17-α-Estradiol Has Sex-Specific Effects on Neuroinflammation That Are Partly Reversed by Gonadectomy.

17-α-Estradiol (17aE2) treatment from 4 months of age extends life span in male mice and can reduce neuroinflammatory responses in the hypothalamus of 12-month-old males. Although 17aE2 improves longevity in males, female mice are unaffected, suggesting a sexually dimorphic pattern of life-span regulation. We tested whether the sex-specific effects of 17aE2 on neuroinflammatory responses are affected by gonadal removal and whether hypothalamic changes extend to other brain regions in old age. We show that sex-specific effects of 17aE2 on age-associated gliosis are brain region specific and are partially dependent on gonadectomy. 17aE2 treatment started at 4 months of age protected 25-month-old males from hypothalamic inflammation. Castration before 17aE2 exposure reduced the effect of 17aE2 on hypothalamic astrogliosis in males. In contrast, sex-specific inhibition of microgliosis generated by 17aE2 was not significantly affected by castration. In the hippocampus, gonadectomy influenced the severity of gliosis and the responsiveness to 17aE2 in a region-dependent manner. The male-specific effects of 17aE2 correlate with increases in hypothalamic estrogen receptor alpha expression, specifically in gonadally intact males, consistent with the idea that 17aE2 might act through this receptor. Our results indicate that neuroinflammatory responses to 17aE2 are partially controlled by the presence of sex-specific gonads. Loss of gonadal function and age-associated neuroinflammation could, therefore, influence late-life health and disease onset, leading to sexual dimorphism in both aging and in response to drugs that modify the pace of aging.

Tratamiento hormonal de la pedofilia: ¿puede curar la pedofilia con la castración química? / Pedophilia hormonal therapy: can pedophilia be cured with chemical castration

Históricamente la sociedad ha rechazado el abuso sexual de menores de 13 años, dictándose leyes al respecto. La justicia luego de un debido proceso condenaba al victimario con reclusión incluso hasta la década del 70-80, con orquiectomía. Los adelantos en neurobiología, endocrinología, sicofarmacología y sicología se consideraron las bases para tratar al pedófilo y someterlo a libertad condicional, ahorrándose el costo financiero de la reclusión de por vida. Diversos países dictaron leyes contra la conducta pedófila. En dicha legislación ejerció gran influencia la promulgación en EE.UU. (estado de Washington "sobre el ofensor sexual" y el dictamen de la Corte Suprema en 1997 en el juicio de Kansas vs Hendricks). En Chile en los 90 el caso del pedófilo apodado "Zacarach" sacó a la luz pública el tema que no se quería ver. En esa fecha se presentó al parlamento un proyecto de Ley para "curar" la pedofilia con acetato de Medroxiprogesterona imitando legislación de EE.UU. Causó sorpresa en el medio endocrinológico que se usara terapia hormonal como "cura" de la pedofilia. Se ha utilizado en varios países la castración química producida por gestágenos o agonístas del GnRH más antiandrógenos (acetato de Ciproterona), para inhibir la secreción y acción de la testosterona disminuyendo líbido y erección. No se ha demostrado que exista curación de la orientación pedófila y existen dudas de la prevención primaria y secundaria de la pedofilia. Pese al adelanto tecnológico en neurociencias para estudio de las zonas vinculadas a la sexualidad, aún no existen marcadores que permitan diagnosticar o pronosticar futuros resultados de la terapia. El tratamiento médico de la pedofilia no garantiza curación ni prevención del delito pedofílico.

Historically, society has rejected sexual abuse of children under 13, with there having been laws enacted in this regard. The judicial system, after a due process, condemned the perpetrator with reclusion and even up until the decades of the 70s and 80s with orchiectomy. Advances in neurobiology, endocrinology, psychopharmacology and psychology were considered the basis for treating the pedophile and putting them on probation, saving the financial cost of imprisonment for life. Multiple countries have enacted laws against pedophilic behaviour. Such legislation was greatly influenced by the enactment in the USA (state of Washington "on the sex offender" and the ruling of the Supreme Court in 1997 in the trial of Kansas against Hendricks). In Chile in the 90s, the case of a pedophile nicknamed "Zacarach" brought to light an issue that nobody wanted to see. Around that time, a bill was presented to Parliament to try and "cure" pedophilia with Medroxyprogesterone acetate, imitating US legislation. It was a surprise in the endocrinological world that hormonal therapy would be used as a "cure" for pedophilia. Chemical castration produced by gestagens or GnRH agonists plus antiandrogens (Cyproterone acetate) has been used in several countries to inhibit the secretion and action of testosterone, reducing libido and erection. It has not been proven that there is a cure for pedophile orientation and there are doubts about the primary and secondary prevention of pedophilia. Despite technological advances in neurosciences for the study of the zones pertaining to sexuality, there are still no indicators that allow for diagnosis or prediction of future results of therapy. The medical treatment of pedophilia does not guarantee cure or prevention of pedophilic crime.

Circulating miRNome of Trachemys scripta after elective gonadectomy under general anesthesia.

Post-surgical management is an important issue in veterinary medicine, requiring biomarkers with high sensitivity and specificity for timely and effective treatment. Emerging evidence suggests that miRNAs are promising stress- and pain-related markers. The aims were to profile the circulating miRNA signature in plasma of turtles (Trachemys scripta) and point out potential candidate biomarkers to assess the status of the animal. The plasma of female turtles underwent surgical gonadectomy were collected 24 h pre-surgery, and 2.5 h and 36 h post-surgery. The expression of miRNAs was profiled by Next Generation Sequencing and the dysregulated miRNAs were validated using RT-qPCR. The diagnostic value of miRNAs was calculated by ROC curves. The results showed that 14 miRNAs were differentially expressed over time. RT-qPCR validation highlighted that 2-miR-499-3p and miR-203-5p-out of 8 miRNAs tested were effectively modulated. The Area Under the Curve (AUC) of miR-203-5p was fair (AUC 0.7934) in discriminating pre- and 36 h post-surgery samples and poor for other time points; the AUC of miR-499-3p was excellent (AUC 0.944) in discriminating pre-surgery and 2.5 h post-surgery samples, and fair in discriminating pre-surgery and 36 h post-surgery (AUC 0.7292) and 2.5 h and 36 h post-surgery (AUC 0.7569) samples. In conclusion, we demonstrated for the first time that miRNAs profile changes in plasma of turtles underwent surgical oophorectomy and identified miR-203-5p and miR-499-3p as potential candidate biomarkers to assess animals' status. Further studies are necessary to confirm their diagnostic value and to investigate functional and mechanistic networks to improve our understanding of the biological processes.

MYBL2 disrupts the Hippo-YAP pathway and confers castration resistance and metastatic potential in prostate cancer.

Rationale: Resistance to androgen-deprivation therapy (ADT) associated with metastatic progression remains a challenging clinical task in prostate cancer (PCa) treatment. Current targeted therapies for castration-resistant prostate cancer (CRPC) are not durable. The exact molecular mechanisms mediating resistance to castration therapy that lead to CRPC progression remain obscure. Methods: The expression of MYB proto-oncogene like 2 (MYBL2) was evaluated in PCa samples. The effect of MYBL2 on the response to ADT was determined by in vitro and in vivo experiments. The survival of patients with PCa was analyzed using clinical specimens (n = 132) and data from The Cancer Genome Atlas (n = 450). The mechanistic model of MYBL2 in regulating gene expression was further detected by subcellular fractionation, western blotting, quantitative real-time PCR, chromatin immunoprecipitation, and luciferase reporter assays. Results: MYBL2 expression was significantly upregulated in CRPC tissues and cell lines. Overexpression of MYBL2 could facilitate castration-resistant growth and metastatic capacity in androgen-dependent PCa cells by promoting YAP1 transcriptional activity via modulating the activity of the Rho GTPases RhoA and LATS1 kinase. Importantly, targeting MYBL2, or treatment with either the YAP/TAZ inhibitor Verteporfin or the RhoA inhibitor Simvastatin, reversed the resistance to ADT and blocked bone metastasis in CRPC cells. Finally, high MYBL2 levels were positively associated with TNM stage, total PSA level, and Gleason score and predicted a higher risk of metastatic relapse and poor prognosis in patients with PCa. Conclusions: Our results reveal a novel molecular mechanism conferring resistance to ADT and provide a strong rationale for potential therapeutic strategies against CRPC.

Prophylactic gonadectomy in 46 XY females; why, where and when?

OBJECTIVES: We compared cases of phenotypic female patients who presented with male karyotype and underwent prophylactic gonadectomy. CASE PRESENTATION: Five patients with female phenotypes presented in early adulthood with primary amenorrhoea with varying degrees of puberty. One was tall with breast development. Another was very short with clitoromegaly and multiple co-morbidities. The other three had no secondary sexual characteristics. They were examined, after which hormonal profile, karyotyping, ultrasound examination and magnetic resonance imaging were done to assess the site of gonads. Gonadectomy was performed once their 46 XY karyotype was confirmed. Results of histopathological examination of their gonads ranged from dysgenetic gonads to having testicular tissues and malignancy. CONCLUSION: Female patients with 46 XY karyotypes require prophylactic gonadectomy performed at different timings depending on diagnosis due to the malignancy risk. Pre-operative assessment is essential to locate the gonads prior to surgery.

Impact of Medical Castration on Malignant Arrhythmias in Patients With Prostate Cancer.

Background Medical castration, gonadotropin-releasing hormone agonists, and antiandrogens have been widely applied as a treatment for prostate cancer. Sex steroid hormones influence cardiac ion channels. However, few studies have examined the proarrhythmic properties of medical castration. Methods and Results This study included 149 patients who underwent medical castration using gonadotropin-releasing hormones with/without antiandrogen for prostate cancer. The changes in the ECG findings during the therapy and associations of the electrocardiographic findings with malignant arrhythmias were studied. The QT and corrected QT (QTc) intervals prolonged during the therapy compared with baseline (QT, 394±32 to 406±39 ms [P<0.001]; QTc, 416±27 to 439±31 ms [P<0.001]). The QTc interval was prolonged in 119 (79.9%) patients during the therapy compared with baseline. In 2 (1.3%) patients who had no structural heart disease, torsade de pointes (TdP) and ventricular fibrillation (VF) occurred ≥6 months after starting the therapy. In patients with TdP/VF, the increase in the QTc interval from the pretreatment value was >80 ms. However, in patients without TdP/VF, the prevalence of an increase in the QTc interval from the pretreatment value of >50 ms was 11%, and an increase in the QTc interval from the pretreatment value >80 ms was found in only 4 (3%) patients. Conclusions Medical castration prolongs the QT/QTc intervals in most patients with prostate cancer, and it could cause TdP/VFs even in patients with no risk of QT prolongation before the therapy. An increase in the QTc interval from the pretreatment value >50 ms might become a predictor of TdP/VF. Much attention should be paid to the QTc interval throughout all periods of medical castration to prevent malignant arrhythmias.

Castration aggravates insulin resistance, reduces immune function and improves quality of life of prostate cancer patients.

PURPOSE: To investigate the influence of castration on insulin resistance, quality of life and immune function of prostate cancer (PCa) patients. METHODS: A total of 57 PCa patients definitely diagnosed via prostate biopsy underwent bilateral orchiectomy. No patient had history of diabetes mellitus before operation. The hemoglobin, leukocyte count, platelet count, albumin and alkaline phosphatase in the blood before operation and at 1 year after operation were analyzed using a full-automatic biochemistry analyzer, and the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) in the peripheral blood were calculated. RESULTS: The levels of serum testosterone (T) and free testosterone (FT) in PCa patients declined remarkably at 1 month after castration. Compared with those before operation, the levels of serum T and FT were decreased significantly at 1, 2, 4 and 8 months as well as 1 year after castration. The levels of triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were elevated gradually with the prolongation of time after operation. The level of high-density lipoprotein cholesterol (HDL-C) displayed an apparent rising trend from 2 months after surgical castration. The results of flow cytometry indicated that the levels of cluster of differentiation (CD) 4+ and CD4+/CD8+ were lowered markedly, while that of CD8+ was raised significantly in comparison with those before castration (p<0.05) After castration, both fasting blood glucose and fasting insulin were increased obviously in the patients (p<0.05). The 2 h postprandial blood glucose and insulin were raised distinctly at 1 month after castration (p<0.05). The insulin resistance index was increased persistently and prominently (p<0.05). CONCLUSION: The treatment of PCa through castration can aggravate the insulin resistance, reduce the immune function and improve the patient quality of life.

Seminoma In A Young Phenotypic Female With Turner Syndrome 45,XO/46,XY Mosaicism: A Case Report With Review Of The Literature.

Turner syndrome is a chromosomal disorder that occurs in an estimated 1 in 2500 female live births. It is estimated that 6%-12% of all Turner syndrome patients will be a mosaic with Y-chromosomal elements putting them at risk for gonadoblastoma and subsequent dysgerminoma. While 30%-50% of this population demonstrate gonadoblastoma, we only found 23 reported cases of dysgerminoma in the literature, and no reported cases of seminoma. We present the first case of seminoma in a phenotypic Turner 15-year-old female after prophylactic gonadectomy.

Variation of Gonadal Dysgenesis and Tumor Risk in Patients With 45,X/46,XY Mosaicism.

OBJECTIVE: To describe the gonadal features of patients with 45,X/46,XY mosaicism, and to evaluate the prevalence of gonadal tumor in different phenotypes. MATERIALS AND METHODS: The medical records of consecutive patients with 45,X/46,XY karyotype or its variants who had undergone gonadal biopsy or gonadectomy at a single institute between 1996 and 2017 were retrospectively reviewed. RESULTS: Of 34 patients with 45,X/46,XY mosaicism, a unilateral dysgenetic testis and a contralateral streak gonad was detected in 20 patients (59%), bilateral streak gonads in 9 (26%), and bilateral dysgenetic testes in 5 (15%). A gonad composed of both streak and dysgenetic testicular portions was observed in 7 gonads of 6 patients. All streak gonads were removed, and bilateral gonadectomy was performed in 15 patients raised as girls. Pathologic examination revealed gonadal tumors in 6 of the 34 (18%) patients, including a gonadoblastoma in 7 gonads among 5 patients and an association of dysgerminoma with gonadoblastoma in 1 gonad. All 6 patients who developed gonadal tumor had female genitalia. Postoperative course was uneventful except 1 boy. A seminoma was developed in his soritaly scrotal testis at the age of 16 years. CONCLUSION: The prevalence of gonadal tumor in patients with 45,X/46,XY mosaicism may vary according to the phenotype, and high in patients with female phenotype. Considering the increased risk of gonadal tumors in such patients, early investigation and individual management, including prophylactic gonadectomy, are recommended. In male patients, a close follow-up of the preserved testes is mandatory until adulthood.

Extragonadal Steroids Contribute Significantly to Androgen Receptor Activity and Development of Castration Resistance in Recurrent Prostate Cancer after Primary Therapy.

PURPOSE: Beyond testosterone, several steroids contribute to the activation of the androgen receptor pathway, but their relative contributions to the activation of the androgen receptor signaling axis in patients with castrated prostate cancer remain unknown. MATERIALS AND METHODS: Serum levels of 9 steroids were measured by mass spectrometry from continuously castrated patients of the PR.7 study (219) and from the PCA24 cohort (116). For each steroid standard curves for dose dependent prostate specific antigen promoter activation were built in castration sensitive (LAPC4) and resistant (VCaP) prostate cancer models. Standard curves were used to determine the androgen receptor activation potency for each steroid measurement from patients in these trials. RESULTS: In LAPC4 and VCaP cells testosterone, dihydrotestosterone and androstenedione induced androgen receptor transcriptional activity, while dehydroepiandrosterone, 5alpha-androstan-3beta,17beta-diol, androstenediol and androsterone stimulated androgen receptor only in VCaP cells. Extragonadal steroids were responsible for 34% (LAPC4) and 88% (VCaP) of the serum total androgen receptor transcriptional activity found in castrated cases. The total androgen receptor transcriptional activity secondary to testosterone, dihydrotestosterone and androstenedione was associated with time to castration resistance in patients from the PR.7 study (HR 2.17, 95% CI 1.12-4.23, p=0.02) in multivariate analysis using the castration sensitive model (LAPC4). Androgen receptor transcriptional activity of extragonadal androstenedione was the only steroid statistically associated with time to castration resistance in univariate analysis (HR 1.89, 95% CI 1.04-3.44, p=0.036). CONCLUSIONS: Extragonadal steroids contribute significantly to the androgen receptor axis activation at castration levels of testosterone in recurrent nonmetastatic prostate cancer and these sustain the development of castration resistance after primary local treatment.

Prepubertal gonadectomy reveals sex differences in approach-avoidance behavior in adult mice.

Adolescence is a developmental period that is associated with physical, cognitive, and affective maturation and a time when sex biases in multiple psychiatric diseases emerge. While puberty onset marks the initiation of adolescence, it is unclear whether the pubertal rise in gonadal hormones generates sex differences in approach-avoidance behaviors that may impact psychiatric vulnerability. To examine the influence of pubertal development on adult behavior, we removed the gonads or performed sham surgery in male and female mice just prior to puberty onset and assessed performance in an odor-guided foraging task and anxiety-related behaviors in adulthood. We observed no significant sex differences in foraging or anxiety-related behaviors between intact adult male and female mice but found significant differences between adult male and female mice that had been gonadectomized (GDX) prior to puberty onset. GDX males failed to acquire the odor-guided foraging task, showed reduced locomotion, and exhibited increased anxiety-like behavior, while GDX females showed the opposite pattern of behavior. These data suggest that puberty may minimize rather than drive differences in approach-avoidance phenotypes in male and female mice.

Surgical versus Medical Castration for Metastatic Prostate Cancer: Use and Overall Survival in a National Cohort.

PURPOSE: Surgical castration for metastatic prostate cancer is used less frequently than medical castration yet costs less, requires less followup and may be associated with fewer adverse effects. We evaluated temporal trends and factors associated with the use of surgical castration. MATERIALS AND METHODS: This retrospective cohort study sampled 24,805 men with newly diagnosed (de novo) metastatic prostate cancer from a national cancer registry in the United States (2004 to 2016). Multivariable logistic regression assessed the association between sociodemographic factors and surgery. Multivariable Cox regression evaluated the association between castration type and overall survival. RESULTS: Overall 5.4% of men underwent surgical castration. This figure decreased from 8.5% in 2004 to 3.5% in 2016 (per year later OR 0.89, 95% CI 0.87-0.91, p <0.001). Compared to Medicare, private insurance was associated with less surgery (OR 0.73, 95% CI 0.61-0.87, p <0.001) while Medicaid or no insurance was associated with more surgery (OR 1.68, 95% CI 1.34-2.11, p <0.001 and OR 2.12, 95% CI 1.58-2.85, p <0.001, respectively). Regional median income greater than $63,000 was associated with less surgery (vs income less than $38,000 OR 0.61, 95% CI 0.43-0.85, p=0.004). After a median followup of 30 months castration type was not associated with differences in survival (surgical vs medical HR 1.02, 95% CI 0.95-1.09, p=0.6). CONCLUSIONS: In a contemporary, real-world cohort surgical castration use is low and decreasing despite its potential advantages and similar survival rate compared to medical castration. Men with potentially limited health care access undergo more surgery, perhaps reflecting a provider bias toward the perceived benefit of permanent castration.

In vivo magnetic resonance imaging reveals the effect of gonadal hormones on morphological and functional brain sexual dimorphisms in adult sheep.

Sex differences in the brain and behavior are produced by the perinatal action of testosterone, which is converted into estradiol by the enzyme aromatase in the brain. Although magnetic resonance imaging (MRI) has been widely used in humans to study these differences, the use of animal models, where hormonal status can be properly manipulated, is necessary to explore the mechanisms involved. We used sheep, a recognized model in the field of neuroendocrinology, to assess brain morphological and functional sex differences and their regulation by adult gonadal hormones. To this end, we performed voxel-based morphometry and a resting-state functional MRI approach to assess sex differences in gonadally intact animals. We demonstrated significant sex differences in gray matter concentration (GMC) at the level of the gonadotropic axis, i.e., not only within the hypothalamus and pituitary but also within the hippocampus and the amygdala of intact animals. We then performed the same analysis one month after gonadectomy and found that some of these differences were reduced, especially in the hypothalamus and amygdala. By contrast, we found few differences in the organization of the functional connectome between males and females either before or after gonadectomy. As a whole, our study identifies brain regions that are sexually dimorphic in the sheep brain at the resolution of the MRI and highlights the role of gonadal hormones in the maintenance of these differences.

First clinical experiences with a high field 1.5 T MR linac.

Purpose: A 1.5 T MR Linac (MRL) has recently become available. MRL treatment workflows (WF) include online plan adaptation based on daily MR images (MRI). This study reports initial clinical experiences after five months of use in terms of patient compliance, cases, WF timings, and dosimetric accuracy. Method and materials: Two different WF were used dependent on the clinical situation of the day; Adapt To Position WF (ATP) where the reference plan position is adjusted rigidly to match the position of the targets and the OARs, and Adapt To Shape WF (ATS), where a new plan is created to match the anatomy of the day, using deformable image registration. Both WFs included three 3D MRI scans for plan adaptation, verification before beam on, and validation during IMRT delivery. Patient compliance and WF timings were recorded. Accuracy in dose delivery was assessed using a cylindrical diode phantom. Results: Nineteen patients have completed their treatment receiving a total of 176 fractions. Cases vary from prostate treatments (60Gy/20F) to SBRT treatments of lymph nodes (45 Gy/3F) and castration by ovarian irradiation (15 Gy/3F). The median session time (patient in to patient out) for 127 ATPs was 26 (21-78) min, four fractions lasted more than 45 min due to additional plan adaptation. For the 49 ATSs a median time of 12 (1-24) min was used for contouring resulting in a total median session time of 42 (29-91) min. Three SBRT fractions lasted more than an hour. The time on the MRL couch was well tolerated by the patients. The median gamma pass rate (2 mm,2% global max) for the adapted plans was 99.2 (93.4-100)%, showing good agreement between planned and delivered dose. Conclusion: MRL treatments, including daily MRIs, plan adaptation, and accurate dose delivery, are possible within a clinically acceptable timeframe and well tolerated by the patients.

Use of infrared thermography to evaluate the inflammatory reaction in cat testis after intratesticular injection of 0. 9% NaCl or 20% CaCl2 with 1% lidocaine / O uso da termografia infravermelha para avaliar a reação inflamatória após a injeção intratesticular de NaCL 0, 9 % e cloreto de cálcio 20% com lidocaína 1%

Due to the doubts and questions about the inflammatory reaction caused by chemical castration, this study aimed to use infrared thermography to detect, evaluate and monitor the inflammatory reaction caused by the intratesticular injection of calcium chloride (CaCl2) 20% with lidocaine 1%. For this, thermographic measurements were taken before (M0), 10 minutes (M1), 1 and 6 hours (M2 and M3), for 7 consecutive days (M4 to M10), at 15 (M11), 30 (M12) and 60 (M13) days after intratesticular injection. Additionally, changes to testicular tissue and effects over spermatogenesis were evaluated by andrological exam before (M0) and 60 days (M13) after intratesticular injection. All cats were orchiectomized at M13, and testicles were submitted to histological analysis. CaCl2 (20%) with lidocaine (1%) administration produced testicular tissue damage and interfered with the spermatogenesis in 70% of treated cats without exacerbating the inflammatory reaction or impairing the cat's welfare. It was concluded that thermographic evaluation is a useful, efficient, easy and quick method to diagnose and monitor cat testicular inflammatory reactions.(AU)

Devido a constantes dúvidas e questionamentos sobre a reação inflamatória ocasionada pela castração química, este estudo objetivou o uso da termografia infravermelha para detectar, avaliar e monitorar a reação inflamatória causada pela injeção intratesticular de cloreto de cálcio (CaCl 2 ) 20% associada à lidocaína 1%. Para isso, medidas termográficas foram aferidas antes (M0), 10 minutos (M1), uma e seis horas (M2 e M3), por sete dias consecutivos (M4 a M10), aos 15 (M11), 30 (M12), e 60 (M13) dias após injeção intratesticular, nos grupos tratado e controle. Todos os gatos foram orquiectomizados no M13, e os testículos submetidos à análise histológica. A injeção CaCl 2 a 20% associada com lidocaína a 1% produziu lesão testicular e interferiu na espermatogênese de 70% dos gatos tratados, sem exacerbar a reação inflamatória ou prejudicar o bem-estar do animal. Foi concluído que a avaliação termográfica é uma ferramenta útil, eficiente, rápida e fácil para o diagnóstico e o monitoramento da reação inflamatória em gatos.(AU)

Laparoscopic Bilateral Gonadectomy and Inguinal Hernia Repair with Mesh for Complete Androgen Insensitivity Syndrome: A Case Report.

BACKGROUND: Complete androgen insensitivity (CAIS) is a difference of sex development, in which there is complete androgen receptor resistance, leading to a female phenotype, despite the presence of normal testes. There is a recognized risk of testicular germ cell tumor in adulthood as high as 15%, and gonadectomy is usually performed in late adolescence or early adulthood. CASE: A 20-year-old patient, with a known diagnosis of CAIS since the age of 16, underwent magnetic resonance imaging of the pelvis, which revealed the testes lying deep into the inguinal canal. The patient was explored laparoscopically and using the technique of transabdominal preperitoneal hernia repair both testes were successfully reduced into the peritoneal cavity and resected. In addition, the defect of the internal inguinal ring was covered and reinforced using a prosthetic polypropylene mesh. SUMMARY AND CONCLUSION: Minimally invasive gonadectomy is feasible even for gonads situated deep into the inguinal canal. Established benefits of laparoscopic surgery such as reduced postoperative pain, rapid recovery, aesthetically small incisions, and early return to normal activities are very important for CAIS patients. Multidisciplinary team work, among gynecologists and general surgeons, provides excellent results in these complex cases.

Revisiting Intermittent Therapy in Metastatic Prostate Cancer: Can Less Be More in the "New World Order"?

CONTEXT: Androgen deprivation therapy (ADT) is the standard of care for men with metastatic hormone-sensitive prostate cancer (HSPC) and a potential treatment option in those with prostate-specific antigen relapse after local therapy. Based on promising biological and preclinical data, several clinical trials compared the efficacy of intermittent androgen deprivation (IAD) versus continuous androgen deprivation (CAD) with the objective of delaying disease progression and improving survival and quality of life (QoL). OBJECTIVE: The objective of this review is to revisit the concept of IAD in the "new world order" and reconsider whether it has a potential clinical role in an era where we have seen unprecedented progress in the management of patients with metastatic HSPC. EVIDENCE ACQUISITION: MEDLINE, Embase, and the Cochrane Library databases were searched for randomized controlled trials comparing IAD and CAD therapies. References of retrieved articles were also searched. Articles with at least 100 randomized patients, which were published in 2008 or later and had data on overall survival or QoL outcomes, were included. EVIDENCE SYNTHESIS: The evidence to date cannot exclude inferiority of IAD compared with CAD with respect to survival outcomes. The hazard ratios in metastatic disease indicate less favorable survival with IAD. No superiority trial conclusively favored IAD or CAD. Two trials demonstrated noninferiority of IAD, although the noninferiority margins (NIMs) are clinically concerning. Another trial could not exclude noninferiority. A modest but temporary QoL and symptom benefit generally favoring IAD was observed. CONCLUSIONS: IAD has not conclusively demonstrated an impact on disease progression or survival, and has only modest effects on QoL and symptoms measured in the short term. As such, it is not the standard of care, particularly in the era where we have seen unprecedented survival impact with combination ADT+docetaxel or abiraterone +prednisone. IAD may need to be reassessed in the context of current therapies, ideally driven by biological rationale, with the goal of minimizing physical and financial toxicities with appropriately designed informative clinical trials. PATIENT SUMMARY: In this report, we looked at two hormone therapy approaches for prostate cancer that is still sensitive to castration: one with treatment breaks and one without. Patients may tolerate therapy with breaks more easily, but this effect is not sustained and is not associated with better longevity. The best longevity is seen in patients who receive newer hormone therapies or chemotherapy in addition to continuous hormone therapy. Whether these newer therapies would be as effective if given intermittently is an important but unanswered question.

Complications associated with closed castration using the Henderson equine castration instrument in 300 standing equids.

OBJECTIVE: To describe a closed castration technique in standing equids, report associated complications, and identify potential risk factors. STUDY DESIGN: Prospective cohort study of 300 standing equids that were castrated with the Henderson Equine Castrating Instrument. METHODS: Thirteen participating veterinarians recorded intraoperative difficulties and postoperative complications. Descriptive statistics, univariate analyses with Fisher's exact tests, and logistic regressions were used to evaluate intraoperative difficulties and postoperative complications and to assess risk factors for postoperative complications. RESULTS: Data were collected on 300 equids (269 horses, 23 ponies, and 8 donkeys). Intraoperative difficulties were experienced in 39 of 300 (13%) procedures. Postoperative complications were reported in 69 of 300 (23%) equids, including excessive swelling (29, 9.67%), surgical site infection (SSI; 27, 9%), severe hemorrhage (3, 1%), and prolapse of the omentum (2, 0.64%). Donkeys were at increased risk of severe hemorrhage (2/8, 25%, P = .0019). Equids that were castrated in a hospital setting (83/300, 27.66%) more frequently developed excessive swelling (P = .0034, odds ratio [OR] = 3.20) and SSI (P = .0047, OR = 3.18) compared with equids that were castrated in a field setting (217/300, 72.33%). Prolonging antimicrobial prophylaxis or age of the equid at the time of castration had no effect on the prevalence of excessive swelling or SSI. CONCLUSION: The method of castration evaluated here resulted in a similar prevalence of postoperative complications to that previously reported for castrations in standing horses but fewer SSI. CLINICAL SIGNIFICANCE: The described method provides a viable option for castrating horses and ponies, but is not recommended in donkeys.

Medical Castration is a Rare but Possible Trigger of Torsade de Pointes and Ventricular Fibrillation.

Prostate cancer is the most common non-cutaneous malignancy in men and has been steadily rising in an aging society. Medical castration therapy is effective for metastatic prostate cancer, but the proarrhythmic properties have not been reported. We present a 71-year-old Japanese man with metastasis prostate cancer that, during medical castration therapy, had torsades de pointes (TdP) with a QT prolongation and ventricular fibrillation (VF). His QT interval diminished after discontinuing the medical castration, and he developed no further VF recurrences for 15 months. Medical castration is a rare but possible trigger of TdP with QT prolongation and VF.