Aim: Real-world evidence on the management of hemorrhoidal disease (HD) is limited. This international study collected clinical practice data on the effectiveness of conservative treatments for acute HD on symptoms and quality of life (QoL), providing perspectives of treatment modalities from different continents. Patients & methods: The 4-week observational prospective CHORALIS study involved adult outpatients consulting for spontaneous complaints of hemorrhoids (graded using Goligher classification) and prescribed conservative treatments according to usual clinical practice. Assessments were: anal pain/discomfort (visual analog scale [VAS]), other signs/symptoms (patient questionnaire), Patient Global Impression of Change (PGI-C) questionnaire and disease-specific QoL (HEMO-FISS-QoL questionnaire). Results: Of 3592 participants, 3505 were analyzed (58.4% male; age 40.5 ± 13.7 years; history of HD in 48.4%; 72.1% Goligher grade I and II). Pain and discomfort were the most common symptoms. Most treatments were venoactive drugs (VADs; 90.9%), particularly micronized purified flavonoid fraction (MPFF; 73.7%) and diosmin (14.6%). All VAD-based therapies improved signs/symptoms (number/intensity/frequency of pain, discomfort, bleeding, swelling, itching and soiling) and QoL. MPFF was associated with a significantly greater proportion of patients with no symptoms (48.8 vs diosmin 34.4%, p < 0.001), pain disappearance (69.7 vs diosmin 52.8%, p < 0.001), treatment impact at 1 week rated on PGI-C as ‘very much better’ (30.5 vs diosmin 17.9%, p < 0.001) and shorter times to improvement (mean ± SD 3.9 ± 1.5 days vs diosmin 4.2 ± 1.7 days). Conclusion: In this prospective real-world study of patients with acute HD, conservative therapies consisting mainly of VADs, including MPFF, improved the clinical signs and symptoms of disease, as well as QoL. This study evidence supports clinical advantages associated with VADs, mostly MPFF, for effectively managing acute HD.

Objectif : Les taux de détection des polypes (TDP) et des adénomes (TDA) sont des indicateurs de qualité de la coloscopie et sont directement corrélés aux risques de cancer d’intervalle et de décès par le cancer du colon. Plus de la moitié des cancers d’intervalle serait liée à des lésions non détectées. Le but de cette étude est de déterminer si Endocuff vision® 2 nde génération (EVC) améliore la détection des adénomes et des polypes coliques dans la pratique courante. Méthodes : C’est une étude monocentrique non randomisée, en ouvert, comparant les données préexistantes de la coloscopie classique, obtenues dans la pratique courante de l’établissement dans la période du 1 er juin au 22 juillet 2017 (période rétrospective) sur 515 sujets sans EVC, et 521 patients avec le dispositif EVC du 18 octobre 2018 au 30 septembre 2019, après information et recueil du consentement (période prospective). Ces deux périodes ont été consécutives afin de limiter le biais de sélection. Le critère de jugement principal correspondait à la détection du taux d’adénomes, réalisée en coloscopie classique avec ou sans EVC sur des patients adultes. L’essai a été analysé par un test de comparaison de proportion entre les groupes pour données indépendantes sur le critère principal. Résultats : Le taux de détection d’au moins un adénome est augmenté avec le dispositif Endocuff® de 16,83 % à 21,11 % (P=0,036). Une meilleure préparation avec un score Boston = 9, améliore la détection des adénomes de 19,76 % à 26,68 % (P=0,003). Avec l’EVC, un temps de progression inférieur à 5 mn est préférable pour améliorer le taux de détection des adénomes (RR = 1,141 (1,130 to 1,752), P=0,0013), et un temps de retrait entre 6 et 10 mn (RR=1,449 (1,161 to 1,810, P=0,0027). Conclusion : L’utilisation du système Endocuff® améliore de façon significative la détection des adénomes pendant la coloscopie chez les patients ayant des antécédents personnels ou familiaux de polypes et de cancer et chez les patients ayant un BMI > à 30 ainsi que le temps de progression. Il est indispensable dans la détection des adénomes pendant la coloscopie. Il n’y a pas eu de complication associée [3, 5]. N°d’enregistrement de l’essai : NCT NCT03758872

Hemorrhoidal disease (HD) is characterized by prolapse of the inflamed and bleeding vascular tissues of the anal canal. Although HD is associated with a high recurrence rate, there is a lack of understanding around interventions that can reduce recurrence and improve outcomes for patients. As such, a systematic literature review (SLR) was conducted to summarize evidence on epidemiology, recurrence, and efficacy of interventions in HD. Real-world evidence (RWE) studies evaluating the incidence, prevalence, or recurrence of HD, as well as SLRs including a meta-analytic component reporting on the efficacy of systemic or topical pharmacological treatments for adults with HD, were included. Systematic searches were conducted in MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Database of Systematic Reviews. The SLR identified 44 eligible publications. Consistent data were limited on the epidemiology of HD or HD recurrence. Specifically, incidence and prevalence reported across geographies were impacted by differences in data collection. Reported risk factors for HD were sedentary behavior, constipation, male gender, and age. Twenty-three RWE studies and one meta-analysis reported HD recurrence rates ranging from 0 to 56.5 Patients with hemorrhoidal disease (HD) can experience recurring disease following a period of improvement or remission. It is not well established how often this might happen, who is at greatest risk, or which treatments can reduce this risk. In this study, a systematic literature review (SLR) was conducted to summarize evidence on the occurrence and recurrence of HD, as well as treatment effectiveness. Several literature databases were searched for articles that described real-world evidence (RWE) studies reporting the epidemiology or recurrence of HD as well as published SLRs that combined the results of multiple studies (meta-analyses) on treatment for adults with HD. Forty of 2037 articles identified by the search were considered relevant, and four others identified by clinicians were also included (total = 44; 39 RWE, 5 meta-analyses). Review of the RWE articles revealed that HD epidemiology was determined differently between studies. Only 23 reported recurrence rates (up to 56.5

La ragade anale (RA) è una lacerazione nella parte distale del canale anale. È localizzata principalmente dietro al margine anale. La sua diagnosi è esclusivamente clinica. Il sintomo dominante è un dolore talvolta violento, ritmato dalle defecazioni. La RA si osserva quando si dispiega il margine. È soprattutto idiopatica, conseguenza del passaggio di feci dure. Il trattamento di prima linea associa lassativi, lubrificanti topici e varie sostanze che alleviano lo spasmo dello sfintere. Diventando cronica, la ragade è accompagnata da annessi (cappuccio cutaneo, ipertrofia papillare a monte). Dopo diversi tentativi medici, si può prendere in considerazione la chirurgia. Indipendentemente dalla tecnica chirurgica, è possibile un’incontinenza anale minore da sequele. La dilatazione anale è abbandonata. In caso di sanguinamento o di diarrea anche intermittente, si deve discutere una colonscopia. Le ragadi o le ulcerazioni anali pongono problemi diversi anche se a volte è possibile una confusione tra di esse. Sono spesso molteplici nel contesto di una patologia dermatologica infettiva o tossica, comprese le infezioni a trasmissione sessuale. In particolare, la RA deve essere distinta soprattutto da un cancro su ragade o da una lesione perineale della malattia di Crohn.

La fisura anal (FA) es un desgarro de la porción distal del conducto anal. Se localiza en la mayoría de los casos en la parte posterior del margen anal. Su diagnóstico es exclusivamente clínico. El síntoma predominante es un dolor, en ocasiones intenso, cuyo ritmo se asocia al de la defecación. La FA se observa al desplegar el margen anal. Es predominantemente idiopática, como consecuencia del paso de las heces duras. El tratamiento de primera línea asocia laxantes, lubricantes tópicos y diversas sustancias que eliminan el espasmo esfinteriano. Cuando se cronifica, la fisura se acompaña de anexos (capuchón cutáneo, hipertrofia papilar proximal). La cirugía puede plantearse después de varios intentos de tratamiento médico. Con independencia de la técnica quirúrgica, puede desarrollarse una incontinencia anal leve como secuela. La dilatación anal se ha abandonado. En caso de hemorragias o de diarrea, incluso intermitente, debe plantearse una colonoscopia. Las ulceraciones anales plantean problemas diferentes, aunque en ocasiones puede haber confusión. Suelen ser múltiples en el marco de una patología dermatológica infecciosa o tóxica, incluidas las infecciones de transmisión sexual. Se debe distinguir en particular la FA de un cáncer ulcerativo o de una lesión perineal en la enfermedad de Crohn.

Hemorrhoidal disease (HD) is common in adults. Treatment is largely conservative, although more invasive procedures may be required. Venoactive drugs such as micronized purified flavonoid fraction (MPFF) are widely used, but a recent and comprehensive review of supporting evidence is lacking. In acute HD, MPFF can reduce HD symptoms such as bleeding, pain, anal discomfort, anal discharge and pruritus. In patients undergoing surgery, postoperative adjunct MPFF consistently reduces pain, bleeding duration and use of analgesia. MPFF treatment is appropriate and effective both as a first-line conservative treatment and as a postoperative adjunct treatment. MPFF reduces the duration of hospital stay following surgery, facilitating a return to normal activity and improving quality of life. MPFF may also prevent HD recurrence.

Background and Aim The CHORUS study (Chronic venous and HemORrhoidal diseases evalUation and Scientific research) was conducted to provide data on patients presenting with hemorrhoidal disease (HD) in clinical practice and to explore the frequency with which it coexists with chronic venous disease (CVD) and shared risk factors. Methods This international, noninterventional study enrolled adult patients attending a consultation for hemorrhoidal complaints. The questionnaire completed by physicians established the subjects' demographic and lifestyle characteristics and collected information on HD grade and symptoms and signs of CVD. Results A total of 5617 patients were analyzed. Symptoms commonly reported were bleeding (71.8%), pain (67.4%), swelling (55.0%), itching (44.1%), and prolapse (36.2%). Multivariate analysis revealed the variables with the strongest association with HD severity were older age, higher CVD CEAP (Clinical manifestations, Etiologic factors, Anatomic distribution of disease, and underlying Pathophysiology) class, constipation, and male gender (all P < 0.0001). Elevated BMI was a risk factor for HD recurrence. Among women, number of births had a significant association with both HD grade and recurrence. The presence of CVD, reported in approximately half the patients (51.2%), was strongly associated with advanced grade of HD (P < 0.0001). Treatments most commonly prescribed were venoactive drugs (94.3%), dietary fiber (71.4%), topical treatment (70.3%), analgesics (26.3%), and surgery (23.5%). Conclusions CHORUS provides a snap shot of current profiles, risk factors, and treatments of patients with HD across the globe. The coexistence of HD and CVD in more than half the study population highlights the importance of examining for CVD among patients with a hemorrhoid diagnosis, particularly when shared risk factors are present.

Little is presently known on the impact of device type for Doppler-guided hemorrhoidal artery ligation/mucopexy (DGHAL) or circular stapled hemorrhoidopexy (CSH) when a surgical treatment is considered for hemorrhoidal disease (HD). In this study, we aimed to compare the outcome in terms of adverse events and recurrence rate, of patients included in the multicenter LigaLongo RCT (ClinicalTrials.gov NCT01240772) according to the type of devices used.

Ascesso e fistola anale sono due fasi di una stessa malattia che inizia con l’infezione di una ghiandola situata nel canale anale. Le fistole sono, il più delle volte, idiopatiche, anche se possono, a volte, rivelare una malattia di Crohn. Il tramite infetto è, il più delle volte, semplice e deve essere trattato mediante chirurgia in un tempo con l’esclusione di qualsiasi terapia antibiotica. La diagnosi è, prima di tutto, clinica: rigonfiamento doloroso vicino all’ano per gli ascessi e secrezione purulenta cronica per le fistole. In caso di ascesso, l’obiettivo è di consentire lo scarico del pus mediante drenaggio; in caso di fistola, l’obiettivo è di mettere a piatto il tramite infetto partendo dalla porta d’ingresso od orifizio primario; la sua identificazione è, a volte, difficile. I tramiti più complessi richiedono una diagnostica per immagini (risonanza magnetica [RM] o ecoendoscopia) per guidare la chirurgia e non ignorare ramificazioni annesse, fonti di recidiva. Le due principali complicanze dopo il trattamento sono la recidiva e l’incontinenza anale da sequele. Per limitare tale rischio, sono stati sviluppati dei trattamenti alternativi detti “di risparmio muscolare”, senza sezione del muscolo sfintere. Essi hanno in comune un minor rischio di incontinenza, ma un tasso di insuccessi più elevato (fino al 60% dei casi).

L’urgence est definie par la survenue rapide ou brutale d’un symptome qui necessite une assistance ou une intervention immediate. En proctologie, en l’absence habituelle de menace vitale, la prise en charge de l’urgence a pour objectif : le controle des symptomes plus que le traitement radical et definitif de la pathologie en cause. Les deux symptomes qui conduisent les patients a consulter en urgence sont la douleur et les saignements. Urgence douloureuse

Closing the internal opening by a clip ovesco has been recently proposed for healing the fistula tract, but, to date, data on benefit are poorly analyzed. The aim was to report a preliminary multicenter experience.

Background: Anal incontinence is a frequent complaint that profoundly affects quality of life. Our aim was to determine whether perineal retraining gives additional benefits to standard medical treatment.Methods: Patients with anal incontinence and a Wexner score >4 were randomly assigned to standard conservative treatment (control) or perineal retraining, including biofeedback, in addition to standard treatments (biofeedback). Diaries, self-administered questionnaires and satisfaction scores quantified the benefits. Self-evaluated improvement was the primary outcome measure. A score >= 3 (in an improvement scale from -5 to + 5) defined success.Results: Overall, 157 patients were included; 80 in the control group (75% females, mean age 60.1 +/- 13.2 years) and 77 in the biofeedback group (79% females, mean age 61.9 +/- 10.2 years). After a 4-month follow-up, the success rate was significantly higher in the biofeedback group (57% versus 37%; p < 0.021). In the biofeedback group, daily stool frequency, leakage, and faecal urgency significantly decreased, and daily non-urgent perception of stool increased. Conversely, symptomatic scores and quality of life scales did not significantly differ between groups. In a multivariate model, the adjusted odds ratio showed that perineal retraining was significantly associated with a higher chance of self-rated improvement (adjusted Odd Ratio [95% CI]: 2.34 [1.14-4.80]; p = 0.021).Conclusions: Perineal retraining offers a moderate but significant benefit for patients suffering from anal incontinence. (C) 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The prognosis of patients with chronic granulomatous disease (CGD) has improved in recent years thanks to earlier recognition and prevention of infectious complications.1Seger R.A. Modern management of chronic granulomatous disease.Br J Haematol. 2008; 140: 255-266Crossref PubMed Scopus (203) Google Scholar In this context an important concern remains the management of inflammatory manifestations (ie, colitis, interstitial pneumonitis, cystitis, or neutrophilic dermatosis). Gastrointestinal tract disorders, the prevalence of which can be as high as 60% and mimic Crohn disease (fistulae, perforations, and aseptic abscesses),2Marks D.J.B. Miyagi K. Rahman F.Z. Novelli M. Bloom S.L. Segal A.W. Inflammatory bowel disease in CGD reproduces the clinicopathological features of Crohn's disease.Am J Gastroenterol. 2009; 104: 117-124Crossref PubMed Scopus (191) Google Scholar can affect the quality of life and prognosis of these patients. Immunosuppressive agents (corticosteroids and azathioprine) are associated with significant adverse effects, mostly infections. Moreover, in a series of 5 patients treated with anti–TNF-α agents,3Uzel G. Orange J.S. Poliak N. Marciano B.E. Heller T. Holland S.M. Complications of tumor necrosis factor-α blockade in chronic granulomatous disease-related colitis.Clin Infect Dis. 2010; 51: 1429-1434Crossref PubMed Scopus (132) Google Scholar infections were more frequent, and 2 deaths occurred despite effectiveness in severe colitis, thus raising concerns regarding their safety in such patients. The alternative in severe cases is allogeneic hematopoietic stem cell transplantation (HSCT).4Horwitz M.E. Barrett A.J. Brown M.R. Carter C.S. Childs R. Gallin J.I. et al.Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft.N Engl J Med. 2001; 344: 881-888Crossref PubMed Scopus (240) Google Scholar However, this procedure can be associated with significant mortality. In this retrospective study we report the clinical efficacy and safety profile of thalidomide, an immunomodulatory agent with TNF-α antagonist properties, in the inflammatory manifestations of CGD. Of 119 patients followed in the Centre de Référence des Déficits Immunitaires Héréditaires5The French national registry of primary immunodeficiency diseases.Clin Immunol. 2010; 135: 264-272Crossref PubMed Scopus (132) Google Scholar between 1968 and 2011, 70 (58.8%) experienced at least 1 inflammatory manifestation. Eight patients (7 male patients with mutations in CYBB and 1 female patient with a mutation in NCF1) received thalidomide for inflammatory manifestations (Table I). Their median age at diagnosis of CGD was 13 months (range, 1-188 months).Table IAssessment of efficacy and tolerance of thalidomidePatient no.12345678Sex/inheritanceM/X-linked (gp91phox)M/X- linked (gp91phox)M/X- linked (gp91phox)M/X- linked (gp91phox)F/AR (p47)M/X- linked (gp91phox)M/X- linked (gp91phox)M/X-linked (gp91phox)Past infectious diseaseBCGitis, colitis (Salmonella dublin)Pulmonary aspergillosis, pneumonia, septicemia (Salmonella typhimurium), adenitis (Staphylococcus aureus)Cutaneous abscesses (Serratia marcescens), mediastinitis (Propionibacterium acnes), pulmonary aspergillosisAdenitis (Staphylococcus aureus), colitis (Salmonella paratyphi B), pleuropneumonia, mandibular osteitisSinusitis, liver abscess, pulmonary tuberculosis, pulmonary aspergillosisAspergillosis, tuberculosis (Mycobacterium tuberculosis), adenitis (Mycobacterium mucogenicum), pneumonia, and pleuritis (Geosmithia argillacea)Cerebral and pulmonary aspergillosis, septicemia (Staphylococcus aureus), nodular pneumonia (Paecilomyces species, Nocardia species)PeritonitisColitis (Salmonella species)Pulmonary aspergillosisNo./type of sites of granulomatous manifestations1/Colitis, stomatitis1/Colitis2/ColitisNodular lung lesions2/Colitis, stomatitisReticulonodular pneumonia2/Colitis and disabling proctitis, stomatitis, micronodular pneumonia2/Nodular lung lesionsSubcorneal pustular dermatosis1/Colitis1/Granulomatous hepatitisSymptomsAbdominal pain, diarrhea, aphtosisAbdominal pain, diarrhea, rectal bleedingDyspnea, Pancoast-Tobias syndrome, diarrheaDiarrhea, aphtosis, dyspneaAbdominal pain, diarrheaDiffuse pustulosis, cough, and dyspnea (New York Heart Association class II)Diarrhea, anal fistula, pneumaturiaAsthenia, weight loss, cholestasis, increased liver enzyme levelsAge at thalidomide initiation (y)2517223457303025Duration of inflammatory symptoms (y)/no. of flares before thalidomide3/<310/>64/<32/3-65/3-610/<318/3-61/<3Other therapies before thalidomideCST, mesalazine, budesonide, HCQ, IFX, AZA, imatinibCST, SLZ, AZA, MTX, IFX, ET, ADACST, mesalazineCSTCST, mesalazineHCQCST, IFX, ADASubtotal colectomy—Initial/maximal thalidomide dosage (mg/d)100/10050/10050/100100/100100/100100/10050/5050/75Clinical efficacyColitis: CR (normal endoscopic control)Colitis: CRu (partial improvement in endoscopic evaluation)Colitis: PR (persistent diarrhea)Lung: CR (resolution of nodular lesions)Colitis: CRu (no endoscopic evaluation)Lung: NR (+stability of micronodules)Colitis: CR (normal endoscopic control)Lung: PR (no symptoms but stability of micronodules)Lung: CR (resolution of nodular lesions)Dermatosis: CRColitis: PR (persistent diarrhea)Liver: CRu (normal liver blood test results, no control biopsy)Time to first improvement (mo)66661363Corticosteroids (mg/kg/d) at thalidomide's initiationNo1110.5NoNoNoDuration of corticosteroid use (mo)—24Ongoing186———Adverse effectsNoNoNoNeuropathy (M42)NoDeep venous thrombosis of right subclavicular vein∗Associated with a central venous catheter.NoConstipationDuration of thalidomide's use/follow-up (mo)62 (ongoing)43 (ongoing)41 (ongoing)42 (stopped)19 (ongoing)9 (stopped)12 (ongoing)11 (ongoing)OutcomeAliveAliveAliveAliveAliveDied (cerebral abscesses [Geosmithia argillacea])AliveAliveADA, Adalimumab; AZA, azathioprine; CR, complete response; CRu, unconfirmed complete response; CST, corticosteroids; ET, etanercept; F, female; HCQ, hydroxychloroquine; IFX, infliximab; MTX, methotrexate; M, male; NR, nonresponse; PR, partial response; SLZ, salazopyrin.∗ Associated with a central venous catheter. Open table in a new tab ADA, Adalimumab; AZA, azathioprine; CR, complete response; CRu, unconfirmed complete response; CST, corticosteroids; ET, etanercept; F, female; HCQ, hydroxychloroquine; IFX, infliximab; MTX, methotrexate; M, male; NR, nonresponse; PR, partial response; SLZ, salazopyrin. Inflammatory conditions were colitis (n = 6, see Fig E1 in this article's Online Repository at www.jacionline.org), interstitial lung disease or nodular consolidation (n = 4), neutrophilic dermatosis (n = 1), and histologically proved granulomatous hepatitis (n = 1). Inflammatory lung disease presented with 2 distinct patterns: mass-like nodular consolidation (patients 3 and 6, see Fig E2, Fig E3 in this article's Online Repository at www.jacionline.org) and interstitial lung disease (patients 4 and 5, see Fig E4 in this article's Online Repository at www.jacionline.org). The nodular consolidations corresponded to granuloma pathologically, and no evidence of infectious pneumonia was found at the time of their occurrence. Overall, 4 patients had only 1 inflammatory manifestation (colitis, n = 3; granulomatous hepatitis, n = 1), and 4 patients presented with 2 manifestations (colitis and pneumonia, n = 3; pneumonia and neutrophilic dermatosis, n = 1), leading to a total of 12 inflammatory flares. The median duration of inflammatory complications at the time of thalidomide's initiation was 5 years (range, 1-18 years). All but patient 8 received at least 1 previous disease-modifying antirheumatic drug, with a median of 2 different drugs (range, 0-7 drugs; Table I). Of note, anti–TNF-α agents did not improve colitis in 3 patients, and 1 patient underwent surgical colectomy because of severe colovesical and anal fistulae. Thalidomide was introduced at an initial dose of 50 to 100 mg/d (n = 4 each) and gradually increased to 100 mg/d in 6 of 8 patients. The maximal dose was 50 mg/d for patient 7 because of good clinical efficacy and 75 mg/d for patient 8 because of constipation. The dosage never exceeded 100 mg/d because good clinical efficacy was reached. A complete response was defined as a total absence of symptoms and morphologic (ie, endoscopy or computed tomographic [CT] scan) normalization to assess the efficacy of thalidomide. An unconfirmed complete response was a clinical complete response without morphologic confirmation. A partial response corresponded to an incomplete improvement in symptoms, which might have required the maintenance of another immunomodulatory agent without increasing the dose. Finally, nonresponse was defined as no improvement or worsening of symptoms. When considering patients with colitis, 4 of 6 patients underwent a clinical response after 6 months, with 2 of them having normalization of their endoscopic lesions (2 with a complete response and 2 with an unconfirmed complete response). The 2 remaining patients had partial responses, with persistence of diarrhea and maintenance of corticosteroids in patient 3 (10 mg/d), without any increase in dosage. When considering lung manifestations, clinical remission was achieved in 3 of 4 patients (all but patient 4, who had persistent dyspnea). We observed a distinct evolutive pattern between nodular lesions and interstitial involvement. Because patients 3 and 6 experienced improvement in their pseudomass lesions after 6 and 12 months (see Fig E2, Fig E3), patients 4 and 5 did not show any improvement in their interstitial pattern, fibrotic pattern, or both (see Fig E4). Unfortunately, neither initial nor longitudinal evaluation of the pulmonary function was available for these patients. Neutrophilic dermatosis (patient 6) and granulomatous hepatitis (patient 8) resolved completely. Overall, the median time to clinical efficacy was 6 months (range, 1-6 months), and corticosteroids were stopped in 3 of 4 patients. After a median follow-up of 30 months (range, 9-62 months), the overall safety profile was good. Thalidomide was stopped in 2 patients because of axonal neuropathy after 42 months in patient 4 and venous thrombosis in patient 6, although this was more related to central venous line insertion than to thalidomide exposure. Although patient 8 had transient constipation, thalidomide administration was neither reduced nor stopped. None of the patients exhibited infectious complications during treatment. It is noteworthy that patient 6 died of a fungal brain abscess 6 months after thalidomide was stopped, which complicated a pneumonia caused by Geosmithia argillacea that was present before thalidomide's introduction. In this group of patients thalidomide was started as an experimental last-resort therapy for refractory conditions in all but patient 8 because other immunosuppressive drugs were considered much more harmful, patients were not eligible for HSCT (because of donor unavailability or severity of the inflammatory disorder with high risk of treatment-related mortality), or both. Our group previously reported a dramatic improvement in the symptoms of severe inflammatory bowel disease in a young patient with CGD (herein reported as patient 26Sokol H. Suarez F. Meatchi T. Malamut G. Pocidalo M.A. Blanche S. et al.Thalidomide as a treatment for refractory CGD colitis.Am J Gastroenterol. 2009; 104: 1069Crossref PubMed Scopus (9) Google Scholar). Freudenberg et al7Freudenberg F. Wintergerst U. Roesen-Wolff A. Albert M.H. Prell C. Strahm B. et al.Therapeutic strategy in p47-phox deficient chronic granulomatous disease presenting as inflammatory bowel disease.J Allergy Clin Immunol. 2010; 125: 943-946.e1Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar reported a series of 8 patients with inflammatory bowel disease as an initial feature of CGD, among whom 2 patients received thalidomide, with efficacy in 1 patient initially given a diagnosis of entero-Behçet or Crohn disease. In our retrospective description we observed a different efficacy pattern depending on the inflammatory condition. A remarkable improvement was obtained in nodular pneumonia (2/2), neutrophilic dermatosis (n = 1), or granulomatous hepatitis (n = 1) while the efficacy was moderate in patients with colitis (4/6). Interestingly, there was no effect in cases of interstitial micronodular pattern or when fibrosis was achieved in contrast to the inflammatory pseudomass. This efficiency has been achieved despite prior failure of conventional therapies, such as corticosteroids, azathioprine, and even anti–TNF-α for 3 patients. We did not observe any new or worsening significant infection during our patients' follow-up. Indeed, thalidomide efficacy might be due to immunomodulation rather than profound immunosuppression, thus allowing preservation of a certain level of anti-infectious immunity. Other major side effects of thalidomide include asthenia, constipation, peripheral neuropathy, and deep venous thrombosis. One patient (patient 6) had deep venous thrombosis with a major predisposing factor (central venous line). However, the prothrombotic risk can be increased by associated inflammatory conditions, such as intercurrent infections, requiring close monitoring of these patients. Only 1 patient (patient 4) had peripheral axonal neuropathy, which usually is a major cause of thalidomide's discontinuation.8Palumbo A. Facon T. Sonneveld P. Bladè J. Offidani M. Gay F. et al.Thalidomide for treatment of multiple myeloma: 10 years later.Blood. 2008; 111: 3968-3977Crossref PubMed Scopus (268) Google Scholar This low frequency of neuropathy might be due to the fact that axonal neuropathies, including iatrogenic ones, can result from reactive oxygen species production,9Fidanboylu M. Griffiths L.A. Flatters S.J.L. Global inhibition of reactive oxygen species (ROS) inhibits paclitaxel-induced painful peripheral neuropathy.PLoS One. 2011; 6: e25212Crossref PubMed Scopus (112) Google Scholar which is impaired in patients with CGD. We did not perform any electromyography in our patients, either before or during treatment, because systematic electromyography is not recommended at the introduction of thalidomide.8Palumbo A. Facon T. Sonneveld P. Bladè J. Offidani M. Gay F. et al.Thalidomide for treatment of multiple myeloma: 10 years later.Blood. 2008; 111: 3968-3977Crossref PubMed Scopus (268) Google Scholar However, the low number of patients in this retrospective study does not allow a global extrapolation, and patients should be regularly monitored for neurologic side effects while receiving thalidomide treatment. Taken together, we observed only limited noninfectious side effects requiring discontinuation of thalidomide. We acknowledge several limitations, such as the small sample size and the retrospective design, which limit the completeness of our data and their interpretation. Because the prolonged use of immunosuppressive drugs can increase infectious risk, we believe that an earlier use of thalidomide could reduce iatrogenic morbidity and requirement of surgery of the gastrointestinal tract in some patients. A global therapeutic approach for inflammatory manifestations of CGD should be discussed to propose immunomodulatory drugs earlier for selected patients in preparation for HSCT to reduce the global risk of HSCT in highly inflammatory patients. Fig E2Pulmonary involvement of patient 6 (CT scan evaluation). A, Sarcoid-like bilateral consolidations in the central position with traction bronchiectasis at thalidomide's introduction. B, Improvement in the pseudomass near the aortic cross (27 vs 44 mm) after 6 months. C, Dramatic improvement in the left-side consolidations with slight improvement in the right lung after 12 months.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig E3A, Left apical subpleural consolidation in patient 3. B, Improvement after 13 months.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig E4A, Interstitial lung involvement in patient 4 (CT scan) at thalidomide's introduction. B, No evolution after 6 months of thalidomide therapy. C, No evolution after 14 months of thalidomide therapy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

BACKGROUND & AIMS Patients with inflammatory bowel disease (IBD) who have been exposed to thiopurines might have an increased risk of skin cancer. We assessed this risk among patients in France. METHODS We performed a prospective observational cohort study of 19,486 patients with IBD, enrolled from May 2004 to June 2005, who were followed up until December 31, 2007. The incidence of nonmelanoma skin cancer (NMSC) in the general population, used for reference, was determined from the French Network of Cancer Registries. RESULTS Before the age of 50 years, the crude incidence rates of NMSC among patients currently receiving or who previously received thiopurines were 0.66/1000 and 0.38/1000 patient-years, respectively; these values were 2.59/1000 and 1.96/1000 patient-years for the age group of 50 to 65 years and 4.04/1000 and 5.70/1000 patient-years for patients older than 65 years. Among patients who had never received thiopurines, the incidence of NMSC was zero before the age of 50 years, 0.60/1000 for the ages of 50 to 65 years, and 0.84/1000 for those older than 65 years. A multivariate Cox regression model stratified by propensity score quintiles showed that ongoing thiopurine treatment (hazard ratio [HR], 5.9; 95% confidence interval [CI], 2.1-16.4; P = .0006) and past thiopurine exposure (HR, 3.9; 95% CI, 1.3-12.1; P = .02) were risk factors for NMSC. They also identified age per 1-year increase as a risk factor for NMSC (HR, 1.08; 95% CI, 1.05-1.11; P < .0001). CONCLUSIONS Ongoing and past exposure to thiopurines significantly increases the risk of NMSC in patients with IBD, even before the age of 50 years. These patients should be protected against UV radiation and receive lifelong dermatologic screening.

Background & Objective: In the United States, colorectal cancer (CRC) is the third most prevalent and deadly malignancy.Development of novel CRC-specific abnormal DNA biomarkers may advance non-invasive, cost-efficient population-based CRC screening and ultimately reduces CRC death.DNA hypermethylation is a common epigenetic abnormality in CRCs and represents a promising class of cancer biomarkers.The objective of the current study was to develop optimal DNA hypermethylation-based biomarkers for use in feces-or serum-based average-risk CRC screening.Design: We first applied DNA methylation microarray analysis in order to identify novel loci demonstrating neoplasia-specific methylation in the colon.This array analysis allowed us to investigate 55% of CpG islands within the genome and was applied to 17 primary CRCs relative to 8 non-neoplastic colonic tissues (NCs) from neoplasia-free subjects.The detected CRC-associated hypermethylation events were then individually measured in 113 colonic tissues comprising 51 CRCs, 9 adenomas, 19 NCs from CRC patients (CRC-NCs), and 34 NCs from neoplasia-free subjects (control NCs) using highly sensitive and quantitative real-time quantitative methylation-specific PCR (qMSP) assays.Receiver-operator characteristics (ROC) curve analysis was applied to the qMSP data in order to assess each individual event as well as combination of events for their ability to discriminate neoplastic from non-neoplastic cases.Results: Microarray-based global methylation profiles discriminated CRCs from NCs.A bioinformatic filtering of the microarray data identified 169 candidate CRC-associated hypermethylation events, including one previously validated hypermethylation marker for fecal DNA-based CRC detection, SFRP2.Fourteen of these 169 loci were evaluated using qMSP assays.Ten of these 14 methylation events significantly distinguished CRCs from control NCs (p<.01).Of these ten events, methylation of VSX2 achieved the highest discriminative accuracy (83.3% sensitivity and 92.3% specificity; Area under ROC curve, or AUC, 0.93, p<1E-6).Similarly, CRC-NCs were significantly discriminated from control NCs by methylation of ALX3 (AUC 0.78, p<1E-4).The discrimination of CRC-NCs from control NCs was improved by a multi-locus methylation panel (AUC 0.83, p<1E-6) relative to ALX3.Although the sample numbers were small, two methylation events significantly distinguished adenomas from control NCs (p<.01).Conclusions: Systematic methylome analysis has identified 11 novel methylation events in neoplastic and non-neoplastic colonic mucosa from CRC patients that accurately discriminate CRC patients from controls.These markers merit further evaluation as candidate biomarkers for stool and circulating DNA-based CRC detection.

745 ± 831 vs 613 ± 752, p=0.38 and median =372; range 25-2902 vs median=295; range 7-3589). There was no impact of years of 5ASA use on outcomes.Conclusion In study I we could not find evidence that 1 or 5 years of consecutive 5-ASA use was chemoprophylactic in IBD (in fact it tended to increase the risk).We could not discount that longer use might have been chemoprophylactic.In Study II with a longer duration of follow up and more CRC cases we could not discern that 5-ASA was chemoprophylactic.Overall, our results support the majority of studies to date that 5-ASA is not chemoprophylactic in IBD for CRC.