Roles of IL-17A and IL-23 in the Pathogenesis of Ulcerative Colitis and Crohn’s Disease

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, the etiology and pathogenesis of which have been suggested to be influenced by cytokines. Two main clinical types of IBD are recognized, namely ulcerative colitis (UC) and Crohn's disease (CD). The present study examined serum levels of two cytokines (IL-17A and IL-23) in 60 IBD patients (30 UC and 30 CD) and 30 healthy controls. The levels were correlated with age, gender, cigarette-smoking status, disease duration, family history, disease extension, symptoms, extra-intestinal manifestations, and medication. The results depicted that IL-17A level was significantly higher in UC and CD patients compared to control (45.2 ± 23.3 and 47.5 ± 34.4 vs. 15.6 ± 7.5 pg/ml, respectively; p < 0.001). Serum level of IL-23 was similarly increased in UC and CD patients compared to control (64.1± 23.7 and 62.5 ± 27.3 vs. 25.2 ± 11.1 pg/ml, respectively). However, the level of both cytokines showed no significant variation between UC and CD patients (p = 0.713 and 0.777, respectively). Distributing UC and CD patients into subgroups according to some characteristics revealed that IL-17A level was significantly increased in UC male compared to female patients (57.3 ± 18.2 vs. 34.5 ± 22.5 pg/ml; p = 0.005). It was also significantly increased in smoker UC patients compared with non-smoker patients (51.9 ± 19.4 vs. 31.6 ± 25.5 pg/ml; p = 0.022). Smoker CD patients also showed a significantly increased level of IL-23 compared to non-smoker patients (72.7 ± 28.5 vs. 52.2 ± 22.6 pg/ml; p = 0.038). In the case of family history, IL-23 level was significantly decreased in UC patients with a family history of IBD compared to CD patients with a family history (84.5 ± 24.3 vs. 50.4 ± 17.0 pg/ml.; p = 0.042). In conclusion, the present data suggest a role for IL-17A and IL-23 in the etiology and pathogenesis of UC and CD.

Does kV Image Guidance for Bone Metastases Improve Pain Control?

Purpose/ObjectivesDespite its widespread availability, the use of kilovoltage (kV) image guidance is often related to factors such as perceived adequacy of clinical patient setup and individual practice patterns. We sought to determine whether kV image guidance in the treatment of painful bone metastases would improve therapeutic efficacy.Materials/MethodsUnder an Institutional Review Board approved protocol, hospital records of 164 patients having received radiation therapy to 257 individual painful osseous metastases were retrospectively reviewed. Marginal logistic regression analyses using the generalized estimating equation (GEE) approach were used to investigate potential associations between pain reduction and several patient, disease, and treatment related variables. Correlation of kV image guidance with pain reduction was analyzed by univariate and multivariate GEE logistic regression analysis.ResultsMedian time to pain reduction was 3 days (range 0~109 days) from the start of radiation therapy. Pain reduction ≥ 50% was noted in 196 (77%) metastatic lesions with 136 (53%) demonstrating complete pain relief. Patients with metastatic lesions from non-small cell lung cancer experienced less pain relief (p = 0.007). Disease extension outside of bone was a negative predictor for pain reduction (p = 0.02). On univariate and multivariate logistic regression, kV image guidance demonstrated a statistically significant correlation with improved pain control in cases involving treatment of the lower extremities (p = 0.03) and those with fewer treatment fractions (p = 0.01), particularly in the setting of extra-osseous disease extension (p = 0.003).ConclusionsKilovoltage image guidance in the treatment of painful bone metastases may offer greater pain control through improved patient setup, particularly for patients with tumors of the lower extremities, extraosseous disease extension, and fewer treatment fractions.

Histological Inflammation in the Endoscopically Uninflamed Mucosa is Associated With Worse Outcomes in Limited Ulcerative Colitis

Background The Montreal classification categorizes patients with ulcerative colitis (UC) based on their macroscopic disease extent. Independent of endoscopic extent, biopsies through all colonic segments should be retrieved during index colonoscopy. However, the prognostic value of histological inflammation at diagnosis in the inflamed and uninflamed regions of the colon has never been assessed. Methods This was a multicenter retrospective cohort study of newly diagnosed patients with treatment-naïve proctitis and left-sided UC. Biopsies from at least 2 colonic segments (endoscopically inflamed and uninflamed mucosa) were retrieved and reviewed by 2 pathologists. Histological features in the endoscopically inflamed and uninflamed mucosa were scored using the Nancy score. The primary outcomes were disease complications (proximal disease extension, need for hospitalization or colectomy) and higher therapeutic requirements (need for steroids or for therapy escalation). Results Overall, 93 treatment-naïve patients were included, with a median follow-up of 44 months (range, 2-329). The prevalence of any histological inflammation above the endoscopic margin was 71%. Proximal disease extension was more frequent in patients with histological inflammation in the endoscopically uninflamed mucosa at diagnosis (21.5% vs 3.4%, P = 0.04). Histological involvement above the endoscopic margin was the only predictor associated with an earlier need for therapy escalation (adjusted hazard ratio, 3.69; 95% confidence interval, 1.05-13.0); P = 0.04) and disease complications (adjusted hazard ratio, 4.79; 95% confidence interval, 1.10-20.9; P = 0.04). Conclusions The presence of histological inflammation in the endoscopically uninflamed mucosa at the time of diagnosis was associated with worse outcomes in limited UC.

P196 Colon-involving versus non-colon-involving Crohn’s disease classification: is the Montreal classification outdated?

Background An appropriate disease classification is essential for the management of Crohn’s disease (CD) patients. Recently, a new classification of colon-involving versus non-colon-involving disease extension was considered to be more predictive of adverse outcomes than the Montreal classification (MRC). We aimed to investigate the association of a colon-based classification with clinically relevant outcomes in patients with CD compared with the MRC. Methods Retrospective cohort-study which consecutively included adult CD patients with at least 1 year of follow-up. Patients were categorized into colon-involving and non-colon-involving disease and according to the MRC. Patients’ demographic, clinical, biochemical, and imaging data were recorded and compared between the two classifications. The primary outcome was the need for treatment with steroids or biologics, hospitalization and major abdominal surgery. Results Of 327 patients, 52.3% were female with a mean age of 43.3±13.1 years. The most common disease location according to MRC was L1 (48.9%), followed by L3 (41.3%) and L2 (9.8%). Overall, 51.1% of patients had colon-involving disease. Although patients with colon-involvement at diagnosis had higher frequency of perianal lesions (27.5% vs 16.9%, P&lt;0.05) and serum inflammatory biomarkers (lower hemoglobin, and higher leucocyte and platelet counts, c-reactive protein and erythrocyte sedimentation rate), this classification was not predictive of relevant outcomes. Considering the two types of colon-involving disease (L2, L3), patients with L2 disease had higher extraintestinal manifestations (43.8% vs 20.7%, respectively, P&lt;0.05), higher B1 disease behavior (87.5% vs 58.5%, respectively, P&lt;0.05) and lower B2 disease behavior (6.25% vs 22.2%, respectively, P&lt;0.05). Disease location according to MRC was predictive of the need for treatment with biologics, hospitalization and major abdominal surgery in univariate analysis, but not in multivariate analysis. Conclusion Although simpler, defining Crohn’s disease extension by colon-involving versus non-colon-involving is not more predictive of adverse outcomes than the Montreal classification. Therefore, the use of Montreal Classification should still be considered essential in the adequate management of IBD patients.

P630 Inflammatory bowel disease in immigrants to Spain: results of the EIIMIGRA study from GETECCU (ENEIDA registry)

Background Previous studies comparing inflammatory bowel disease(IBD) features between migrant and native patients have shown clinical phenotype differences. To date, no study has focused on IBD immigrants(MP) in Spain. The aim of this study was to explore the features of MP in Spain and to compare age of disease onset, IBD phenotype and therapeutic requirements with native-born IBD patients(NP). Methods This was an observational, multicentric and case-control study of the nationwide ENEIDA registry. We selected all IBD patients who were born outside of Spain and compared with a control cohort of NP. All included patients were diagnosed with IBD before 2015. Results A total of 13,524 patients were included(1864 MP and 11660 NP).The most prevalent ethnic migrant group was Caucasian(771, 41%), followed by Latin American(572, 31%) and Arabian(341,18%), whereas Asian represented only 6%. Table 1 summarizes the demographic and phenotypic features. 71% of MP were diagnosed with IBD in Spain. There was not a gender predisposition to IBD in the overall migrant group, however more female UC MP were detected compared to UC NP(52 % vs 45%, p&lt;0.001). MP were younger at the onset of the disease and had a shorter disease duration compared to NP, in both UC and CD patients. Significantly more CD patients were diagnosed under 16 years(A1) among MP, and more patients over 40 years(A3) among NB. More NB patients had CD stricturing phenotype(24% vs 19%, p=0,002) compared to MP. Disease extension in CD and UC did not differ between groups. The overall proportion of abdominal or perianal surgery was similar in both groups but the use of biologic therapy was more common in MP(36% vs 30%, p=0,001). Conclusion In the largest cohort of migrant IBD patients in Spain, immigrants were younger, had a shorter disease duration and required a higher use of biologics than natives, pointing phenotypic differences in this population and a universal access to the healthcare system all over the country.

Diagnosing necrotizing external otitis on CT and MRI: assessment of pattern of extension

Background and purpose Necrotizing external otitis (NEO) is a serious complication of external otitis. NEO can be classified according to—anterior, medial, posterior, intracranial, and contralateral—extension patterns. Currently there is no consensus on the optimal imaging modality for the identification of disease extension. This study compares NEO extension patterns on MR and CT to evaluate diagnostic comparability. Methods Patients who received a CT and MR within a 3-month interval were retrospectively examined. Involvement of subsites and subsequent spreading patterns were assessed on both modalities by a radiologist in training and by a senior head and neck radiologist. The prevalence of extension patterns on CT and MR were calculated and compared. Results All 21 included NEO cases showed an anterior extension pattern on CT and MR. Contrary to MR, medial extension was not recognized on CT in two out of six patients, and intracranial extension in five out of eight patients. The posterior extension pattern was not recognized on MR. Overall, single anterior extension pattern (62%) is more prevalent than multiple extension patterns (38%). Conclusion All anterior NEO extension pattern were identified on CT as well as MR. However, the medial and intracranial spreading patterns as seen on MR could only be identified on CT in a small number of patients. The posterior spreading pattern can be overlooked on MR. Thus, CT and MR are complimentary for the initial diagnosis and work-up of NEO as to correctly delineate disease extent through the skull base.

Laterally located mucocele in a hyperpneumatized frontal sinus causing exophthalmos: A total endoscopic approach

Frontal sinus mucoceles are mucous secretory lesions within the sinus, presenting a slow – growing pattern, mostly behaving like a space-occupying mass with subtle symptoms until a bone erosion of the surrounding structures takes place. Intracranial and intraorbital expansion are regarded as the most considerable complications, demanding adequate surgical management in order to avoid recurrence. Endoscopic drainage is thought to be the current treatment of choice, with external approaches or combined approaches being considered for more severe cases where anatomy and disease extension restricts adequate endoscopic visualization of the lesion. We present a case of a 31-year-old female patient with a left frontal sinus mucocele, demonstrating with an unusual lateral frontal expansion and orbit invasion, causing exophthalmos and ophthalmoplegia. She was adequately managed by a Draf III endoscopic procedure achieving wide marsupialization and enough drainage of the mucocele. No sign of recurrence was noticed during the last 6-month follow-up. Giant mucoceles of the frontal sinus are a rare pathology. To our knowledge, endoscopic endonasal approach is a treatment modality that can provide an adequate drainage pathway, thus resulting in optimal clinical outcomes, compared with external approaches. Keywords: Frontal sinus; Mucocele; Exophalmos; Pneumosinus dilatans; Pneumocele.