Endoscopic assessment and treating to target increase the likelihood of mucosal healing in patients with Crohn's disease

International audienceBACKGROUND & AIMS: Mucosal healing has been proposed as a goal for treatment because it is associated with improved clinical outcomes of patients with Crohn's disease (CD). However, little is known about the feasibility or probability of achieving mucosal healing in clinical practice. We evaluated the feasibility of treating patients to achieve mucosal healing based on endoscopic evaluation (treating to target). METHODS: We reviewed the endoscopic outcomes of 67 patients with CD who had lesions detected by endoscopy. Patients underwent 2 to 4 subsequent endoscopic evaluations at the University of California San Diego and were followed up from 2011 through 2012; data were collected on therapies and patient management. The cumulative incidences of mucosal healing and endoscopic improvement were estimated using the Kaplan-Meier method. Factors independently associated with mucosal healing were identified using a Cox proportional hazards model. RESULTS: After a median follow-up period of 62 weeks, 34 patients (50.7%) had mucosal healing and 41 patients (61.1%) had endoscopic improvement. The cumulative probabilities of mucosal healing were 12.7% and 45.0% at 24 and 52 weeks of treatment, respectively. Factors associated with mucosal healing were as follows: fewer than 26 weeks between endoscopic procedures (hazard ratio, 2.35; 95% confidence interval, 1.15-4.97; P = .035) and adjustment to medical therapy when mucosal healing was not observed (hazard ratio, 4.28; 95% confidence interval, 1.9-11.5; P = .0003). CONCLUSIONS: In an endoscopic study of patients with CD, we found that assessment of endoscopic disease activity and adjustments to medical therapy (treat to target) increase the likelihood of mucosal healing

Feasibility of endoscopic assessment and treating to target to achieve mucosal healing in ulcerative colitis.

International audienceMucosal healing (MH) as a treatment target for ulcerative colitis is of growing interest because it is associated with improved clinical outcomes. However, the feasibility and probability of reaching MH in clinical practice is unknown. We therefore evaluated the feasibility of "treating to target" according to endoscopic findings to reach MH. All endoscopic outcomes of patients with ulcerative colitis followed in a single inflammatory bowel disease unit from 2011 to 2012 were reviewed and subsequent therapeutic management. Cumulative incidence of MH and histologic healing (HH) were estimated using a Kaplan-Meier method. A total of 60 patients underwent at least 2 consecutive endoscopic assessments, of whom 45 and 48 patients had endoscopic and histologic evidence of active disease, respectively. After a median follow-up of 76 weeks, 27 of 45 (60%) patients with endoscopic disease activity at baseline achieved MH and 24 (50%) of 48 patients with histologic disease activity at baseline had HH. The cumulative probabilities of MH were 26%, 52%, and 70% at 26, 52, and 76 weeks, respectively. The cumulative probabilities of HH at weeks 26, 52, and 76 from the time of initial procedure were 19%, 41%, and 57%, respectively. Any adjustment in medical therapy in case of persistent endoscopic activity was associated with both MH and HH. Repeated assessment of endoscopic disease activity with adjustment of medical therapy to the target of MH is feasible in clinical practice in patients with ulcerative colitis, and seems to be of benefit

Transanal Endoscopic Surgical Proctectomy for Proctitis Case Series Report: Diversion, Radiation, Ulcerative Colitis, and Crohn’s Disease

Abstract: Background: With recent trends in natural orifice surgery, there has been a rising interest in the evolution of transanal endoscopic surgery (TES) and transanal access platforms. Transanal endoluminal removal of rectal masses has matured into transanal endoscopic surgical resection of the rectum for benign and malignant disease. The purpose of this study is to evaluate the surgical outcomes of TES completion proctectomy in patients with proctitis in a retained rectum.Methods: This is a retrospective case series report. Patient demographics and peri-operative outcome variables were recorded.Results: TES proctectomy was successfully performed in 6 patients using a disposable transanal access platform. The patient's ages ranged from 22 – 74 years, 4 women and 2 men, BMI ranged from 22 – 51 kg/m2. The indication for surgery was proctitis in a retained rectum: diversion (n=1), radiation (n=1), ulcerative colitis (n=2), and Crohn's disease (n=2). Four applications of TES proctectomy were employed: TES completion proctectomy (n=2), TES assisted single incision abdominal perineal resection (n=1), TES assisted laparoscopic restorative proctectomy with colo-anal anastomosis (n=1), and TES assisted laparoscopic restorative total proctocolectomy with ileal pouch anal anastomosis (n=1). The operative time for TES completion proctectomy ranged from 140 – 238 minutes (n=4). The operative time for TES restorative proctectomy was longer at 446 min and 557 min (n=2). The hospital length of stay for both TES completion and restorative proctectomy ranged from 2 – 5 days (n=5). Complications included 1 urinary tract infection, 1 chronic draining perineal sinus tract, and 1 perineal wound dehiscence requiring re-operation. All six patients are doing well at the time of follow up (range 3 – 19 months).Conclusions: TES completion proctectomy alone or in combination with laparoscopic abdominal surgery is a safe and effective method to perform proctectomy and restorative proctectomy in this small case series of patients with proctitis in a retained rectum due to diversion, radiation, ulcerative colitis, and Crohn's disease

Validation of Gene Expression Biomarker Analysis for Biopsy-based Clinical Trials in Crohn's Disease

BackgroundThe ability to measure the expression of proinflammatory cytokines from intestinal biopsies in patients with Crohn's disease in an accurate and reproducible way is critical for proof-of-concept and mechanism-of-action trials; however, the number of biopsies from a segment of the ileum or colon required to yield reproducible results has not been rigorously evaluated. We examined intestinal biopsies from patients with Crohn's disease to validate methods for detecting changes in inflammatory gene expression.MethodsTo evaluate the reproducibility of gene expression measurements, intestinal biopsies were obtained from designated segments from 6 healthy controls, 6 patients with active Crohn's disease, and 6 patients with inactive Crohn's disease. Disease activity was based on the simple endoscopic score for Crohn's disease. Expression of 7 proinflammatory genes was measured from each biopsy using quantitative polymerase chain reaction. Using a linear mixed effects model, the power to detect transcriptional changes corresponding to active and inactive Crohn's disease was calculated.ResultsTotal simple endoscopic score for Crohn's disease score corresponds with expression of most inflammatory biomarkers. For most genes, 2 to 5 biopsies are needed to reduce sampling error to <25% for most genes. To measure changes in mRNA expression corresponding to active versus inactive Crohn's disease, 1 to 2 intestinal biopsies from 3 patients before and after treatment are needed to yield power of at least 80%.ConclusionsMeasuring proinflammatory gene expression from mucosal biopsies from patients with Crohn's disease is practicable and provides objective biomarkers that can be used in proof-of-concept and mechanism-of-action trials to assess response to therapy

Validation of Gene Expression Biomarker Analysis for Biopsy-based Clinical Trials in Crohnʼs Disease

Hall of the Two Sisters (Sala de Dos Hermanas) dome of mocarabes on octagonal drum; The palaces of the Alhambra and Generalife form the most important architectural ensemble to survive from the Nasrid period (1232-1492). The walled Alhambra city which sits on a steep hill, comprised the Alcazaba (alqaṣaba: "fortress"), palaces, mansions, two mosques, baths (ḥammams), an industrial zone with tanneries, a mint, kilns, workshops, and some adjacent royal estates such as the Generalife. The Generalife was built on ascending terraces. The sovereign reached the Generalife’s royal mansion, the Dar al-Mamlaka al-Sa'ida ("royal house of felicity"), from the Alhambra’s Puerta de Hierro, also built by Muhammad II. He ascended through orchards, crossed a first courtyard and entered the second through a guarded south portico, to ascend to a vestibule with a structural bench and up a steep staircase to the Patio de la Acequia. Gardens and fountains are interspersed throughout the palace complex. A UNESCO World Heritage Site. Source: Grove Art Online; http://www.oxfordartonline.com/ (accessed 7/29/2012