Transmural inflammation is not pathognomonic for Crohn's disease of the pouch.

BACKGROUND: Transmural inflammation shown by imaging and histology has been considered a hallmark of Crohn's disease (CD). However, the diagnostic and prognostic value of this feature in CD of the pouch has not been evaluated. This study aimed to evaluate the clinical utility of transmural inflammation in patients with ileal pouch-anal anastomosis (IPAA) using in vivo optical coherence tomography (OCT) and histopathology. METHODS: All the patients were recruited from the subspecialty Pouchitis Clinic. The study consisted of two parts: (1) a prospective study with in vivo through-the-scope OCT for the evaluation of transmural disease in patients with normal or diseased pouches and (2) a retrospective pathology re-review for transmural inflammation in excised pouch specimens of CD and chronic pouchitis. RESULTS: This prospective OCT study enrolled 53 patients: 11 (20.8%) with normal pouches or irritable pouch syndrome, 10 (18.9%) with acute pouchitis, 11 (20.8%) with chronic antibiotic-refractory pouchitis (CARP), and 21 (39.6%) with CD of the pouch. Transmural inflammation, characterized by the loss of layered structure on OCT, was detected in 16 patients (30.2%): 4 with chronic pouchitis and 12 with CD of the pouch. None of the patients with normal pouches, irritable pouch syndrome, or acute pouchitis had transmural disease shown on OCT. Of the 26 patients with pouch failure who had pouch excision, the surgical specimens showed transmural disease in 30% of the CARP patients (3/10) and 12.5% (2/16) of those with CD of the pouch. CONCLUSIONS: Transmural disease in the setting of IPAA is not pathognomonic of CD. Transmural inflammation shown by imaging or histopathology was seen in both CD and CARP. Transmural inflammation of the pouch appeared to be associated with poor pouch outcome.

Effect of femtosecond laser energy level on corneal stromal cell death and inflammation.

PURPOSE: To analyze the effects of variations in femtosecond laser energy level on corneal stromal cell death and inflammatory cell influx following flap creation in a rabbit model. METHODS: Eighteen rabbits were stratified in three different groups according to level of energy applied for flap creation (six animals per group). Three different energy levels were chosen for both the lamellar and side cut: 2.7 microJ (high energy), 1.6 microJ (intermediate energy), and 0.5 microJ (low energy) with a 60 kHz, model II, femtosecond laser (IntraLase). The opposite eye of each rabbit served as a control. At the 24-hour time point after surgery, all rabbits were euthanized and the corneoscleral rims were analyzed for the levels of cell death and inflammatory cell influx with the terminal uridine deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunocytochemistry for monocyte marker CD11b, respectively. RESULTS: The high energy group (31.9+/-7.1 [standard error of mean (SEM) 2.9]) had significantly more TUNEL-positive cells in the central flap compared to the intermediate (22.2+/-1.9 [SEM 0.8], P=.004), low (17.9+/-4.0 [SEM 1.6], P< or =.001), and control eye (0.06+/-0.02 [SEM 0.009], P< or =.001) groups. The intermediate and low energy groups also had significantly more TUNEL-positive cells than the control groups (P< or =.001). The difference between the intermediate and low energy levels was not significant (P=.56). The mean for CD11b-positive cells/400x field at the flap edge was 26.1+/-29.3 (SEM 11.9), 5.8+/-4.1 (SEM 1.6), 1.6+/-4.1 (SEM 1.6), and 0.005+/-0.01 (SEM 0.005) for high energy, intermediate energy, low energy, and control groups, respectively. Only the intermediate energy group showed statistically more inflammatory cells than control eyes (P=.015), most likely due to variability between eyes. CONCLUSIONS: Higher energy levels trigger greater cell death when the femtosecond laser is used to create corneal flaps. Greater corneal inflammatory cell infiltration is observed with higher femtosecond laser energy levels.

The efficacy and tolerability of AST-120 (spherical carbon adsorbent) in active pouchitis.

OBJECTIVES: Although a majority of patients with pouchitis respond favorably to antibiotic therapy, many relapse frequently, and nonabsorbable and non-antibiotic-based agents are desirable for reducing bacterial resistance and the systemic adverse effects associated with long-term antibiotic exposure. AST-120 (a spherical carbon adsorbent) comprises highly adsorptive, porous carbon microspheres with the ability to adsorb small-molecular-weight toxins, inflammatory mediators,and harmful bile acids. The aim of this pilot trial was to evaluate the efficacy and tolerability of AST-120 in the treatment of active pouchitis. METHODS: Eligible patients were recruited from two subspecialty pouchitis clinics. Inclusion criteria were(i) ileal pouch-anal anastomosis performed for ulcerative colitis; (ii) active pouchitis with Pouchitis Disease Activity Index (PDAI) scores > or =7; and (iii) discontinuation of antibiotic therapy for at least 2 weeks. Exclusion criteria included Crohn's disease of the pouch, isolated cuffitis, pouch strictures, abscess, and sinuses. All eligible patients received AST-120 in 2-g sachets (oral) open label, thrice a day for 4 weeks. The primary efficacy end point was remission as defined by a PDAI score of < 7 points; the main secondary end point was clinical response, defined by a reduction of the PDAI score of > or =3 points. RESULTS: Nineteen of 20 patients completed the trial. Eleven patients (55.0 % ) had a clinical response to the therapy and 10 patients (50.0 % ) entered remission. Median reduction in the PDAI symptom, endoscopy, and histology subscores, and PDAI total scores after 4 weeks were -2( P = 0.002), -2 ( P = 0.003), 0 ( P = 0.32), and -4 ( P = 0.001) points, respectively. The agent was well tolerated; one patient experienced transient mild elevation of alkaline phosphatase of uncertain significance and one patient experienced an upper respiratory infection after taking one dose of AST-120 and was excluded from the fi nal analysis for the calculation of pre- and post-trial PDAI scores. CONCLUSIONS: AST-120 seems to be effective and well tolerated in treating patients with active pouchitis.A randomized, placebo-controlled trial is warranted for assessing the long-term efficacy and safety of AST-120 in the disease.

Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma.

The classification of primary cutaneous large B-cell lymphoma (PCLBCL) is based on standard morphology, immunohistochemistry, and clinical presentation. There are two major subtypes in the current WHO-EORTC classification: follicle center lymphoma and diffuse large B-cell lymphoma, leg-type (DLBCL-LT). The goals of this study were to examine a series of DLBCLs to determine (1) whether the immunohistochemical paradigm of germinal center B-cell and non-germinal center B-cell types of systemic DLBCL could be applied to PCLBCL; (2) whether application of the newly described germinal center B-cell marker, human germinal center-associated lymphoma (HGAL) also discriminates between these types as a further support for germinal center B-cell origin for primary cutaneous center lymphoma; and (3) whether any of these biologic markers were of prognostic significance. To this end, 32 cases of diffuse PCLBCL (22 primary cutaneous follicular center lymphomas and 10 DLBCL-LT) were classified based on the WHO-EORTC criteria and studied for expression of CD20, BCL2, BCL6, CD10, MUM-1, and HGAL by immunohistochemistry. Results were correlated with clinical features. HGAL and BCL6 expression and germinal center B-cell phenotype were associated with primary cutaneous follicular center lymphoma. The combination of HGAL and BCL6 positivity had the highest sensitivity (88%) and specificity (100%) for predicting subtype compared to either marker alone. Both HGAL and BCL6 were associated with the germinal center B-cell phenotype. The correlation of HGAL expression with the germinal center B-cell phenotype demonstrates the role of this marker in the classification of cutaneous large B-cell lymphomas. BCL6 expression was the only immunohistochemical marker associated with overall survival. Characterizing PCLBCLs with markers of B-cell maturation stage is a useful framework for studying, classifying, and clinically stratifying these lymphomas.