Clinical Utility of Germline Genetic Testing in Japanese Men Undergoing Prostate Biopsy.

Background: Multiple common variants and also rare variants in monogenic risk genes such as BRCA2 and HOXB13 have been reported to be associated with risk of prostate cancer (PCa); however, the clinical setting in which germline genetic testing could be used for PCa diagnosis remains obscure. Herein, we tested the clinical utility of a 16 common variant-based polygenic risk score (PRS) that has been developed previously for Japanese men and also evaluated the frequency of PCa-associated rare variants in a prospective cohort of Japanese men undergoing prostate biopsy. Methods: A total of 1336 patients undergoing first prostate biopsy were included. PRS was calculated based on the genotype of 16 common variants, and sequencing of 8 prostate cancer-associated genes was performed by multiplex polymerase chain reaction based target sequencing. PRS was combined with clinical factors in logistic regression models to assess whether addition of PRS improves the prediction of biopsy positivity. Results: The top PRS decile was associated with an odds ratio of 4.10 (95% confidence interval = 2.46 to 6.86) with reference to the patients at average risk, and the estimated lifetime absolute risk approached 20%. Among the patients with prostate specific antigen 2-10 ng/mL who had prebiopsy magnetic resonance imaging, high PRS had an equivalent impact on biopsy positivity as a positive magnetic resonance imaging finding. Rare variants were detected in 19 (2.37%) and 7 (1.31%) patients with positive and negative biopsies, respectively, with BRCA2 variants being the most prevalent. There was no association between PRS and high-risk rare variants. Conclusions: Germline genetic testing could be clinically useful in both pre- and post-PSA screening settings.

A comparison of laparoendoscopic single-site surgery versus conventional procedures for laparoscopic donor nephrectomy: a Japanese multi-institutional retrospective study.

PURPOSE: Laparoendoscopic single-site donor nephrectomy (LESSDN) is a feasible and effective procedure because of its non-invasiveness and better cosmetic outcomes. However, there have been few multi-institutional studies conducted by multiple surgeons on LESSDN. We retrospectively compared the clinical data and outcomes between LESSDN and conventional laparoscopic donor nephrectomy (LDN) at multiple institutes in Japan. MATERIALS AND METHODS: From 2009 to 2015, the clinical data of 223 donors who underwent LESSDN and 151 donors who underwent LDN were collected from 10 institutes. All LESSDNs were performed transperitoneally, whereas LDNs were performed transperitoneally (P-LDN) in 75 patients and retroperitoneally (R-LDN) in 76 patients. RESULTS: In the LESSDN group, the single-incision site was pararectal in 155 (69.5%) patients and umbilical in 65 (29.1%) patients. Multiple surgeons (one to eight per institute) performed the LESSDN. No significant differences were observed between the three groups regarding estimated blood loss and warm ischemic time. The operative time was significantly shorter in the LESSDN group than in the R-LDN group (p = 0.018). No significant differences were observed regarding the rates of blood transfusion, open conversion, visceral injuries, and postoperative complications. Furthermore, no significant differences were observed regarding the dose of analgesic and the rate of delayed graft function. One patient required open conversion due to injury to the renal artery. Selection of LESS procedure was not an independent risk factor for the median serum creatinine level of above 1.27 mg/dL in recipients at 1 year after kidney transplantation. CONCLUSION: The results showed the technical feasibility of LESSDN compared with the standard LDNs in a multi-institutional and multi-surgeon setting. A few observed non-negligible complications and the significantly higher levels of serum creatinine in patients who underwent LESSDN indicate that this procedure should be employed cautiously when performed by surgeons without ample experience in performing LESS procedures.

The efficacy and toxicity of cabazitaxel for treatment of docetaxel-resistant prostate cancer correlating with the initial doses in Japanese patients.

BACKGROUND: We analyzed the efficacy and toxicity of cabazitaxel (CBZ) at high and low initial doses in Japanese patients with docetaxel-resistant castration-resistant prostate cancer (CRPC). METHODS: We retrospectively evaluated 118 patients who received CBZ for docetaxel-resistant CRPC in 10 university hospitals in Japan between 2014 and 2016. The rate of decrease of prostate-specific antigen (PSA), adverse events, progression-free survival (PFS), and overall survival (OS) were compared between patients receiving initially high (≥22.5 mg/m2, n = 36) and low (≤20 mg/m2, n = 80) CBZ doses. Factors associated with survival and grade 4 neutropenia were evaluated. RESULTS: PSA values decreased by > 50% in 22 patients (19%), with a higher frequency in the high-dose group than in the low-dose group (29 and 14%, P = 0.073). The median PFS time for the all-patient, high- and low-dose groups was 2.8 months (95% confidence interval [CI] 1.9-4.4), 2.1 months (1.2-5.5), and 3.0 months (2.0-4.4), respectively (P = 0.904). The median OS times were 16.3 months (95% CI 9.7-30.9), 30.9 months (11.8-47.4), and 10.2 months (8.6-20), respectively (P = 0.020). In multivariate analyses, PFS was significantly associated with existing bone metastasis at diagnosis (P = 0.005) and OS with PSA > 100 ng/ml (P = 0.007), hemoglobin < 12 g/dl (P = 0.030), and low initial CBZ dose (P = 0.030). Grade 4 neutropenia occurred in 53 patients (45%) and was associated with a low CBZ dose (hazard ratio 0.21, 95% CI 0.08-0.59, P = 0.002). CONCLUSIONS: CBZ at a higher initial dose may have similar response rate and response duration, but longer survival duration after treatment with higher toxicity than a lower initial dose for docetaxel-resistant CRPC in Japanese patients.

Endoscopic surgery in Japan: The 13th national survey (2014-2015) by the Japan Society for Endoscopic Surgery.

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, the operative procedure has been standardized, and the safety and usefulness of endoscopic surgery have been evaluated. In accordance with the social acceptance of endoscopic surgery as a less-invasive surgery, the number of endoscopic procedures has been increasing in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has played an important role in the development of endoscopic surgery in Japan. For example, JSES established a technical skills certification system for surgeons to train instructors how to teach safe endoscopic surgery, and the organization performs a national survey every 2 years. In 2015, a total of 211 953 patients underwent endoscopic surgery in all surgical domains, including abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The course of laparoscopic surgery's development and its current status are reported here based on the results of the most recent questionnaire survey conducted by JSES.

Pfannenstiel laparoendoscopic reduced-port bilateral radical nephrectomy for a patient with renal cell carcinoma undergoing hemodialysis.

We performed Pfannenstiel laparoendoscopic reduced-port bilateral radical nephrectomy on a patient with renal cell carcinoma undergoing hemodialysis. A 4-cm Pfannenstiel incision was made, and a GelPOINT access was inserted. Three trocars were placed through the access platform, and additional 5- and 3-mm trocars were inserted in the umbilicus and paraumbilical area, respectively. After left nephrectomy, right nephrectomy was successfully completed in 401 min, with an estimated blood loss of 70 mL. There were no intraoperative or postoperative complications, and the patient was discharged 10 days postoperatively. The umbilical scar was concealed within the umbilical fold, and the scar from the 3-mm trocar was almost invisible. The Pfannenstiel scar was minimal and concealed by the patient's underwear. Pfannenstiel laparoendoscopic reduced-port simultaneous bilateral radical nephrectomy is a safe and technically feasible procedure that offers great cosmesis for patients with bilateral renal tumors and end-stage renal disease.

Urological laparoendoscopic single-site and reduced port surgery: A nationwide survey in Japan.

OBJECTIVES: To evaluate the current status of urological laparoendoscopic single-site and reduced port surgery in Japan. METHODS: Of the 152 institutions to which councilors of the Japanese Society of Endourology belong, 42 (28%) have carried out laparoendoscopic single-site and reduced port surgery. A total of 32 of these institutions agreed to participate in this survey. Patients who had undergone surgery between January 2008 and March 2014 were included in the present study. RESULTS: Overall, 1145 cases of laparoendoscopic single-site and reduced port surgery were recorded during the study period. The most frequent procedures were adrenalectomy and radical nephrectomy. Laparoendoscopic single-site and reduced port surgery represented 12% (872/7311) of all laparoscopic procedures carried out at participating institutions. The number of patients who underwent pyeloplasty, donor nephrectomy and simple nephrectomy tended to increase, whereas those who underwent adrenalectomy, radical nephrectomy and nephroureterectomy peaked in 2012, and then tended to decrease in 2013. The rates of conversion, perioperative and postoperative complications, were 2.7%, 2.2% and 4.5%, respectively. CONCLUSIONS: The number of laparoendoscopic single-site and reduced port urological surgeries in Japan has increased for benign indications, such as pyeloplasty, donor nephrectomy and simple nephrectomy. In contrast, procedures such as adrenalectomy and radical nephrectomy are trending down after reaching a peak in 2012. Overall, laparoendoscopic single-site and reduced port urological surgery in Japan is being safely carried out when compared with other reported series of laparoendoscopic single-site surgery and conventional laparoscopic surgery.

Laparoendoscopic single-site nephrectomy for hemodialysis patients with dialysis-related renal tumors.

PURPOSE: The purpose of this study is to assess the efficacy of laparoendoscopic single-site (LESS) nephrectomy in hemodialysis patients, we compared outcomes between LESS nephrectomy and conventional laparoendoscopic nephrectomy in hemodialysis patients with dialysis-related renal tumors. MATERIAL AND METHODS: A total of 16 hemodialysis patients who underwent LESS nephrectomy (LESS-N; n = 8) or conventional laparoendoscopic nephrectomy (C-N; n = 8) between November 2003 and July 2012 were retrospectively evaluated. Outcomes were compared between the two groups. RESULTS: Patient and tumor characteristics were similar between the LESS-N and C-N groups. The mean operative duration was longer in the LESS-N than in the C-N group (231.0 ± 26.7 min versus 188.6 ± 36.4 min; p = .025). The mean estimated blood loss was lower in the LESS-N compared with the C-N group (26.4 ± 14.4 ml versus 65.6 ± 45.2 ml; p = .047). Postoperative complications were observed in three cases, comprising one case of retroperitoneal hematoma in the LESS-N group and one case each of peritoneal hematoma and retroperitoneal abscess in the C-N group. Surgical scarring was minimal in the LESS-N group. CONCLUSIONS: Although there is a little extension of the operating time, LESS nephrectomy in hemodialysis patients is a feasible procedure compared with the conventional method.

Endoscopic surgery in Japan: The 12th national survey(2012-2013) by the Japan Society for Endoscopic Surgery.

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, operative procedures have been standardized, and the safety and usefulness of endoscopic surgery have been evaluated. With the acceptance of endoscopic surgery as less invasive than open surgery, the number of the endoscopic procedures continues to increase in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has had an important role in the development of endoscopic surgery in Japan. For example, JSES established a technical skills certification system for physicians to train instructors to teach safe endoscopic surgery. Additionally, JSES has performed a national survey every 2 years. In 2013, 178 084 patients underwent endoscopic surgery in all surgical domains, including abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The development and current status of laparoscopic surgery are reported here based on the results of the most recent questionnaire survey conducted by JSES.

Three-flap umbilicoplasty: a novel and preliminary method of laparoendoscopic single-site transumbilical surgical approach for urachal remnants.

PURPOSE: Symptomatic urachal remnants are rare benign anomalies affecting young adults. For these patients, both curative treatment and acceptable postoperative aesthetic outcomes are important. Here, we describe a novel transumbilical approach, using Y-shaped incisions and three-flap umbilicoplasty techniques, to improve repair and aesthetic outcomes. MATERIALS AND METHODS: The clinical and perioperative data of 16 patients (11 men; median age, 25 years; range 16-46 years) who underwent LESS surgery and three-flap umbilicoplasty (LESS group) between December 2013 and March 2017 were analyzed. For comparison, the perioperative data of those who underwent conventional laparoscopic surgery (CL group) between May 2010 and November 2013 at the same institutions were investigated. RESULTS: The median operative time of the LESS group was longer than that of the CL group (146.5 vs 107 min; p = 0.009). The estimated blood loss and postoperative hospital stay were not significantly different between the two groups. The two perioperative complications were injury to the transverse colon serosa and minor surgical site infection. Both complications were resolved with appropriate management. CONCLUSIONS: This novel umbilical approach is useful for patients with symptomatic urachal remnants, with the reduction in port-site scarring resulting in good postoperative cosmesis.

Impact of Surgeon and Hospital Volume on the Safety of Robot-Assisted Radical Prostatectomy: A Multi-Institutional Study Based on a National Database.

INTRODUCTION: We aimed to perform a multi-institutional study using a national database led by the Japanese Society of Endourology to investigate the effect of surgeon or hospital volume on the safety of robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Clinical data of 3,214 patients who underwent RARP for the treatment of clinically localized prostate cancer between April 2012 and March 2013 in Japan were evaluated. Surgical outcomes and all intra- and perioperative complications were collected. RESULTS: The intraoperative complication rate was 0.56%. In a total number of 241 patients, 261 perioperative complications were observed. The following percentages of patients presented the Clavien-graded complications: 7.2%, grades 1-2; 0.84%, grade 3; and 0.093%, grade 4a. No cases of multiple organ dysfunction or death (grades 4b and 5) were found. Multivariable logistic regression analysis showed that the hospital volume (OR 3.6; p = 0.010) for intraoperative complications and surgeon volume (OR 0.19; p < 0.0001) and extended lymph node discectomy (OR 3.9; p < 0.0001) for perioperative complications were significant independent risk factors. CONCLUSIONS: Hospital volume for intraoperative complications and surgeon volume and extended lymph node dissection for perioperative complications were significantly associated with increased risk of each complication in RARP.

Reality of nerve sparing and surgical margins in surgeons' early experience with robot-assisted radical prostatectomy in Japan.

OBJECTIVE: To analyze nerve sparing performance at an early stage of robot-assisted radical prostatectomy, and the correlation between the surgeons' experience and the risk of a positive surgical margin in patients treated with robot-assisted radical prostatectomy. METHODS: Patients' records from January 2009 to March 2013 were retrospectively reviewed, and 3469 patients with localized prostate cancer were identified at 45 institutions. Individual surgeon's experience with nerve sparing was recorded as the number of nerve sparing cases among total robot-assisted radical prostatectomies beginning with the first case during which nerve sparing was carried out. Patients were selected by propensity score matching for nerve sparing, and predictive factors of positive surgical margins were analyzed in patients with and without positive surgical margins. RESULTS: A total of 152 surgeons were studied, and the median number of robot-assisted radical prostatectomy cases for all surgeons was 21 (range 1-511). In all, 54 surgeons (35.5%) undertook nerve sparing during their first robot-assisted radical prostatectomy case. For 2388 patients selected with (1194) and without (1194) nerve sparing, predictive factors for positive surgical margin were high initial prostate-specific antigen level (P < 0.0001), high biopsy Gleason score (P = 0.0379), presence of neoadjuvant hormone therapy (P = 0.0002) and surgeon's experience with >100 cases (P = 0.0058). Thus, nerve sparing was not associated with positive surgical margins. CONCLUSION: The surgeon's experience influences the occurrence of positive surgical margins, although a considerable number of surgeons carried out nerve sparing during their early robot-assisted radical prostatectomy cases. Surgeons should consider their own experience and prostate cancer characteristics before carrying out a nerve sparing robot-assisted radical prostatectomy.

Scientific Skill Assessment of Basic Surgical Dissection and Overall Laparoscopic Performance.

To improve surgical education, objective and scientific skill assessments are required. There are two types of skill evaluations: assessments of basic surgical skills and assessments of overall surgical performance. To establish a reliable assessment method for surgical dissection, we measured the force applied on the tip of a surgical instrument during dissection of the renal vessels of pigs. The experiments revealed that, during surgical dissection, expert laparoscopic surgeons applied vertical force at the beginning of the stroke and then horizontal force, with minimum vertical force, at the end of the stroke. As an assessment of overall surgical performance, the Endoscopic Surgical Qualification system was developed and has been used for 12 years in Japan. More than 3700 surgeons, including urologists, were determined to have appropriate laparoscopic surgical skills after assessments of unedited videos by referees.

A phase III multicenter, randomized, controlled study of combined androgen blockade with versus without zoledronic acid in prostate cancer patients with metastatic bone disease: results of the ZAPCA trial.

OBJECTIVE: To examine the antitumor activity of zoledronic acid (ZA) combined with androgen deprivation therapy (ADT) for men with treatment-naive prostate cancer and bone metastasis. METHODS: We enrolled 227 men with treatment-naive prostate cancer and bone metastasis. Participants were randomly assigned (1:1 ratio) to receive combined androgen blockade alone (CAB group) or ZA with combined androgen blockade (CZ group). Time to treatment failure (TTTF), time to the first skeletal-related event (TTfSRE), and overall survival (OS) rates were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazards model. Median follow-up duration was 41.5 months. RESULTS: Median TTTFs were 12.4 and 9.7 months for the CZ and CAB groups, respectively (HR 0.75; 95 % CI 0.57-1.00; p = 0.051). For men with baseline prostate-specific antigen levels <200 ng/mL, median TTTFs were 23.7 and 9.8 months for the CZ and CAB groups, respectively (HR 0.58; 95 % CI 0.35-0.93; p = 0.023). Median TTfSREs were 64.7 and 45.9 months for the CZ and CAB groups, respectively (HR 0.58; 95 % CI 0.38-0.88; p = 0.009). OS was similar between the groups. CONCLUSIONS: This study failed to demonstrate that combined use of ZA and ADT significantly prolonged TTTF in men with treatment-naive prostate cancer and bone metastasis. However, it generates a new hypothesis that the combined therapy could delay the development of castration resistance in a subgroup of patients with low baseline prostate-specific antigen values <200 ng/mL. The treatment also significantly prolonged TTfSRE but did not affect OS.

Laparoendoscopic single-site surgeries: A multicenter experience of 469 cases in Japan.

OBJECTIVE: To report on a multi-institutional series of non-robotic urological laparoendoscopic single-site surgery in Japan. METHODS: Consecutive cases of laparoendoscopic single-site surgery carried out between February 2009 and December 2012 at nine academic institutions were included. We examined the surgical outcomes, including conversion and complications rates. RESULTS: Four hundred and sixty-nine cases were included in the analysis. The most common procedure was adrenalectomy (n = 177) and the second most common procedure was radical nephrectomy (n = 143). The procedures also included nephroureterectomy (n = 40), living donor nephrectomy (n = 40), pyeloplasty (n = 30), urachal remnant excision (n = 9), simple nephrectomy (n = 7), radical prostatectomy (n = 6) and others (n = 17). The access sites included umbilicus (n = 248, 53%) and other sites (n = 221, 47%). A transperitoneal approach was used in 385 cases (82%), and retroperitoneal approach in 84 cases (18%). The median operation time of all procedures was 198 min. Conversion to reduced port surgery, conventional laparoscopy, or open surgery was noted in 27 cases (5.8%), 12 cases (2.6%), and two cases (0.4%), respectively, with an overall conversion rate of 8.7%. Intraoperative complications occurred in 10 cases (2.1%). Post-operative complications were noted in 29 cases (6.2%), including five major complications (1.1%). No mortality was recorded in this series. CONCLUSIONS: Non-robotic laparoendoscopic single-site surgery is technically feasible and safe for various urologic diseases in Japan. Furthermore, urological laparoendoscopic single-site surgery is a promising minimally invasive surgical option that is feasible for experienced urological surgeons in intermediate-volume centers as well as high-volume centers.

Purified Human Skeletal Muscle-Derived Stem Cells Enhance the Repair and Regeneration in the Damaged Urethra.

BACKGROUND: Postoperative damage of the urethral rhabdosphincter and nerve-vascular networks is a major complication of radical prostatectomy and generally causes incontinence and/or erectile dysfunction. The human skeletal muscle-derived stem cells, which have a synchronized reconstitution capacity of muscle-nerve-blood vessel units, were applied to this damage. METHODS: Cells were enzymatically extracted from the human skeletal muscle, sorted using flow cytometry as CD34/45 (Sk-34) and CD29/34/45 (Sk-DN/29) fractions, and separately cultured/expanded in appropriate conditions within 2 weeks. Urethral damage was induced by manually removing one third of the wall of the muscle layer in nude rats. A mixture of expanded Sk-34 and Sk-DN/29 cells was applied on the damaged portion for the cell transplantation (CT) group. The same amount of media was used for the non-CT (NT) group. Urethral pressure profile was evaluated via electrical stimulation to assess functional recovery. Cell engraftments and differentiations were detected using immunohistochemistry and immunoelectron microscopy. Expression of angiogenic cytokines was also analyzed using reverse transcriptase-polymerase chain reaction and protein array. RESULTS: At 6 weeks after transplantation, the CT group showed a significantly higher functional recovery than the NT group (70.2% and 39.1%, respectively; P < 0.05). Histological analysis revealed that the transplanted human cells differentiated into skeletal muscle fibers, nerve-related Schwann cells, perineuriums, and vascular pericytes. Active paracrine angiogenic cytokines in the mixed cells were also detected with enhanced vascular formation in vivo. CONCLUSIONS: The transplantation of Sk-34 and Sk-DN/29 cells is potentially useful for the reconstitution of postoperative damage of the urethral rhabdosphincter and nerve-vascular networks.

Mutations in the Mitochondrial ND1 Gene Are Associated with Postoperative Prognosis of Localized Renal Cell Carcinoma.

We analyzed mutations in the mitochondrial ND1 gene to determine their association with clinicopathological parameters and postoperative recurrence of renal cell carcinoma (RCC) in Japanese patients. Among 62 RCC cases for which tumor pathology was confirmed by histopathology, ND1 sequencing revealed the presence of 30 mutation sites in 19 cases. Most mutations were heteroplasmic, with 16 of 19 cases harboring one or more heteroplasmic sites. Additionally, 12 sites had amino acid mutations, which were frequent in 10 of the cases. The 5-year recurrence-free survival (RFS) rate was significantly worse in patients with tumors >40 mm in diameter (p = 0.0091), pathological T (pT) stage ≥3 (p = 0.0122), Fuhrman nuclear atypia grade ≥III (p = 0.0070), and ND1 mutations (p = 0.0006). Multivariate analysis using these factors revealed that mutations in ND1 were significantly associated with the 5-year RFS rate (p = 0.0044). These results suggest a strong correlation between the presence of ND1 mutations in cancer tissue and postoperative recurrence of localized RCC in Japanese patients.

[Neuroendocrine Tumor Possibly Originating from the Kidney : A Case Report].

A 40-year-old woman was referred to our hospital with right lower back pain as the chief complaint. Contrast-enhanced computed tomography (CT) showed a partially-solid tumor within a cyst measuring approximately 6 cm in diameter in the right renal hilum. The solid part was enhanced in the early phase and contrast medium was washed out earlier in the solid part than in the parenchyma in the equilibrium phase. Plain CT revealed partial cyst wall calcification. A soft tissue shadow approximately 10 mm in diameter in the dorsal inferior vena cava at the upper pole of the kidney and a solid tumor adjacent to the iliopsoas muscle and the kidney were detected. We performed radical nephrectomy and lymph node dissection with transperitoneal approach. The histopathological diagnosis was neuroendocrine tumor. Her clinical course has since been observed on an outpatient basis, for nearly 10 months to date, without any recurrence.

A Case of Mixed Germ Cell Tumor in the Intramedullary Spinal-cord.

A 28-year-old man was hospitalized with advancing paraplegia. Under the diagnosis of Guillain-Barre syndrome, steroid pulse therapy was administered and plasmapheresis was performed. However, the paraplegia gradually progressed. Subsequently, a spinal cord tumor was revealed by magnetic resonance imaging (MRI). The pathological diagnosis, obtained by open biopsy, confirmed a mixed germ cell tumor in the spinal cord. Multiple lung and lymph nodes metastases were also detected upon computed tomography, along with increased serum alpha-fetoprotein (33.9 ng/mL) and human chorionic gonadotropin (182.5 mIU/mL) levels. Consequently, he received chemotherapy comprising three courses of BEP (bleomycin, etoposide, and cisplatin) as first-line therapy, followed by four courses of TGN (paclitaxel, gemcitabine, and nedaplatin) as second-line treatment. As a result, the spinal cord lesion area was significantly decreased and the alpha-fetoprotein and human chorionic gonadotropin levels were normalized. Four years after chemotherapy, MRI revealed pituitary gland and pineal organ recurrence of the germ cell tumor and additional TGN chemotherapy was performed.

Low-dose docetaxel, estramustine and prednisolone combination chemotherapy for castration-resistant prostate cancer.

The objective of this study was to report our experience with weekly low-dose docetaxel (DOC) chemotherapy for patients with castration-resistant prostate cancer (CRPC). From 2007 to 2014, 39 consecutive patients received weekly low-dose DOC; the oncological effectiveness, side effects and tolerability were prospectively analyzed. The median patient age, serum prostate-specific antigen (PSA) level and Gleason score at diagnosis of prostate cancer were 71 years (range, 55-83 years), 187 ng/ml (range, 2.0-1711 ng/ml) and 8 (range, 5-10), respectively. The median number of cycles of DOC was 7 (range, 1-45 cycles). Of the 39 patients, the PSA level decreased by >50% in 13 (33%). In the multivariate analysis of prediction of patient overall survival, a decrease of the PSA level to <50% was a significant predictor (hazard ratio = 6.913; 95% confidence interval: 1.147-41.669; P=0.035). The median cancer-specific overall survival from the diagnosis of CRPC was 16.7 months (range, 2-54 months). Grade 3 toxicities were observed in 5 patients (13%); specifically, limb edema, nausea and hepatic disorders were detected in 2 (5%), 2 (5%) and 1 patient (3%), respectively. Treatment-related death (grade 5) occurred in 1 patient due to interstitial pneumonia after two courses of chemotherapy. The chemotherapy was completed in the majority of the patients (n=37, 94.8%) in the outpatient department, without interruption. These findings suggest that weekly low-dose DOC is feasible and safe for selected patients with CRPC, without treament with novel agents, such as abiraterone, enzalutamide and cabazitaxel.

A Rare Case of Subclinical Primary Aldosteronism and Subclinical Cushing's Syndrome without Cardiovascular Complications.

We report a rare case of subclinical primary aldosteronism (PA) and subclinical Cushing's syndrome (CS). A 49-year-old woman was referred to our hospital for the evaluation of an adrenal incidentaloma. The patient had no previous medical history and no family history of notable illness. Her blood pressure was 103/60 mmHg. She had no Cushingoid features. Routine laboratory examinations were within the normal ranges including normokalemia. Based on the endocrinological results and imaging findings, we finally made a diagnosis of subclinical PA caused by both adrenal glands and subclinical CS caused by bilateral adrenal tumors. Interestingly, this patient had no risk factors for cardiovascular disease. In addition, the optimal management of patients with subclinical CS and subclinical PA has not been established. Therefore, we are observing her without medical therapy. Four years after diagnosis, no cardiovascular complications have been detected, including cerebral infarction, chronic kidney disease, cardiomegaly on echocardiography, and atherosclerosis on carotid ultrasonography. One important question is why the excessive hormone secretion did not affect the cardiovascular status of this patient. In this regard, we discuss several possible mechanisms including mineralocorticoid resistance and glucocorticoid sensitivity.