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.

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.

Interactions between enhancer of rudimentary and Notch and deltex reveal a regulatory function of enhancer of rudimentary in the Notch signaling pathway in Drosophila melanogaster.

Enhancer of rudimentary, e(r), encodes a small nuclear protein, ER, that has been implicated in the regulation of pyrimidine metabolism, DNA replication, and cell proliferation. In Drosophila melanogaster, a new recessive Notch allele, N (nd-p) , was isolated as a lethal in combination with an e(r) allele, e(r) (p2) . Both mutants are viable as single mutants. N (nd-p) is caused by a P-element insertion in the 5' UTR, 378-bp upstream of the start of translation. Together the molecular and genetic data argue that N (nd-p) is a hypomorphic allele of N. The three viable notchoid alleles, N (nd-p) , N (nd-1) , and N (nd-3) , are lethal in combination with e(r) (-) alleles. Our present hypothesis is that e(r) is a positive regulator of the Notch signaling pathway and that the lethality of the N e(r) double mutants is caused by a reduction in the expression of the pathway. This is supported by the rescue of the lethality by a mutation in Hairless, a negative regulator of N, and by the synthetic lethality of dx e(r) double mutants. Further support for the hypothesis is a reduction in E(spl) expression in an e(r) (-) mutant. Immunostaining localizes ER to the nucleus, suggesting a nuclear function for ER. A role in the Notch signaling pathway, suggests that e(r) may be expressed in the nervous system. This turns out to be the case, as immunostaining of ER shows that ER is localized to the developing CNS.

HBIg discontinuation with maintenance oral anti-viral therapy and HBV vaccination in liver transplant recipients.

BACKGROUND: Hepatitis B (HBV) is an uncommon indication for liver transplantation in the US accounting for approximately 5% of cases. Recurrence prophylaxis is typically long-term hepatitis B immune-globulin (HBIg) and an oral anti-HBV agent. Because of high HBIg costs and improving efficacy of new oral agents, there is increasing interest in HBIg discontinuation. AIM: To describe results of a protocol at our center including HBV vaccination and HBIg discontinuation. METHODS: All patients received HBIg therapy and an oral anti-viral agent from the time of transplant. Patients transplanted for HBV with a stable post-operative clinical course underwent HBV vaccination and HBIg discontinuation. After HBIg discontinuation, patients were monitored for HBV recurrence for at least one year. Recurrence was defined as either viral (HBV-DNA 10(4) copies/ml on two consecutive occasions) or hepatitis (viral recurrence with elevated liver transaminases). RESULTS: Of 1182 recipients, 36 (3%) had HBV. Twenty-four were excluded from the protocol, and the remaining 12 patients underwent HBIg withdrawal. Median age at HBIg discontinuation was 56 (range, 36-70) years, median time from transplant to HBIg discontinuation was 62.8 (range, 27.5-128) months, and median time of follow-up after discontinuation was 27.4 (range, 13-69) months. Of the 12 patients vaccinated, no patients maintained HBSAb >or= 10 IU/l at last follow-up. There was no viral or hepatitis recurrence and no deaths or graft loss. CONCLUSIONS: HBIg discontinuation with maintenance oral anti-viral monotherapy is safe and effective for HBV liver transplant recipients. Vaccination is not effective in this population.

Corticosteroid elimination in simultaneous liver-kidney transplantation recipients.

BACKGROUND: Simultaneous liver-kidney transplantation (SLK) has more than doubled since 2002. While less common in kidney transplant alone recipients (KTA), corticosteroid discontinuation is performed routinely in liver transplantation, raising the question of optimal immunosuppression for SLK recipients. METHODS: A retrospective case series of 16 SLK recipients under a steroid withdrawal protocol was performed to compare short-term outcomes to a contemporaneous cohort of 32 KTA recipients. RESULTS: In 69% of SLK recipients, corticosteroids were eliminated compared to 3% of KTA recipients, p < 0.0001. When comparing SLK and KTA recipients one yr post-transplant, there were no significant differences in renal graft rejection (23.1% vs. 6.3%), death-censored renal graft survival (100% vs. 97%), estimated glomerular filtration rate (74.4 vs. 62.6 mL/min), serum creatinine (1.10 vs. 1.39 mg/dL), or maintenance immunosuppression, respectively. CONCLUSIONS: Corticosteroids may be withdrawn safely in SLK recipients with one-yr renal outcomes comparable to a KTA cohort.