Practice Variation in the Management of Adult Hydroceles: A Multinational Survey.

Background: Although hydrocele is one of the most common urologic pathologies, it is seldom studied, and the major urologic associations have no guidelines for the management of adult hydroceles. Objective: To characterize international practice variation in the treatment of adult hydroceles. Design setting and participants: An international survey was conducted addressing the management of hydroceles among urologists in Belgium, Denmark, Finland, Iceland, Japan, and the Netherlands from September to December 2020. We invited a random sample of 170 urologists from each country (except Iceland). Outcome measurements and statistical analysis: Urologists' treatment options, factors relevant for decision-making, expected patient satisfaction, and outcomes after aspiration versus surgery were assessed. Results and limitations: Of the 864 urologists contacted, 437 (51%) participated. Of the respondents, 202 (53%) performed both hydrocelectomies and aspiration, 147 (39%) performed hydrocelectomies only, and 30 (8%) performed aspiration only. In Belgium (83%), the Netherlands (75%), and Denmark (55%), urologists primarily performed hydrocelectomies only, whereas in Finland (84%), Japan (61%), and Iceland (91%), urologists performed both hydrocelectomies and aspiration. Urologists favored hydrocelectomy for large hydroceles (78.8% vs 37.5% for small), younger patients (66.0% for patients <50 yr vs 41.2% for ≥70 yr), patients with few or no comorbidities (62.3% vs 23.1% with multiple comorbidities), and patients without antithrombotic agents (53.5% vs 36.5% with antithrombotic agents). Most urologists considered patient satisfaction to be highest after hydrocelectomy (53.8% vs 9.9% after aspiration) despite believing that hydrocelectomy is more likely to cause complications (hematoma 77.8% vs 8.8% after aspiration). Estimates varied between countries. Conclusions: We found a large variation in the treatment of adult hydroceles within and between countries. Optimization of hydrocele management globally will require future studies. Patient summary: Our international survey shows that treatment of adult hydrocele varies considerably within and between countries.

Dynamic change and preventive role of stress response via Keap1-Nrf2 during renal crystal formation.

Oxidative stress is a major risk factor for calcium oxalate nephrolithiasis. Reports suggest that oxidative stress response is induced in animals and humans with kidney stones. Keap1, Nrf2, and HO-1 are known as oxidative stress mediators. However, the association between oxidative stress response and stone formation is unclear. In this study, we analyzed oxidative stress response from the acute to the crystal formation phase when crystal formation was applied to renal crystal mice model and bioimaging mice and investigated the effect on crystal formation. In renal tissues, after glyoxylate administration, HO-1 increased for up to 6 h and returned to baseline at 24 h. This was observed following each daily dose until five days after the crystallization phase; however, the range of increase was attenuated. The possibility that Nrf2 activity influenced the number of crystals was considered in the experiment. Crystal formation increased in Nrf2-deficient mice and could be reduced by Nrf2 activators. In conclusion, the oxidative stress response via the Keap1-Nrf2 pathway may contribute to crystal formation. Particularly, this pathway may be a prospective target for drug development to prevent and cure nephrolithiasis.

Recurrence of renal cell carcinoma after simultaneous radical nephrectomy and cadaver renal transplant.

Introduction: Generally, renal transplantation is contraindicated in cancer patients, and a certain follow-up period is required. We report a case of late recurrence of renal cell carcinoma in a patient who underwent simultaneous radical nephrectomy and cadaver renal transplantation due to renal cell carcinoma observed during renal transplantation after 12 years. Case presentation: Incidental renal cell carcinoma was found in a 48-year-old man during kidney transplantation who subsequently underwent simultaneous cadaver kidney transplantation and radical nephrectomy. Twelve years after transplantation, he developed an anterior mediastinal tumor, a lung tumor which was resected and a right adrenal gland mass which was resected along with the right kidney. Currently, he is being treated with tyrosine kinase inhibitors owing to the metastasis in the left adrenal gland. Conclusion: In patients with metastatic carcinoma undergoing renal transplant, the indications for surgical procedures and choice of immunosuppressants should be carefully considered.

Effects of the xanthine oxidase inhibitor, febuxostat, on the expression of monocyte chemoattractant protein-1 and synchronous genes in MDCK cells treated with calcium oxalate monohydrate crystals.

OBJECTIVES: To examine the effects of the selective xanthine oxidase inhibitor febuxostat on the expression of inflammation-related genes involved in stone formation. METHODS: Madin-Darby canine kidney cells were exposed to febuxostat, followed by calcium oxalate monohydrate crystals. Monocyte chemoattractant protein-1 messenger ribonucleic acid expression levels were determined by real-time reverse transcription polymerase chain reaction analysis. Deoxyribonucleic acid microarray analysis was utilized to evaluate gene expression. RESULTS: Calcium oxalate monohydrate crystals activated monocyte chemoattractant protein-1 messenger ribonucleic acid expression in a time- and concentration-dependent manner. Febuxostat suppressed monocyte chemoattractant protein-1 expression. The expression levels of a group of inflammatory genes, including interleukin-8 and chemokine (C-X-C motif) ligand 10, which are downstream of reactive oxygen species, fluctuated similarly to the observed monocyte chemoattractant protein-1 fluctuations and were reduced by febuxostat pretreatment. CONCLUSIONS: Febuxostat exerts preventive effects against reactive oxygen species production and oxidative stress, and might represent a potential treatment for calcium oxalate stones. In the present study, febuxostat downregulated the calcium oxalate monohydrate crystal-induced monocyte chemoattractant protein-1 messenger ribonucleic acid expression.

Intracytoplasmic Lumen in Urine Cytology Predicts Worse Prognosis in Non-Muscle-Invasive Bladder Cancers.

BACKGROUND: Intracytoplasmic lumina (ICL) are observed in several cancers, including urothelial carcinoma (UC). We have reported that ICL in urine cytology (cICL) is more frequent in high-grade UCs than in low-grade UCs; however, the correlation between the presence of ICL and prognosis is unclear. OBJECTIVES: The aim of this work was to determine the association between cICL and prognosis in bladder cancer. METHOD: We retrospectively investigated 87 patients with bladder cancer who received a histological diagnosis within 3 months of urine cytology at Kanazawa Medical University between 2003 and 2007. The cytological diagnosis and the number of cICL, histological diagnosis, tumor grade or variant, pT stage, ICL in histological specimens, and immunohistochemistry for mucins were evaluated. Data on the treatment type, recurrence, survival, cause of death, and length of follow-up were collected from electronic medical records. RESULTS: Muscle invasion, high-grade UC, lymph node metastasis, distant metastasis, adjuvant therapy, and disease-related mortality were more frequent in patients with cICL-positive bladder cancer than in those without cICL-positive bladder cancer. Immunohistochemistry revealed the expression of Muc-1 and Muc-4 in patients with cICL-positive bladder cancer. Univariate analysis revealed that cytological diagnosis by the Paris system and the 2015 version of the Japanese reporting system, muscle invasion, high-grade UC, lymph node metastasis, distant metastasis, and adjuvant chemotherapy and/or radiotherapy were significant factors associated with prognosis. Furthermore, survival was shorter in patients with cICL-positive non-muscle-invasive bladder cancer than in those with cICL-negative non-muscle-invasive bladder cancer. In the multivariate analysis, only distant metastasis was significantly associated with survival. CONCLUSIONS: cICL predicted shorter survival in patients with non-muscle-invasive bladder cancer, suggesting that ICL is one of the important diagnostic features of high-grade UC with a worse prognosis in urine cytology.

Potential of an Interorgan Network Mediated by Toxic Advanced Glycation End-Products in a Rat Model.

Excessive intake of glucose and fructose in beverages and foods containing high-fructose corn syrup (HFCS) plays a significant role in the progression of lifestyle-related diseases (LSRD). Glyceraldehyde-derived advanced glycation end-products (AGEs), which have been designated as toxic AGEs (TAGE), are involved in LSRD progression. Understanding of the mechanisms underlying the effects of TAGE on gene expression in the kidneys remains limited. In this study, DNA microarray analysis and quantitative real-time polymerase chain reaction (PCR) were used to investigate whether HFCS-consuming Wister rats generated increased intracellular serum TAGE levels, as well as the potential role of TAGE in liver and kidney dysfunction. HFCS consumption resulted in significant accumulation of TAGE in the serum and liver of rats, and induced changes in gene expression in the kidneys without TAGE accumulation or upregulation of receptor for AGEs (RAGE) upregulation. Changes in specific gene expression profiles in the kidney were more correlated with TAGE levels in the liver tissue than in the serum. These findings suggest a direct or indirect interaction may be present between the liver and kidneys that does not involve serum TAGE or RAGE. The involvement of internal signal transduction factors such as exosomes or cytokines without IL-1ß and TNF-α is suggested to contribute to the observed changes in kidney gene expression.

High-salt diet promotes crystal deposition through hypertension in Dahl salt-sensitive rat model.

OBJECTIVES: To study the promotive effect of salt-induced hypertension on crystal deposition and urolithiasis using a salt-sensitive rat hypertension model. METHODS: Hyperoxaluria and hypercalciuria were induced in male Dahl salt-sensitive rats with administration of ethylene glycol and alfacalcidol. Hypertension was induced by a high-salt diet. Eplerenone, a selective mineralocorticoid receptor antagonist, was given. Blood and urine were collected to evaluate renal function, electrolytes and the blood renin-angiotensin-aldosterone system. Renal calcium content was also evaluated. Histological examination, transcriptome analysis with DNA microarray and semiquantitative reverse transcriptase polymerase chain reaction were carried out. RESULTS: A high-salt diet increased crystal deposition in Dahl salt-sensitive rats with hypertension, and eplerenone administration significantly suppressed it. The mRNA expression profile was associated with crystal formation, growth, adhesion and cellular injury, and it was regulated in the group exposed to a high-salt diet and ethylene glycol. CONCLUSIONS: A high-salt diet has a promotive effect on salt-sensitive hypertension and urolithiasis. This promotive effect can be prevented by eplerenone administration. Hence, salt-sensitive hypertension has promotive effects on crystal deposition in Dahl salt-sensitive rats.

[CLINICAL STUDY OF THE PROSTATE CANCERS WITH A SERUM PROSTATE SPECIFIC ANTIGEN LEVEL OF MORE THAN 100 ng/ml AT THE FIRST DIAGNOSIS].

In patients with prostate cancer high serum prostate specific antigen (PSA) at diagnosis was generally regarded as a strong impression of advanced disease with distant metastasis and poor prognosis. (Objective) We reported a retrospective study of prognostic factor and Overall survival (OS) in patients with prostate specific antigen (PSA) level of greater than 100 ng/ml (PSA≥100 ng/ml). (Subjects and methods) Between January 2002 and December 2015, 60 patients were diagnosed prostate cancer with PSA≥100 ng/ml and performed hormonal monotherapy at Kanazawa Medical University hospital. We evaluated initial PSA level, Gleason score, Gleason Grading Group, clinical stage, site of metastasis, PSA nadir level, Time to PSA nadir (TTN), serum Hemoglobin (Hb) level, serum C-Reactive Protein (CRP) level, serum Lactate Dehydrogenase (LDH) level, serum Alkaline Phosphatase (ALP) level, clinical passage and survival time. (Results) The median age of the patients was 73 years old (54-90) and the initial PSA levels ranged from 100 ng/ml to 15,823 ng/ml (median 390).Prognostic factors of overall survival were site of metastasis, Gleason score, Gleason Grading Group, PSA nadir level, TTN, serum CRP level, serum LDH level and serum ALP level at the diagnosis. In multivariate analysis serum LDH level remained an independent predictor of OS.

Chronological changes in epidemiological characteristics of lower urinary tract urolithiasis in Japan.

OBJECTIVES: To determine changes and trends in the annual incidence and epidemiological aspects of lower urinary tract stones in Japan. METHODS: Data about patients who had been diagnosed by urologists in 2015 with first and recurrent lower urinary tract stones were collected from 301 hospitals approved by the Japanese Board of Urology. The estimated annual incidence according to sex, age and stone composition was compared with previous nationwide surveys between 1965 and 2005. RESULTS: The incidence of lower urinary tract stones in Japan has steadily increased from 4.7 per 100 000 in 1965 to 12.0 per 100 000 in 2015. However, the age standardized annual incidence of lower urinary tract stones has remained relatively stable over the same period at 5.5 per 100 000 and 6.0 per 100 000 in 1965 and 2015, respectively. The increase in incidence was most evident among individuals aged ≥80 years. The incidence of calcium oxalate stones has steadily increased among males and females, whereas that of infection-related stones has significantly decreased from 26.2% to 14.3% among men over the past 50 years. CONCLUSIONS: Nationwide surveys suggest a steady increase in the incidence of lower urinary tract stones over a 50-year period in Japan. This trend might reflect changes in the aging population and improved Japanese medical standards.

Ureterosciatic hernia treated with ureteral stent placement.

A 92-year-old female with a history of asthma and chronic heart failure presented with left lumber back pain. Physical examination revealed knocking tenderness at the left costal-vertebral angle. Laboratory test results were within normal limits. Abdominal CT showed a left hydroureteronephrosis and an obstruction in the left distal ureter with herniation into the sciatic foramen. A ureteral stent was inserted into the left ureter and was removed after 2 months. She has not complained of pain or showed symptoms since the removal. Our case suggests that doctors consider the possibility of ureterosciatic hernias when examining older patients complaining of lower back pain.

Chronological changes in the epidemiological characteristics of upper urinary tract urolithiasis in Japan.

OBJECTIVES: To assess epidemiological and chronological trends of upper urinary tract stones in Japan in 2015. METHODS: Patients with a first episode of upper urinary tract stones in 2015 were enrolled in this nationwide survey. The study included all hospitals approved by the Japanese Board of Urology, therefore covering most of the hospitals where urologists practice in Japan. The annual incidence and composition of urolithiasis were evaluated by age and sex. These results were compared with the previous results of the nationwide surveys from 1965 to 2005 to analyze temporal trends. RESULTS: The estimated annual incidence of a first-episode upper urinary tract stone in 2015 was 137.9 (191.9 in men and 86.9 in women) per 100 000. The estimated age-standardized first-episode upper urinary tract stone incidence in 2015 was 107.8 (150.6 in men and 63.3 in women) per 100 000, which did not represent a significant increase since 2005. An equivalent incidence was observed in patients aged >50 years, whereas a reduced incidence was observed in patients aged <50 years in both sexes. The proportion of patients who received percutaneous nephrolithotomy and/or ureteroscopy increased by approximately fivefold in the past 10 years. CONCLUSIONS: The steady increase in the annual incidence of upper urinary tract stones since 1955 leveled off in 2015. The current results show novel trends in the incidence and treatment modalities in the nationwide surveys of urolithiasis in Japan.

[Clinical Study on the Efficacy and Continuous Docetaxel Based Chemotherapy Treatment for Castration-Resistant Prostate Cancer].

We report a retrospective study on the efficacy, adverse events and the factors for continuous docetaxel (DOC) therapy for patients with castration-resistant prostate cancer (CRPC). Between April 2007 and April 2015, 37 CRPC patients were treated with DOC therapy at Kanazawa Medical University Hospital. DOC was administered every 3 weeks at 70 mg/m2. Prostatic specific antigen (PSA) level, adverse events, cycles of DOC therapy, survival time and clinical passage were examined. Fifteen patients showed a decrease in PSA level of 50% or more, 9 patients showed less than 50% decrease in PSA level and 13 patients showed no decrease in PSA level. Adverse effect of grade 3 consisted of neutropenia in 29.7% and leukocytopenia in 10.8%. The median number of treatment cycles was 11.7 courses. The patients were divided into two groups ; the first group comprised of 26 patients who received short-term DOC therapy (≤10 cycles) and the second group comprised of 11 patients who received long-term DOC therapy (≥11 cycles). The 1-year survival rate was 59 and 100% for the short-term and long-term groups, respectively. Long-term treatment was related to pretreatment PSA nadir, time to progression of CRPC and serum lactate dehydrogenase level.

Epidemiology of stone disease across the world.

Nephrolithiasis is a highly prevalent disease worldwide with rates ranging from 7 to 13% in North America, 5-9% in Europe, and 1-5% in Asia. Due to high rates of new and recurrent stones, management of stones is expensive and the disease has a high level of acute and chronic morbidity. The goal of this study is to review the epidemiology of stone disease in order to improve patient care. A review of the literature was conducted through a search on Pubmed®, Medline®, and Google Scholar®. This review was presented and peer-reviewed at the 3rd International Consultation on Stone Disease during the 2014 Société Internationale d'Urologie Congress in Glasgow. It represents an update of the 2008 consensus document based on expert opinion of the most relevant studies. There has been a rising incidence in stone disease throughout the world with a narrowing of the gender gap. Increased stone prevalence has been attributed to population growth and increases in obesity and diabetes. General dietary recommendations of increased fluid, decreased salt, and moderate intake of protein have not changed. However, specific recommended values have either changed or are more frequently reported. Geography and environment influenced the likelihood of stone disease and more information is needed regarding stone disease in a large portion of the world including Asia and Africa. Randomized controlled studies are lacking but are necessary to improve recommendations regarding diet and fluid intake. Understanding the impact of associated conditions that are rapidly increasing will improve the prevention of stone disease.

THE EFFECT OF RADIATION THERAPY FOR BONE METASTASIS IN URINARY ORGAN CANCER.

(Objective) Bone metastasis symptoms are complications that greatly reduce the quality of life (QOL) of cancer patients. We report a retrospective study on the efficacy of radiation therapy for patients with bone metastasis in urinary organ cancer. (Subjects and methods) Subjects are comprised of 17 patients; total irradiated areas consist of 25 sites. There are 5 patients diagnosed with renal cell carcinoma, 1 patient with bladder cancer and 11 patients with prostatic cancer. All of them have undergone radiation therapy for bone metastasis in urinary organ cancer between April 2007 and March 2014 in the Department of Urology, Kanazawa Medical University. The mean age of the patients was 66.7 years old. We looked at irradiated areas, exposure dose and changes of symptom in all patients. (Results) Irradiated areas are thoracolumbar vertebrae (14 sites), cranial base (2 sites), pubic bone (1 site), ilium bone (2 sites), sacral bone (1 site), rib bone (1 site) and hip joint (1 site). The mean exposure dose of one area is 37.5 Gy (13.5-60). 19 irradiated sites which were previously reported to have sharp pain have gained improvement at 16 sites. These 16 sites have comparatively lesser pain or no pain. 8 cases in acknowledgment of walk difficulty, it was with 7 cases walking alone possibility again. (Conclusion) This study showed that radiation therapy have significant improvement in terms of symptoms and QOL for the patients with bone metastasis in urinary organ cancer.

Immunohistochemical expression of four different stem cell markers in prostate cancer: High expression of NANOG in conjunction with hypoxia-inducible factor-1α expression is involved in prostate epithelial malignancy.

Cancer stem cells (CSCs) have been identified in a variety of cancer types, including prostate cancer. The aim of the present study was to evaluate the immunohistochemical expression of NANOG, octamer 4 (OCT4), cluster of differentiation 133 (CD133) and NESTIN, which are all CSC markers, and assess their function in prostate carcinogenesis. A total of 114 patients were referred to the Kanazawa Medical University Hospital (Uchinada, Japan) having presented with elevated serum prostate-specific antigen levels and/or abnormal digital rectal examinations, and underwent transrectal ultrasound sonography guided eight core biopsies. The prostate pathological specimens were re-evaluated for selection in this study. When specimens were diagnosed as prostate cancer, immunohistochemical analysis of the four different stem cell markers (NANOG, OCT4, CD133 and NESTIN) and hypoxia-inducible factor (HIF)-1α was performed. Prostate cancer was found in 38 cases (33.3%), while the other patients had benign prostate hyperplasia with prostatitis. All prostate cancers were histopathologically identified as adenocarcinomas of various grades, and cancer cells and intraepithelial neoplasia (high grade) were immunohistochemically shown to express NANOG and OCT4, but not CD133 and NESTIN. The intensity of NANOG expression was much greater than that of OCT4, and the positivity and intensity of the four stem cell markers, including NANOG, were elevated with high Gleason scores. A significant correlation was observed between the NANOG- and HIF-1α-positive regions. The CSC markers, in particular OCT4 and NANOG, were immunohistochemically expressed in prostate cancers. Furthermore, HIF-1α expression may affect NANOG and/or OCT4 expression. The findings of the current study suggested that NANOG expression may be a biomarker for the diagnosis of prostate cancer, and the coexpression of NANOG and HIF-1α may be involved in prostate carcinogenesis.

Factors influencing patient satisfaction with antimuscarinic treatment of overactive bladder syndrome: results of a real-life clinical study.

OBJECTIVES: To investigate patient satisfaction with antimuscarinic treatment of overactive bladder syndrome, and to identify factors having a significant influence on satisfaction. METHODS: A cross-sectional questionnaire survey was carried out to assess treatment satisfaction among male and female patients with overactive bladder (age ≥20 years) in the Hokuriku district of Japan. The overactive bladder symptom scores, treatment efficacies, adverse events (dry mouth and constipation), and patient satisfaction scores were investigated and compared among patients using different antimuscarinic therapeutics. RESULTS: In total, 977 survey respondents (52.6% men; mean age 73.6 years) received antimuscarinic treatment. The mean overactive bladder symptom score of these patients was 6.17; in addition, 32.3% patients were satisfied with their treatment, but 33.1% were dissatisfied. Factors having a significant influence on treatment satisfaction were sex (men were less satisfied), efficacy, adverse events and the overactive bladder symptom score. Constipation negatively influenced patient satisfaction to a greater extent than did dry mouth. Patient satisfaction varied according to the drug used. Constipation was less severe with the immediate-release-type agents (imidafenacin and oxybutynin) than with the extended-release-type (propiverine, solifenacin or tolterodine). CONCLUSIONS: Just one-third of Japanese Hokuriku patients with overactive bladder seem to be satisfied with their antimuscarinic treatment. Patient satisfaction is impaired by poor efficacy and the presence of adverse events; furthermore, constipation should be recognized as an adverse event that negatively influences patient satisfaction to a greater extent than dry mouth. Patient satisfaction differs according to the antimuscarinic agent used, with higher patient satisfaction being associated with less severe constipation.