Symptomatic Crohn's Disease Research Articles

P435 Real-world comparison of effectiveness between ustekinumab and a second anti-TNF agent in patients with symptomatic stenosing Crohn's disease after failure of a first anti-TNF agent: results of the USTEKNOSIS study

Abstract Background While surgery was considered as the reference for stricturing Crohn's disease (CD), anti-TNF agents are now the first-line treatment thanks to the CREOLE study. However, there is no efficacy data after anti-TNF failure. We aimed to compare the effectiveness of ustekinumab and a second anti-TNF agent after failure of a first anti-TNF in symptomatic stricturing Crohn’s disease (CD). Methods In this multicenter study, we retrospectively included all adult patients with CD treated with ustekinumab or anti-TNF for symptomatic stricture (confirmed on imaging or endoscopy) after prior exposure ≥ one anti-TNF for the current stricture, without surgery between the failure of the last anti-TNF and the study. The primary endpoint was clinical remission (composite endpoint) at 6 months was defined as no pain, no vomiting, no food restriction, no sub-occlusive episode, no steroid, no surgery or discontinuation of treatment. The long-term endpoints were discontinuation of treatment for failure, bowel damage progression and surgery. The comparisons were performed after using propensity score analysis adjusted on potential confounders. Results Overall, 70 patients were analyzed, including 34 in the ustekinumab group and 36 in the anti-TNF group (29 on infliximab and 7 on adalimumab). The two groups were similar for age (38.5 vs 37.6 years), CD duration (12.2 vs 13.5 years), female gender (41.2% vs 51.8%), CD location (p=0.43) and CD phenotype (p=0.38). Concomitant immunosuppressant was observed in 63.9% with an anti-TNF versus 8.8% with ustekinumab. The number (p=0.56) and the length (p=0.10) of stricture were also similar. The proportion of patients ≥ 2 prior biologics was higher in the ustekinumab group (41.2% vs 8.3%; p=0.001). The rate of primary failure to anti-TNF agent was comparable (16.7% vs 20.6%). After adjustment based on propensity scores, the rate of clinical remission at 6 months was 73.9% and 42.7% (p = 0.24), under ustekinumab and anti-TNF, respectively. The predictive factors of remission in patients receiving ustekinumab were prior bowel resection (p=0.001) and length of stricture < 12 cm (p=0.042), while no predictor was found in those treated with anti-TNF agent. The risk of treatment discontinuation for failure (HR =2.86 [1.33-6.15]; p=0.008) or bowel damage progression (HR=3.90 [1.64-9.24]; p=0.003) were significantly greater in patients receiving another anti-TNF agent compared to those on ustekinumab. We did not observe any significant difference concerning the risk of surgery (HR=2.60 [0.70-9.61]; p=0.15). Conclusion Ustekinumab seems to be more effective than a 2nd anti-TNF to treat symptomatic stricturing CD after failure of a first anti-TNF. However, these data need to be confirmed by independent prospective data.

Retreatment with anti-tumor necrosis factor therapy in combination with an immunomodulator for recurrence of Crohn's disease after ileocecal resection results in prolonged continuation as compared to anti-tumor necrosis factor monotherapy.

A considerable proportion of Crohn's disease patients that undergo ileocecal resection (ICR) have failed anti-tumor necrosis factor (TNF) therapy preoperatively. This study aimed to assess the effectiveness of retreatment of anti-TNF therapy in patients with postoperative recurrence. A real-world cohort study was performed on Crohn's disease patients who underwent primary ICR after anti-TNF therapy failure, and who were retreated with anti-TNF therapy for postoperative symptomatic Crohn's disease. The primary outcome was treatment failure (the need for (re)introduction of corticosteroids, immunosuppressants, or biologicals or the need for re-resection). Sub-analyses were performed on the nature of preoperative anti-TNF failure (primary non-response, secondary loss of response, intolerance), indication for ICR (refractory, stricturing, penetrating disease), combination therapy with immunomodulators, retreatment with the same anti-TNF agent and preoperative exposure to 1 vs. >1 anti-TNF agents. In total, 66 of 364 patients retreated with anti-TNF therapy following ICR. Cumulative rates of treatment failure at 1 and 2 years were 28% and 47%. Treatment failure rate at 2 years was significantly lower in patients receiving combination therapy as compared to anti-TNF monotherapy (30% vs. 49%, P = 0.02). No difference in treatment failure was found with regards to the nature of preoperative anti-TNF failure (P = 0.76), indication for ICR (P = 0.88) switch of anti-TNF agent (P = 0.55) agent, and preoperative exposure to 1 vs. >1 anti-TNF agents (P = 0.88). Retreatment with anti-TNF therapy for postoperative Crohn's disease recurrence is a valid strategy after preoperative failure. Combination therapy is associated with a lower rate of treatment failure.

Computed tomography enterography predicts surgical-free survival in symptomatic stricturing Crohn's disease.

The study aimed to predict surgical risks for patients with symptomatic stricturing Crohn's disease (CD) using computed tomography enterography (CTE) and to assess the association between CTE findings and pathological changes. Crohn's disease patients with symptomatic stricture(s) were included. Exclusion criteria were concomitant penetrating disease, intra-abdominal abscess, previous bowel resection, or asymptomatic. Patients from January 2016 to December 2019 were identified as the primary cohort and those from January 2020 to June 2020 were identified as the validation cohort. Two independent experienced radiologists evaluated CTE variables including mucosal enhancement, mural stratification, wall enhancement, comb sign, lymphadenopathy, thick non-enhancing wall, bowel wall thickness, luminal diameter, and upstream lumen. Receiver operating characteristic, logistic regression, and nomogram were performed to identify the independent predictors of surgical-free survival. Histopathological scores of surgical specimens were also evaluated. 198 patients (primary cohort, 123 with surgery and 75 under non-surgical intervention, and 41 patients (validation cohort) were analyzed. Bowel wall thickness < 5.9mm, luminal stenosis > 3.35mm, and upstream lumen < 27.5mm were predictors of surgical-free survival for symptomatic stricturing CD patients. Logistic analysis showed the three CTE variables were the independent predictors of surgical-free survival (p < 0.001). A nomogram was developed with the concordance indexes of 0.905 and 0.892 in the primary and validation cohorts. Histopathological analysis showed bowel wall muscular hyperplasia/hypertrophy significantly correlated with luminal stenosis (r = - 0.655, p = 0.008) and combined CTE variable (r = - 0.683, p = 0.005). CTE is highly predictive of disease course and surgical-free survival for patients with symptomatic stricturing CD, suggesting the important role of CTE in decision-making of treatment.

781 COMPARATIVE EFFECTIVENESS OF MEDITERRANEAN DIET AND SPECIFIC CARBOHYDRATE DIET FOR CROHN'S DISEASE

Objective Therapeutic diets have been used to treat symptomatic Crohn's disease (CD). The Specific Carbohydrate Diet (SCD) and Mediterranean Diet (MD) have been associated with reduced CD symptoms. This study compared the effectiveness of these two diets for mild to moderate CD symptoms. Methods The Diet to INducE Remission in Crohn's Disease (DINE CD) study was a multicenter randomized comparative effectiveness trial of SCD vs MD. The study included adult patients with CD and with mild-moderate symptoms defined as a short Crohn's Disease Activity Index (sCDAI) score 176-399. Patients were randomly assigned 1:1, stratified by use of biologic medications, to consume either the SCD or MD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks compliant with their assigned diet. After 6 weeks, participants could purchase some or all of their food while following the diet on their own. The primary outcome was symptomatic remission (sCDAI 50% from baseline among those with baseline FC >250 μg/g), C Reactive Protein (CRP) response (high-sensitivity CRP (hsCRP) 50% reduction from baseline among those with hsCRP >5mg/L), short IBDQ and PROMIS measures of fatigue, pain, sleep and social isolation. Comparisons between groups used Cochrane-Mantel-Haenszel chi2 or t-test and within groups used paired t-test. Results 194 patients were randomized, but due to an error, 3 participants had a baseline sCDAI 0.2 for all comparisons). The percentage of participants who achieved symptomatic remission at week 6 did not differ by diet (43.5% with MD and 46.5% with SCD; p=0.77) (Figure). Clinical remission was achieved in 47.8% with MD and 48.5% with SCD (p=0.93). FC response was achieved in 4 participants (30.8%) with MD and 8 participants (34.8%) with SCD (p=0.83). CRP response was achieved in only 1 participant (3.6%) with MD and 2 participants (5.4%) with SCD (p=0.68). There was no evidence of heterogeneity of response based on presence or absence of confirmed inflammation at screening (Figure; test for interaction P=0.68). Conclusions Symptomatic remission was achieved in ≥40% with both diets regardless of confirmed inflammation. CRP response was uncommon. None of the effectiveness measures were significantly different by treatment group. Download : Download high-res image (86KB) Download : Download full-size image Table 1 . Change in symptoms from screening to week 6 by treatment arm Download : Download high-res image (73KB) Download : Download full-size image Figure 1 . Comparative effectiveness of Specific Carbohydrate Diet and Mediterranean Diet

The Role of Autologous Flap Reconstruction in Patients with Crohn's Disease Undergoing Abdominoperineal Resection.

Patients with symptomatic Crohn's disease who undergo abdominoperineal resection can experience impaired postoperative wound healing. This results in significant morbidity, burdensome dressing changes, and increased postoperative pain. When abdominoperineal resection is performed for oncological reasons, autologous flap reconstruction is occasionally performed to optimize wound healing and reconstruction outcomes. However, the role of flap reconstruction after abdominoperineal resection for Crohn's disease has not been established. This study examines the utility of flap reconstruction in patients with symptomatic Crohn's disease undergoing abdominoperineal resection. We hypothesize that patients with immediate flap reconstruction after abdominoperineal resection will demonstrate improved wound healing. This study is a retrospective chart review. Eligible patients at our institution were identified from 2010 to 2018 by using a combination of Current Procedural Terminology, International Classification of Diseases, Ninth Revision, and International Classification of Diseases, Tenth Revision codes. Of 40 adult patients diagnosed with Crohn's disease, 20 underwent abdominoperineal resection only and 20 underwent abdominoperineal resection with flap reconstruction. Immediate autologous flap reconstruction was performed after abdominoperineal resection. The primary outcomes measured were the presence of postoperative perineal wounds and postoperative wound care burden. Patients in the abdominoperineal resection with flap reconstruction group demonstrated significantly worse preoperative disease traits, including fistula burden, than patients in the abdominoperineal resection only group. A lower number of patients tended to be associated with a persistent perineal wound in the flap group at 30 days (abdominoperineal resection with flap reconstruction = 55% vs abdominoperineal resection only = 70%; p = 0.327) and at 6 months (abdominoperineal resection with flap reconstruction = 25% vs abdominoperineal resection only = 40%; p = 0.311) postoperatively. There was also a trend toward a lower incidence of complications in the flap group. Patients in the abdominoperineal resection with flap reconstruction group tended to experience lower postoperative pain than patients in the abdominoperineal resection only group. This retrospective cohort study was limited by its reliance on data in electronic medical records, and by its small sample size and the fact that it was a single-institution study. In select patients who have severe perianal fistulizing Crohn's disease, there may be a benefit to immediate flap reconstruction after abdominoperineal resection to lower postoperative wound care burden without significant intraoperative or postoperative risk. In addition, flap reconstruction may lead to lower postoperative pain. See Video Abstract at http://links.lww.com/DCR/B416. ANTECEDENTES:Los pacientes con enfermedad de Crohn sintomática que se someten a una resección abdominoperineal pueden experimentar una curación posoperatoria deficiente de la herida. Esto da como resultado una morbilidad significativa, cambios de apósito molestos y un aumento del dolor posoperatorio. Cuando se realiza una resección abdominoperineal por razones oncológicas, ocasionalmente se realiza una reconstrucción con colgajo autólogo para optimizar los resultados de la curación y reconstrucción de la herida. Sin embargo, no se ha establecido la función de la reconstrucción con colgajo después de la resección abdominoperineal para la enfermedad de Crohn.OBJETIVO:Este estudio examina la utilidad de la reconstrucción con colgajo en pacientes con enfermedad de Crohn sintomática sometidos a resección abdominoperineal. Presumimos que los pacientes con reconstrucción inmediata con colgajo después de la resección abdominoperineal demostrarán una mejor curación de la herida.DISEÑO:Revisión retrospectiva de expedientes.MARCO:Los pacientes elegibles en nuestra institución se identificaron entre 2010 y 2018 mediante una combinación de los códigos de Terminología actual de procedimientos, Clasificación internacional de enfermedades 9 y Clasificación internacional de enfermedades 10.PACIENTES:Cuarenta pacientes adultos diagnosticados con enfermedad de Crohn que se someten a resección abdominoperineal solamente (APR-solo = 20) y resección abdominoperineal con reconstrucción con colgajo (APR-colgajo = 20).INTERVENCIÓN (ES):Reconstrucción inmediata con colgajo autólogo después de la resección abdominoperineal.MEDIDAS DE RESULTADOS PRINCIPALES:Presencia de herida perineal posoperatoria y carga de cuidado de la herida posoperatoria.RESULTADOS:Los pacientes del grupo APR-colgajo demostraron rasgos de enfermedad preoperatoria significativamente peores, incluida la carga de la fístula, en comparación con los pacientes del grupo APR-solo. Un número menor de pacientes tendió a asociarse con una herida perineal persistente en el grupo de colgajo a los 30 días (APR-colgajo = 55% vs APR-solo = 70%; p = 0.327) y 6 meses (APR-colgajo = 25% vs APR-solo = 40%; p = 0.311) postoperatoriamente. También hubo una tendencia hacia una menor incidencia de complicaciones en el grupo APR-colgajo. Los pacientes del grupo APR-colgajo tendieron a experimentar menos dolor posoperatorio en comparación con el grupo APR-solo.LIMITACIONES:Estudio de cohorte retrospectivo basado en datos de historias clínicas electrónicas. Tamaño de muestra pequeño y estudio de una sola institución.CONCLUSIONES:En pacientes seleccionados que tienen enfermedad de Crohn fistulizante perianal grave, la reconstrucción inmediata del colgajo después de la resección abdominoperineal puede beneficiar a reducir la carga posoperatoria del cuidado de la herida sin riesgo intraoperatorio o posoperatorio significativo. Además, la reconstrucción con colgajo puede resultar un dolor posoperatorio menor. Consulte Video Resumen en http://links.lww.com/DCR/B416.

The Efficacy of Anti-Tumor Necrosis Factor Alpha for Symptomatic Stricturing Small Bowel Crohn's Disease.

IntroductionCrohn’s disease (CD) is a chronic inflammatory disease. Current treatment aims to prevent complications and the need for surgical intervention. In patients with symptomatic complications, such as strictures, the possible benefits of anti-tumor necrosis factor-alpha (anti-TNF-α) therapy are currently the subject of considerable debate. This study aims to determine whether anti-TNF-α therapy could decrease the need for or delay the time until surgery in patients with CD presenting with symptomatic strictures of the small bowel in the King Abdulaziz University Hospital (KAUH), Saudi Arabia.MethodsWe conducted a retrospective, single-center study that assessed the need for surgical treatment in adult patients with symptomatic stricturing CD who were treated conventionally or with TNF-α inhibitors. Simple logistic regression was used to examine the association between surgical resection and biologics therapy and stepwise elimination logistic regression analysis was used to identify predictors of surgical resection.ResultsIn total, 75 patients fulfilled the study criteria with 50 in the anti-TNF-α arm and 25 in the conventional arm. Surgical resection was required for six patients (12.2%) in the anti-TNF-α treatment arm and one patient (4%) in the conventional treatment arm (P=0.26). Endoscopic balloon dilatation was performed in two patients (4%) in the anti-TNF-α arm and one patient (4%) in the conventional arm (P=0.69). No statistically significant association was observed between surgical resection and treatment with biologic therapy (odds ratio [OR]=0.50, 95% CI: 0.16-1.53, P=0.22). Stepwise elimination identified age (OR=4.54, 95% CI: 0.79-25.11, P=0.09) and disease duration (OR=1.01, 95% CI: 1.00-1.02, P=0.004) as significant predictors of surgery.ConclusionsIn this cohort, anti-TNF-α therapy did not provide additional benefits with regards to avoiding or delaying surgery in CD patients with stricturing of the small bowel.

Therapeutic resolution of focal, predominantly anastomotic Crohn’s disease strictures using removable stents: outcomes from a single-center case series in the United Kingdom

Intestinal and anastomotic strictures in Crohn's disease (CD) produce considerable morbidity. The development of surgery-sparing, endoscopic modalities for stricture resolution is essential. Removable stent therapy is emerging as an efficacious and safe means of stricture resolution. We present outcomes from the largest, single-center series of patients with CD undergoing removable self-expanding metal stent (SEMS) therapy to resolve focal intestinal strictures. Patients with symptomatic CD were assessed with magnetic resonance enterography. Short (≤6 cm), fibrostenotic strictures of the terminal ileum or ileocolonic anastomoses were considered by a multidisciplinary team and put forward for stent therapy. Strictures were examined endoscopically and impassable strictures were treated with SEMSs. The Hanaro HRC-20-080-230 partially covered SEMS was used for all patients. Endoscopically inaccessible or inflammatory strictures were excluded. Stent retrieval was scheduled for 7 days after insertion. Therapeutic benefit was assessed with validated inflammatory bowel disease scoring tools. Twenty-one patients underwent 23 stent episodes, with 2 patients requiring repeat therapy in the follow-up period. Most treated strictures were anastomotic (19 of 21); 2 of 21 were de novo. Of those patients attending follow-up, 81% (13 of 16) reported symptom improvement or resolution; 88% (14 of 16) were in clinical remission at follow-up. Across all stent episodes, only 5 adverse events were noted (2 episodes of stent-related discomfort, 3 asymptomatic stent migrations). There were no direct stent-related adverse events such as perforation, impaction, or bleeding. No patient has required stricture-related surgery in the follow-up period (range, 3-50 months). In this series, removable SEMS therapy for ileal and anastomotic strictures was found to be clinically efficacious. The absence of perforation events and need for stricture-related surgery are noteworthy. These results suggest that the efficacy of stent therapy in this context merits powered, head-to-head investigation with other modalities for stricture resolution.

735 Crohn's Disease Patients Who Do Not Qualify for Clinical Trials Have Similar Clinical and Endoscopic Response Rates to Ustekinumab to Those Who Qualify for Clinical Trials

INTRODUCTION: The UNITI clinical trial demonstrated ustekinumab (UST) safety and efficacy for moderate to severe Crohn's disease (CD) patients. However, exclusion criteria preclude enrollment of complex patients impacting external validity of the findings. The aim of this study was to evaluate UST response in active CD patients who would not have qualified for the randomized controlled trials (RCTs). METHODS: A retrospective cohort study of UST-treated CD patients who would not qualify (DNQ) and who would qualify (Q) for RCTs from 2016 to 2018 was performed. Inclusion criteria included symptomatic luminal CD activity (defined as abdominal pain and stool frequency), induction with UST infusion at CD dosing and ≥1 clinic visit post-induction. Criteria for DNQ patients were extracted from the published UNITI study protocol. The primary outcome of interest was week 8 clinical response rates (&gt;50% improvement in abdominal pain and stool frequency from baseline) between Q vs DNQ groups. Secondary outcomes were endoscopic response, corticosteroid free clinical remission, dose escalation and adverse events between the two groups. RESULTS: 201 patients (Q = 111; DNQ = 90) with a median 6 months follow up (IQR 4-9 months) were included. The DNQ cohort had lower hemoglobin levels, more active perianal disease, upper tract disease, ileocolonic disease, and prior surgeries (Table 1). Week 8 clinical response rates were similar between Q and DNQ (64.0% vs 60.0%; P = 0.56). Clinical response, remission and steroid-free remission rates during maintenance were also similar between the two groups (Table 2). However, more patients in the DNQ group required dose escalation (64.4%) compared to the Q group (46.8%), P = 0.01, especially after induction dosing. Endoscopic response rates were similar between Q and DNQ groups, with complete mucosal healing achieved in 13.2% vs 13.6% of Q and DNQ patients (P = 0.94) (Table 2). CONCLUSION: These findings suggest that ustekinumab is equally efficacious for complex CD patients who would not have qualified for RCTs. Adverse events were infrequent for all UST treated patients. The majority of DNQ patients required dose escalation during their treatment course, suggesting more intensive therapy may be warranted for this patient subgroup. Further studies are needed to determine durable clinical and endoscopic response from dose escalation in this complex CD group.

Associations between quantitative evaluation of bowel wall microvascular flow by contrast-enhanced ultrasound and indices of disease activity in Crohn's disease patients using both bolus and infusion techniques.

The aim is to investigate whether baseline contrast-enhanced ultrasound (CEUS) correlates with indices of activity in Crohn's disease (CD) and can predict response to medical treatment. In this prospective study, symptomatic CD patients underwent baseline CEUS performed with Definity using both bolus and infusion methods. Time-intensity curves (TIC), peak intensity (PI), and area under curve (AUC) from a region of interest over the diseased bowel were calculated for both bolus and infusion acquisitions. We used Mann-Whitney U test for continuous and chi-square/two-tailed Fisher's exact test for categorical variable comparison and Spearman's correlation coefficient to correlate clinical score and CEUS kinetic parameters. Twenty-one patients (9 men, 12 women, median age 32 years) were accrued. Fifteen patients had clinically active disease defined as Harvey-Bradshaw Index (HBI) score ≥5. Median values of baseline CEUS parameters PI (bolus: 26 vs 8.86; P = .023 and perfusion: 7.6 vs 3.2; P = .009) and AUC (bolus: 769 vs 248.8; P = .036 and perfusion: 188.9 vs 73.9; P = .012) differed significantly in patients with active vs inactive disease. Nine patients with active disease underwent escalated or new treatment. Five were nonresponders. Responders had higher median values of baseline parameters (PI, bolus: 35 vs 18.8; P = .556, and perfusion: 7.6 vs 3.9; P = 190), (AUC, bolus: 1473.9 vs 314; P = .111, and perfusion: 154.7 vs 74.4, P = .286). CEUS kinetic parameters correlate with clinical and laboratory indices and are significantly higher in patients with active disease. The responders had higher CEUS kinetic parameters than nonresponders that did not reach statistical significance in our small cohort.

Visceral fat area measured with computed tomography does not predict postoperative course in Crohn´s disease patients.

The role of visceral fat measured by computer tomography is yet not well defined in patients with Crohn's disease. Therefore, the present study was designed to assess the impact of visceral fat area on postoperative short-term outcome and surgical characteristics. We analyzed 95 patients, who underwent intestinal resection for symptomatic Crohn's disease at an academic tertiary referral center between 2003 and 2008. Visceral fat area was measured on preoperative computed tomography scans. Postoperative morbidity was graded according to the Clavien-Dindo classification. Visceral fat area was correlated with baseline characteristics, disease phenotype and 30-day morbidity. Body mass index and age were significantly associated with a higher visceral fat area (p = 0.001). Overall 19 (20.0%) postoperative complications were observed, of whom 7 (7.4%) patients required surgical re-intervention. No significant difference was found with regard to visceral fat area between patients with an uneventful and eventful postoperative course (no complications: median visceral fat area 52.0 cm2 SD 59.7, complications: 41.3 cm2 SD 42.8; p = 0.465). In contrast to current literature, we cannot support the role of visceral fat area for predicting postoperative course in Crohn's disease. In addition, no correlation of the visceral fat area and disease behavior was detected.

The modified Glasgow prognostic score in Crohn's disease-does it predict short-term outcome?

SummaryBackgroundThe modified Glasgow prognostic score (mGPS) has recently gained increased attention as a prognostic marker for malignant disease survival and postoperative short-term complications. Due to lacking data, the present study was conducted to correlate the mGPS with the postoperative course in patients following surgery for Crohn’s disease.MethodsWe enrolled 341 patients who underwent intestinal resection for symptomatic Crohn’s disease at a tertiary referral centre between 2000 and 2014. All relevant data were obtained from the institutional database and individual chart review. Thirty-day morbidity was defined according to the Clavien–Dindo classification.ResultsA total of 79 (23.17%) postoperative complications were identified (grade I and II: n = 54, 15.84%; grade III and IV: n = 23, 6.74%; grade V: n = 2, 0.59%). The mGPS did not show any correlation with an eventful postoperative course following surgery (no complication: median mGPS: 1, range 0–2; complications: median mGPS: 1, range 0–2; p = 0.8521). In addition, the occurrence of an anastomotic leakage was not associated with a higher mGPS (p = 0.8592). Patients with an acute indication for surgery (n = 29, 11.44%) had higher median mGPS (median: 2, range 0–2) in contrast to patients who were operated on electively (median: 1, range 0–2; p = 0.0003). No other correlation between surgical characteristics and mGPS was detected.ConclusionsIn the present study, we could clearly demonstrate that an acute indication for surgery in symptomatic Crohn’s disease is associated with higher mGPS scores. However, the mGPS did not correlate with postoperative complications. Further studies are required to define the prognostic value of mGPS in Crohn’s disease patients.

Prognostic value of preoperative neutrophil-to-lymphocyte ratio in Crohn's disease.

SummaryBackgroundThe Neutrophil-to-lymphocyte-ratio has recently gained increased attention as a prognostic marker for malignant disease and short term outcomes. There is little data available in patients with Crohn’s disease, thus the present study was conducted to correlate preoperative Neutrophil-to-lymphocyte-ratio values with disease phenotype and postoperative course.MethodsWe comprised 373 patients, who underwent intestinal resection for symptomatic Crohn’s disease at an academic tertiary referral centre between 2000 and 2014. Preoperative Neutrophil-to-lymphocyte-ratio values were calculated and analyzed in regard to disease phenotype and 30-day morbidity rate. All relevant data were obtained from the institutional database and individual chart review.ResultsMale patients had significantly higher preoperative Neutrophil-to-lymphocyte-ratio values compared to female patients (5 vs. 4; p = 0.0075). A higher Neutrophil-to-lymphocyte-ratio was also found in patients with an acute indication for surgery (6.15 vs. 4.3; p = 0.0374), presenting with abscesses (5.36 vs. 4.28; p = 0.0254), inflammatory masses (5.23 vs. 4.08; p = 0.0294) or malignancy in the resected specimen (9.06 vs. 4.35, p = 0.0231). Surprisingly, patients developing postsurgical complications showed significantly lower Neutrophil-to-lymphocyte-ratio values (3.77 vs. 4.67; p = 0.0461).ConclusionsElevated preoperative Neutrophil-to-lymphocyte-ratio in symptomatic Crohn’s disease is not predictive for complications. However, Neutrophil-to-lymphocyte-ratio showed a significant correlation with specific disease phenotypes. Most strikingly, Neutrophil-to-lymphocyte-ratio was highly elevated in patients with a colorectal cancer in the resected specimen, which needs to be addressed in future studies.

Evaluation of Gastrointestinal Patient Reported Outcomes Measurement Information System (GI-PROMIS) Symptom Scales in Subjects With Inflammatory Bowel Diseases.

Patient reported outcomes (PROs) are important treatment endpoints in inflammatory bowel diseases (IBD). We evaluated the gastrointestinal (GI) PRO Measurement Information System (PROMIS) in IBD subjects. Crohn's and Colitis Foundation of America's Partners is an Internet-based cohort of IBD subjects. Participants complete surveys, including demographics, disease characteristics, PROMIS domains, disease activity (short Crohn's disease activity index or simple clinical colitis activity index) and quality of life (QoL) indices. In a nested cross-sectional study, we used univariate and bivariate analyses to assess associations between 8 GI-PROMIS domains (reflux, swallowing, diarrhea, nausea, belly pain, gas, incontinence, and constipation) and QoL and disease activity indices. The study included 2,378 Crohn's Disease (CD) and 1,455 ulcerative colitis (UC) respondents with a median age of 41 years. Median disease duration was 11 years for CD subjects and 8 years for UC subjects; 57% of CD subjects and 42% of UC subjects were in remission. Among symptomatic CD subjects, those with active CD reported significantly worse symptoms on all 8 domains than those in remission. The same was observed for UC subjects with the exception of disrupted swallowing. IBD subjects with worse QoL reported significantly worse symptoms on all 8 domains compared to those with better QoL. In IBD subjects experiencing GI symptoms, GI-PROMIS domains were strongly associated with disease activity and QoL indices. GI-PROMIS holds potential as PRO measures in IBD and correlates with other validated indices in this population.

P318 Accuracy of magnetic resonance enterography for extraluminal complications of Crohn's disease

Background: Crohn's disease (CD) can be associated with intraluminal and extraluminal complications like abscess and fistula. More than half of patients with Crohn's disease need surgery to treat these complications at least once in their life. Aiming to make an appropriate choice of intervention, the magnetic resonance enterography (MRE) is largely used to assess the type and severity of these complications. In a previous prospective study pre-operative MRE has been able to predict surgical approach in the most of symptomatic patients, showing low sensitivity and high specificity for the diagnosis of fistula or abscess and high sensitivity and low specificity for stenosis. Methods: We reviewed a sample from a referral center of 42 consecutive symptomatic CD patients addressed to surgery who underwent preoperative MRE. All data were recorded in an electronic database (Excel Microsoft). We analyzed the concordance between MRI and surgical findings for presence of fistulas or abscesses and other stenosis-related characteristics (location, number and extent). We calculated the proportions of VP, FN, FP and VN with 95% confidence limits and the accuracy of the index test (MRE) compared to the reference test (surgery) for the diagnosis of stenosis, fistula or abscess. Results: Fifty-two percent of patients were male, mean age was 40.5±13.6 years. Forthy-one (98%) were symptomatic. The median time between MRE performance and surgery was 2 months (range 1–24); time was 3 months in 29 pts (69%). A laparoscopic approach was performed in 69% of patients. The prevalence of fistula at surgery was 24% and of abscess 17%. MRE failed in detecting fistulas in 2 patients and falsely identified abscess in one patient. Sensitivity and specificity of MRE were 40% and 99% for fistula and 67% and 94% for abscess, respectively. Accuracy of MRE for fistula was 76% (95% CI 60–88%) and for abscess 88% (95% CI 69–93). For detection of single and multiple stenosis the sensitivity of MRE was 93% and 88% respectively. Conclusions: The MRE was a fairly accurate imaging test for the characterization of stenosis and for the diagnosis of fistula or abscess. Taking into account limitations due to retrospective data, MRE shows high specificity and low sensitivity for the diagnosis of fistula and abscess according to data from literature. Moreover, it appears more useful to identify the site and extension of stenosis and the single stenosis with respect to the multiple. Aiming to optimize the decision about surgery, there is still a need for development of shared criteria among radiologists and surgeons to further assess the reproducibility of MRE and its accuracy for the diagnosis of complications in prospective studies of patients with CD

Cytokine Levels After Consumption of a Medicinal Agaricus blazei Murill-Based Mushroom Extract, AndoSan™ , in Patients with Crohn's Disease and Ulcerative Colitis in a Randomized Single-Blinded Placebo-Controlled Study.

Ingestion of the Agaricus blazei Murill-based mushroom extract AndoSan™ has been shown in randomized placebo-controlled studies to improve symptoms in Crohn's disease (CD) and ulcerative colitis (UC) and also fatigue and quality of life in the latter patients. The aim was to examine whether this clinical impact of AndoSan™ intake could be explained by influence on foremost pro-inflammatory cytokines in the patients. Fifty patients with symptomatic UC and CD were randomized and blinded for oral daily intake of AndoSan™ or placebo. Blood samples taken before (visit 1) and after 21days' (visit 3) consumption were analysed for cytokines IL-1ß, IL-2, IL-4-8, IL-10, IL-12-13, IL-17, G-CSF, GM-CSF, IFN-γ, MCP-1, MIP-1ß and TNF-α. Baseline cytokine levels were similar in CD and UC. In CD, cytokine levels at visit 1 versus visit 3 were unaltered within the AndoSan™ and the placebo groups. Only IL-2 was significantly reduced at visit 3 in the Andosan™ compared with the placebo group. However, when combining IL-1ß, IL-6 and G-CSF in the patients with CD, the cytokine levels were significantly lower in the AndoSanTM - versus the placebo group, visit 3. In UC, levels of IL-2, IL-5 and MIP-1ß were reduced within the AndoSan™ group. IL-5 was also reduced at visit 3 compared with placebo. Generally, the effect on reduction in systemic cytokine levels by consumption of AndoSan™ was limited and supported only marginally anti-inflammatory effects in these patients. Therefore, other explanations behind the clinical anti-inflammatory effects than the contribution of cytokines seem more pertinent, including anti-allergic and antioxidant activities.

Advanced age impacts surgical characteristics and postoperative course in patients with Crohn's disease

PurposeDue to a lack of data, the present study was designed to assess the impact of advanced age on surgical characteristics and short-term outcome of patients operated on for symptomatic Crohn's disease. MethodsWe enrolled 454 consecutive Crohn's disease patients, who underwent intestinal resection at an academic tertiary referral center between 1997 and 2012. Patients were divided into 3 groups according to their age (group I: <30 years, group II: 30–50 years, group III: >50 years) and analyzed retrospectively. ResultsAltogether, 152 (33.5%) patients were included in group I, 234 (51.5%) in group II and 68 (15.0%) in group III. Abscess formation and penetrating disease were significantly more common in younger patients (p = 0.0014 and p = 0.0182). The number of intestinal resections was higher in older patients (p < 0.0001), whereas the laparoscopic approach was more frequently observed in younger adults (p = 0.0006).Group II (n = 58 (24.8%)) and group III (n = 15 (22.1%)) showed significantly more complications compared to group I (n = 20 (13.2%)) (p = 0.0346). Notably, major complications and anastomotic leaks were significantly higher in older patients (p = 0.0004). ConclusionCrohn's disease patients of advanced age show different surgical characteristics compared to younger patients and are at an increased risk of developing postoperative complications.

Minimal-invasive approach for penetrating Crohn's disease is not associated with increased complications.

BackgroundLaparoscopic surgery for penetrating Crohn’s disease (CD) still remains highly conflicting due to a lack of sufficient data. Therefore, the following large study was designed to compare postoperative outcomes after minimal-invasive resections for penetrating and non-penetrating CD.MethodsConsecutive patients, who underwent laparoscopic intestinal resection for symptomatic CD at a tertiary academic referral center, were included. Patients were divided according to perioperative findings in penetrating and non-penetrating type of disease. All clinical data were obtained from an institutional database and analyzed retrospectively.ResultsOf 234 patients enrolled, 101 patients [females: n = 54 (53.5 %)] were operated on for non-penetrating CD and 133 patients [females: n = 50 (37.6 %)] for penetrating CD. Fistulas (p < 0.001), inflammatory mass (p < 0.001) and abscess formation (p < 0.001) were observed more frequently in the perforating group. Ileocolic resections were performed predominantly in both groups [perforating CD: n = 110 (82.7 %), non-perforating CD: n = 82 (81.2 %)], with more complex resections (>1 intestinal resection) found in perforating CD (p < 0.001). Conversion rates did not differ significantly. Notably, 30-day postoperative morbidity was comparable for both groups [perforating CD: n = 20 (15 %), non-perforating CD: n = 19 (18.8 %), p = 0.44]. Postoperative complication rates graded according to the Clavien–Dindo classification showed no difference too (p = 0.49).ConclusionLaparoscopic surgery can be conducted safely in selected patients with penetrating CD without increasing the risk of postoperative complications. This finding needs to be implemented in future guidelines.

Opening (and Swallowing) A Can of Worms to Treat My Crohn's Disease.

Editor's Note: This article discusses the experience, ingenuity, and determination of Sean Ahrens, a young patient with Crohn's disease who took it upon himself to treat his longstanding, symptomatic Crohn's disease with pig whipworm eggs. Reading this story will make some of you uncomfortable. You might question whether this work belongs in a medical journal or sends the wrong message to readers. However, we recognize that this topic is controversial and that N=1 reports cannot and should not change practice. The purpose of this story is not to encourage the use of pig whipworm or to demonstrate its efficacy (or lack thereof). We firmly believe that patients are uniquely qualified to provide insights into how they view their illnesses, weigh risks and benefits, and ultimately achieve self-efficacy. Stories like this are important for us to acknowledge and understand, even if they do not change our practice.

Clinical Outcomes of Surgery Versus Endoscopic Balloon Dilation for Stricturing Crohn’s Disease

Endoscopic balloon dilation and surgery are commonly practiced in stricturing Crohn's disease. Nonetheless, there are still scant data directly comparing these 2 strategies. The aim of this study was to compare the short- and long-term outcomes of endoscopic balloon dilation versus surgical resection in symptomatic Crohn's strictures. This was a retrospective cohort study. The study was conducted at a single tertiary center. Seventy-nine patients were identified, 40 in the surgical group and 39 in the endoscopic balloon dilation group (mean age 42.8 ± 13.9 versus 38.5 ± 12.2 years). The outcomes of all patients referred for endoscopic balloon dilation were compared with patients referred to surgery because of stricturing disease between the years 2006 and 2013. The primary outcome was the need for reintervention (either endoscopic balloon dilation or surgery) for symptomatic Crohn's disease during follow-up. The proportion of patients who required any reintervention during follow-up was significantly lower in the surgical group versus the endoscopic balloon dilation group (OR = 5.62 (95% CI, 1.66-19.01); p = 0.005). The need for surgery/resurgery during follow-up was also significantly lower in the surgically treated group (OR = 3.53 (95% CI, 1.01-12.29); p = 0.047). Reintervention-free survival and surgery-free survival were both significantly shorter in the endoscopically treated group in a Kaplan-Mayer analysis. The rate of major complications was similar in the endoscopically and surgically treated groups (7.6% versus 7.5%; p = 0.7). The small cohort and the retrospective data collection were limitations of this study. In our cohort of patients with fibrostenotic Crohn's disease, a direct comparison showed reduced need for reinterventions with a similar rate of immediate major complications after surgery compared with endoscopic balloon dilation.

Physical Fitness in Adolescence and Subsequent Inflammatory Bowel Disease Risk.

OBJECTIVES:Physical fitness may reduce systemic inflammation levels relevant to the risk of symptomatic Crohn's disease (CD) and ulcerative colitis (UC); we assessed if fitness in adolescence is associated with subsequent inflammatory bowel disease (IBD) risk, independent of markers of risk and prodromal disease activity.METHODS:Swedish registers provided information on a cohort of 240,984 men (after exclusions) who underwent military conscription assessments in late adolescence (1969–1976). Follow-up started at least 4 years after the conscription assessment until 31 December 2009 (up to age 57 years). Cox's regression assessed the association of physical fitness with CD (n=986) and UC (n=1,878) in separate models, with adjustment including: socioeconomic conditions in childhood; physical fitness, height, body mass index, and erythrocyte sedimentation rate (ESR) in adolescence; and subsequent diagnoses of IBD.RESULTS:Low fitness was associated with a raised risk of IBD, with unadjusted hazard ratios (and 95% confidence intervals) of 1.62 (1.31–2.00) for CD and 1.36 (1.17–1.59) for UC. The results were attenuated by adjustment, particularly for markers of prodromal disease activity to 1.32 (1.05–1.66) and 1.25 (1.06–1.48), respectively. Raised ESR in adolescence was associated with increased risks for subsequent CD (5.95 (4.47–7.92)) and UC (1.92 (1.46–2.52)).CONCLUSIONS:The inverse association of physical fitness with IBD risk is consistent with a protective role for exercise. However, evidence of disease activity before diagnosis was already present in adolescence, suggesting that some or all of the association between fitness and IBD may be due to prodromal disease activity reducing exercise capacity and therefore fitness.