Glucocorticoid-Induced Leucine Zipper Inhibits Interferon-Gamma Production in B Cells and Suppresses Colitis in Mice

Glucocorticoid-induced leucine zipper (GILZ) is transcriptionally upregulated by glucocorticoids (GCs) and mediates many of the anti-inflammatory effects of GCs. Since B cell activity has been linked to cytokine production and modulation of inflammatory responses, we herein investigated the role of GILZ in B cells during colitis development. B cell-specific gilz knock-out (gilz B cKO) mice exhibited increased production of the pro-inflammatory cytokine IFN-γ in B cells, and consequently CD4+ T cell activation. Increased IFN-γ production in B cells was associated with enhanced transcriptional activity of the transcription factor activator protein-1 (AP-1) on the IFN-γ promoter. Moreover, GILZ deficiency in B cells was linked to enhanced susceptibility to experimental colitis in mice, and this was reversed by administering GILZ protein. Interestingly, we observed increased production of IFN-γ in both B and T cells infiltrating the lamina propria (LP) of gilz B cKO mice. Together, these findings indicate that GILZ controls IFN-γ production in B cells, which also affects T cell activity, and increased production of IFN-γ by B and T cells in LP is associated with predisposition to inflammatory colitis in mice

Neonatal Thyroid Function in Seveso 25 Years after Maternal Exposure to Dioxin

Andrea Baccarelli and colleagues show that maternal exposure to a dioxin following the industrial accident in Seveso, Italy in 1976 is associated with modified neonatal thyroid function even many years later

Unidirectional barbed suture versus standard monofilament for urethrovesical anastomosis during robotic assisted laparoscopic radical prostatectomy

PURPOSE: V-LocTM180 (Covidien Healthcare, Mansfield, MA) is a new unidirectional barbed suture that may reduce loss of tension during a running closure. We evaluated the use of the barbed suture for urethrovesical anastomosis (UVA) during robotic assisted laparoscopic prostatectomy (RALP). Time to completion of UVA, post-operative anastomotic leak rate, and urinary incontinence were compared in patients undergoing UVA with 3-0 unidirectional-barbed suture vs. 3-0 MonocrylTM (Ethicon, Somerville, NJ). MATERIALS AND METHODS: Data were prospectively collected for 70 consecutive patients undergoing RALP for prostate cancer between November 2009 and October 2010. In the first 35 patients, the UVA was performed using a modified running van Velthoven anastomosis technique using two separate 3-0 monofilament sutures. In the subsequent 35 patients, the UVA was performed using two running novel unidirectional barbed sutures. At 7-12 days postoperatively, all patients were evaluated with a cystogram to determine anastomotic integrity. Urinary incontinence was assessed at two months and five months by total daily pad usage. Clinical symptoms suggestive of bladder neck contracture were elicited. RESULTS: Age, PSA, Gleason score, prostate size, estimated blood loss, body mass index, and clinical and pathologic stage between the 2 groups were similar. Comparing the monofilament group and V-LocTM180 cohorts, average time to complete the anastomosis was similar (27.4 vs. 26.4 minutes, p = 0.73) as was the rate of urinary extravasation on cystogram (5.7 % vs. 8.6%, p = 0.65). There were no symptomatic bladder neck contractures noted at 5 months of follow-up. At 2 months, the percentage of patients using 2 or more pads per day was lower in the V-LocTM180 cohort (24% vs. 44%, p < 0.02). At 5 months, this difference was no longer evident. CONCLUSIONS: Time to complete the UVA was similar in the intervention and control groups. Rates of urine leak were also comparable. While the V-LocTM180 was associated with improved early continence, this difference was transient

Comparison of positive surgical margin rates in high risk prostate cancer: open versus minimally invasive radical prostatectomy

Objective We compared positive surgical margin (PSM) rates for patients with high risk prostate cancer (HRCaP) who underwent open radical retropubic (RRP), robotic (RALP), and laparoscopic (LRP) prostatectomy at a single institution. Materials and Methods We performed a retrospective review of our prospectively maintained IRB approved database identifying prostate cancer patients who underwent RRP, RALP, or LRP between January 2000 and March 2010. Patients were considered to have HRCaP if they had biopsy or final pathologic Gleason score ≥ 8, or preoperative PSA ≥ 20, or pathologic stage ≥ T3a. A positive surgical margin (PSM) was defined by the presence of tumor at the inked surface of the specimen. Patients who received neoadjuvant hormonal therapy and those who underwent a perineal prostatectomy were excluded from the study. Results Of the 445 patients in this study, surgical technique for prostatectomy included RRP (n = 153), RALP (n = 152), and LRP (n = 140). PSM rate for the three groups were not different: 52.9% RRP, 50% RALP, and 41.4% LRP, (p = 0.13). The PSM rate did not differ when comparing RRP to a combined group of RALP and LRP (p = 0.16). Among patients with a PSM, there was no statistical difference between the three groups in terms of the number of patients with a pathologic stage of T3 or higher (p = 0.83). On univariate analysis, a higher preoperative PSA value was associated with a positive margin (p = 0.04). Conclusion In this HRCaP series, the PSM rate did not differ based on the surgical approach. On univariate analysis, patients with a higher preoperative PSA value were more likely to have a PSM

Comparative Effectiveness of Treatment Strategies for Squamous Cell Carcinoma of the Bladder.

BACKGROUND: While there is established evidence supporting the use of radical cystectomy (RC) and perioperative chemotherapy for muscle-invasive urothelial carcinoma of the bladder, such evidence does not exist for squamous cell carcinoma. OBJECTIVE: We present the largest study to date of patients with squamous cell carcinoma and compare the effectiveness of possible treatment regimens for overall survival. DESIGN, SETTING, AND PARTICIPANTS: The National Cancer Data Base was queried for cases of localized, muscle-invasive pure squamous cell bladder cancer, classified as clinical stage T2/3N0M0. Permutations of surgery (RC), chemotherapy, and external beam radiation were selected. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A multinomial propensity score method was used to create treatment weights based on clinical characteristics predicting the probability of treatment receipt. These were then applied in weighted Cox proportional hazards models to assess the comparative effectiveness of treatments for overall survival, adjusting for age, TNM clinical stage, Charlson comorbidity index, race, sex, and facility and county level variables. RESULTS AND LIMITATIONS: A total of 828 cases were included, comprising 465 RC alone, 53 neoadjuvant chemotherapy+RC, 48 RC+adjuvant chemotherapy, 72 chemotherapy alone, 88 radiation alone, and 102 chemoradiation cases. On weighted regression, RC treatment with or without perioperative chemotherapy was associated with significantly better overall survival compared to the other treatment modalities; chemotherapy alone, radiation alone, and chemoradiation were associated with a hazard ratio (HR) of death of 2.43 (95% confidence interval [CI] 1.65-3.59), 4.78 (95% CI 3.33-6.86), and 1.61 (95% CI 1.16-2.25), respectively, compared to RC alone (all p CONCLUSIONS: RC with or without perioperative chemotherapy should be considered an upfront therapy for squamous cell carcinoma of the bladder. PATIENT SUMMARY: Using a national database, we compared treatments for muscle-invasive squamous cell bladder cancer. Patients undergoing radical cystectomy with or without chemotherapy had longer survival. Radical cystectomy with or without chemotherapy should be the standard of care for this disease