Prolactin promotes a partial recovery from the atrophy of both male and female gerbil prostates caused by castration.

BACKGROUND: The male and female prostates are controlled by steroid hormones, suffering important morphological and physiological changes after castration. Prolactin is involved in the regulation of the male prostate, having already been identified in the tissue, acting through its receptor PRLR. In the Mongolian gerbil, in addition to the male prostate, the female prostate is also well developed and active in its secretion processes. The aim of the present study was to evaluate the effects of exposure to exogenous prolactin in the prostate of both intact and castrated male and female gerbils in order to establish if prolactin administration can sustain prostate cell activity in conditions of sexual hormone deprivation. METHODS: The morphological analyses were performed by biometric analysis, lesion histological analysis and morphometric-stereological aspects. In addition, immune-cytochemical tests were performed for prolactin and its receptor, as well as for the receptors of androgen and oestrogen and serum prolactin dosage. All data were submitted to ANOVA or Kruskal-Wallis tests for comparison between groups. P < 0.05 was considered to be statistically significant. RESULTS: The results showed a strong influence of prolactin on the morphology of the prostate, with the development of important epithelial alterations, after only 3 days of administration, and an expressive epithelial cell discard process after 30 days of administration. Prolactin acts in synergy with testosterone in males and mainly with oestrogens in females, establishing different steroid hormonal receptor immunoreactivity according to sex. It was also demonstrated that prolactin can assist in the recovery from some atrophic effects caused in the gland after castration, without causing additional tissue damage. CONCLUSIONS: The prolactin and its receptor are involved in the maintenance of the homeostasis of male and female gerbils, and also cause distinct histological alterations after exogenous exposure for 3 and 30 days. The effects of prolactin are related to its joint action on androgens and oestrogens and it can also assist in the recovery from the atrophic effects of castration.

Contemporary Trends in Presentation and Management of Spermatocytic Seminoma.

OBJECTIVE: To characterize the presentation and management of spermatocytic seminoma (SS) compared to classic seminoma in adults utilizing a large cancer registry. METHODS: Patients >18 years of age in the National Cancer Database from 2006 to 2016 who underwent orchiectomy for testicular tumors were identified. Demographics, oncologic characteristics, and treatment patterns were compared between patients with SS and classic seminoma. RESULTS: Of 53,481 adults receiving orchiectomy, 29,208 were diagnosed with classic seminoma and 299 (1%) with SS. Compared to patients with classic seminoma, SS patients were older (57 vs 39 years) and more likely to be African-American (odds ratio (OR) 1.8) and insured by Medicare (OR 2.0; all P <.05). SS patients had larger tumors on presentation (3-6 cm: OR 1.8; >6 cm: OR 1.8), but were less likely to have ≥pT2 stage (OR 0.5), regional nodal involvement (Clinical Stage II: OR 0.3), or distant metastatic disease (Clinical Stage III: OR 0.1; all P <.01). For postorchiectomy management, 73.6% of SS patients underwent surveillance while 24.5% had active treatment (retroperitoneal lymph node dissection, chemotherapy, radiation, or a combination). When stratified by year, there was an increasing trend toward surveillance compared to active treatment. CONCLUSION: SS is a rare germ cell tumor that typically presents as a larger tumor in older patients. Although these tumors are less likely to be characterized by advanced disease compared to classic seminoma, many patients have undergone aggressive postorchiectomy treatment in the past. Importantly, treatment trends have shifted toward surveillance in recent years with adjuvant therapy limited primarily to higher stage tumors.

A combination of an antioxidant with a prebiotic exerts greater efficacy than either as a monotherapy on cognitive improvement in castrated-obese male rats.

Previous studies by ourselves and others have demonstrated that both obesity and testosterone deprivation have been related to cognitive decline. We have also shown that a prebiotic and n-acetyl cysteine (NAC) improved cognitive dysfunction in obese rats and castrated-male rats. However, the effects of NAC, a prebiotic (inulin), and a combination of the two on cognition in castrated-obese rats has never been investigated. The hypothesis was that NAC and inulin attenuated cognitive decline in castrated-obese rats by improving gut dysbiosis, and decreasing oxidative stress, glial activation and apoptosis. Male Wistar rats (n = 36) were fed with either a normal diet (ND: n = 6) or a high-fat diet (HFD: n = 30) for twenty-eight weeks. The resultant obese rats had a bilateral orchiectomy (ORX) and were randomly divided into five subgroups (n = 6/ subgroup). Each subgroup was treated with one of five therapies: a vehicle; testosterone replacement (2 mg/kg/day); NAC (100 mg/kg); inulin (10%, w/w), or a combination of the NAC and inulin for four weeks. The results demonstrated that castrated-obese rats developed gut dysbiosis, metabolic disturbance, brain pathologies, and cognitive decline. All of the pathological conditions in the brain were ameliorated to an equal extent by testosterone replacement, NAC, and inulin supplementation. Interestingly, a combination of NAC and inulin had the greatest beneficial effect on cognitive function by synergistically reducing hippocampal inflammation and ameliorating glial dysmorphology. These findings suggest that a combination of NAC and inulin may confer the greatest benefits in improving cognitive function in castrated-obese male rats.

Utilization and Outcomes of Surgical Castration in Comparison to Medical Castration in Metastatic Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT) is the gold standard for metastatic prostate cancer, which can be achieved either by surgical or medical castration. In this study, we evaluated the trends of utilization of surgical castration and also assess the survival differences of patients who underwent surgical castration when compared with those who underwent medical castration. MATERIALS AND METHODS: The National Cancer Database was used to identify patients with metastatic prostate cancer from 2004 to 2014. Cochran-Armitage tests were used to assess temporal trends in the proportion of patients receiving surgical castration relative to medical castration. Logistic and Cox regression models were utilized to estimate the odds of utilization of surgical castration and the effect of castration on overall survival (OS). RESULTS: A total of 33,585 patients with metastatic prostate cancer were identified; 31,600 (94.1%) had medical castration, and 1985 (5.9%) underwent surgical castration. There was significant decline in the trend of utilization of surgical castration from 8.6% in 2004 to 3.1% in 2014. On multivariable analysis, being of a non-Caucasian race, having lower median income levels, having non-private insurance, and earlier years of diagnosis were found to be associated with increased odds of choosing surgical castration over medical castration. Notably, the odds of surgical castration were lower at academic centers. On univariable analysis, a survival difference between castration modality was evidenced (P < .01); 5-year OS for medical castration and surgical castration were 24.3% and 18.2%, respectively. However, on multivariable analysis, there was no OS difference between surgical castration and medical castration (P = .13). CONCLUSIONS: In this large contemporary analysis, the utilization of surgical castration has declined over time, with no OS difference when compared with medical castration. Increasing the utilization of surgical castration could help reduce health care expenditures. With rising health care costs, patients and physicians need to be aware of treatment options and their financial implications.

Vortioxetine reverses medial prefrontal cortex-mediated cognitive deficits in male rats induced by castration as a model of androgen deprivation therapy for prostate cancer.

RATIONALE: Androgen deprivation therapy (ADT) is an effective treatment for prostate cancer, but induces profound cognitive impairment. Little research has addressed mechanisms underlying these deficits or potential treatments. This is an unmet need to improve quality of life for prostate cancer survivors. OBJECTIVES: We investigated mechanisms of cognitive impairment after ADT in rats and potential utility of the multimodal serotonin-targeting drug, vortioxetine, to improve the impairment, as vortioxetine has specific efficacy against cognitive impairment in depression. METHODS: Male Sprague-Dawley rats were surgically castrated. Vortioxetine (28 mg/kg/day) was administered in the diet. The attentional set-shifting test was used to assess medial prefrontal cortex (mPFC) executive function. Afferent-evoked field potentials were recorded in the mPFC of anesthetized rats after stimulating the ventral hippocampus (vHipp) or medial dorsal thalamus (MDT). Gene expression changes were assessed by microarray. Effects of vortioxetine on growth of prostate cancer cells were assessed in vitro. RESULTS: ADT impaired cognitive set shifting and attenuated responses evoked in the mPFC by the vHipp afferent, but not the MDT. Both the cognitive impairment and attenuated vHipp-evoked responses were reversed by chronic vortioxetine treatment. Preliminary investigation of gene expression in the mPFC indicates that factors involved in neuronal plasticity and synaptic transmission were down-regulated by castration and up-regulated by vortioxetine in castrated animals. Vortioxetine neither altered the growth of prostate cancer cells in vitro nor interfered with the antiproliferative effects of the androgen antagonist, enzalutamide. CONCLUSIONS: These results suggest that vortioxetine may be useful in mitigating cognitive impairment associated with ADT for prostate cancer.

Pediatric testicular torsion: does patient transfer affect time to intervention or surgical outcomes at a rural tertiary care center?

BACKGROUND: Testicular torsion (TT) is a urologic emergency that requires prompt surgical intervention. In rural Appalachia, patients are often transferred from surrounding communities due to lack of urologic care. We hypothesized that those transferred would have delayed intervention and higher rates of orchiectomy when compared to those who presented directly to our hospital. METHODS: We performed a retrospective review of patient charts with an ICD-9 diagnosis of TT from 2008 to 2016. Patients met inclusion criteria if diagnosis was confirmed by operative exploration. We compared rate of testicular loss and time until surgical intervention between groups. RESULTS: Twenty-three patients met inclusion criteria (12 transferred, 11 direct). Patient demographics did not significantly differ between groups. Transferred patients had a higher orchiectomy rate (33% v 22%,p = 0.41) although this was not statistically significant. Time to surgery from symptom onset was significantly longer in those transferred (12.9 h) compared to those not transferred (6.9 h, p = 0.02). Distance of transfer was not correlated with time of delay (r2 = 0.063). CONCLUSIONS: Transferred patients with TT have numerically higher rates of orchiectomy which may reach significance in an appropriately powered study, and relative delays in surgical intervention. This study highlights the need for improved access to urologic care in rural areas.

Investigating the effect of testosterone by itself and in combination with letrozole on 1,25-dihydroxy vitamin D and FGF23 in male rats.

BACKGROUND: Testosterone deficiency might be associated with vitamin D levels in hypogonadal men, but it is not clear whether testosterone can affect vitamin D and fibroblast growth factor-23 (FGF23), either directly or indirectly via aromatization to estradiol. We aimed to investigate the role of testosterone on vitamin D metabolism and serum FGF23 in male rats. METHODS: A total of 48 male rats were divided into 4 equal groups: sham; O, orchiectomy; O + T, orchiectomized rats treated with testosterone; and O + T + L, orchiectomized rats treated with combination of testosterone and letrozole. We compare the vitamin D metabolism biochemical parameters in these four groups, before and after the study. RESULTS: We detected a significant reduction in 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (DBP), FGF23, and 1,25-dihydroxyvitamin D (1,25(OH)2D) serum level in O group compared to sham group (p = 0.004, p = 0.009, p < 0.001 and p < 0.001, respectively), and a significant increase in serum phosphorus, parathyroid hormone (PTH), and alkaline phosphatase (ALP) levels in orchiectomized rats in comparison to sham group (p < 0.001, p = 0.022, and p = 0.006, respectively). However, these changes were corrected by testosterone replacement in O + T and O + T + L groups. In addition, we found that DBP and 1,25(OH)2D serum levels were significantly higher in O + T group in comparison to O + T + L group (p = 0.030 and p = 0.026, respectively). CONCLUSIONS: Testosterone plays a significant role on regulating 25(OH)D, DBP, FGF23, phosphate (Phos), PTH, and 1,25(OH)2D serum levels in male rats. Also, testosterone has a potent effect on 1,25(OH)2D and DBP by its conversion to estradiol.

Omega-3 fatty acids decrease prostate cancer progression associated with an anti-tumor immune response in eugonadal and castrated mice.

BACKGROUND: Several lines of evidence suggest effects of dietary fat on prostate cancer (PCa) development and progression. Targeting omega (ω)-3:ω6 fatty acids (FA) ratio could be beneficial against PCa by favorably modulating inflammation. Here, we studied the effects of ω3- and ω6-enriched diets on prostate tumor growth and inflammatory response in androgen-deprived and non-deprived conditions. METHODS: Immune-competent eugonadal and castrated C57BL/6 mice were injected with TRAMP-C2 prostate tumor cells and daily fed with ω3- or ω6-enriched diet. FA and cytokine profiles were measured in blood and tumors using gas chromatography and multiplex immunoassay, respectively. Immune cell infiltration in tumors was profiled by multicolor flow cytometry. RESULTS: ω3-enriched diet decreased prostate TRAMP-C2 tumor growth in immune-competent eugonadal and castrated mice. Cytokines associated with Th1 immune response (IL-12 [p70], IFN-γ, GM-CSF) and eosinophil recruitment (eotaxin-1, IL-5, and IL-13) were significantly elevated in tumors of ω3-fed mice. Using in vitro experiments, we confirmed ω3 FA-induced eotaxin-1 secretion by tumor cells and that eotaxin-1 secretion was regulated by androgens. Analysis of immune cell infiltrating tumors showed no major difference of immune cells' abundance between ω3- and ω6-enriched diets. CONCLUSIONS: ω3-enriched diet reduces prostate tumor growth independently of androgen levels. ω3 FA can inhibit tumor cell growth and induce a local anti-tumor inflammatory response. These findings warrant further examination of dietary ω3's potential to slow down the progression of androgen-sensitive and castrate-resistant PCa by modulating immune cell function in tumors.

Work-up and treatment of prostate cancer before and after publication of the first national guidelines on prostate cancer care in Sweden.

BACKGROUND AND OBJECTIVES: In 2007, the Swedish National Board of Health and Welfare published the first Swedish guidelines on prostate cancer (PCa) to improve care and decrease geographical and social inequalities. The aim of this analysis was to assess how these guidelines affected PCa care. MATERIALS AND METHODS: Work-up and treatment for men diagnosed with PCa between 1998 and 2014 were assessed by use of data in the Prostate Cancer data Base Sweden (PCBaSe) with information from the National Prostate Cancer Register (NPCR) and other healthcare registries and demographic databases. RESULTS: Overall, there were modest improvements in the performance for 14 selected quality indicators, with some notable exceptions. There was a strong increase in the use of active surveillance for very low-risk PCa, up from 56% in 2009 to 92% in 2014, and use of bone imaging for high-risk PCa up from 50% in 2008 to 77% in 2014. There were large differences in work-up and treatment of PCa between healthcare providers with modest decreases over time. The differences between counties were larger than differences according to socioeconomic status with one exception: use of curative treatment for high-risk PCa was more common in men with high income, highest versus lowest tertile, OR 2.74 (95% CI, 1.85-4.06). CONCLUSION: The modest improvements in PCa care after the publications of national guidelines indicate that if these are to make an impact on care, feedback to each point of care on their performance as well as local quality improvement programs implementing the guidelines are needed.

Phospholipase C signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized mice.

BACKGROUND: The age-related osteoporosis is an increasing risk severely threatening the live quality of aged people. Human parathyroid hormone (hPTH) is applied to the therapy of osteoporosis successfully, however, the mechanism, especially the signaling pathway activated in the healing fracture by PTH is still unknown. METHODS: The once daily injections of hPTH(1-34) and GR (1-34) (the PLC deficient analog) into the orchiectomized male mice with bone fracture, were started at the second day after fracture and lasted for 4 weeks. To explore the role of phospholipase C signaling in the androgen-deficient fracture healing, the fracture healing were evaluated via radiography, micro-CT, biomechanics testing, serum biochemistry, bone marrow cell culture and gene expression quantification. RESULTS: After two weeks of fracture, both peptides significantly increased bone mineral density (BMD), bone mass content (BMC) and bone volume (BV/TV) in the healing area. However, compared to hPTH(1-34), GR(1-34) induced more woven bones, the higher BMC and BMD, as well as the less serum TRAP and osteoclasts. After four weeks of treatment, the effects of hPTH(1-34) on fracture healing showed no difference to those of GR(1-34). Consistently, GR(1-34) induced the similar osteogenesis but less osteoclastogenesis under the ex vivo condition immediately after administration compared to hPTH(1-34), which was verified by the weaker activation of RANKL, NFATC1, TRAP and Cathepsin K in GR(1-34) treatment. CONCLUSION: These results indicated that the PLC signaling activated by the intermittent injection of hPTH(1-34) leads to the bone resorption by rapidly activating the osteoclastogenesis in the fracture healing zone.

Update on epidemiologic considerations and treatment trends in testicular cancer.

PURPOSE OF REVIEW: We aim to give an overview of the epidemiology and treatment trends of testicular germ cell tumors (TGCTs), with an emphasis on recent trends. RECENT FINDINGS: The incidence of TGCT appears to be increasing, particularly in developed countries, although the reasons are not well understood. There is evidence of racial differences in predisposition to TGCT, with white men having highest risk and men of African or Asian descent having lower risk. In the United States, the incidence of TGCT among Hispanics appears to be rising most quickly. A recent genomic analysis indicates there is no highly penetrant major TGCT susceptibility gene. Incorporation of multidisciplinary care has led to excellent long-term cure rates; however, access to care and insurance remains barriers in young men. Recent treatment trends have centered on maximizing oncologic outcomes while minimizing long-term morbidity. SUMMARY: Emerging population-level data provide critical insight into the evolving demographics of TGCT, which may allow for elucidation of biologic and environmental determinants of TGCT. Further, identification of socioeconomic barriers to excellent clinical outcomes will allow for targeted interventions to patients with unique demographic and socioeconomic considerations. Treatment trend analyses suggest that the field is moving toward minimizing treatment-related morbidity.

[Non-palpable testicular tumors in adults: A management based on imaging? Issue from the French Urologic Association Genital Cancer committee's edit]. / Tumeurs testiculaires non palpables chez l'adulte : vers une prise en charge guidée par l'imagerie ? Une mise au point du Groupe organe génitaux externes du comité de cancérologie de l'Association française d'urologie.

BACKGROUND: Help in management of non-palpable testicular tumors. French Urologic Association Genital cancer committee's Edit. OBJECTIVES: To review their characterization at imaging findings of non-palpable testicular tumors. DOCUMENTARY SOURCES: Literature review (PubMed, Medline) of urological and radiological studies dealing with testicular tumors using keywords: non-palpable/incidental testicular tumors; color Doppler ultrasound; US elastography; magnetic resonance imaging; contrast enhanced sonography; partial surgery. RESULTS: Color Doppler is the basic exam. The size, the presence of microlithts/microlithiasis/macrocalcifications, the vascular architecture are major semiological findings to suggest the benign or the malignant nature of the lesion. Other techniques like multiparametric MRI, contrast-enhanced sonography, sonographic elastography are still in evaluation. The frequency of benign tumors such as Leydig cell tumors lead to preservation management, through improved characterization, monitoring or tumorectomy. LIMITS: Non-randomized study - a very few prospective studies. CONCLUSION: The era of total orchiectomy for any uncertain testicular lesion is over. We try the challenge of characterization, and define management's algorithms based on the suspected nature of the tumors.

Soy Phytoestrogens Do Not Fully Reverse Changes in Rat Pituitary Castration Cells: Unbiased Stereological Study.

The aim of the study was to examine the potential of the principal soy isoflavones, genistein and daidzein, or isoflavone rich soy extract to recover pituitary castration cells in orchidectomized adult male rats in comparison with the effects of estradiol. Two weeks post orchidectomy (Orx), animals received estradiol-dipropionate, genistein, daidzein or soy extract subcutaneously for 3 weeks. Control sham-operated (So) and Orx rats received just the vehicle. Changes in the volumes of pars distalis, of individual follicle-stimulating hormone (FSH) and luteinizing hormone (LH) containing cells, their volume, numerical density and number were determined by unbiased design-based stereology. The intracellular content of ßFSH and ßLH was estimated by relative intensity of fluorescence (RIF). Orchidectomy increased all examined stereological parameters and RIF. Compared to Orx, estradiol increased the volume of pars distalis, but reversed RIF and all morphometric parameters of gonadotropes to the level of So rats, except their number. Treatments with purified isoflavones and soy extract decreased RIF to the control So level, expressing an estradiol-like effect. However, the histological appearance and morphometrical features of gonadotropes did not follow this pattern. Genistein increased the volume of pars distalis, decreased the volume density of LH-labeled cells and raised the number of gonadotropes. Daidzein decreased the cell volume of gonadotropic cells but increased their number and numerical density. Soy extract induced an increase in number and numerical density of FSH-containing cells. Therefore, it can be concluded that soy phytoestrogens do not fully reverse the Orx-induced changes in pituitary castration cells. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.

Tratamiento de tumores de células Leydig del testículo: ¿puede la cirugía conservadora de testículo reemplazar la orquiectomía radical? Resultados de una revisión sistemática / Treatment of leydig cell tumours of the testis: can testis-sparing surgery replace radical orchidectomy? Results of a systematic review

Introducción: El modelo de referencia para los tumores de células de Leydig todavía se considera la orquiectomía radical, pero la cirugía conservadora de testículo en conjunción con la congelación intraoperatoria de secciones ha sido recientemente tratada con resultados prometedores. Adquisición de evidencia: Se identificaron estudios mediante búsquedas en bases de datos electrónicas y exploración de las listas de referencias de los artículos. Se llevó a cabo una búsqueda bibliográfica que abarca el período comprendido entre enero de 1980 a diciembre 2012 mediante las bases de datos PubMed/MEDLINE y EMBASE. Se consideraron las búsquedas adicionales a mano de las listas de referencias de los estudios incluidos, opiniones, metaanálisis y guías sobre el manejo quirúrgico de TCL de los testículos. Síntesis de evidencia: El presente análisis se basa en un total de 13 estudios que cumplían con los criterios de inclusión predefinidos. Un total de 247 participantes se incluyeron en los 13 estudios examinados en esta revisión sistemática. Ciento cuarenta y cinco fueron tratados con orquiectomía radical y 102 con TSS. En el grupo de cirugía radical 7 estudios informaron del seguimiento de los pacientes que va desde 6 a 249 meses. En el grupo de TSS 10 estudios informaron del seguimiento de los pacientes que va desde 6 a 192 meses. La congelación de secciones se realizó en un total de 96 pacientes. La sensibilidad fue del 87,5%. Ninguno de los pacientes tratados con TSS presentó una recurrencia metastásica, mientras que en los pacientes tratados con orquiectomía radical 3 pacientes presentaron recurrencia metastásica. Nuestro análisis añade información completa a las recientes directrices internacionales, que es altamente recomendable realizar un procedimiento de preservación de órganos en cada lesión intraparenquimatosa pequeña. Conclusiones: Los resultados confirman el curso favorable de TCL tratados con TSS. Los resultados obtenidos son alentadores y el concepto es atractivo para convertirse en el tratamiento estándar en todos los pacientes, y no solo en las personas afectadas por la (sub) fertilidad o con testículo solitario

Introduction: The gold standard for Leydig cell tumours (LCTs) is still considered radical orchidectomy, but testis sparing surgery (TSS) in conjunction with intraoperative frozen section (FSE) has been recently attempted with promising results. Acquisition of evidence: Studies were identified by searching electronic databases. A bibliographic search covering the period from January 1980 to December 2012 was conducted using PubMed/MEDLINE and EMBASE database. Studies were excluded if they were single case reports, meeting abstracts and conference proceedings. Synthesis of evidence: The present analysis is based on a total of 13 studies that fulfilled the predefined inclusion criteria. A total of 247 participants were included in the 13 studies examined in this systematic review. 145 were treated with radical orchiectomy and 102 with TSS. In the radical surgery group, the follow-up varied from 6 to 249 months). In the TSS group, the follow-up varied from 6 to 192 months. Frozen section was performed in a total of 96 patients. Sensitivity was 87.5%. None of the patients treated with TSS presented a metastatic recurrence, while in patients treated with radical orchiectomy three patients presented with metastatic recurrence. In selected cases radical surgery appears excessive and the potential for a shift to TSS as the standard management is gathering momentum. Conclusions: The results confirm the favourable course of LCT treated with TSS. The results obtained are encouraging and the concept is attractive to become the standard therapy in all patients and not only in people affected by (sub)fertility or with solitary testis

Treatment patterns, testicular loss and disparities in inpatient surgical management of testicular torsion in boys: a population-based study 1998-2010.

OBJECTIVES: To examine temporal trends in inpatient testicular torsion (TT) treatment and testicular loss (TL), and to identify risk factors for TL using a large nationally representative paediatric cohort, stratified to established high prevalence TT cohorts (neonatal TT [NTT]; age <1 years) and adolescent TT (ATT; age 12-17 years). METHODS: Boys (age ≤17 years, n = 17 478) undergoing surgical exploration for TT were identified within the Nationwide Inpatient Sample (1998-2010). Temporal trends in inpatient TT management (salvage surgery vs orchiectomy) and TL were examined using estimated annual percent change methodology. Multivariable logistic regression models were used to identify risk factors for TL. RESULTS: Teaching hospitals treated 90% of boys with NTT, compared with 55% with ATT (P < 0.001). Of boys with NTT, 85% lost their testis, compared with 35% with ATT (P < 0.001). Inpatient management of NTT declined during the study period, from 7.5/100 000 children in 1998 to 3/100 000 in 2010 (estimated annual percent change -4.95%; P < 0.001). The decrease was similar but less dramatic in ATT. TL patterns did not improve. In adjusted analyses, for NTT, orchiectomy was more likely at teaching hospitals. For ATT, orchiectomy was more likely in children with comorbidities (odds ratio 5.42; P = 0.045), Medicaid coverage or self-pay (P < 0.05) and weekday presentation (P = 0.001). Regional or racial disposition was not associated with TL. CONCLUSIONS: There has been a gradual decrease in inpatient surgical treatment for both NTT and ATT, presumably as a result of increased outpatient and/or non-operative management of these children. Concerningly, TL patterns have not improved; targeted interventions such as parental and adolescent male health education may lead to timely recognition/intervention in children at-risk for ATT. We noted no regional/racial disparities in contrast to earlier studies.

Patterns of androgen deprivation therapies among men diagnosed with localised prostate cancer: a population-based study.

AIM: Many men diagnosed with localised prostate cancer will eventually be treated with androgen deprivation therapy (ADT). ADT is associated with adverse effects and its timing is controversial. Data on patterns of use are scarce. We describe patterns of ADT use, defined as castration (medical and surgical) or antiandrogen monotherapy initiated after primary treatment, in a population-based cohort. METHODS AND MATERIALS: Data were extracted from the population-based Prostate Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and 2009 with clinical stage T1-2, N0-NX, M0-MX and prostate specific antigen (PSA)<50ng/ml without primary ADT were included. Outcomes in the period 2006 through 2010 were analysed using a period analysis approach. RESULTS: The cumulative incidence of castration at 10years after diagnosis was 11.6% (95% confidence interval (CI), 11.0-12.2%). The corresponding proportion of antiandrogen monotherapy was 10.8% (95% CI, 10.2-11.4%). Castration was the dominant therapy among men on deferred treatment. The probability of receiving castration rather than antiandrogen monotherapy increased with age. Estimated median durations of castration ranged from 4years in the deferred treatment high-risk group to 17years in the prostatectomy low-risk group. The main limitation was the lack of information on progression to metastatic disease and PSA at the time for initiation of ADT. CONCLUSION: When initiated early after curative treatment, the duration of castration can be decades. The findings indicate that more accurate tools are necessary to guide which men should be selected for ADT as secondary treatment.

Impact of castration on changes in left ventricular diastolic pressure-volume relations induced by chronic adrenergic stimulation in rats.

A reduced testosterone concentration characterizes heart failure and independently predicts outcomes. Although testosterone replacement therapy may have non cardiac-related therapeutic benefits in heart failure, whether reduced testosterone concentrations protect against adverse left ventricular remodeling (LV dilatation) is uncertain. We therefore evaluated whether surgical castration modifies LV dilatation after 6 months of daily injections of the ß-adrenergic receptor (AR) agonist, isoproterenol (ISO) (0.015 mg·kg(-1)·d(-1)), to rats. The extent of LV dilatation and LV systolic chamber dysfunction were determined using both echocardiography and isolated perfused heart procedures. The extent of LV dilatation was determined from LV diastolic pressure-volume (P-V) relationships. As compared with the saline vehicle-treated group, after 6 months of ß-AR activation in sham-castrated rats, a marked right shift in the LV diastolic P-V relationship was noted with an increased LV volume intercept at 0 mm Hg diastolic pressure (LV V(0) in milliliters) (ISO = 0.38 ± 0.02, saline vehicle = 0.30 ± 0.02, P < 0.05). However, chronic ß-AR activation did not alter LV systolic chamber function either in vivo (LV endocardial fractional shortening, echocardiography) or ex vivo (LV end systolic elastance). Although castration decreased body weight, castration failed to modify the impact of ISO on the LV diastolic P-V relationships or the LV volume intercept at 0 mm Hg diastolic pressure (LV V(0) in milliliters) (castration ISO = 0.35 ± 0.02, castration saline vehicle = 0.27 ± 0.03, P < 0.05). In conclusion, castration does not influence the extent of LV dilatation induced by chronic adrenergic activation in an animal model, where adverse LV remodeling precedes LV systolic chamber dysfunction.

Experience with the treatment of testicular yolk sac tumor in children: a report of 14 cases.

OBJECTIVE: This paper discusses the optimal treatment for testicular yolk sac tumor at stage I in children. PATIENTS AND METHODS: Fourteen children with testicular yolk sac tumor (including 10 cases of stage I and 4 cases of stage II) underwent high ligation of internal spermatic cord vein and orchiectomy. Among these, seven cases of stage I were below 1 year of age. Retroperitoneal lymph node dissection without postoperative systemic chemotherapy was implemented in 9 cases (5 cases of stage I and 4 cases of stage II), and only one was positive. RESULTS: Among the 12 cases followed, 9 cases were alive (of these, 5 children < 1 year old, in stage I, underwent high ligation of internal spermatic cord vein and orchiectomy, with a survival time of 25 months to 10 years and 4 cases with radical retroperitoneal lymph node dissection). Three cases older than 1 year died of retroperitoneal lymph node and lung metastases. CONCLUSIONS: For the high ligation of internal spermatic cord vein, orchiectomy is a kind of simple and effective treatment for children younger than 1 year with stage I, without recurrence and metastases. However, attention to the accuracy of staging and close observation are important aspects of the treatment.