Is glans penis width a risk factor for complications after hypospadias repair?

INTRODUCTION: Recent studies have suggested that a smaller glans penis size may be associated with a higher likelihood of complications after hypospadias repair. Accurate identification of risk factors other than the well-understood variable of meatal location would allow development of better prognostic models and individualized risk stratification. OBJECTIVE: To test the hypothesis that a smaller width of the glans penis predicts adverse outcomes after hypospadias surgery. METHODS: Prospectively recorded clinical data were reviewed from a single-institution registry of primary hypospadias repairs performed between 2011 and 2014. Follow-up records were examined for occurrence of complications. Urethroplasty complications were defined to include meatal stenosis, dehiscence, urethrocutaneous fistula, urethral stricture, and/or urethral diverticulum. The subset of meatal stenosis and dehiscence were regarded as glanular complications. Regression analyses were performed to determine association between glans width and occurrence of complications. Because pre-operative androgen stimulation is known to increase glans penis size, separate subgroup analyses were included of patients with and without pre-operative use of testosterone cream. RESULTS: A total of 159 patients met criteria for inclusion in the study cohort: 140 patients underwent a single-stage repair, while 19 patients had a two-stage repair. The median glans penis width was 15 mm (range 10-22). Eighty-four patients (53%) received testosterone cream pre-operatively and had a significantly wider glans penis than the 75 patients who did not (median 15.5 vs 14 mm; P < 0.001). Median clinical follow-up was 7 months (IQR 1-12), with a minimum time elapsed since surgery of 10 months at the time of chart review. Twenty-four patients (15%) had one or more urethroplasty complications, including 11 (7%) with glanular complications. Overall, there was no statistically significant association between glans width and urethroplasty complications (P = 0.26) or glanular complications (P = 0.90) (Summary Table). Subgroup analyses of patients with and without pre-operative testosterone also revealed no significant associations between glans width and complications. CONCLUSIONS: Glans penis width was not a risk factor for complications after hypospadias repair. This finding differs from the results of other recent studies and encourages further research into the value of measuring penile parameters in patients undergoing hypospadias repair.

An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas.

BACKGROUND: To determine efficacy and safety of bevacizumab, a recombinant humanized antibody against vascular endothelial growth factor (VEGF), in the treatment of metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas. PATIENTS AND METHODS: In this single-arm phase II trial, 32 patients were enrolled and they received bevacizumab 15 mg/kg IV infusion in 21-day cycles. Patients had disease that was deemed not surgically resectable, Eastern Cooperative Oncology Group (ECOG) performance status of ≤1, adequate organ function and had not received any radiation treatment in the last 28 days. RESULTS: Of the 30 patients evaluated for efficacy and toxic effect, four (two angiosarcoma and two epithelioid hemangioendothelioma; 17%) had a partial response. Fifteen patients (11 angiosarcoma and 4 epithelioid hemangioendothelioma; 50%) showed stable disease with a mean time to progression of 26 weeks. Bevacizumab was well tolerated with only one grade 4 adverse event. Expected known toxic effects of the drug were manageable. CONCLUSION: Bevacizumab is an effective and well-tolerated treatment for metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas. Further phase III studies of bevacizumab in combination with other chemotherapeutic agents and/or radiation treatment are warranted.

Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports.

BACKGROUND: Rituximab has been associated with hepatitis B virus reactivation (HBV-R). However, the characteristics and scope of this association remain largely undefined. METHODS: We completed a comprehensive literature search of all published rituximab-associated HBV-R cases and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) MedWatch database. Literature and FDA cases were compared for completeness, and a meta-analysis was completed. RESULTS: One hundred and eighty-three unique cases of rituximab-associated HBV-R were identified from the literature (n = 27 case reports, n = 156 case series). The time from last rituximab to reactivation was 3 months (range 0-12), although 29% occurred >6 months after last rituximab. Within FDA data (n = 118 cases), there was a strong signal for rituximab-associated HBV-R [proportional reporting ratio = 28.5, 95% confidence interval (CI) 23.9-34.1; Empiric Bayes Geometric Mean = 26.4, 95% CI 21.4-31.1]. However, the completeness of data in FDA reports was significantly inferior compared with literature cases (P < 0.0001). Among HBV core antibody (HBcAb(+)) series, the pooled effect of rituximab-based therapy showed a significantly increased risk of HBV-R compared with nonrituximab-treated patients (odds ratio 5.73, 95% CI 2.01-16.33; Z = 3.33, P = 0.0009) without heterogeneity (χ(2) = 2.12, P = 0.5473). CONCLUSIONS: The FDA AERS provided strong HBV-R safety signals; however, literature-based cases provided a significantly more complete description. Furthermore, meta-analysis of HBcAb(+) series identified a more than fivefold increased rate of rituximab-associated HBV-R.

Characterization of a method for profiling gene expression in cells recovered from intact human prostate tissue using RNA linear amplification.

Coupling array technology to laser capture microdissection (LCM) has the potential to yield gene expression profiles of specific cell populations within tissue. However, remaining problems with linear amplification preclude accurate expression profiling when using the low nanogram amounts of RNA recovered after LCM of human tissue. We describe a novel robust method to reliably amplify RNA after LCM, allowing direct probing of 12K gene arrays. The fidelity of amplification was demonstrated by comparing the ability of amplified RNA (aRNA) versus that of native RNA to identify differentially expressed genes between two different cell lines, demonstrating a 99.3% concordance between observations. Array findings were validated by quantitative polymerase chain reaction analysis of a randomly selected subset of 32 genes. Using LCM to recover normal (N=5 subjects) or cancer (N=3) cell populations from intact human prostate tissue, three differentially expressed genes were identified. Independent investigators have previously identified differential expression of two of these three genes, hepsin and beta-microseminoprotein, in prostate cancer. Taken together, the current study demonstrates that accurate gene expression profiling can readily be performed on specific cell populations present within complex tissue. It also demonstrates that this approach efficiently identifies biologically relevant genes.

A simple analysis of gene expression and variability in gene arrays based on repeated observations.

BACKGROUND AND AIM: At the present time there is an explosion of research in the area of gene arrays, and their application for detection of genes related to disease as well as its therapeutic manipulation. However, as individual arrays are expensive, comparisons of gene expression are often not repeated. In the current study, gene array experiments were repeated multiple times in order to understand the variability associated with measurements of gene expression. By focusing upon the pharmacologically important target of prostate cancer cell detachment, the current study employed multiple repeats of gene array experiments. This was used as a model system to demonstrate the utility of the experimental approach and statistical methods used. METHODS: To identify genes involved in detachment of prostate cancer cells (a prerequisite for metastases), we analyzed gene expression changes in metastatic variant PC3-M cells undergoing spontaneous detachment in culture. The data were interpreted using an elementary statistical approach. The between-experiment and within-repeated-observations variability in expression of 3582 genes possibly related to prostate cancer was also evaluated. RESULTS: One important gene related to prostate cell detachment was identified, based on the magnitude of its change in expression, as measured by a ratio of the expression after cell detachment and expression before detachment. On average, the variation between experiments was greater by about 30 to 40% than the variation between repeated observations. CONCLUSION: These findings have implications relating to the use of gene arrays to detect variance of gene expression, and should be taken into consideration in the prospective design of array experiments.

Safety evaluation and confidence intervals when the number of observed events is small or zero.

A common objective in many clinical studies is to determine the safety of a diagnostic test or therapeutic intervention. In these evaluations, serious adverse effects are either rare or not encountered. In this setting, the estimation of the confidence interval (CI) for the unknown proportion of adverse events has special importance. When no adverse events are encountered, commonly used approximate methods for calculating CIs cannot be applied, and such information is not commonly reported. Furthermore, when only a few adverse events are encountered, the approximate methods for calculation of CIs can be applied, but are neither appropriate nor accurate. In both situations, CIs should be computed with the use of the exact binomial distribution. We discuss the need for such estimation and provide correct methods and rules of thumb for quick computations of accurate approximations of the 95% and 99.9% CIs when the observed number of adverse events is zero.

New assumptions concerning IPAs and cost of dental care.

OBJECTIVES: Previous studies suggest that fee-for-service (FFS) patients receive more treatment and at a greater cost than capitation patients. In this study treatment plans of dentists who are members of an independent practice association (IPA), a preferred provider organization (PPO), or who are paid their usual fee for service are compared. METHODS: A carefully selected and trained professional actor, with actual dental disease and recent radiographs, was sent to the offices of general practice dentists for an examination and treatment plan. To one group of dentists (n = 21) the patient said he was a member of a PPO plan served by that dentist, to a second group (n = 15) he said he was a member of an IPA plan served by that dentist, and to the third group (n = 19) he said he would pay by the traditional FFS method. RESULTS: IPA dentists recommended more restorations (mean = 9.60) than those in the PPO program (mean = 5.95) or those paid by the traditional FFS method (mean = 5.58). The anticipated mean cost to the patient was higher for the IPA dentists ($1,815.20) compared to the other two types (PPO = $1,186.24, FFS = $1,470.42). CONCLUSIONS: The IPA models studied in this investigation permitted dentists to charge copayments for most treatments beyond basic services. This type of IPA might be similar to a fee-for-service model that provides practitioners with an incentive to do more rather than less treatment.

Infection control in the dental office: has anything changed?

Using data collected in two studies, the authors compare infection control practices used in dental offices in 1988 and 1992. During that time, dentists increased their use of barrier protection but still asked and learned very little about their patients. This lack of communication hinders dentists' ability to deliver the best care possible. The authors recommend that dentists improve communication with their patients to obtain better information about their health status.