Fatal tumoral hemorrhage from brain metastases of renal cell carcinoma after stereotactic radiotherapy and immune checkpoint inhibitor and vascular endothelial growth factor-targeted therapy combinations.

Introduction: Brain metastasis in renal cell carcinoma, which is reported in 10% of cases, leads to significant morbidity and mortality. Establishment of appropriate and safe treatment for brain metastasis renal cell carcinoma remains a pressing need. Case presentation: A 56-year-old female patient, presenting with anorexia, headache, and occipital swelling, was subsequently diagnosed with clear cell renal cell carcinoma with multiple metastases, including intracranial and epicranial tumors. The patient initially underwent stereotactic radiotherapy for metastatic brain tumors and then received combination therapy with pembrolizumab and lenvatinib. However, after 30 days of treatment, the patient experienced a sudden loss of consciousness due to massive multifocal intracranial hemorrhage, leading to her death the following day. Conclusion: Although fatal tumoral hemorrhage during combined stereotactic radiotherapy and immune checkpoint inhibitor/VEGF-targeted therapy for patients with brain metastasis renal cell carcinoma is an extremely rare complication, it should always be considered a possibility.

Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

A retroperitoneal primary undifferentiated pleomorphic sarcoma.

A 52-year-old male had pain in the right back and right hypochondrium, and an abdominal CT scan revealed a 49-mm tumor in the right upper perirenal space. Additional MRI and PET-CT suggested that the tumor may be a primary adrenal carcinoma and could invade the liver and diaphragmatic leg. The tumor was completely removed by laparotomy and histopathologically diagnosed as retroperitoneal primary undifferentiated pleomorphic sarcoma. The patient has remained recurrence-free for 1.5 years after the surgery.

Association between nocturnal polyuria and 24-h blood pressure fluctuations in males with lower urinary tract symptoms: A multicenter prospective study.

OBJECTIVES: Nocturnal polyuria (NP) is one of the causes of nocturia that impairs quality of life. It is necessary to consider that NP is latent when the initial treatment for nocturia is unsatisfactory. Therefore, it is important to establish a treatment for NP based on the pathophysiology. We have previously reported the relationship between NP and fluctuation in blood pressure. The present study aimed to investigate the association between NP and 24-h blood pressure fluctuations in a multicenter prospective study. METHODS: This study included male patients with lower urinary tract symptoms. We categorized the patients into the nonnocturnal polyuria (non-NP) group (≤0.33) and the NP group (>0.33) based on the nocturnal polyuria index from the frequency volume chart. We measured the 24-h diurnal blood pressure and compared the two groups. RESULTS: Among 90 patients, 46 in the non-NP group and 44 in the NP group were included. There was no significant difference in the systolic and diastolic blood pressure during waking time between the two groups; however, the degree of systolic blood pressure reduction during sleep time in the NP group was significantly less than that in the non-NP group (p = 0.039). In the multivariate analysis, systolic BP during sleep was significantly associated with NP (OR 0.970, p = 0.028). CONCLUSION: NP is associated with inadequate nocturnal blood pressure reduction in males, suggesting that reduction in nocturnal blood pressure may lead to improvement in nocturia.

Prognostic significance of serum fucosylated pro-haptoglobin in advanced renal cell carcinoma patients treated with immune checkpoint inhibitors.

With the widespread use of immune checkpoint inhibitors (ICIs), identifying predictive biomarkers is critical. Recently, serum fucosylated haptoglobin (Fuc-Hp) was thought to play an important role in tumour immunity in several types of cancer. Therefore, evaluating serum Fuc-Hp in the peripheral blood can potentially identify non-invasive predictive biomarkers for the clinical efficacy of ICIs. In this study, 31 patients with advanced renal cell carcinoma (RCC) treated with nivolumab were enrolled and defined as responders or non-responders according to RECIST criteria. Serum samples were collected before and 1 month after treatment initiation, and an ELISA assay was performed using Aleuria Aurantia Lectin (AAL) and 10-7G monoclonal antibodies that recognise Fuc-mature Hp (Fuc-mHp) and Fuc-pro Hp (Fuc-pHp), respectively. We first measured AAL-haptoglobin (Fuc-mHp) and total haptoglobin levels before nivolumab and found that neither value could predict the clinical response. Notably, serum 10-7G levels were significantly lower in the responder group (p = 0.035). We also confirmed the use of serum 10-7G levels for predicting progressive disease after nivolumab (area under the curve, 0.816). Accordingly, low 10-7G levels were significantly correlated with better progression-free survival (p = 0.041). In conclusion, serum Fuc-pHp analysis may identify patients with advanced RCC who benefit from ICIs.

Therapeutic efficacy and safety of a free-standing motorized ejaculation aid for patients with intravaginal ejaculatory dysfunction.

Purpose: There are no approved drugs or devices for the treatment of intravaginal ejaculation disorders, and treatment is often difficult. This study aimed to evaluate the efficacy and safety of the A10 Cyclone SA + PLUS® ejaculation aid (Rends Co., Ltd., Chiba, Japan), which allows the user to adjust the intensity of stimulation, for intravaginal ejaculation disorders. Methods: Each participant was instructed to perform practice masturbation with the A10 Cyclone SA + PLUS to simulate vaginal ejaculation. After 8 weeks of training, the participants were asked about their intravaginal ejaculation status. Sexual function was also evaluated before and after the training using several specific questionnaires, including the numerical rating scale for ejaculatory satisfaction. Results: Among the 10 participants (41.5 ± 3.21 years) who completed the training and questionnaire evaluation, four (40%) became capable of intravaginal ejaculation. The questionnaire evaluation showed predominant improvement after training in the ejaculation-capable group according to the numerical rating scale, which expresses satisfaction with ejaculation. The participants experienced no significant adverse events. Conclusion: As no effective treatment currently exists for intravaginal ejaculation disorders, we conclude that the A10 Cyclone SA + PLUS may be one treatment tool for intravaginal ejaculation disorders with good efficacy and no adverse events.

A case of retroperitoneal liposarcoma extending through the inguinal canal to the thigh and lesser trochanter.

Introduction: Liposarcoma is the most common retroperitoneal soft tissue tumor. Liposarcomas are often asymptomatic and are discovered after they become huge. Surgical resection is the first-line treatment for retroperitoneal liposarcoma, but the surrounding organs are often resected with the liposarcoma. Case presentation: A man saw a hospital with a complaint of left lower abdominal distention, and a left retroperitoneal mass was noted on imaging examination. The patient was referred to our hospital. The mass extended from the retroperitoneum through the inguinal canal to the thigh and involved the femoral nerve and psoas major muscle. A well-differentiated liposarcoma was suspected, and an open surgical resection was performed. Complete resection of a retroperitoneal liposarcoma extending to the thigh was achieved without postoperative complications. Conclusion: Treatment strategies for huge retroperitoneal liposarcomas are important to balance antitumor efficacy and postoperative quality of life.

Surgical resection of primary leiomyosarcoma of retro-hepatic inferior vena cava extending from bilateral renal veins across the diaphragm.

Vascular leiomyosarcoma of the inferior vena cava is a rare malignant soft tissue tumor that requires surgical treatment to prevent tumor-related symptoms such as pulmonary embolism and Budd-Chiari syndrome. However, a treatment strategy for surgical resection of advanced cases has not yet been determined. This report describes the case of advanced leiomyosarcoma of the inferior vena cava that was successfully treated with surgery and subsequent chemotherapy. A 44-year-old man was found to have a 12 × 10 cm retroperitoneal tumor on computed tomography. The tumor originated in the inferior vena cava and extended beyond the diaphragm into the renal vein. The surgical plan was determined in joint consultation with the multidisciplinary team. It was safely resected and the inferior vena cava was closed caudal to the porta hepatis without a synthetic graft. The tumor was diagnosed as leiomyosarcoma. Doxorubicin, followed by pazopanib were administered as treatment for metastatic disease. Eighteen months after the surgery, the patient's performance status was maintained.

Drug-induced interstitial pneumonia after intravesical Bacillus Calmette-Guerin administration for bladder cancer with scleroderma.

Introduction: Intravesical Bacillus Calmette-Guerin administration is the standard therapy for high-risk nonmuscle invasive bladder cancer and is usually well tolerated. However, some patients experience severe, potentially fatal, complications including interstitial pneumonitis. Case presentation: A 72-year-old female with scleroderma was diagnosed with bladder carcinoma in situ. She developed severe interstitial pneumonitis with the first administration of intravesical Bacillus Calmette-Guerin after the cessation of immunosuppressive agents. Six days after the first administration, she experienced dyspnea at rest, and computed tomography revealed scattered frosted shadows in the upper lung. The following day, she required intubation. We suspected drug-induced interstitial pneumonia and started steroid pulse therapy for 3 days, resulting in a complete response. No exacerbation of scleroderma symptoms or recurrence of cancer was observed 9 months after Bacillus Calmette-Guerin therapy. Conclusion: For patients receiving intravesical Bacillus Calmette-Guerin therapy, close observation of the respiratory condition is necessary for early therapeutic intervention.

Mucinous cystadenoma of the renal parenchyma presenting as a Bosniak IIF complex renal cyst.

Introduction: A primary retroperitoneal mucinous cystadenoma should be surgically resected because of the risk of malignant transformation. However, mucinous cystadenoma of the renal parenchyma is very rare, and preoperative imaging mimics complicated renal cysts. Case presentation: A 72-year-old woman presented with a right renal mass on computed tomography that was followed up as a Bosniak IIF complicated renal cyst. One year later, the right renal mass gradually increased in size. Abdominal computed tomography showed an 11 × 10 cm mass in the right kidney. A laparoscopic right nephrectomy was performed because cystic carcinoma of the kidney was suspected. Pathologically, the tumor was diagnosed as mucinous cystadenoma of the renal parenchyma. Eighteen months after resection, the disease has not recurred. Conclusion: Here, we experienced a case of a renal mucinous cystadenoma as a slowly enlarging Bosniak IIF complex renal cyst.

Seronegative rheumatoid arthritis after combination therapy with ipilimumab and nivolumab for postoperative pancreatic and liver metastases from renal cell carcinoma.

Introduction: Since the approval of immune checkpoint inhibitors for renal cell carcinoma treatment, therapeutic efficacy has been enhanced. However, although autoimmune-related side effects may occur, rheumatoid immune-related adverse events seldom develop. Case presentation: A 78-year-old Japanese man with renal cell carcinoma developed pancreatic and liver metastases after bilateral partial nephrectomy and was treated with ipilimumab and nivolumab. After 22 months, he developed arthralgia in limbs and knee joints, accompanied by limb swelling. The diagnosis was seronegative rheumatoid arthritis. Nivolumab was discontinued, and prednisolone was initiated, quickly improving symptoms. Although nivolumab was resumed after 2 months, arthritis did not recur. Conclusion: Immune checkpoint inhibitors may cause a wide variety of immune-related adverse events. When arthritis is encountered during immune checkpoint inhibitor administration, seronegative rheumatoid arthritis should be differentiated from other types of arthritis, despite being less frequent.

A case of mediastinal teratoma with malignant transformation into angiosarcoma and relapse with multiple bone metastases that was cured by a multidisciplinary treatment.

Introduction: Complete resection is essential for the treatment of teratoma with malignant transformation, and if metastasis occurs, it will be difficult to cure. We report a case of primary mediastinal teratoma with differentiation into angiosarcoma that caused bone metastases but was cured by multidisciplinary treatment. Case presentation: A 31-year-old man with a primary mediastinal germ cell tumor underwent primary chemotherapy followed by post-chemotherapy resection, with angiosarcoma due to malignant transformation found in the surgical specimen. Femoral diaphyseal metastasis was manifested, and he underwent femur curettage followed by radiation therapy of 60 Gy in parallel with 4 cycles of chemotherapy combining gemcitabine and docetaxel. Although thoracic vertebral bone metastasis emerged 5 months after treatment, intensity-modulated radiation therapy was successful, and metastatic lesions have remained shrunken for 39 months after treatment. Conclusion: Even if complete resection is difficult, teratoma with malignant transformation may be cured by multidisciplinary treatment based on histopathology.

Evaluation of the efficacy of creatine chemical exchange saturation transfer imaging in assessing testicular maturity.

Purpose: Microscopic testicular sperm extraction is the most effective treatment for NOA, but the sperm retrieval rate is low and depends on testicular maturity. However, there are limited useful tests to assess testicular maturity. Chemical exchange saturation transfer (CEST) imaging is a new magnetic resonance imaging (MRI) technique that can image the distribution of trace substances in vivo. We focused on the potential role of creatine (Cr) in testes and hypothesized that Cr-CEST could indicate intratesticular spermatogenesis. Methods: We performed Cr-CEST by using 7T MRI on wild-type C57B6/J mice and several types of male infertility models such as Sertoli-cell only (SCO) (Kitw/Kitwv), maturation arrest (MA) (Zfp541 knockout mouse and Kctd19 knockout mouse), and teratozoospermia (Tbc1d21 knockout mouse). After performing Cr-CEST, histological analysis was performed. Results: The SCO and MA models showed decreased CEST signal intensity (p < 0.05), while no reduction was observed in the teratozoospermia model (p = 1.0). CEST signal intensity increased as the spermatogenesis stage progressed from the SCO model to the MA and teratozoospermia models. Furthermore, CEST signal intensity was reduced in 4-week-old wild-type mice with immature testes (p < 0.05). Conclusions: This study suggests that Cr-CEST evaluates intratesticular spermatogenesis noninvasively and provides a new therapeutic strategy for treating male infertility.

Summary of the clinical practice manual for late-onset hypogonadism.

Testosterone plays an important role in maintaining both physical and mental function. Age-related testosterone depletion contributes to the development of angina, arteriosclerosis, obesity, metabolic syndrome, dementia, frailty, and a range of other conditions. A condition involving age-related testosterone depletion and the associated clinical symptoms is defined as late-onset hypogonadism (LOH). LOH is treated by testosterone replacement therapy. Indications for testosterone replacement therapy are determined by evaluating symptoms and signs.

Creatine Chemical Exchange Saturation Transfer (Cr-CEST) Imaging Can Evaluate Cisplatin-induced Testicular Damage.

PURPOSE: This study aimed to investigate the ability of creatine-chemical exchange saturation transfer (Cr-CEST) technique assessed through 7-T MRI to evaluate cisplatin-induced testicular damage. METHODS: We used 8-10 weeks C57BL/6 mice (n = 10) that were divided into a control group (n = 5) and a cisplatin-treated group (n = 5). The cisplatin group received cisplatin at a dose of 15 mg/kg, via intraperitoneal injection, while the control group received saline. MR images of mouse testes were acquired under anesthesia 18 days after the injection using a horizontal 7-T scanner. The pulse sequence consisted of rapid acquisition with a relaxation enhancement (RARE) with magnetization transfer. The Z-spectra were collected using a 2000-ms saturation pulse at a B1 amplitude of 1.2 µT, with frequencies varying from -4.8 to +4.8 parts per million (ppm). Maps of magnetization transfer ratio with asymmetric analysis (MTRasym) were reconstructed at a Cr metabolite concentration of 1.8 ppm. RESULTS: The Cr-CEST effect was significantly reduced in the cisplatin-treated group compared to the control group (MTRasym of control mice vs. cisplatin-treated mice: 6.9 [6-7.5] vs. 5.2 [4-5.5], P = 0.008). Correlation analysis revealed a strong correlation between the Cr-CEST effect and the pathological score (ρ = 0.93, P < 0.001). CONCLUSION: Cr-CEST MRI can be useful for the evaluation of cisplatin-induced testicular damage in mice.