoking habit: there were 29% smokers in ASCA+ versus 50% in ASCA- CD patients (P = 0.03). This low proportion of smokers was more prominent in ASCA IgA+ patients than in isolated ASCA IgG+ patients (25.6% versus 45.5%) and was minimal in patients with high titers of ASCA IgA (0/8). Logistic regression showed smoking habit still borderline for significance (P = 0.057). CONCLUSIONS: Our results suggest a negative association between smoking and ASCA positivity in CD. This association was more prominent for ASCA IgA+. It indicates that smoking habit should be taken into account when analysing ASCA status in CD patients and may suggest an influence of smoking on immunization against intestinal material.

Frequently relapsing Crohn's disease is characterized by persistent elevation in interleukin-6 and soluble interleukin-2 receptor serum levels during remission.

We examined immune and inflammatory activation during remission in patients with Crohn's disease who presented with various clinical profiles (prolonged remission vs. relapsing disease). Thirty-six patients with at least 3 years' follow-up starting from a remission period were studied retrospectively. Relapses were defined by a retrospective calculation of the Crohn's disease activity index or by the clinical judgement of the physicians in charge of the patients. Disease course over the study period was assessed by the mean number of annual relapses. Analysis used measurements during remission of the following: erythrocytes sedimentation rate, relative lymphocytosis, acid alpha1-glycoprotein, interleukin-6 (IL-6), and soluble interleukin-2 receptor (sIL-2R) serum levels. During the study period 21 patients experienced at least one relapse and 15 did not. Mean serum levels of sIL-2R and mean relative lymphocytosis in remission significantly discriminated between relapsing and nonrelapsing patients. Only the mean sIL-2R serum level was selected by multivariate analysis, with a cutoff value of 82 pM/1 (sensitivity of 76% and specificity of 80%). The only features correlated with mean number of annual relapses in the relapsing patients were mean serum levels of sIL-2R (r=0.58, P=0.015) and IL-6 in remission (r=0.45, P=0.039). Multivariate analysis demonstrated statistical significance only for the mean serum level of IL-6 (P=0.014). In Crohn's disease the persistent elevation in sIL-2R serum levels during remission corresponds to chronic active disease, while high serum levels of IL-6 in these patients is associated with a high frequency of relapse.

[Guidelines for the management of Helicobacter pylori: recent opinion of the French National Society of Gastroenterology]. / Recommandations dans la prise en charge de l'Helicobacter pylori: point de vue récent de la Société nationale française de Gastroentérologie.

Guidelines for management of Helicobacter pylori are in constant evolution since its discovery in 1982 by Marshall and Warren. This article presents and comments recent guidelines developed under the auspices of the "Société Nationale Française de Gastroentérologie".

[Controversies in the treatment of Helicobacter pylori]. / Controverses dans le traitement de l'Helicobacter pylori.

Helicobacter pylori is a worldwide infection. In gastro-duodenal ulcer disease no doubt remains about the necessity of H. pylori eradication. Controversies subsisting in other pathologies such gastro-esophageal reflux, dyspepsia, gastritis, gastric adenocarcinoma or MALT lymphoma are reviewed. Multiple drug combinations have been proposed to cure the infection. These are discussed in the clinical setting of Belgian practice.