Philippe Zerbib

Mu opioid receptor expression is increased in inflammatory bowel diseases: implications for homeostatic intestinal inflammation

Background and aims: Recent studies with μ opioid receptor (MOR) deficient mice support a physiological anti-inflammatory effect of MOR at the colon interface. To better understand the potential pharmacological effect of certain opiates in inflammatory bowel diseases (IBD), we (1) evaluated the regulation in vivo and in vitro of human MOR expression by inflammation; and (2) tested the potential anti-inflammatory function of a specific opiate (DALDA) in inflamed and resting human mucosa. Patients and methods: Expression of MOR mRNA and protein was evaluated in healthy and inflamed small bowel and colonic tissues, isolated peripheral blood mononuclear cells and purified monocytes, and CD4+ and CD8+ T cells from healthy donors and IBD patients. The effect of cytokines and nuclear factor κB (NFκB) activation on MOR expression in lymphocyte T and monocytic human cell lines was assessed. Finally, DALDA induced anti-inflammatory effect was investigated in mucosal explants from controls and IBD patients. Results: MOR was expressed in ileal and colonic enteric neurones as well as in immunocytes such as myeloid cells and CD4+ and CD8+ T cells. Overexpressed in active IBD mucosa, MOR was significantly enhanced by cytokines and repressed by NFκB inhibitor in myeloid and lymphocytic cell lines. Furthermore, ex vivo DALDA treatment dampened tumour necrosis factor α mRNA expression in the colon of active IBD patients. Conclusions: Given the increased expression of MOR and the ex vivo beneficial effect of DALDA in active IBD, natural and/or synthetic opioid agonists could help to prevent overt pathological intestinal inflammation.

Pre-operative management is associated with low rate of post-operative morbidity in penetrating Crohn?s disease

Aliment Pharmacol Ther 2010; 32: 459–465

Prise en charge d’un malade opéré

C’est une éventualité fréquente lors du premier mois [1, 2, 5]. Elle est le principal facteur d’échec tardif (35-80 %) [6-8] (niveau 2). Les causes les plus souvent invoquées sont la tension excessive, des facteurs généraux (poussée aiguë sévère, dénutrition, corticothérapie prolongée) et des facteurs anatomiques (étroitesse du bassin, surcharge pondérale) [5, 9, 10] (niveau 3). L’âge (plus de 60 70 ans), n’est pas, en soi, un facteur de ris(1) Service de chirurgie digestive et transplantation, Hôpital Claude Huriez, 59034 Lille ; (2) Service d’hépato-gastroentérologie et nutrition, Hôpital Saint Antoine, 75012 Paris ; (3) Département d’hépato-gastroentérologie, Hôpital Charles Nicolle, 76041 Rouen ; (4) Service de chirurgie, Hôpital Sainte Marguerite, 13274 Marseille ; (5) Service de chirurgie digestive, Hôpital Lariboisière Louis, 75010 Paris.

Giant colon diverticulum

Giant colonic diverticulum is defined by a diverticulum whose diameter is greater than 4 cm. This is a rare entity, arising mainly in the sigmoid colon. The diagnosis is based on abdominal computed tomography that shows a gas-filled structure communicating with the adjacent colon, with a smooth, thin diverticular wall that does not enhance after injection of contrast. Surgical treatment is recommended even in asymptomatic diverticula, due to the high prevalence and severity of complications. The gold standard treatment is segmental colectomy. Some authors propose a diverticulectomy when the giant diverticulum is unique.

Post-operative recurrence of Crohn’s disease after definitive stoma: an underestimated risk

IntroductionCrohn’s disease (CD) is a progressive inflammatory disease affecting the entire gastrointestinal tract. The need for a definitive stoma (DS) is considered as the ultimate phase of damage. It is often believed that the risk of further disease progression is small when a DS has been performed.AimsThe goals of the study were to establish the rate of CD recurrence above the DS and to identify predictive factors of CD recurrence at the time of DS.MethodsWe retrospectively reviewed all medical records of consecutive CD patients having undergone DS between 1973 and 2010. We collected clinical data at diagnosis, CD phenotype, treatment, and surgery after DS and mortality. Stoma was considered as definitive when restoration of continuity was not possible due to proctectomy, rectitis, anoperineal lesions (APL), or fecal incontinence. Clinical recurrence (CR) was defined as the need for re-introduction or intensification of medical therapy, and surgical recurrence (SR) was defined as a need for a new intestinal resection.ResultsEighty-three patients (20 males, 63 females) with a median age of 34xa0years at CD diagnosis were included. The median time between diagnosis and DS was 9xa0years. The median follow-up after DS was 10xa0years. Thirty-five patients (42%) presented a CR after a median time of 28xa0months (2–211) and 32 patients (38%) presented a SR after a median time of 29xa0months (4–212). In a multivariate analysis, APL (HRxa0=xa05.1 (1.2–21.1), pxa0=xa00.03) and colostomy at time of DS (HRxa0=xa03.8 (1.9–7.3), pxa0=xa00.0001) were associated factors with the CR.ConclusionAfter DS for CD, the risk of clinical recurrence was high and synonymous with surgical recurrence, especially for patients with APL and colostomy.

Chronic radiation enteritis

Radiation enteritis is an iatrogenic disease of the intestines caused by radiation therapy. Two entities, chronic and acute radiation enteritis, are described. The acute symptoms (abdominal pain, loss of appetite, diarrhea) develop within the first hours or days after radiation therapy and can be treated medically. Chronic radiation enteritis leads to a chronic sub-obstructive and/or malabsorption syndrome developing at least two months after the end of radiation therapy. Cases occurring 30 post-radiation are reported. Treatment is surgical with extended resection of all involved elements of the digestive tract and ileocolonic anastomosis in healthy zones. The diagnosis is confirmed by the anatomopathology report of fibrous intestinal lesions associated with obliterating arterial lesions.

Persistent perineal sinus after abdominoperineal resection

Background and aimsPersistent perineal sinus (PPS) defined as a perineal wound remaining unhealed more than 6xa0months after abdominoperineal resection (APR) is a well-known complication. The aim of our study was (1) to evaluate the incidence of PPS after APR for Crohn’s disease (CD) in the era of biotherapy, (2) to determine long-term outcome of PPS, (3) to study risk factors associated with delayed perineal healing, and (4) to compare the results in this CD patient group with patients without CD.MethodsFrom 1997 to 2013, the records of patients who underwent APR for CD and for non-CD rectal cancer with or without radiochemotherapy at two French university hospitals were studied retrospectively. Perineal healing was evaluated by clinical examination at 1, 6, and 12xa0months after surgery.ResultsThe cumulative probability of perineal wound unhealed at 6 and 12xa0months after surgery was 85 and 48%, respectively, for 81 patients who underwent APR for CD patients in contrast to 21 and 13%, respectively, for 25 non-CD patients with rectal cancer. Eight patients with CD (10%) remained with PPS after a median follow up of 4xa0years and spontaneous perineal healing occurred with time for all non-CD patients. Factors associated with delayed perineal healing in CD included age at surgery <xa049xa0years (pxa0=xa00.001) and colonic-only Crohn’s disease location (pxa0=xa00.045). Medical treatments had no significant impact on perineal healing.ConclusionsPPS beyond 6xa0months post-APR remains a frequent complication but mostly resolves over time. CD is a risk factor for developing PPS and factors associated with higher incidence of PPS were age at surgery <xa049xa0years and colonic-only Crohn’s disease location. Prevention of PPS in this population with muscle flap during APR deserves to be evaluated.

Incontinence anale associée au syndrome de résection antérieure du rectum : la neuromodulation sacrée est-elle efficace ?

Introduction Une incontinence anale (IA) ou un syndrome de resection anterieure (LARS), greve frequemment le resultat fonctionnel et altere la qualite de vie apres une resection rectale, isolee ou accompagnant une colectomie totale avec anastomose ileo-anale (AIA). Les traitements symptomatiques habituels sont inefficaces. Dans ces situations, une neuromodulation des racines sacrees (NMS) a parfois ete realisee, procurant un resultat fonctionnel satisfaisant. L’objectif de ce travail multicentrique etait d’evaluer les resultats fonctionnels de la NMS pour IA/LARS, apres proctectomie ou AIA. Methodes Tous les malades ayant eu une implantation de NMS pour ces indications etaient inclus (2006-2014). L’efficacite therapeutique et la qualite de vie etaient evaluees par la comparaison de la frequence des episodes d’IA, et des scores de Wexner, de LARS et de FIQL. Resultats Quinze malades (9 femmes, 54 [22-78] ans) ont ete implantes, 2,6 [1,2-11,7] ans apres AIA (n = 6, 40 %), coloproctectomie avec anastomose colo-anale (n = 6, 40 %) ou anastomose colorectale (n = 3, 20 %). Il y a eu deux echecs (13 %). La frequence des selles, le nombre d’episodes d’IA mineure, les imperiosites, ainsi que les scores de Wexner, LARS et FIQL etaient significativement ameliores pour tous les autres cas. Conclusion La NMS semble donc efficace sur l’IA ou le LARS compliquant une resection rectale ou une AIA. Un travail prospectif multicentrique est mis en place pour confirmer ces resultats preliminaires. Declaration d’interet Les auteurs n’ont pas transmis de conflits d’interets.