Surgical Castration Research Articles

Vortioxetine Reverses Impairment of Visuospatial Memory and Cognitive Flexibility Induced by Degarelix as a Model of Androgen Deprivation Therapy in Rats

Introduction: Androgen deprivation therapy (ADT) is a mainstay treatment for prostate cancer, but many patients experience cognitive impairment in domains mediated by the medial prefrontal cortex (mPFC) and hippocampus. Prostate cancer typically occurs in older patients (>65 years). As age is often accompanied by cognitive decline, it may impact the efficacy of any treatment aimed at restoring cognitive impairment induced by ADT. Vortioxetine, a multimodal antidepressant that improves cognition in depression, has been shown to be efficacious in elderly patients. Therefore, vortioxetine may improve cognition in older patients who experience cognitive decline after ADT. Methods: Young (3 months) and middle-aged (13 months) rats were used to investigate the influence of age on treating ADT-induced cognitive decline. As our previous studies used surgical castration, we tested if vortioxetine would reverse cognitive deficits associated with more translationally relevant chemical castration using degarelix. Vortioxetine was given in the diet for 21 days. Animals underwent behavioral testing to assess visuospatial memory mediated by the hippocampus and cognitive flexibility mediated by the mPFC. We also investigated changes in afferent-evoked responses in these regions in middle-aged rats. Results: Degarelix induced impairments in both visuospatial memory and cognitive flexibility that were reversed by vortioxetine. Vortioxetine also rescued afferent-evoked responses in the mPFC and hippocampus. However, modest age-related reductions in baseline visuospatial memory limited our ability to detect further decreases induced by degarelix in middle-aged rats due to a floor effect. Conclusion: These results suggest that vortioxetine may be a treatment option for older prostate cancer patients who experience cognitive decline after ADT.

The histomorphological appearance of the testes in Alloxan-induced diabetic rabbits

This study assessed the histomorphological changes in testicular tissues due to the experimental diabetes mellitus (DM) generated in rabbits with Alloxan. Twenty-four adult male rabbits were used and allocated randomly into two equal groups (n=12 of each). The first group served as a control group and received normal saline only. The second group (diabetic group) was injected with Alloxan at a 100mg/kg IP dose. The serum glucose level was estimated at (0 min), 3 days and then (1,2 and 3 months), by aspiration of a blood sample from the jugular vein mixed with anticoagulant (EDTA) to obtain serum. The testosterone hormone was assayed from the serum obtained by centrifugation of blood samples using a special kit. Testicular biopsies were harvested through surgical castration at (1,2, and 3 months) post-administration of Alloxan. Results displayed a marked increase in glucose levels in the diabetic group starting from day three till the end of the experiment, with high differences between the two groups. Moreover, testosterone levels significantly decreased in the diabetic group compared to the control group. Our histomorphological examination confirmed that Alloxan leads to testicular damage in rabbits, represented by testicular atrophy, necrosis focusing in spermatogenic cells and separation of germinal epithelium. In conclusion, the injection of Alloxan succeeded in inducing (DM) with clear alteration in studied parameters. . Key Words: Biochemical, Testicular Parameters, Alloxan, Rabbits.

Incidental discovery of seminoma after simple orchiectomy in transgender individuals: A case series

Introduction: Seminoma is a common malignancy reported in young, cisgender men. However, there is sparse literature describing cases of seminoma in the transgender and gender diverse patient population. Case Series: We present two cases of seminoma incidentally discovered after simple bilateral orchiectomy performed as part of genital gender affirming surgery. In both instances, patients had not reported any testicular firmness or abnormality prior to surgery. After a thorough literature review, only two other such cases have been reported. Herein, we discuss our two cases and their implications for surgical management of suspected testicular malignancy intraoperatively, a methodical inspection of testicles removed during gender affirming surgery and providing affirming care when navigating discussions of genitalia with transgender and gender diverse patients. Conclusion: Testicular malignancy such as seminoma may be found incidentally when transgender and gender diverse patients undergo genital gender affirming surgery. Thus, special attention is required to identify suspicious exam findings, adjust surgical techniques as indicated, and properly examine surgical specimens. As there is a significant paucity of literature surrounding testicular malignancies in the transgender and gender diverse patient population, it is crucial to continue to investigate how to provide affirming care in these situations.

Efficacy of Treatment for Metastatic Hormone-Sensitive Prostate Cancer: An Umbrella Review of Systematic Reviews and Meta-Analyses.

This umbrella review focused on evaluating the efficacy and adverse events of the metastatic hormone-sensitive prostate cancer patients receiving any treatment regimens, including ADT alone or combination treatments. This study conducted an umbrella review following the PRISMA 2020 checklist, aiming to summarize the available studies to evaluate the efficacy of medical treatments for metastatic hormone-sensitive prostate cancer. A literature search was performed to identify systematic reviews and meta-analyses (SRMAs) that included only randomized controlled trials (RCTs) up to September 2023. This study summarized their findings, evaluated overlapping data (i.e., the same RCTs were included in >one SRMA), tested for excessive significance (i.e., observed number of statistically significant studies > expected number by chance) and assessed the quality of the studies. A total of 4191 studies were identified, but only 27 were included. Among those 27 studies, 12 were network meta-analyses and 15 were direct meta-analyses. Most studies showed no statistically significant difference in overall mortality among GnRH agonists, antagonists and bilateral orchiectomy. Combination treatment is more beneficial than ADT alone in both OS and PFS outcomes with more adverse events. Nevertheless, there is no OS advantage of any combination regimen over the others. Combination treatments demonstrated clear benefits in OS and PFS over ADT alone with more AEs. Further studies are needed to compare among combination treatments.

Major adverse cardiovascular events of enzalutamide versus abiraterone in prostate cancer: a retrospective cohort study

BackgroundWhile the cardiovascular risks of androgen receptor pathway inhibitors have been studied, they were seldom compared directly. This study compares the risks of major adverse cardiovascular events (MACE) between enzalutamide and abiraterone among prostate cancer (PCa) patients.MethodsAdult PCa patients receiving either enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between 1 December 1999 and 31 March 2021 were identified in this retrospective cohort study. Patients who switched between enzalutamide and abiraterone, initiated abiraterone used without steroids, or experienced prior cardiac events were excluded. Patients were followed-up until 30 September 2021. The primary outcomes were MACE, a composite of stroke, myocardial infarction (MI), Heart failure (HF), or all-cause mortality and a composite of adverse cardiovascular events (CACE) not including all-cause mortality. The secondary outcomes were individual components of MACE. Inverse probability treatment weighting was used to balance covariates between treatment groups.ResultsIn total, 1015 patients were analyzed (456 enzalutamide users and 559 abiraterone users; mean age 70.6 ± 8.8 years old) over a median follow-up duration of 11.3 (IQR: 5.3–21.3) months. Enzalutamide users had significantly lower risks of 4P-MACE (weighted hazard ratio (wHR) 0.71 [95% confidence interval (CI) 0.59–0.86], p < 0.001) and CACE (wHR 0.63 [95% CI: 0.42–0.96], p = 0.031), which remained consistent in multivariable analysis. Such an association may be stronger in patients aged ≥65 years or without diabetes mellitus and was independent of bilateral orchidectomy. Enzalutamide users also had significantly lower risks of MI (wHR 0.57 [95% CI: 0.33–0.97], p = 0.040) and all-cause mortality (wHR 0.71 [95% CI: 0.59–0.85], p < 0.001).ConclusionEnzalutamide was associated with lower cardiovascular risks than abiraterone in PCa patients.

Scrotum Apocrine Adenocarcinoma Mimicking Testicular Cancer with Infiltration to the Scrotum: A Case Report with Literature Review

Apocrine carcinoma is a rare tumor of the skin that typically arises in areas rich in apocrine glands. In our report, a 64-year-old man came to the emergency department with a complaint of an enlarging, tender mass in the scrotum growing over the previous 3 months associated with discomfort. Tumor markers were checked, and elevation of lactate dehydrogenase (LDH) and beta-human chorionic gonadotropin (HCG) was found. The patient was initially diagnosed with testicular cancer with infiltration to the scrotum. Wide mass excision with bilateral orchidectomy was performed. Results from histopathological examination revealed an apocrine adenocarcinoma of the scrotum. We report a case of primary apocrine adenocarcinoma of the scrotum initially suspected as testicular cancer.

#205 : Pre-Orchidectomy Fertility Preservation in a Regional Queensland Centre - Patient Attitudes to Sperm Banking

Background and Aims: Fertility preservation for testicular cancer remains an essential part of the pre-operative radical orchidectomy discussion. In Australia, testicular cancer is estimated to account for 1.1% of all new male cancer diagnoses, with greater than 800 new cases a year diagnosed in Australia. Toowoomba Hospital and its urology service covers a large geographical area, extending from Toowoomba to the northern territory border. This poses both an access issue for both urological review and subsequent fertility interventions. Despite geographical barriers, pre-operative sperm banking (cryopreservation) remains generally recommended prior to operative intervention. The aim of this study was to investigate adherence to guidelines and identification of barriers or reasons for patients not wanting to engage with fertility preservation. Method: A retrospective analysis of patients undergoing a radical inguinal orchidectomy for the purposes of testicular cancer. Patient records were examined for discussion of fertility preservation and patient outcomes for attending a fertility-consultation. Results: Between 2016-2022, 54 patients underwent a radical orchidectomy at the Toowoomba Hospital. All patients pre-operatively had discussion surrounding fertility preservation and where patient accepted, referrals were made to the closest fertility provider. The majority of patients who refused pre-operative sperm banking had clear reasoning including completion of family. Conclusion: Fertility preservation discussions were part of all interactions pre-operatively where appropriate. Patient reasoning for declining preservation services were varied.

Testicular lymphoma: A case report

Primary testicular lymphoma (PTTL) is a rare and aggressive form of extraganglionic malignant non-Hodgkin's lymphoma (NML). It accounts for 1% of malignant non-Hodgkin's lymphomas, 2% of extranodal lymphomas and 5% of malignant testicular tumours. LTP is the most common form of testicular malignancy in men over 60. An enlarged inguinal orchiectomy should be performed for diagnostic and therapeutic purposes(1). Adjuvant treatment is based on systemic chemotherapy, administration of rituximab in the presence of CD20+ cells and intrathecal injection of methotrexate for neuro-meningeal prophylaxis. In this article, we report a case of testicular lymphoma in a 73-year-old patient who underwent inguinal orchiectomy followed by systemic and intrathecal CHOP chemotherapy.

Effects of Field Pea Diet and Immunocastration in Heavy Pigs on Fresh Pork and Dry-Cured Ham

Peas are an alternative to soybeans to supply protein in livestock feeds. Immunocastration avoids surgical castration of male pigs and increases fat deposition in female pigs. This work aimed to assess the effects of pea inclusion on the amount of fat and fatty acid profile of loins and on weight losses of dry-cured hams in different sexes of pigs; in addition, growth performance and feeding behavior in immunocastrated female pigs were evaluated. Two experiments were conducted with crossbred immunocastrated female (IF) and immunocastrated (IM) or surgically castrated (CM) male pigs from Duroc dams sired by Berkshire, which were assigned to one of two diets (soybean vs. pea-based). The effect of castration type on the afore-mentioned variables was evaluated in male pigs, and the growth performance, and feeding behavior in female pigs. The pea-based diet in IF had no effect on average daily gain nor on carcass traits; although, it increased feeding time (p &lt; 0.001) and reduced n-3 polyunsaturated fatty acid (PUFA) content (p &lt; 0.05). In male pigs, the pea-based diet did not change carcass fatness either but reduced the n-3 PUFA levels (p &lt; 0.05). Likewise, IM had lower (p &lt; 0.001) monounsaturated fatty acid (MUFA) and higher (p &lt; 0.05) n-6 PUFA than CM. Diet did not affect dry-cured ham weight losses during the process, while IM showed greater (p &lt; 0.001) losses than CM. Pigs fed a pea-based diet complied with the requirements of cured ham production, while immunocastration in male pigs increased weight losses, partly explained by lower fat content and higher fatty acid unsaturation.

Surgical versus medical castration in the treatment of metastatic prostate cancer: A systematic review and meta-analysis

Introduction: Metastatic disease is found in up to 20% of prostate cancer (PCa) cases at diagnosis. Since their introduction in the 1980s, long acting gonadotropin-releasing hormone (GnRH) analogues, administered subcutaneously or intramuscularly every 1–6 months have widely replaced bilateral orchidectomy as the method of castration for this cohort of patients. Recent evidence suggests that surgical castration confers a superior side-effect profile and cost. We aimed to perform a systematic review and meta-analysis to compare these two treatment methods particularly in terms of survival, side-effect profile and cost-effectiveness. Methods: A systematic review of the literature was performed for studies comparing medical and surgical castration for metastatic PCa. Outcome measurements included overall survival, side-effect profile and cost. Results: Fifteen studies on 63,682 participants ( n = 59,045 for medical and n = 4637 for surgical) met inclusion criteria. Our analysis demonstrated a trend towards significance in overall survival rates in favour of surgical castration (hazard ratio = 0.89, 95% confidence interval (CI) = 0.79 to 1.01, p = 0.06), a trend towards significance in cardiovascular complications in favour of the surgical group (odds ratio (OR) = 0.79, 95% CI = 0.62 to 1.00, p = 0.05) and a significantly lower nadir prostate-specific antigen (PSA) level in favour of medical castration (MD PSA 1.17 less in medical castration group, 95% CI = 0.67 to 1.67, p &lt; 0.01). Conclusion: Surgical castration appears to be a safe, feasible and efficacious alternative to medical castration, with evidence to suggest a potential survival benefit and limited evidence of a financial benefit in the treatment of men with metastatic PCa. Further studies are required to further quantify the financial burden of one method over another, as well as to identify which subgroup of patients respond best to each method of castration. Level of evidence: Level 1

Treatment results of Para-Testicular Rhabdomyosarcoma (PT-RMS) using radiation as an alternative to retro-peritoneal nodal dissection: A single Institution experience.

Para-testicular Rhabdomyosarcoma (PT-RMS) has a favorable treatment outcome adopting multidisciplinary management; resection, namely high inguinal orchiectomy ± retro-peritoneal lymph node dissection (RPLND) followed by standard or intensive chemotherapy ± adjuvant radiation therapy. This is a retrospective study including all patients with pathologically proven PT-RMS, presented to the National Cancer Institute, Cairo University, during the period from 2005 to 2020. Endpoints included overall survival, disease free survival and patterns of failure of different treatment modalities. Forty one patients were identified. Median age in our cohort was 15 years (range: 2-54 years). After a median follow up of 26 months (range, 3-75 months) ,two and five years OS were 100% and 91.7% respectively and median survival was not reached. Patients who underwent retro-peritoneal nodal dissection had a 5-year DFS rate of 100% versus 73% for those who received radiation to para-aortic nodes (p = 0.185). Limitations include retrospective nature and deviation from COG protocol. This study shows promising results suggesting that less aggressive local treatment modalities including radiation to para-aortic chain could be an option in PT-RMS, given the excellent results of this subtype. However further validation in a prospective study is warranted.

External beam radiotherapy in treatment of high-volume metastatic hormone-sensitive prostate cancer: clinical case

The standard treatment for metastatic hormone-sensitive prostate cancer does not include external beam radiotherapy (EBRT) and radionuclide therapy with radium-223.The article describes a clinical case of successful use of EBRT and radionuclide therapy with radium-223 in a patient with primary high-volume metastatic hormone-sensitive prostate cancer.The patient received diagnosis of prostate cancer сT3bN1M1b (Gleason score 8 (4 + 4)), stage IV (metastases in the bones, extraperitoneal and intrathoracic lymph nodes; prostate specific antigen (PSA) level was 4280 ng/mL). Between October of 2017 and January of 2018, the patient received 6 cycles of chemohormonal therapy (degarelix + docetaxel). Bilateral orchiectomy was performed on 05.02.2018, and the patient underwent palliative EBRT on cervical vertebrae between 04.10.2017 and 19.10.2017 with total dose of 32.6 Gy (equivalent to 38.5 Gy). The patient received systemic radiotherapy with one injection of samarium oxabifor (153Sm) 40 mCi (21.03.2018) and radium-223 (4 injections once a month (17.04.2018, 15.05.2018, 14.06.2018, 10.07.2018) + 2 injections 1 time per 3 months (October 2018, January 2019)). Partial response was achieved in the form of PSA decrease from 4280 ng/mL (September 2017) to 0.505 ng/mL (May 2019). Palliative EBRT for the prostate and pelvis was performed between 14.11.2018 and 19.12.2018 for total dose of 62.5 Gy (equivalent to 69 Gy). For 2 years remission was observed with PSA level of 0.3–0.5 ng/mL. In December of 2020, biochemical recurrence was diagnosed: PSA level increased from 0.61 ng/mL in October to 1.43 ng/mL on 28.12.2020. The second course of radionuclide therapy with radium-223 5,500 MBq/mL was performed (22.01.2021, 05.03.2021, 02.04.2021) with increase of PSA level to 1.92 ng/mL (May of 2021) and independent decrease to 0.542 ng/mL (June of 2022). In December of 2022, biochemical recurrence was observed with a small increase of PSA level to 1.67 ng/mL. Currently, the disease is stabilized.

26 The Kisspeptin Knockout Pig: a New Model for Dissecting Mechanisms Controlling Reproduction

Abstract The biological role of kisspeptin in the reproduction of swine has been far less studied than in other species. In the porcine hypothalamus, kisspeptin is coexpressed with neurokinin B and dynorphin in KNDy neurons. Although kisspeptin-stimulated secretion of gonadotropin hormones in gilts was established early, increased expression of hypothalamic KISS1 was only recently confirmed to be associated with puberty and cyclicity in pigs. Gene knockout (KO) models to study kisspeptin in livestock did not exist until TALEN gene editing technology was used to knockout KISS1R in pigs, resulting in a hypogonadotropic-hypogonadal (HH) phenotype that caused pubertal failure. Little is known about the reproductive physiology of KISS1R KO pigs, except that exogenous follicle-stimulating hormone and gonadotropin-releasing hormone only partially restored gonadal development in boars. To further explore the biological function of kisspeptin and its receptor in swine, we recently used CRISPR/cas9-ribonucleoproteins to knockout KISS1 in pigs (10.3389/fgene.2022.1078991). A total of 684 zygotes were injected resulting in 69 piglets with 58% bearing KISS1 KO alleles (KISS1-/-). The proportion of KISS1-/- alleles did not affect BW or ADG in these mosaic founder pigs. Two boars and 2 gilts with complete KISS1 KO exhibited HH and failed to become pubertal. Germ and Sertoli cells were disorganized in small seminiferous tubules. Mating mosaic F0 pigs (frequency of KISS1-/-, 35 to 88%) resulted in 170 F1 piglets with KISS1-/- alleles observed in a Mendelian frequency. These KISS1-/- pigs displayed normal BW growth during development but were also HH. Ovarian development of KISS1-/- gilts was arrested at a juvenile state, although antral follicles were present. The KISS1-/- boars lacked testicular development and had dramatically reduced concentrations of androgens and skatole, suggesting the lack of boar taint in their meat. Importantly, KISS1 and KISS1R are expressed in ovarian, uterine and testicular tissue; however, the direct role of kisspeptin in these reproductive organs remains unknown in livestock. These KISS1-/- pigs provide a unique animal model that opens new avenues for understanding the role of kisspeptin and gonadotropin hormones in regulation of reproductive development and function in pigs as well as livestock in general. These animals facilitate our ability to explore questions such as: 1) how KNDy neurons function and control gonadotropin pulses or 2) what role does KISS1 play in the development and function of the ovary, uterus and testis in domestic animals. Some of these questions have heretofore only been addressable with difficult surgical modifications, and therefore, KISS1-/- pigs represent an alternative to painful procedures in livestock research. Pursuing these fundamental studies is expected to lead to methods that restore fertility in KISS1-/- pigs. This, in turn, could provide new possibilities for the elimination of surgical castration from pork production. The USDA is an equal opportunity provider and employer.

Neo-Natal Castration Leads to Subtle Differences in Porcine Anterior Cruciate Ligament Morphology and Function in Adolescence.

Female adolescent athletes are at a higher risk of tearing their anterior cruciate ligament (ACL) than male counterparts. While most work related to hormones has focused on the effects of estrogen to understand the increased risk of ACL injury, there are other understudied factors, including testosterone. The purpose of this study was to determine how surgical castration in the male porcine model influences ACL size and function across skeletal growth. Thirty-six male Yorkshire crossbreed pigs were raised to 3 (juvenile), 4.5 (early adolescent), and 6 months (adolescent) of age. Animals were either castrated (barrows) within 2 weeks after birth or were left intact (boars). Posteuthanasia, joint and ACL size were assessed via MRI, and biomechanics were assessed via a robotic testing system. Joint size increased throughout age, yet barrows had smaller joints than boars. ACL cross-sectional area (CSA), length, volume, and in situ stiffness increased with age, as did the percent contribution of the ACL anteromedial (AM) bundle to resisting loads. Boar ACL, AM bundle, and PL bundle volumes were 19%, 25%, and 15% larger than barrows across ages. However, ACL CSA, in situ stiffness, and bundle contribution were similar between boars and barrows. The barrows had smaller temporal increases in AM bundle function than boars, but these data were highly variable. Early and sustained loss in testosterone leads to subtle differences in ACL morphology but may not influence measures associated with increased injury risk, such as CSA or bundle forces in response to applied loads.

Docetaxel in hormone-sensitive advanced prostate cancer; GENESIS-SEFH evaluation reporta

Prostate cancer (PC) is the most common urogenital malignancy in older men and the second leading cause of death by cancer in men in Europe. Current therapeutic practice considers Androgen Deprivation Therapy (ADT) as first line treatment for clinically localized prostate cancer at high-risk, either locally advanced or metastatic. ADT can be achieved through orchiectomy (surgical castration), luteinizing hormone-releasing hormone (LHRH) agonists, or through complete androgen blockade (LHRH agonist combined with an anti-androgen). Docetaxel in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone-refractory metastatic prostate cancer. The CHAARTED and STAMPEDE clinical trials studied the effect of bringing forward the use of docetaxel added on to ADT in the context of hormone-sensitive patients. The CHAARTED clinical trial showed a significant increase in a variable with maximum relevance such as Overall Survival (OS), with a difference of 13.6 months between medians. There was also clinical benefit in the secondary variables: median time until castration-resistant disease or until clinical progression. In the STAMPEDE clinical trial, which included 39% of non-metastatic patients, a 10-month difference between medians was demonstrated in OS, and 17 months in the primary co-variable of Progression Free Survival. The most frequent adverse events were: neutropenia, febrile neutropenia, leucopenia, and general disorders such as asthenia, lethargy or fever. According to data from the CHAARTED and STAMPEDE studies, and the incremental cost of € 3 196.98 for adding on docetaxel to standard treatment, the estimated additional cost for each year of life gained is compatible with an incremental cost-effectiveness ratio between € 2 26736 and € 3 851.78. In view of the efficacy and safety results, the proposed positioning is: to advance the use of docetaxel added to androgen deprivation therapy to first-line metastatic hormone-sensitive prostate cancer, regardless of metastatic volume, in those patients who meet the CHAARTED study criteria.

Prediction model for real-world survival in men with castration-resistant prostate cancer and bone metastases in the United States: A real-world database study.

507 Background: Bone metastases (bm) are common in men with castration-resistant prostate cancer (CRPC) and are associated with poor prognosis. Therefore, identifying prognostic factors for survival is key to aid decision-making. While several models exist for predicting survival in men with mCRPC, most were derived using randomized controlled trial (RCT) data, which may have limited application to real-world (RW) populations and utilized traditional linear methods. We aimed to develop and validate a prediction model of real-world survival (rwOS) in men with bmCRPC using a national RW electronic medical record (EMR) database with traditional and advanced machine learning (ML) methods. Methods: A retrospective cohort of men diagnosed with bmCPRC between 2010 and 2021 was identified using the Optum EMR. rwOS was identified as documented evidence of death in the EMR derived through either the Social Security Death Index or EMR-reported death date. Independent variables were demographic (age, race), clinical conditions (Charlson comorbidity index, pain, prior phases of PC), PC-related medications, and laboratory parameters during a 6-month baseline period. A dynamic model was used to predict survival at 1, 2, and 3 years after diagnosis of bmCRPC using traditional (logistic, Cox regression) and ML (light gradient boosting (LGB)) models. Training, calibration, and validation were performed by splitting the data and utilizing 5-fold cross-validation on the training sample and calibration plots. Diagnostic performances were evaluated using area-under-the-curve (AUC), precision-recall curve (PRC), and calibration curves across three models. Results: The study cohort included 4,097 men with a median age of 76 years (interquartile range: 68-82), predominantly white (81.2%), and residing in the Midwest (48.2%). Over a median follow-up period of 19.2 months, 2,220 (54.2%) men died with median rwOS of 31.0 months (95% CI: 29.6-32.9). The AUC for Cox, logistic and LGB models at 1 year were well within the acceptable range of (≥0.7.0) 0.78, 0.79, and 0.81 respectively. Similar findings were observed at 2 and 3-year landmark analyses with marginal improvement in model performance with LGB. Top predictors of rwOS were consistent across all time points in the LGB models and included laboratory parameters (prostate-specific antigen level, alkaline phosphatase, albumin, hemoglobin), age, presence of pain, transition from mHSPC to mCRPC, surgical castration, and baseline use of androgen receptor inhibitors. Conclusions: Study findings highlight consistency in the predictors of rwOS in a large cohort of men with bmCRPC using a national EMR database. ML-based models predicted rwOS with modest performance improvement compared to traditional models and could provide rwOS prediction to aid treatment decision-making.

The effect of diagnosis delay in testis cancer on tumor size, tumor stage and tumor markers

IntroductionIn testicular cancer, the positive effect of early diagnosis on survival has been known for many years. In this study, we aimed to determine the diagnostic features of testicular cancer patients, to examine the effect of duration of diagnosis delay (DD) on tumor size, tumor stage, and serum tumor markers, and to reveal the possible benefits of early diagnosis. MethodsA total of 71 patients who underwent inguinal orchiectomy due to suspicion of testicular cancer and whose pathology was found to be the germ cell tumor were included in the study. The relationship between the duration of diagnosis delay and tumor size, level of tumor markers, TNM stage, presence of LAP, and presence of metastasis were examined. ResultsSeminoma was detected in 39 (54.9%) patients and non-seminoma tumor was detected in 32 (45.1%) patients. In the correlation analysis between the markers, a significant and positive correlation was found between DD and radiological tumor size, pathological tumor size, retroperitoneal LAP detection rate, LDH and AFP levels, and N stage (respectively; r=0.345 p=0.003, r=0.324 p=0.006, r=0.244 p=0.041, r=0.286 p=0.015, r=0.244 p=0.040, r=0.238 p=0.046). It was determined that a 1-day increase in DD caused an increase of 0.431mm in the pathological size of the tumor. ConclusionDuration of diagnosis delay is an issue that still keeps its importance for testicular tumors. Delay in diagnosis not only leads to an increase in tumor size but also negatively affects tumor stage and prognostic factors.

To castrate or not to castrate? That is the question….

There is growing evidence that surgical castration of dogs may not bring all the benefits previously assumed. Times have changed too, and vets and clients are increasingly questioning whether routine castration should continue to be considered best practice.

GnRH-immunocastration: an alternative method for male animal surgical castration.

Castration of male animals is intended to produce high-enhance quality of animal meat, prevent unpleasant taste, reduce aggressive behavior, and manage overbreeding. Over the years, Tranditional methods of mechanical and surgical castration have been employed over the years, but they fall short of meeting animal welfare requirements due to the associated risk of infection, pain, and stress. Immunocastration, specifically Gonadotropin-releasing hormone (GnRH)-immunocastration, targeting the hypothalamic-pituitary-testis (HPT) axis, has emerged as an animal-friendly alternative to surgical castration, effectively addressing these issues. This review seeks to systematically summarize the principles, development, current applications and challenges of GnRH-immunocastration, offering insights into its role in promoting animal welfare.

Experimental androgen deficiency and associated structural changes in the muscle tissue of the external anal sphincter

Aim. We aimed to study the histological and ultramicroscopic structure of the striated muscle tissue of the external anal sphincter (EAS) of mature male rats under experimental androgen deficiency.Materials and methods. The study included 10 male laboratory rats aged 8 months, which were randomly divided into 2 groups of 5 each. The experimental group underwent bilateral orchiectomy to create testosterone deficiency. After 45 days, rats were sacrificed. We studied the concentration of testosterone in histological sections of EASs using light microscopy and ultramicroscopy. We also determined the diameter of muscle fibers and the thickness of endomysium, the area of muscle fibers, connective tissue, myofibrils and cytoplasm, identification of glycogen granules in the cytoplasm and intermyofibrillar space, as well as changes in mitochondria. Results. In the experimental group, on the 45th day after surgical castration, the testosterone level was 2.5 times lower than in the control group 2.69 (2.52; 2.73) nmol/l vs. 7.20 (6.83; 7.21) nmol/l, p = 0.008. Using morphometric analysis, we found that in the experimental group after surgical castration the diameter of the muscle fibers was statistically significantly smaller than in the control group: 6.56 (3.96; 7.24) µm vs. 9.52 (8.88; 10.44) µm, p &lt; 0.001, while the thickness of the endomysium in the experimental group was greater: 3.34 (3.11; 3.78) µm vs. 1.62 (1.51; 1.86) µm, p &lt; 0.0001. The ratio of muscle fiber area/connective tissue area was statistically significantly lower in the group after castration: 1.64 (1.50; 1.78) vs. 4.00 (3.17; 5.25), p &lt; 0.0001. The ratio of myofibril area/cytoplasmic area changed in the experimental group towards the predominance of cytoplasm 0.79 (0.67; 0.79) vs. 5.25 (5.25; 7.33), p &lt; 0.0001. With an increase in cytoplasmic volume, an increase in the number of glycogen granules was observed; pathological forms of mitochondria were identified: swelling, destruction of cristae and vacuolization of their matrix. Conclusion. Under conditions of testosterone deficiency, along with atrophic processes, compensatory and adaptive mechanisms are formed in the striated skeletal muscle tissue of the EAS, aimed at restoring its metabolic and functional organization