Radiological Response Is Associated With Better Long-Term Outcomes and Is a Potential Treatment Target in Patients With Small Bowel Crohn's Disease.

OBJECTIVES: Crohn's disease (CD) management targets mucosal healing on ileocolonoscopy as a treatment goal. We hypothesized that radiologic response is also associated with better long-term outcomes. METHODS: Small bowel CD patients between 1 January 2002 and 31 October 2014 were identified. All patients had pre-therapy computed tomography enterography (CTE)/magnetic resonance enterography (MRE) with follow-up CTE or MRE after 6 months, or 2 CTE/MREs≥6 months apart while on maintenance therapy. Radiologists characterized inflammation in up to five small bowel lesions per patient. At second CTE/MRE, complete responders had all improved lesions, non-responders had worsening or new lesions, and partial responders had other scenarios. CD-related outcomes of corticosteroid usage, hospitalization, and surgery were assessed using Kaplan-Meier survival analysis and multivariable Cox models. RESULTS: CD patients (n=150), with a median disease duration of 9 years, had 223 inflamed small bowel segments (76 with strictures and 62 with penetrating, non-perianal disease), 49% having ileal distribution. Fifty-five patients (37%) were complete radiologic responders, 39 partial (26%), and 56 non-responders (37%). In multivariable Cox models, complete and partial response decreased risk for steroid usage by over 50% (hazard ratio (HR)s: 0.37 (95% confidence interval (CI), 0.21-0.64); 0.45 (95% CI, 0.26-0.79)), and complete response decreased the risk of subsequent hospitalizations and surgery by over two-thirds (HRs: HR, 0.28 (95% CI, 0.15-0.50); HR, 0.34 (95% CI, 0.18-0.63)). CONCLUSIONS: Radiological response to medical therapy is associated with significant reductions in long-term risk of hospitalization, surgery, or corticosteroid usage among small bowel CD patients. These findings suggest the significance of radiological response as a treatment target.

Clinical characteristics and imaging features of small bowel adenocarcinomas in Crohn's disease.

PURPOSE: Small bowel adenocarcinoma is uncommon in patients with Crohn's disease but has an extremely poor prognosis. There is a paucity of data on the clinical characteristics and radiologic features of this entity. We sought to update our institutional experience with small bowel adenocarcinoma occurring in the setting of Crohn's disease and to systematically re-examine pre-operative imaging findings. METHODS: Medical records were abstracted to identify all patients with Crohn's disease and small bowel adenocarcinoma who were evaluated at Mayo Clinic, Rochester, Minnesota and Mayo Clinic, Scottsdale, Arizona between 1976 and 2012. Clinical, demographic, and outcomes data were obtained for each patient. Pre-diagnosis radiologic imaging was re-evaluated by two gastrointestinal radiologists. RESULTS: Thirty-four patients (21 males) were identified. Median ages at Crohn's disease and cancer diagnoses were 22.4 and 52.9 years, respectively. Median follow-up after cancer diagnosis was 272.0 days; 22 patients (64.7%) had persistent or recurrent adenocarcinoma at last follow-up. 1- and 2-year mortality rates were 29.6% and 48.0%. Pre-operative imaging studies were available for re-review in 14 cases. Features concerning for malignancy included annular mass, nodularity at the extraluminal margins of the mass, and perforation. Nearly all tumors arose in regions of chronic inflammation and caused luminal narrowing with pre-stenotic dilatation. CONCLUSIONS: Small bowel adenocarcinoma is rare in patients with Crohn's disease but results in significant mortality. CT or MR imaging findings can be suggestive of the pre-operative diagnosis, but it is usually diagnosed at an advanced stage with laparotomy.

Validation of a CT-derived method for osteoporosis screening in IBD patients undergoing contrast-enhanced CT enterography.

OBJECTIVES: Osteoporosis and bone fractures are of particular concern in patients with inflammatory bowel disease (IBD). Biomechanical computed tomography (BCT) is an image-analysis technique that can measure bone strength and dual-energy X-ray absorptiometry (DXA)-equivalent bone mineral density (BMD) from noncontrast CT images. This study seeks to determine whether this advanced technology can be applied to patients with IBD undergoing CT enterography (CTE) with IV contrast. METHODS: Patients with IBD who underwent a CTE and DXA scan between 2007 and 2011 were retrospectively identified. Femoral neck BMD (g/cm(2)) and T-scores were measured and compared between DXA and BCT analysis of the CTE images. Femoral strength (Newtons) was also determined from BCT analysis. RESULTS: DXA- and CTE-generated BMD T-score values were highly correlated (R(2)=0.84, P<0.0001) in this patient cohort (n=136). CTE identified patients with both osteoporosis (sensitivity, 85.7%; 95% confidence interval (CI), 48.7-97.4 and specificity, 98.5%; 95% CI, 94.5-99.6) and osteopenia (sensitivity, 85.1%; 95% CI, 72.3-92.6 and specificity, 85.4%; 95% CI, 76.6-91.3). Of the 16 patients who had "fragile" bone strength by BCT (placing them at the equivalent high risk of fracture as for osteoporosis), 6 had osteoporosis and 10 had osteopenia by DXA. CONCLUSIONS: CTE scans can provide hip BMD, T-scores, and clinical classifications that are comparable to those obtained from DXA; when combined with BCT analysis, CTE can identify a subset of patients with osteopenia who have clinically relevant fragile bone strength. This technique could markedly increase bone health assessments in IBD patients already undergoing CTE to evaluate small bowel disease.

Predictors of Durability of Radiological Response in Patients With Small Bowel Crohn's Disease.

Background: The long-term significance of radiological transmural response (TR) as a treatment goal at the first follow-up scan in small bowel Crohn's disease (CD) has been previously shown. We examined the durability of a long-term strategy of treating to a target of radiological TR and the influence of baseline predictors on the maintenance of TR. Methods: Small bowel CD patients between January 1, 2002, and December 31, 2014, were identified with serial computed tomography enterography (CTE)/magnetic resonance enterography (MRE) before and after initiation of therapy or on maintenance therapy. Overall TR (inflammatory lesions with/without strictures) w1as characterized by abdominal radiologists in up to 5 small bowel lesions per patient at each serial scan until last follow-up or small bowel resection, as response, partial response, or nonresponse. The rate of conversion between TR states and transition to surgery, including the effect of baseline patient/disease characteristics, was examined using a multistate model (mstate R-package). Results: CD patients (n = 150, 705 CTE/MRE) with a median of 4 CTE/MRE during 4.6 years of follow-up, 49% with ileal-only distribution, had 260 examined bowel segments. Conversion from response to partial response/nonresponse was 37.4% per year of follow-up with no transitions seen directly from response to surgery. Current smoking status (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.1-4.3) and internal penetrating disease at baseline scan (HR, 2.2; 95% CI, 1.2-4.1) were associated with a 2-fold increased risk of transition from partial response/nonresponse to surgery. Conclusions: Achievement and maintenance of radiological response is associated with avoidance of small bowel surgery. Continued follow-up with CTE/MRE is recommended to identify loss of response, especially in current smokers and patients with internal penetrating disease at baseline CTE/MRE.

Tacrolimus salvage in anti-tumor necrosis factor antibody treatment-refractory Crohn's disease.

BACKGROUND: Several small retrospective studies have reported encouraging response rates in patients with Crohn's disease (CD) treated with tacrolimus. METHODS: We conducted a retrospective study of the use of oral tacrolimus for severe CD refractory to anti-tumor necrosis factor agents. Response was defined as a clinician's assessment of improvement after at least 7 days of treatment of one or more of the following: bowel movement frequency, fistula output, rectal bleeding, abdominal pain, extraintestinal manifestations, or well-being. Remission required all of the following: <3 stools per day, no bleeding, abdominal pain or extraintestinal manifestations, and increased well-being. RESULTS: Twenty-four eligible patients were treated with tacrolimus for a median of 4 months. Approximately 37% were steroid dependent or steroid refractory. Response and steroid-free remission rates were 67% and 21%, respectively, and lasted for a median of 4 months. Approximately 42% of patients were able to stop steroids and 54% of patients ultimately required surgery within a median of 10 months after starting tacrolimus. Patients with mean tacrolimus trough levels of 10 to 15 ng/mL had the highest rates of response (86%) and remission (57%). Surgery seemed to be postponed in this group compared with others. An adverse event occurred in 75% of patients. Eight of these events (33%) required dose reduction and 6 (25%) led to treatment discontinuation. There were no irreversible side effects or deaths attributable to tacrolimus over a median follow-up of 56 months. CONCLUSIONS: Oral tacrolimus seems to be safe and effective in some patients with severe CD refractory to anti-tumor necrosis factor therapy, particularly at a mean trough level of 10 to 15 ng/mL.

Comparative outcomes of younger and older hospitalized patients with inflammatory bowel disease treated with corticosteroids.

BACKGROUND: Data on the differences in inpatient treatment approaches and outcomes between younger and older patients with inflammatory bowel disease (IBD) are limited. Therefore, we used a parallel cohort study design to compare outcomes between younger and older patients with IBD. METHODS: All anti-tumor necrosis factor (TNF)-naive patients aged 60 years and older hospitalized at our institution between 2003 and 2011 and treated with corticosteroids for an IBD flare were matched 1:1 to younger patients aged 18 to 50 years. Rates of corticosteroid response, colectomy, and initiation of anti-TNF therapy were compared. RESULTS: Sixty-five patients were identified in each cohort. Median ages were 70 years (range, 60-94) and 30 years (range, 18-50) for the older and younger groups, respectively. Twenty-three percent of older patients were refractory to corticosteroids compared with 38% of the younger cohort (odds ratio, 0.5; 95% confidence intervals, 0.2-1.1). Older corticosteroid-refractory patients had surgery (80% versus 72%) and were started on anti-TNF therapy (20% versus 12%; P = 0.71), at a similar frequency as younger patients. Older steroid-responsive patients were less likely to start an anti-TNF agent during the first year of follow-up than younger patients (7% versus 31%, P = 0.006), but there was no difference in 1-year colectomy rates (27% versus 28%, P = 0.63). CONCLUSIONS: Corticosteroid response was similar in older and younger patients hospitalized for IBD. Inpatient treatment for corticosteroid-refractory patients was similar between cohorts. Older corticosteroid-responsive patients were less likely to be treated with an anti-TNF than younger patients.