Use of Concomitant Stress Incontinence Surgery at Time of Pelvic Organ Prolapse Surgery Since Release of the 2011 Notification on Serious Complications Associated with Transvaginal Mesh.

PURPOSE: There is controversy regarding the performance of concomitant anti-incontinence procedures at the time of pelvic organ prolapse repair. Data support improvement in stress urinary incontinence with a concomitant sling but increased adverse events. We assessed trends in preoperative stress urinary incontinence evaluation, concomitant anti-incontinence procedure at pelvic organ prolapse surgery and postoperative anti-incontinence procedures at our institution before and after the 2011 FDA (U.S. Food and Drug Administration) Public Health Notification pertaining to vaginal mesh. MATERIALS AND METHODS: We retrospectively reviewed the records of patients who underwent pelvic organ prolapse surgery from 2009 to 2015. Preoperative workup included assessment of subjective stress urinary incontinence and/or evaluation for leakage with reduction of pelvic organ prolapse on physical examination, urodynamics or a pessary trial. The percentages of concomitant and postoperative anti-incontinence procedures were compared before and after the 2011 FDA notification. RESULTS: A total of 775 women underwent pelvic organ prolapse repair. The percentage of anti-incontinence procedures at pelvic organ prolapse repair decreased from 54.8% to 38.0% after the FDA notification (p = 0.002) while the incidence of preoperative objective stress urinary incontinence on examination, urodynamics and pessary trials remained constant. The incidence of postoperative anti-incontinence procedures within 1 year of the index surgery remained low. CONCLUSIONS: We found a decrease in the incidence of concomitant anti-incontinence procedures at the time of pelvic organ prolapse repair following the 2011 FDA notification despite no significant decline in subjective stress urinary incontinence or demonstrable stress urinary incontinence on preoperative evaluation. Further analysis is warranted to assess the impact of the FDA notification on treatment patterns in women with pelvic organ prolapse and stress urinary incontinence.

Nationwide, population-based study of prostate cancer stage migration between and within clinical risk categories.

OBJECTIVE: In countries with widespread prostate cancer screening there has been strong stage migration, but little is known about changes within clinical risk categories. Such data are important for the proper interpretation of studies that recruited cases in an earlier era. The purpose of this study was to examine stage migration between and within clinical risk categories. MATERIAL AND METHODS: Using the population-based National Prostate Cancer Register (NPCR) of Sweden, changes in the distribution of prostate-specific antigen (PSA), Gleason score, tumor stage and volume overall between and within clinical risk categories were examined in 120 228 prostate cancer cases diagnosed from 1998 to 2011. RESULTS: Between 1998 and 2011, there was a two-fold increase in the proportion of low-risk prostate cancer (stage T1/T2, Gleason score 2-6 and PSA <10 ng/ml), from 14% to 28%, and more than a two-fold decrease in the proportion of metastatic disease, from 25% to 11%. The proportion of men in the low-risk category with T1c tumors increased two-fold, from 36% to 71%, and PSA levels between 4 and 6 ng/ml increased from 24% to 38%; T2 tumors decreased from 39% to 20% and PSA between 8 and 10 ng/ml decreased from 24% to 15%. The proportion of men with less than 25% of cores involved with cancer increased from 41% to 52% between 2003-2006 and 2007-2011. CONCLUSIONS: Low-risk cases today have substantially lower tumor volume and PSA levels than low-risk cases diagnosed in 1998, indicating that outcomes in studies that recruited cases in previous decades represent worst case scenarios.

Unusual presentation of ectopic insertion of duplicated collecting system in an adult male.

Ectopic ureters are rare congenital mesonephric duct malformations with a higher prevalence in women than men. In women, ectopic ureters are often associated with a duplicated collecting system, whereas in men, ectopic ureters usually drain a single system and are associated with renal dysplasia and obstruction. Presentation and diagnosis generally occurs in the pediatric age group. Herein, we present an unusual case of delayed diagnosis of ectopic insertion of the upper pole ureter in a completely duplicated left kidney causing massive hydroureteronephrosis in an adult man.

Renal function and genetic polymorphisms in pediatric heart transplant recipients.

BACKGROUND: Common genetic variations influence rejection, infection, drug metabolism, and side effect profiles after pediatric heart transplantation. Reports in adults suggest that genetic background may influence post-transplant renal function. In this multicenter study, we investigated the association of genetic polymorphisms (GPs) in a panel of candidate genes on renal function in 453 pediatric heart transplant recipients. METHODS: We performed genotyping for functional GPs in 19 candidate genes. Renal function was determined annually after transplantation by calculation of the estimated glomerular filtration rate (eGFR). Mixed-effects and Cox proportional hazard models were used to assess recipient characteristics and the effect of GPs on longitudinal eGFR and time to eGFR < 60 mL/min/1.73m(2). RESULTS: Mean age at transplantation was 6.2 ± 6.1 years. Mean follow-up was 5.1 ± 2.5 years. Older age at transplant and black race were independently associated with post-transplant renal dysfunction. Univariate analyses showed FASL (C-843T) T allele (p = 0.014) and HO-1 (A326G) G allele (p = 0.0017) were associated with decreased renal function. After adjusting for age and race, these associations were attenuated (FASL, p = 0.075; HO-1, p = 0.053). We found no associations of other GPs with post-transplant renal function, including GPs in TGFß1, CYP3A5, ABCB1, and ACE. CONCLUSIONS: In this multicenter, large, sample of pediatric heart transplant recipients, we found no strong associations between GPs in 19 candidate genes and post-transplant renal function. Our findings contradict reported associations of CYP3A5 and TGFß1 with renal function and suggest that genotyping for these GPs will not facilitate individualized immunosuppression for the purpose of protecting renal function after pediatric heart transplantation.

Gene polymorphisms impact the risk of rejection with hemodynamic compromise: a multicenter study.

BACKGROUND: Rejection with hemodynamic compromise (RHC) is associated with high mortality in heart recipients. This study investigates the association between genetic polymorphisms and RHC in pediatric heart recipients. METHODS: Data from 532 pediatric heart recipients from six centers in the Pediatric Heart Transplant Study were analyzed for time to RHC by recipient race, age at transplantation, and genotype at 13 genetic polymorphisms (TNF-α A-308G, IL-6 G-174C, INF-γ T+874A, IL-10 G-1082A, C-819T, and C-592A; FAS A-670G, FASL C-843T, and ACE I/D; and VEGF A-2578C, C-1451T, C+405G, and -2549 I/D). RESULTS: RHC occurred in 126 (23.7%) patients during the study period. Adjusting for age and race, IL-10 G-1082A, FAS A-670G, and ACE I/D genotypes were associated with RHC. IL-10 G-1082A GG genotype was associated with decreased risk of RHC with an adjusted hazard ratio (HR) of 0.49 (95% confidence interval [CI], 0.27-0.90; P=0.020). FAS A-670G AA genotype was associated with increased risk of RHC with an adjusted HR of 1.84 (95% CI, 1.25-2.69; P=0.002). ACE II genotype was associated with decreased risk of RHC with an adjusted HR of 0.58 (95% CI, 0.36-0.95; P=0.031). CONCLUSIONS: Recipients with a high anti-inflammatory and immune-regulatory genetic profile (high interleukin-10) were protected from RHC. Conversely, recipients with a pro-apoptotic genetic profile (high Fas) or high angiotensin-1-converting enzyme producing genotype were at increased risk of RHC. This represents progress toward understanding the genetic risk factors of posttransplantation outcomes in pediatric heart recipients.

The utility of fine needle aspiration to identify unusual pathology in a parapharyngeal mass.

The parapharyngeal space is a complex and well-defined anatomical zone lying lateral to the pharynx and medial to the ramus of the mandible. Although tumors of this space are rare, the parapharyngeal space is difficult to examine clinically; and diagnostic modalities of computerized tomographic scanning and magnetic resonance imaging are primarily used in the evaluation of parapharyngeal space lesions. We present a case report of a second branchial cleft sinus of the parapharyngeal space diagnosed with the assistance of fine needle aspiration (FNA), and we recommend FNA of parapharyngeal masses to provide definitive preoperative diagnoses.

Association of genetic polymorphisms and risk of late post-transplantation infection in pediatric heart recipients.

BACKGROUND: Late infections are common causes of morbidity and mortality after pediatric heart transplantation. In this multicenter study from 6 centers, we investigated the association between genetic polymorphisms (GPs) in immune response genes and late post-transplantation infections in 524 patients. METHODS: Late infection was defined as a clinical infectious process occurring >60 days after transplantation and requiring hospitalization, intravenous antimicrobial therapy, or a life-threatening infection requiring oral therapy. All patients provided a blood sample for GP analyses of 18 GPs in cytokine, growth factor, and effector molecule genes by single specific primer-polymerase chain reaction and/or sequencing. Significant associations in univariable analyses were tested in multivariable Cox regression models. RESULTS: Late infection was common, with 48.7% of patients experiencing ≥ 1 late infection, 25.2% had ≥ 1 late bacterial infection, and 30.5% had ≥ 1 late viral infection. Older age at transplantation was a protective factor for late infection, both bacterial and viral (hazard ratio [HR] 0.89-0.92 per 1-year age increase, p < 0.001). Adjusting for age, race, and transplant etiology, late bacterial infection was associated with HMOX1 A+326G AG and GG genotypes (HR, 2.41, 95% confidence interval [CI] 1.35-4.30; p = 0.003) and GZMB A-295G AA genotype (HR, 1.47; 95% CI; 1.03-2.1; p = 0.036). Late viral infection was associated with FAS A-670G GG genotype (HR, 1.42; 95% CI, 1.00-2.00; p = 0.050) in the adjusted model and with CTLA4 A+49G AA and AG genotypes (HR, 1.49; 95% CI, 1.02-2.19; p = 0.041) in univariable analysis. CONCLUSION: We found an association between late bacterial infection and GP of HMOX1, which may control macrophage activation. A weaker association was also found between late viral infection and GP of CTLA4, a regulator of T-cell activation. This represents progress toward understanding the clinical and genetic risk factors of outcomes after transplantation.

Inosine 5'-monophosphate dehydrogenase 1 haplotypes and association with mycophenolate mofetil gastrointestinal intolerance in pediatric heart transplant patients.

MMF, the most commonly used adjuvant immunosuppressant in pediatric heart transplantation, has frequent GI adverse events. SNPs in inosine 5'-monophosphate dehydrogenase I (IMPDH1) may contribute to MMF GI intolerance. Phased haplotypes may have more utility than individual SNPs in candidate gene association studies for complex traits. This study defined common IMPDH1 haplotypes and investigated whether these haplotypes influence MMF GI intolerance in 59 pediatric heart recipients. Genotypes were assessed by Taqman analysis of IMPDH1 rs2288553, rs2288549, rs2278293, rs2278294, and rs2228075, and haplotypes were inferred using Arlequin 3.01 software. GI intolerance was defined as diarrhea, vomiting, nausea, or abdominal pain requiring MMF dose holding for > 48 h or MMF discontinuation. GI intolerance occurred in 21 patients (35.6%). Ten IMPDH1 haplotypes were identified in this population. In univariable analyses, one haplotype was strongly associated with MMF GI intolerance with 59.1% of carriers of this haplotype experiencing MMF GI intolerance compared to 21.6% of non-carriers (p = 0.005). In this study, we identify a common IMPDH1 haplotype associated with MMF GI intolerance in a population of pediatric heart transplant patients. This haplotype of interest did not demonstrate stronger association with MMF GI intolerance than an individual IMPDH1 SNP.

Genetic polymorphisms influence mycophenolate mofetil-related adverse events in pediatric heart transplant patients.

BACKGROUND: Mycophenolate mofetil (MMF) is an effective and commonly used immunosuppressant but has frequent adverse events. Genetic polymorphisms may contribute to variability in MMF efficacy and related complications. In this study we explore the distribution frequencies of common single nucleotide polymorphisms (SNPs) of IMPDH1, IMPDH2 and ABCC2 and investigate whether these SNPs influence MMF adverse events in 59 pediatric heart recipients. METHODS: Genotypes were assessed by TaqMan analysis of: ABCC2 rs717620; IMPDH2 rs11706052; and IMPDH1 rs2288553, rs2288549, rs2278293, rs2278294 and rs2228075. Gastrointestinal (GI) intolerance was defined as diarrhea, vomiting, nausea or abdominal pain requiring dose-holding for >48 hours or MMF discontinuation. Bone marrow toxicity was evaluated using Common Terminology Criteria for Adverse Events Version 3 (CTCAE). RESULTS: GI intolerance occurred in 21 patients, and 21 had bone marrow toxicity. The ABCC2 rs717620 A variant was significantly associated with GI intolerance leading to drug discontinuation (p < 0.001); the IMPDH1 rs2278294 A variant and rs2228075 A variant were also associated with greater GI intolerance (p = 0.029 and p = 0.002, respectively). The IMPDH2 rs11706052 G variant was associated with more frequent neutropenia requiring dose-holding (p = 0.046). CONCLUSIONS: In this small sample of pediatric heart transplant patients receiving MMF, ABCC2, IMPDH1 and IMPDH2 SNPs were associated with MMF GI intolerance and bone marrow toxicity. Thus, genetic polymorphisms may directly influence MMF adverse events.