[Experience of Pembrolizumab Administration in A Patient with Castration-Resistant Microsatellite Instability-High Prostate Cancer].

Castration-resistant prostate cancer and multiple lymph node and ventral bladder metastases in an 87 year-old man progressed despite various systemic therapies, including chemotherapy. Because his prostate surgical specimen displayed a microsatellite instability (MSI) -high status, pembrolizumab 200 mg/body treatment was started. After six courses of treatment, his prostate-specific antigen (PSA) level decreased by 83% versus that at treatment initiation (from 408.78 ng/ml to 69.54 ng/ml), and the para-aortic lymph node metastasis was reduced in size on imaging. After 13 courses, his PSA level (462.59 ng/ml) exceeded that at the start of treatment, and progressive disease was detected on imaging. Although case reports of pembrolizumab for MSI-high prostate cancer remain few because of its rarity, it is an important therapeutic option and further clinical research is required.

[A Case of Castration-Resistant Prostate Cancer, for which Washed Platelet Concentrate Transfusions were Effective in Treating Disseminated Intravascular Coagulation].

A 62-year-old man was treated for castration-resistant prostate cancer (CRPC) ; however, his condition progressed. The patient planned to visit our department for treatment, including palliative care. However, he visited the emergency room with a complaint of a persistent nose bleed just before visiting our department. He had an active nose bleed, disseminated intravascular coagulation (DIC), and leukoerythroblastosis upon admission. After hospitalization, we performed a bone marrow puncture and biopsy to investigate the cause of the DIC, which revealed a dry tap and hypoplastic bone marrow. This was believed to be due to the progression of CRPC. He developed wheals upon receiving repeated platelet transfusions for the DIC. Although we administered antihistamine and steroids to control these side effects, he additionally developed chills and fever. Because of the difficulty in controlling side effects, we decided to use washed platelets. Thereafter, blood transfusions of washed platelets were performed without the occurrence of side effects. However, the patient died because of the worsening of his condition.

Testicular sperm extraction in a patient with ejaculatory dysfunction after combined androgen blockade therapy for prostate cancer.

INTRODUCTION: Prostate cancer is the most prevalent urological cancer for older men. However, there is still a possibility that a few prostate cancer patients may still wish to have children. CASE PRESENTATION: A 49-year-old male was diagnosed with low-risk prostate cancer. Combined anti-androgen blockade therapy was performed for 8 months prior to radiation therapy. However, he suffered from ejaculatory dysfunction and wished to conceive with his partner. Hormonal therapy was discontinued and he was referred to our clinic for sperm preservation. His ejaculatory function did not recover after 4 months discontinuation of hormonal therapy, subsequently micro-testicular sperm extraction for sperm preservation was successfully performed. CONCLUSION: Sperm preservation in patients with prostate cancer is unusual but it should be considered if the patient's fertility is an issue.

[Ischemic Priapism Associated with Essential Thrombocythemia : A Case Report].

A 71-year-old man visited a local urologist with the complaint of continuous painful erection for three days. Penile cavernosal blood data showed acidosis and hypoxia. Thus he was diagnosed with ischemic priapism. After penile aspiration and injection of phenylephrine, erection was temporary improved. The blood platelet count was 94.5×104/µl and myeloproliferative disease was suspected. He was referred to our hospital and visited us the following day. Since priapism relapsed, we aspirated corpus cavernosum of the penis and injected phenylephrine which was successful. A bone marrow biopsy and genetic test were performed at the department of hematology and the diagnosis of essential thrombocythemia with JAK2 gene mutation was confirmed. By treatment with hydroxyurea, the blood platelet count decreased without priapism recurrence.

The efficacy and safety of short-acting testosterone ointment (Glowmin) for late-onset hypogonadism in accordance with testosterone circadian rhythm.

INTRODUCTION: It is well known that there is a reduction of circadian rhythm in blood testosterone levels with aging. Our previous report revealed that 3 mg of short-acting testosterone ointment (Glowmin: GL) elevated serum testosterone levels to within the physiological range for 4-6 h. The aim of this study was to clarify the clinical efficacy and safety of GL used topically once every morning, to enhance the circadian rhythm of testosterone, for late-onset hypogonadism (LOH). METHODS: A total of 61 LOH patients received 3 mg of GL topically once a day in the morning on scrotal skin for 24 weeks. The clinical efficacy of GL was evaluated by the aging males symptoms (AMS) scale, and blood sampling tests were measured before and after GL treatment. RESULTS: Mean patients age was 55.3 ± 9.2 years old. Total AMS scores at 4, 12, and 24 weeks after GL treatments significantly decreased. The results of sub-analysis of AMS, including psychological, physical, and sexual factors also significantly improved after GL treatments. No severe adverse reactions or abnormal laboratory data were reported. CONCLUSIONS: This study shows that TRT for LOH with once daily GL treatment supports testosterone circadian rhythm and should be considered to be an effective and safe therapy for LOH.

Administration of daily 5 mg tadalafil improves endothelial function in patients with benign prostatic hyperplasia.

INTRODUCTION: Tadalafil is a promising phosphodiesterase (PDE) 5 inhibitor prescribed for erectile dysfunction (ED). Daily low dose (5 mg) of tadalafil has also been used for the treatment of male lower urinary tract symptoms (LUTS) associated with benign prostate hyperplasia (BPH). PDE5 inhibitors induce relaxation of smooth muscle cells in the urethra, prostate, bladder neck, and blood vessels. The aim of this study was to investigate the efficacy of tadalafil on vessels endothelial function, in patients with male LUTS symptoms associated with BPH. METHODS: The Institutional Review Board (IRB) approved this clinical study and informed consents had been obtained from 81 BPH patients. The following male LUTS parameters: international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), voiding volume, max and mean voiding flow on voiding flowmetry examination and post-voiding residual urine (RU) were compared at 0, 1, 3, 6, and 12 months after a daily dose of 5 mg tadalafil. In addition, erectile function was evaluated by the sexual health inventory for men (SHIM) score and vessels endothelial function and peripheral neuropathy were assessed by the brachial-ankle pulse wave velocity (baPWV), ankle brachial index (ABI), and vibration perception threshold (VPT) at 0, 3, 6, and 12 months after treatment. RESULTS: The mean age of 81 patients was 66.4 ± 11.4 years old. Their prostate size was 30.2 ± 22.1 ml. Male LUTS parameters including IPSS, OABSS, and RU showed significant improvement from 1 to 12 months after tadalafil administration. Max and mean voiding flow was significantly increased at 6 months after tadalafil treatment. The SHIM score showed significant improvement after 3 months. Whilst, the results of baPWV also showed significant improvement from 3 to 12 months. ABI was also significantly improved at 6 months. However, there was no change in the VPT at any time point. CONCLUSIONS: Tadalafil is effective for both male LUTS and ED. It is also shown that tadalafil improves baPWV, which we can conclude that higher vessels elasticity has been obtained. This major finding of this study shows that tadalafil has the potency to improve vessels endothelial dysfunction in patients with BPH.

Are urge incontinence and aging risk factors of erectile dysfunction in patients with male lower urinary tract symptoms?

INTRODUCTION: Several studies have indicated that erectile dysfunction (ED) patients also suffer from lower urinary tract symptoms (LUTS). We investigated a group of men with LUTS and assessed their sexual function with the aim of being able to predict ED risk factors and introduce ED treatments earlier for this patient group. METHODS: International Prostate Symptom Score (IPSS), Overactive Bladder Symptoms Score (OABSS) and Sexual Health Inventory for Men (SHIM) score were obtained from 236 men with LUTS at their first out-patients visit. Clinical parameters such as body mass index, prostate volume, residual urine volume and prostate specific antigen were also evaluated. The relationship between the SHIM score and other clinical data was analyzed. RESULTS: According to the SHIM score, ED in men with LUTS was severe 15%, moderate 19%, moderate to mild 28%, mild 17%, normal 7% and data was incomplete in 14%. Based on the results of a multivariate analysis, aging (p < 0.001) and OAB severity (p = 0.024) were significantly correlated to severe and moderate ED. Furthermore, among OAB symptoms score items, urge urinary incontinence was a risk factor for severe and moderate ED (p = 0.005). CONCLUSION: Aging and OAB (notably urinary urge incontinence) are risk factors for severe and moderate ED in men with LUTS.

Male infertility and androgen replacement therapy for subjects with bilateral testicular tumors.

PURPOSE: The purpose of this study was to investigate andrological aspects, including male infertility and androgen deficiency, after treatments of bilateral testicular tumors. METHODS: Five subjects with bilateral testicular cancer were clinically analyzed between April 1996 and March 2013. RESULTS: The mean age at initial treatment was 29.4 ± 3.3 years old. In the 4 metachronous cases, a contralateral tumor occurred after 79.0 ± 50.0 months. Histologically, bilateral seminoma occurred in 3 cases and seminoma and nonseminoma was combined in 2 cases. All subjects underwent bilateral orchiectomy, with additional chemotherapy, radiation therapy, and surgery for metastasis. No tumor recurrence was observed in the 5-34 years following initial treatment. Two subjects married following bilateral orchiectomy after receiving informed consent from their wives. One had two children before contralateral testicular treatment. The other was single and had undergone micro-testicular sperm extraction at contralateral orchiectomy, although no sperm was found. The other one was unknown because long-term followup failed. Androgen replacement therapy (ART) was applied for 4 subjects, and relieved physical and psychological symptoms due to testosterone deficiency without adverse reactions. CONCLUSIONS: ART safely and effectively relieves symptoms in subjects with bilateral testicular tumors. However, male infertility treatment is insufficient, and more aggressive management may be required.

[Laparoscopic resection of retroperitoneal schwannoma : report of three cases and review of 22 cases in Japanese literature].

Retroperitoneal schwannoma is a rare tumor. Only 19 cases have been reported to be treated by laparoscopic surgery. We performed successful laparoscopic excision of retroperitoneal schwannoma using the four-trocar in three patients who had a left retroperitoneal mass. The patients were two women and one man. They were 62, 60 and 57 years old. The tumor was 70, 45 and 50 mm in greatest diameter and operative time was 204, 243 and 254 min. respectively. The pathological diagnosis of the tumor was schwannoma. There was no morbidity or mortality. Preoperative diagnosis of schwannoma is very difficult. However schwannoma is a benign tumor with a good prognosis. This laparoscopic excision for retroperitoneal schwannoma is effective and rather safe.

[Laparoscopic nephrectomy for patients with infected nonfunctioning kidney due to ureteropelvic junction stenosis : report of two cases].

We report two cases of infected nonfunctioning kidney due to ureteropelvic junction (UPJ) stenosis treated by laparoscopic surgery. Patient 1 : A 78-year-old woman was referred to our clinic complaining of left flank pain and high fever up. Asymptomatic UPJ stenosis with mild hydronephrosis was diagnosed 9 years ago at our clinic. Therefore we followed her up with no treatment. Computed tomography (CT) scan revealed left severe hydronephrosis. Antibiotic chemotherapy was performed without percutaneous nephrostomy. Laparoscopic nephrectomy was performed with the resected renal size of 10 cm in greatest diameter and the operative time of 262 min. The pathological diagnosis was atrophic kidney with pyelonephritis. Patient 2 : A 28-year-old man was referred to our clinic complaining of left flank pain and high fever up. CT scan revealed a left severe hydronephrosis due to UPJ stenosis. Following percutaneous nephrostomy,antibiotic chemotherapy was performed. Laparoscopic nephrectomy was performed with the resected renal size of 6 cm in greatest diameter and the operative time of 140 min. The pathological diagnosis was atrophic kidney with pyelonephritis. Laparoscopic nephrectomy for infected nonfunctioning kidney due to UPJ stenosis is feasible and safe. With dense perinephric adhesions and failure to progress,we should consider early open conversion to reduce morbidity.

[Adrenalectomy for metastatic adrenal tumor from uterine leiomyosarcoma: a case report].

A 63-year-female was referred to our department for close examination and treatment of a left adrenal tumor found by positron emission tomography and computed tomography. She underwent abdominal total hysterectomy and bilateral salpingo-oophorectomy for uterine leiomyosarcoma 19 years ago. After the operation, she received 2 resections for peritoneal recurrence and 7 resections for pulmonary metastases. Magnetic resonance imaging showed a heterogeneous mass with a diameter of 7 cm at the left adrenal grand. We carried out open adrenalectomy and pathological findings were a metastatic adrenal tumor from uterine leiomyosarcoma. No signs of recurrence or metastasis have been observed for 6 months after the operation.

[Brain tumor (germinoma) diagnosed after assessment for male late-onset hypogonadism syndrome: a case report].

A 44-year-old man suffered from sleep disturbance, headache, lack of energy and appetite loss. His local doctor recommended he consult our clinic for further examination of late-onset hypogonadism. His aging males' symptoms (AMS) and international index of erectile function (IIEF-5) scores were 62 and 1, respectively. His biochemistry revealed 0.29 mIU/ml luteinizing hormone (LH), 1.36 mIU/ml follicular stimulating hormone (FSH), 0.16 ng/ml total testosterone (TT) and＜0.6 pg/ml free testosterone (FT). Male hypogonadotropic hypogonadism was suspected from these results, He was then referred to a neurosurgeon for discrimination of intracranial disease where magnetic resonance imaging (MRI) revealed multiple intracranial tumors. An open brain biopsy was performed, and germinoma was diagnosed. After 4 courses of anti-cancer chemotherapy, complete remission was achieved. He was followed up endocrinologically by administration of testosterone injections along with other endocrinology replacement treatments. However, MRI 3 months later revealed tumor recurrence in the left lateral ventricle, and he has been receiving radiation therapy.

The usefulness of vibration perception threshold as a significant indicator for erectile dysfunction in patients with diabetes mellitus at a primary diabetes mellitus clinic.

INTRODUCTION: The aim of this study is to clarify the relationship of erectile dysfunction (ED) and diabetes mellitus (DM) parameters (referred to with '1'), including peripheral neuropathy (referred to with '2'). METHODS: (1) The DM parameters including age, serum levels of blood sugar, hemoglobin A1c, duration of DM and number of DM complications were obtained from 145 patients at a general DM clinic. (2) The peripheral neuropathy examinations by vibration perception threshold (VPT) and Achilles tendon reflex were performed in 97 DM patients. Erectile functions in DM patients were evaluated by the International Index of Erectile Function (IIEF 5). The DM patients' parameters were compared with the IIEF 5 scores. RESULTS: (1) The data showed IIEF 5 scores were significantly correlated with patient age, duration of DM and number of DM complications. (2) IIEF 5 scores were significantly correlated with VPT time. Furthermore, multiple regression analysis revealed that patient age and VPT time were independent risk factors for predicting ED in DM patients. CONCLUSIONS: The severity of ED in DM patients depended on age, duration of DM, number of DM complications and VPT. Significantly, the age of DM patients and the measurement of VPT are considered to be simple and useful indicators to diagnose ED in DM patients.

Metastatic ureteral involvement of non-small cell lung cancer.

Metastases from a variety of malignant tumors can involve the ureters, but ureteral involvement by lung cancer is extremely rare and usually described at autopsy. We report a rare case of a 76-year-old man who presented with a three-month history of right flank dullness and was noted to have a nonhomogeneous retroperitoneal mass with hydronephrosis of the right kidney on computed tomography of the abdomen. Computed tomography of the thorax showed a nodule in the lower lobe, measuring 3 × 2 cm, in the right lung. After excluding the presence of other primary tumors and metastases, we reached a final diagnosis of solitary retroperitoneal metastasis of adenocarcinoma of the lung. Although rare, in patients of non-small cell lung cancer, presence of hydronephrosis should alert the physician to the possibility of metastasis.

Leiomyosarcoma of the renal vein.

A 43-year-old woman was referred to our clinic for evaluation of a left retroperitoneal mass. She presented to our internal medicine department complaining of back pain. Computed tomography (CT) scan revealed a left retroperitoneal mass 55 mm in size in the hilum of the left kidney. Enhanced CT scan and magnetic resonance imaging (MRI) disclosed a poorly staining mass. Metaiodobenzylguanidine scintigraphy demonstrated no accumulation in the mass; moreover, endocrinologic examination was normal. Laparoscopic resection of the left retroperitoneal tumor was attempted; however, strong adhesion between the tumor and the left renal vein was encountered. Thus, left nephrectomy after open conversion was performed. Histological findings indicated leiomyosarcoma originating from the left renal vein. The postoperative course has been uneventful; neither recurrence nor metastasis is evident 2 years postsurgery.

Normal delivery following resection of an androgen-secreting adrenal carcinoma.

A 31-year-old female presented to a gynecological clinic complaining of amenorrhea and virilism over a 2-month period. Blood tests revealed high serum total testosterone and free testosterone levels. A left adrenal tumor was identified following computed tomography and she was referred to our clinic where a laparoscopic left adrenalectomy was performed. The tumor weighed 98 g and the pathological diagnosis according to Weiss' criteria was adrenocortical carcinoma. The post-operative course was uneventful; her serum free testosterone level normalized and regular menstruation was observed 1 month post-operatively. The patient became pregnant 1 year later, resulting in the normal delivery of a girl.

Testosterone replacement therapy by testosterone ointment relieves lower urinary tract symptoms in late onset hypogonadism patients.

INTRODUCTION: Patients with late onset hypogonadism (LOH) also suffered from lower urinary tract symptoms (LUTS) and LOH symptoms. The objects of this study are to evaluate the efficacy of testosterone replace therapy (TRT) by testosterone ointment (Glowmin: GL) for LUTS in LOH patients. METHODS: The Aging Male Symptom (AMS) scale, Medical Outcomes Study (MOS) 36-Item Short-Form Health Survey (SF-36), International Index of Erectile Function (IIEF-5) and the International Prostate Symptom Score (IPSS) were obtained from patients with LOH. A total of 41 patients with LOH have been treated with TRT using 6 mg/day of GL for 3 months. Serum free testosterone levels (FT) and these four scores were compared before and after TRT. RESULTS: Serum FT levels and the scores for the four parameters of AMS, six of eight domains in SF-36, IIEF-5 and total IPSS improved significantly after 3 months TRT. In addition, all IPSS domains also improved significantly, and voiding disturbance seems to have improved more than storage disturbance (P = 0.0280 vs. 0.0483). CONCLUSION: TRT by administration of GL is considered to be effective in the improvement of not only ED and LOH symptoms, but also LUTS (especially voiding disturbance) of patients with LOH.

Clinical efficacy of Japanese traditional herbal medicine (Kampo) in patients with late-onset hypogonadism.

INTRODUCTION: In addition to hormone replacement therapy, non-hormonal therapy, particularly Japanese traditional herbal medicine (Kampo), has been used to alleviate the various symptoms of female menopause. The efficacy and safety of Japanese traditional herbal medicine for male late-onset hypogonadism (LOH) are investigated. METHODS: One hundred fifty-one patients with LOH were treated via the administration of Japanese traditional herbal medicine. The most appropriate Japanese traditional herbal medicine was administered to patients according to their pathogenic alteration. After 4 weeks, the clinical efficacy was evaluated based on improvement of LOH symptoms and the score of the simplified menopausal index (SMI). Additionally, predictive factors of efficacy of Japanese traditional herbal medicine were analyzed. RESULTS: Among 151 patients with LOH, 63 (41.8%) achieved both relief from LOH symptoms and normalized SMI score (Excellent response group), whereas 44 (29.1%) achieved either relief from LOH symptoms or normalized SMI score (Fair). However, 44 (29.1%) patients displayed neither relief from LOH symptoms nor normalized SMI score (Poor). Adverse reactions were observed only in four (2.6%) patients. Patients displaying excess conditions and mild LOH symptoms appeared to be superior candidates for Japanese traditional herbal medicine. CONCLUSION: Japanese traditional herbal medicine is an effective and safe treatment for LOH.

[Ejaculatory disorder caused by doxazosin administration for blood pressure control in patient with pheochomocytoma].

A 29-year-old man had been treated for hypertension for 10 years. He suffered from speech disturbance caused by cerebral infarction, and further examinations were performed. Computerized tomography scan and magnetic resonance imaging revealed a left adrenal tumor 6 cm in size. The radioisotope (MIBG) accumulated in the left adrenal gland. The serum noradrenalin levels were high. Thus, the diagnosis of pheochomocytoma in left adrenal tumor was made. He noticed ejaculation disturbance 5 days after starting administration of doxazosin at the dose of 3 mg/day for pre-operative blood pressure control. Sperm was observed in the urine sampling obtained after masturbation, thus his ejaculation disturbance was considered to be retrograde ejaculation. Laparoscopic left adrenalectomy was performed. After the operation, his blood pressure normalized and the administration of doxazosin has not been necessary. He could perform ejaculation without any trouble after stopping doxazosin intake. The bladder neck conditions measured by ultrasonography were the same before and after the administration of doxazosin. The present case is a very rare case of ejaculation disturbance caused by non-selective alpha 1 blocker doxazosin.

[Full-term delivery following intracytoplasmic sperm injection in a case of male hypogonadotropic hypogonadism after 8-year treatment with HCG and HMG].

A 19-year-old male, who had undergone bilateral orchiopexy at 5 years of age in the Department of Pediatric Surgery, was referred to our clinic presenting with bilateral small testes. Bilateral testis volume was 4 ml involving a small penis and scant pubic hair per Tanner Stage 2. Serum luteinizing hormone, follicle stimulating hormone and testosterone levels were low. Results of hormonal loading tests, including luteinizing hormone-releasing hormone (LH-RH) and human chorionic gonadotropin (HCG), were positive. Brain computed tomographic scan revealed no abnormal findings. The diagnosis of male hypogonadotropic hypogonadism was rendered based on these data. Administration of LH-RH for 1 year was ineffective. Subsequently, HCG and human menopausal gonadotropin (HMG) treatments were initiated. The symptoms of male insufficiency improved; moreover, sperm formation was apparent following HCG and HMG treatments. The patient has received HCG and HMG injections for eight years; furthermore, his wife delivered a boy consequent to the first intracytoplasmic sperm injection.