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.

[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.

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.

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.

[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.

Use of the enteroscope for colo-ileoscopy: low yield in unexplained lower gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: The small intestine is a potential origin of bleeding in patients with unexplained gastrointestinal tract hemorrhage or iron-deficiency anemia. Most reports on the investigation of these patients describe the use of upper tract enteroscopy. The diagnostic yield of combined upper and lower enteroscopy has not been widely assessed and remains to be clarified. The aim of this study was to assess the benefit of lower gastrointestinal tract enteroscopy in occult digestive bleeding. PATIENTS AND METHODS: Between 1 December 1995 and 15 January 1998, 54 patients with gastrointestinal bleeding of unknown origin were prospectively studied using upper and lower video push enteroscopy (44 for chronic iron-deficiency anemia and 10 for unexplained gastrointestinal tract hemorrhage with no potential site having been identified by other investigations). Examinations were done using a Olympus video enteroscope (SIF-100) under general anesthesia in a one-day clinic. An upper tract examination was done first, directly followed by the lower tract investigation. RESULTS: The upper tract enteroscopy was successful in 53 patients (98%) and retrograde ileoscopy in 21 patients (39%). In 18 (38%) cases the technical failure resulted from the impossibility of intubating the ileocecal valve. A potential source of upper gastrointestinal bleeding was detected in 35% of patients with chronic iron-deficiency anemia and in 20% of those with unexplained gastrointestinal tract hemorrhage. The most common lesion in the small bowel was angiodysplasia (25%). The lower tract video push enteroscopy disclosed 11 lesions in patients with chronic anemia. However the lesions, including two ileocecal valve cancers, were mainly located in the colon and had been missed by previous colonoscopy. No case of ileal lesion was detected in this group of patients. In patients with unexplained gastrointestinal tract hemorrhage, three lesions were detected but only one of these was in the ileum. Associated colonic and jejunal lesions were observed in three patients (5.5%). Overall, the diagnostic yield of lower video push enteroscopy was less than 2%. CONCLUSION: This prospective study has shown that using an enteroscope as a colonoscope in the management of patients with gastrointestinal bleeding of unknown origin is of little help. It might actually be more appropriate to perform a second colonoscopy. This however remains controversial and a prospective study is needed to answer that question.

A high serum concentration of interleukin-6 is predictive of relapse in quiescent Crohn's disease.

BACKGROUND/AIMS: Relapses of Crohn's disease are difficult to predict. We assessed the value of serum level of interleukin-6, tumour necrosis factor alpha (TNF-alpha) and soluble TNF receptors as predictors of relapse in quiescent Crohn's disease. PATIENTS/METHODS: Thirty-six patients with inactive Crohn's disease, treated or not, were included. Various clinical and biological parameters, including interleukin-6, TNF-alpha and soluble TNF receptors serum levels were measured at inclusion in the study and the patients were followed clinically for 1 year. The relapse was defined as a Crohn's Disease Activity Index (CDAI) greater than 150 with an increase greater than 100 compared to the inclusion value. We analysed the ability of these parameters to predict relapse in parallel to clinical characteristics and other laboratory parameters. RESULTS: Among the 32 variables tested, interleukin-6 serum level had the greatest ability to predict the time-to-relapse, with 17-fold chance of relapse over a 1-year period for patients with an interleukin-6 serum level greater than 20 pg/ml than for patients with a lower level (P < 0.001). A high serum level of the soluble TNF receptors p55 and p75 also had significant predictive value, in contrast to TNF-alpha serum levels. An interleukin-6 serum level greater than 20 pg/ml and either an acid alpha-1-glycoprotein level greater than 1.1 g/l or a soluble interleukin-2 receptor serum level greater than 95 pM/l were risk factors selected by a stepwise multivariate analysis. In both models a good prognosis group was defined by the absence of the two risk factors, a bad prognostic group by the presence of the two risk factors and an intermediate in between. With both models, the good prognosis group included 17 patients who experienced no relapse over the 1-year follow-up, whereas all patients (seven with the first model and six with the second) in the bad prognosis group had a relapse during the follow-up. Looking specifically at two homogeneous subgroups including either naturally/5-aminosalicylic acid (5-ASA) quiescent or corticoid quiescent patients, a very good predictive value for interleukin-6 serum concentration was also found. CONCLUSION: Interleukin-6 serum level alone or in association with other biological parameters such as acid alpha-1-glycoprotein or the soluble interleukin-2 receptor serum level may be useful for predicting the course of the disease in patients with quiescent Crohn's disease.

Soluble interleukin-2 receptor in Crohn's disease. Assessment of disease activity and prediction of relapse.

In Crohn's disease, the activity of the disease is difficult to evaluate and the evolution of the disease is difficult to predict. The soluble interleukin-2 receptor serum level has been reported to correlate with clinical activity of the disease and with mucosal immune activation. We compared serum soluble interleukin-2 receptor to classical inflammatory markers and other immune parameters in the assessment of clinical disease activity and prediction of relapse in patients with Crohn's disease. Soluble interleukin-2 receptor serum levels correlated well with the Crohn's disease activity index, and multivariate analysis showed that this correlation was independent of the other inflammatory and immune markers. The correlation was not greater, However, than that between some inflammatory markers, such as ESR, and Crohn's disease activity index. Longitudinal follow-up showed that a high soluble interleukin-2 receptor serum level was highly predictive of relapse. Multivariate analysis showed that the soluble interleukin-2 recepteur serum level was complementary to other inflammatory and clinical markers in the prediction of relapse of disease. We conclude that soluble interleukin-2 receptor is of use in monitoring Crohn's disease, particularly in prediction of relapse.