Clinical outcome of pediatric and young adult subclinical varicoceles: a single-institution experience.

Subclinical varicocele represents an abnormality of veins of the pampiniform plexus on scrotal ultrasound (US) without a clinically palpable varicocele. Its significance remains unclear. While guidelines do not recommend surgical intervention, clinical management is variable. As there is limited information on long-term outcome of subclinical varicoceles due to challenges in diagnosis and management, we performed a single-institution, retrospective review of patients from October 1999 to October 2014 with subclinical varicocele and with available US studies reviewed by a single radiologist. Subclinical varicocele was defined as dilation of the pampiniform venous plexus on US involving ≥2 vessels with diameter >2.5 mm, without clinical varicocele on physical examination or prior inguinal surgery. Thirty-six of 98 patients identified were confirmed as having a subclinical varicocele and analyzed. The mean age at initial visit was 15.5 years, with a mean follow-up of 26.5 months. The majority were right-sided (69.4%, n = 25), usually with a contralateral clinical varicocele. Testicular asymmetry (>20% volume difference of the affected side by testicular atrophy index formula) was assessed in 9 patients with unilateral subclinical varicocele without contralateral clinical or subclinical varicocele and observed in 1 patient. Of 17 patients with follow-up, 3 (17.6%) progressed to clinical varicocele without asymmetric testicular volume, as most remained subclinical or resolved without surgery. In our experience, subclinical varicoceles appeared unlikely to progress to clinical varicoceles, to affect testicular volume, or to lead to surgery. Although our study is limited in numbers and follow-up, this information may aid clinical management strategies and guide future prospective studies.

Children's experience with daytime and nighttime urinary incontinence - A qualitative exploration.

BACKGROUND: Much of our knowledge about the impact of urinary incontinence (UI) on children is derived from surveys. While these studies provide an overview of the UI experience, personal interviews may offer additional nuances and a more detailed perspective of what the experience of UI is for children. Objective To conduct interviews and use qualitative analysis to explore the experiences of children with UI, with a particular focus on (1) the impact of UI on participants' lives, (2) which coping strategies children with UI use, and (3) the emotional effects of UI. STUDY DESIGN: Semi-structured interviews of children with non-neurogenic and non-anatomic UI recruited from a pediatric urology clinic were audio recorded and verbatim transcribed. Eligibility included: age 8-17 years, history of UI, English fluency, and being able to participate in a 30 min interview. Conventional content analysis was performed to identify themes directly from the transcripts. Coders independently and iteratively coded transcripts (intercoder reliability >0.85) until inductive thematic saturation was achieved. RESULTS: There were substantial practical and emotional impacts on the 30 (14 males, 16 females) children (median age 11.5 years) with UI. Participants relayed significant interference with social activities like sports and sleepovers, which often lead to avoidant behavior of these activities. By contrast, most stated that UI did not impair school performance. The most strongly and consistently expressed emotions were embarrassment and anxiety. Nevertheless, children described a wide variety of adaptations, including behavioral and cognitive, to manage their incontinence and its effects on their lives (Summary Table). DISCUSSION: This is the first qualitative study that describes the experiences and perspectives of children with UI. Surveys of this population suggest a lower health-related quality of life, particularly in emotional well-being, self-esteem and relationships. This work augments this body of literature and shows how UI interferes with their daily life and is a major source of embarrassment and anxiety. Despite this, children with UI display strong resilience and adapt to their condition. The study was limited in that the sample was biased to those presenting to a urology clinic and was not designed to compare differences in UI experience between ages, genders, or treatment types. CONCLUSION: This study, the first qualitative exploration of the emotional responses and coping behaviors of children with UI, shows significant social impact and negative emotional responses but marked resiliency. These findings should be considered when developing a comprehensive treatment strategy for children with UI.

Atrial invasion and showering phenomenon in primary lung cancer: A case report.

Advanced lung cancer can have numerous extra-pulmonary complications. Due to the proximity to the heart, cardiac invasion and the subsequent seeding of the tumor into the vascular system present numerous challenges in physician team care coordination. Here we have a 55-year-old male who presented with stroke symptoms in the setting of undiagnosed advanced lung cancer complicated by direct tumor invasion into the left atria and mixed embolic showering phenomenon and thrombotic hypercoagulability. Review of both the embolic showering phenomenon and hypercoagulability will be discussed as both can result in embolic occlusion or metastatic seeding at distant sites. Fewer than ten cases of spontaneous tumor embolization resulting from lung cancer invasion of the pulmonary vein have been reported. Poor prognosis of advanced lung cancer requires delicate, yet pragmatic conversations between care teams and the patient.

Characterizing Patients with Recurrent Urinary Tract Infections in Vesicoureteral Reflux: A Pilot Study of the Urinary Proteome.

Recurrent urinary tract infections (UTIs) pose a significant burden on the health care system. Underlying mechanisms predisposing children to UTIs and associated changes in the urinary proteome are not well understood. We aimed to investigate the urinary proteome of a subset of children who have vesicoureteral reflux (VUR) and recurrent UTIs because of their risk of developing infection-related renal damage. Improving diagnostic modalities to identify UTI risk factors would significantly alter the clinical management of children with VUR. We profiled the urinary proteomes of 22 VUR patients with low grade VUR (1-3 out of 5), a history of recurrent UTIs, and renal scarring, comparing them to those obtained from 22 age-matched controls. Urinary proteins were analyzed by mass spectrometry followed by protein quantitation based on spectral counting. Of the 2,551 proteins identified across both cohorts, 964 were robustly quantified, as defined by meeting criteria with spectral count (SC) ≥2 in at least 7 patients in either VUR or control cohort. Eighty proteins had differential expression between the two cohorts, with 44 proteins significantly up-regulated and 36 downregulated (q <0.075, FC ≥1.2). Urinary proteins involved in inflammation, acute phase response (APR), modulation of extracellular matrix (ECM), and carbohydrate metabolism were altered among the study cohort.

Accuracy of orchidometry in boys with varicocele.

INTRODUCTION: Orchidometric evaluation of the testis has been proposed as a cost-effective alternative to measurement of the testis with high-frequency linear ultrasound, which may be costly in terms of hospital resources and patient time. It is known from animal experiments, autopsy series, and small clinical studies that, under ideal conditions, orchidometry may approximate ultrasound measurement. However, little is known of the effectiveness of orchidometry in the clinical setting in a large sample of adolescents with varicocele. OBJECTIVE: We sought to analyze the performance characteristics of Rochester orchidometry and its agreement with ultrasound testis volumes in boys with varicocele. STUDY DESIGN: Our institutional varicocele database was analyzed from March 2000 to May 2013, including all boys with Rochester orchidometric measurement and ultrasound-based volume measurement performed on the same day. The Lambert formula (L*W*H*0.71) was used to calculate ultrasound volumes. Seven-hundred and twenty measurements were included: 360 of the left testis, and 360 of the right testis. Each subject was included once; in the event of serial measurements the earliest measurement was analyzed. Bland-Altman plots with 95% limits of agreement were used to compare orchidometry and ultrasound measurements. Analysis was performed with JMP, v11 Pro. RESULTS: Age at exam ranged from 11.2 to 18.5 years (median 15.8). With respect to varicocele grade, 183 (50.8%) were grade III, 113 (31.4%) were grade II, 42 (11.7%) were grade I, 12 (0.3%) were bilateral, and 10 (0.3%) were ungraded. Mean ultrasound left testis volume was 13.6 cc (SD 6.6) and mean right testis volume was 15.1 cc (SD 6.9). Eleven surgeons performed the orchidometric measurements; one surgeon performed 71% of the exams. Mean overestimation on the right was 2.0 cc (SD 4.2) and on the left was 1.9 cc (SD 4.1); each was highly statistically significant (p < 0.0001, paired t test). Error was correlated with testis size, implying a greater degree of overestimation with increasing volume (p < 0.01, Pearson's correlation 0.09). Amount of volume overestimation and variability was not significantly different for right and left testis. Sensitivity and specificity of Rochester orchidometry to detect a testis volume differential (TVD) of 20% were 33% (95% CI 23-42%) and 96% (95% CI 92-97%), respectively. Testis size, varicocele grade, or examining surgeon had no effect on sensitivity or specificity. DISCUSSION: We have shown in a large series of boys with adolescent varicocele that in clinical practice there is a modest degree of overestimation of testis volume on average (1.9-2.0 cc), although there is a large range of volume estimation, such that the 95% confidence interval ranges are quite wide, from approximately 6 cc lower than the true volume to 10 cc greater than the true volume. Furthermore, the low sensitivity (33%) of orchidometry for 20% testis volume differential renders this a suboptimal screening tool for this clinical parameter, which has been shown to be associated with semen analysis outcomes. Knowledge of the performance characteristics of orchidometry is similarly important for research, as factors such as the prevalence of testis volume differential are then dependent on the modality of measurement. Lastly, that this was conducted over a long time course with several surgeons involved suggests that these data reflect real-world application of orchidometry. CONCLUSIONS: Appropriate caution should be exercised when relying solely on orchidometric evaluation of the testis. Rochester orchidometry in general appears to overestimate testis size, and there is wide variability in the estimation. In clinical practice, the sensitivity of Rochester orchidometry is modest in detecting a 20% testis volume differential; this difference would be missed in approximately two out of three of boys screened with orchidometry alone.

Semen parameters in adolescents with varicocele: association with testis volume differential and total testis volume.

PURPOSE: We evaluated the relationship between testicular volume differential, total testis volume and total motile sperm count in adolescents with varicocele. Prior reports have been inconclusive regarding the association of testis volume with semen analysis parameters. MATERIALS AND METHODS: We retrospectively reviewed a single institution database of Tanner 5 adolescents with nonoperated left varicocele with at least 1 semen analysis available. Patients were included in analysis if they had clinical left varicocele, ultrasound measurement of testis volume and no prior inguinal or scrotal surgery. RESULTS: We analyzed the records of 100 patients. Mean ± SD age at presentation was 15.2 ± 3.5 years. The mean testicular volume differential was 8% ± 23% and 31 patients (31%) had a greater than 20% testicular volume differential. Mean total testis volume was 30.4 ± 13.3 cc. Varicocele was grade 3 in 39 patients, grade 2 in 50, grade 1 in 8 and ungraded in 3. Median total motile sperm count in the cohort was 42.0 (IQR 9.2, 105.8). ROC analysis with the Youden index indicated an optimal total testis volume cutoff of 30 cc to predict the total motile sperm count. In a multivariable logistic model accounting for age and varicocele grade a testicular volume differential of greater than 20% was associated with twice the odds of a total motile sperm count of less than 20 million per cc (OR 2.1, 95% CI 1.02-4.12, p = 0.04). Total testis volume less than 30 cc more than quadrupled the odds of a total motile sperm count of less than 20 million per cc (OR 4.2, 95% CI 1.8-9.7, p <0.001). CONCLUSIONS: Total testis volume and the testicular volume differential are associated with semen analysis outcomes in adolescents with varicocele. A testicular volume differential of greater than 20% doubles the odds of a low total motile sperm count. A total testis volume of less than 30 cc quadruples the odds of a low total motile sperm count.

Lymphangiogenesis and metastasis--a closer look at the neuropilin/semaphorin3 axis.

Metastasis is the leading cause of cancer-related deaths. Understanding how the lymphatic system responds to its environment and local stimuli may lead to therapies to combat metastasis and other lymphatic-associated diseases. This review compares lymphatic vessels and blood vessels, discusses markers of lymphatic vasculature, and elucidates some of the signaling motifs involved in lymphangiogenesis. Recent progress implicating the neuropilin and semaphorin axes in this process is discussed.

Identification of genes regulating migration and invasion using a new model of metastatic prostate cancer.

BACKGROUND: Understanding the complex, multistep process of metastasis remains a major challenge in cancer research. Metastasis models can reveal insights in tumor development and progression and provide tools to test new intervention strategies. METHODS: To develop a new cancer metastasis model, we used DU145 human prostate cancer cells and performed repeated rounds of orthotopic prostate injection and selection of subsequent lymph node metastases. Tumor growth, metastasis, cell migration and invasion were analyzed. Microarray analysis was used to identify cell migration- and cancer-related genes correlating with metastasis. Selected genes were silenced using siRNA, and their roles in cell migration and invasion were determined in transwell migration and Matrigel invasion assays. RESULTS: Our in vivo cycling strategy created cell lines with dramatically increased tumorigenesis and increased ability to colonize lymph nodes (DU145LN1-LN4). Prostate tumor xenografts displayed increased vascularization, enlarged podoplanin-positive lymphatic vessels and invasive margins. Microarray analysis revealed gene expression profiles that correlated with metastatic potential. Using gene network analysis we selected 3 significantly upregulated cell movement and cancer related genes for further analysis: EPCAM (epithelial cell adhesion molecule), ITGB4 (integrin ß4) and PLAU (urokinase-type plasminogen activator (uPA)). These genes all showed increased protein expression in the more metastatic DU145-LN4 cells compared to the parental DU145. SiRNA knockdown of EpCAM, integrin-ß4 or uPA all significantly reduced cell migration in DU145-LN4 cells. In contrast, only uPA siRNA inhibited cell invasion into Matrigel. This role of uPA in cell invasion was confirmed using the uPA inhibitors, amiloride and UK122. CONCLUSIONS: Our approach has identified genes required for the migration and invasion of metastatic tumor cells, and we propose that our new in vivo model system will be a powerful tool to interrogate the metastatic cascade in prostate cancer.