Robotic-assisted laparoscopic radical prostatectomy for treatment of a newly identified lesion revealed no viable cells in the previously treated area with microwave focal therapy.

Introduction: Histological outcome of the targeted focal therapy is in principle confirmed by targeted needle biopsy from the treated area in clinical trial. Herein, we report a rare case in which the MFT was followed by RARP. Case presentation: A 68-year-old man with PSA 9.6 ng/mL and PI-RADS 4 lesion in the right transition zone on multi-parametric MRI underwent MR/ultrasound fusion-guided targeted biopsy, which revealed grade-group 1 cancer. Targeted focal therapy with microwave ablation was performed, resulting in disappearance of the PI-RADS 4 lesion at post-operative 4 months. However, PSA rose to 11.5 ng/mL, and a new PI-RADS 4 lesion, was identified in the left peripheral zone. RARP was performed to reveal new grade-group 3 cancer, and no viable cells in the previously treated area with MFT. Conclusion: RARP was safely performed even after MFT and proved the pathological complete response of microwave ablation.

Does intensity-modulated radiation therapy by helical tomotherapy for prostate cancer increase the subsequent risk of bladder cancer? A propensity score-matched analysis.

OBJECTIVES: This study aimed to evaluate the risk of bladder cancer after intensity-modulated radiation therapy (IMRT) using helical tomotherapy for prostate cancer in comparison to the risk post-radical prostatectomy (RP) using propensity score-matched analysis and to assess the risk factors for bladder cancer. METHODS: This retrospective study included 2067 patients with non-metastatic prostate cancer treated at our institution between June 2007 and December 2016. Of these, 1547 patients were treated with IMRT and 520 underwent RP. The propensity scores were calculated using age, National Comprehensive Cancer Network risk classification, prostate volume, Brinkman index, and follow-up time as matched covariates. A propensity score-matched patient cohort (n = 718; IMRT: 359, RP: 359) was created, and the risk of bladder cancer after treatment was compared. RESULTS: In total, bladder cancer was detected in 33 patients. Five patients in the IMRT group and one in the RP group died of bladder cancer. In the propensity score-matched analysis, the 5-year bladder cancer-free survival rate was significantly lower in the IMRT group than in the RP group (91.7% and 96.2%, respectively; p < 0.001). Multivariate analysis revealed that IMRT and the Brinkman index were the risk factors for bladder cancer in this cohort (odds ratio = 5.085, 95% confidence interval = 1.436-18.008, p = 0.012 and odds ratio = 1.001, 95% confidence interval = 1.000-1.001, p = 0.010, respectively). CONCLUSIONS: IMRT for prostate cancer using helical tomotherapy increases the subsequent risk of bladder cancer compared with RP and is an independent risk factor for bladder cancer similar to smoking.

Trichoscopic evaluation of dental pulp stem cell conditioned media for androgenic alopecia.

BACKGROUND: Conditioned media (CM) derived from mesenchymal stem cells (MSC) is known to induce hair regrowth in androgenic alopecia. OBJECTIVES: The objectives of the study were to assess the efficacy and safety of one type of MSC-CM, the CM derived from dental pulp stem cells obtained from human exfoliated deciduous teeth (SHED-CM) and to compare the efficacy of SHED-CM with and without dihydrotestosterone synthesis inhibitor (DHT-inhibitor). METHODS: Eighty-eight male androgenic alopecia subjects with Hamilton-Norwood Classification (H-N C) I-VII were evaluated by trichoscopy to explore which trichoscopic factors statistically correlated with H-N C. After being screened, 33 subjects received six SHED-CM treatments at 1-month intervals. Clinical severity was assessed through global and trichoscopic images from baseline to 9th month. RESULTS: SHED-CM was effective for 75% of subjects regardless of disease severity, concomitant DHT-inhibitor use, and age. Adverse effects including pain and small hemorrhages were transient and mild. We also found that clinical hair status evaluated by absolute values of three quantitative trichoscopic factors (maximum hair diameter, vellus hair rate, and multi-hair follicular unit rate) showed a good correlation with H-N C stages, and what is more-a scoring system of these three factors can be a possible predictor of SHED-CM efficacy. CONCLUSIONS: We have shown that SHED-CM provides global and trichoscopic image improvement for androgenic alopecia, regardless of concomitant DHT-inhibitor use.

The Long-Term Effect of Intensity Modulated Radiation Therapy for Prostate Cancer on Testosterone Levels.

Purpose: Concern about a long-term effect of the delivery of intensity modulated radiation therapy (IMRT) for prostate cancer on serum testosterone levels remains unelucidated. We evaluated how IMRT for localized prostate cancer affects serum testosterone levels during a follow-up period of up to 10 years. Methods and Materials: We retrospectively evaluated data from 182 patients with localized prostate cancer who underwent definitive IMRT alone between 2007 and 2014. Serum total testosterone (TT) levels were measured by blood draws between 6 AM and 11 AM before treatment and at every posttreatment follow-up for 10 years. Pretreatment values and each posttreatment testosterone value were compared using a Wilcoxon signed rank test. The data set was stratified into 4 groups based on the pretreatment testosterone (pre-TT) values using quartiles. Results: The median absolute or relative changes in TT levels from pretreatment were -0.42 ng/mL or -12.0% at 3 months after radiation therapy (P < .0001). Subsequently, TT levels gradually recovered to nearly the pretreatment levels 24 to 36 months after IMRT. When analyzed according to the pre-TT quartile, median TT levels initially decreased at the 3- to 12-month period in all the quartiles; however, median TT levels increased from the 18-month period in the first and second quartile groups, whereas they were maintained at less than the pretreatment levels in the third and the fourth quartile groups throughout the entire decade after radiation therapy. The proportion of patients with hypogonadal status, defined as TT levels <3.00 ng/mL, did not increase over time. Conclusions: A transient and modest decrease of TT levels after IMRT spontaneously recovered to the pretreatment levels at the 24- to 36-month period except in patients in the higher quartile of pre-TT. This might have been partly owing to a variable sensitivity of individual testicular function to scattered radiation. Patients with lower pre-TT did not demonstrate a progressive overall rate of hypogonadism until 10 years after radiation therapy.

Efficacy of a cultured conditioned medium of exfoliated deciduous dental pulp stem cells in erectile dysfunction patients.

Majority of current treatment strategies against erectile dysfunction (ED) has been consisted of only a supportive care to sustain enough erection during a sexual intercourse. In this study, we investigated whether the cultured conditioned medium of human exfoliated deciduous dental pulp stem cells (SHED-CM) had an ability to treat ED through fundamentally repairing the pathological damage of vascular endothelial cells of the corpus cavernosum. An open-label pilot study was performed from April 2016 to October 2020. SHED-CM was injected directly into the corpus cavernosum of penis of 38 ED patients who visited our clinic and fulfilled the inclusion criteria. Efficacy was assessed using the simplified International Index of Erectile Function (IIEF-5) questionnaire. The average age and initial IIEF-5 score of the patients enrolled in this study was 56 (31-79) years old and 13.1 (5-20) points, respectively. Medical history revealed 7 patients with diabetes, 7 patients with hypertension and 1 patient with priapism undergone shunt operation. Of these, 37 patients (97.4%) showed an improvement in IIEF-5 of an average of 19.3 (7-25) points or 64.4 (10-300) % increase after three injections of SHED-CM. Eighteen patients (47.4%) achieved more than 21 points (no ED) in IIEF-5. No adverse events were encountered. This is the first clinical report of ED treatment in the literatures evaluating the efficacy of SHED-CM. Treatment with SHED-CM is expected to repair vascular damages of the corpus cavernosum, which are the main cause of ED, and to be widely spread as a fundamental clinical application for ED.

Mortality Comparison of Hemodialysis and Peritoneal Dialysis Patients at a Single Japanese Center.

To investigate whether peritoneal dialysis (PD) is useful as a first modality in Japan, where hemodialysis (HD) is used in 97% of all patients on maintenance dialysis, we used intention-to-treat (ITT) and as-treated analyses to examine patient survival at our center, where HD and PD are used almost equally. In the ITT analysis, survival was significantly better in the PD group than in the HD group (p = 0.009). Meanwhile, the as-treated analysis did not reveal any significant differences in survival between the HD and PD groups. Survival for patients who underwent combined therapy with PD and HD was very good at 93.75% after 4 years, despite a young age of introduction (56 years). Our results confirm the usefulness of PD as an initial modality of maintenance dialysis and indicate that combined therapy can serve as a useful treatment option for dialysis patients.

Vildagliptin is Effective for Glycemic Control in Diabetic Patients Undergoing either Hemodialysis or Peritoneal Dialysis.

INTRODUCTION: Vildagliptin can be used in patients with type 2 diabetes mellitus and renal impairment. However, there have been few reports investigating the clinical effectiveness of vildagliptin in diabetic patients undergoing hemodialysis. No previous studies have evaluated the use of vildagliptin in patients undergoing peritoneal dialysis. The authors determined the usefulness of vildagliptin for treating type 2 diabetic patients receiving chronic dialysis, including peritoneal dialysis. METHODS: A retrospective study of ten diabetic patients undergoing peritoneal dialysis and five diabetic patients undergoing hemodialysis who were treated with 50 mg/day of vildagliptin was performed. Clinical parameters were investigated for a period of 6 months starting from the vildagliptin therapy. RESULTS: The hemoglobin A1c (HbA1c) levels were significantly reduced after baseline in both the peritoneal dialysis and hemodialysis groups, whereas the hemoglobin levels did not change during the follow-up period. The mean change in the HbA1c level (ΔHbA1c) was -0.6 ± 0.9% and -0.5 ± 0.7% among the patients undergoing peritoneal dialysis and hemodialysis, respectively. The glycated albumin (GA) levels were also significantly reduced compared with baseline in the peritoneal dialysis group, although the serum albumin levels did not change. The mean change in the GA level (ΔGA) was -3.4 ± 3.1% and -2.1 ± 2.5% among the patients undergoing peritoneal dialysis and hemodialysis, respectively. Stepwise multivariate analyses demonstrated the level of HbA1c at baseline to be significantly associated with the ΔHbA1c and that the level of GA at baseline was significantly associated with the ΔGA. CONCLUSION: Vildagliptin exhibits effectiveness in patients with type 2 diabetes mellitus undergoing peritoneal dialysis or hemodialysis. The degree of improvement in the HbA1c and GA levels was dependent on these levels at baseline, similar to the findings of previous reports of subjects without end-stage kidney disease.

Safety and efficacy of docetaxel, estramustine phosphate and hydrocortisone in hormone-refractory prostate cancer patients.

OBJECTIVE: To assess the combination of docetaxel (DTX), estramustine phosphate (EMP) and hydrocortisone for patients with hormone-refractory prostate cancer (HRPC). METHODS: A total of 63 patients with HRPC were treated with a chemotherapeutic regimen including DTX, EMP, and hydrocortisone. Clinical and pathological features were correlated to serum prostate-specific antigen (PSA) recurrence and survival rates. Incidence and degree of toxicities were also retrospectively reviewed. RESULTS: A median of 11 courses of chemotherapy was administered per patient. PSA levels decreased by >50% in 32 (51%) patients and >90% in 18 (29%) patients. Median time to PSA progression was 6 months (range from 1 to 41 months) and median time of overall survival was 14 months (range from 1 to 56 months). In a univariate analysis to predict overall survival, PSA, hemoglobin, alkaliphosphatase, and performance status prior to the chemotherapy were significant factors. Despite grade 3-4 neutropenia in 87% of patients, grade 5 interstitial pneumonia in one patient and grade 4-5 myocardial infarction in two patients were recognized, the regimen seemed to be relatively safe. CONCLUSIONS: Combination chemotherapy with DTX, EMP and hydrocortisone provides survival benefits for patients with HRPC with an acceptable toxicity profile. We need to further evaluate who might benefit most from this regimen.

Effects of direct injection of dehydrated ethanol on PC3 human prostate cancer cells in nude mice: preliminary study.

OBJECTIVES: The effect of direct local injection of dehydrated ethanol on hormone-independent prostatic carcinoma cells (PC3 cells) implanted in nude mice was investigated. METHODS: PC3 tumors were implanted subcutaneously into 30 nude mice. Three weeks later, dehydrated ethanol was injected directly into the tumors. Twenty-three animals received an injection of ethanol at a volume of 40 microL, 80 microL, or 160 microL, and were divided into a low-dose group (n = 11) and a high-dose group (n = 12) on the basis of the ethanol/tumor volume ratio (<30% versus> or =30%). The control group (n = 7) was injected with 40 microL of physiological saline. The tumor volume before treatment was 324.9 +/- 110.9 mm(3) and was assessed as well as 1 day, 4 days, 1 week, 2 weeks, and 3 weeks after injection. Then the changes of tumor volume were compared between the two ethanol groups (low-dose group and high-dose group) and the control group. Histological examination was performed for up to 3 weeks after injection. RESULTS: Assessment of tumor volume showed that the ethanol/tumor volume ratio was 16.1 +/- 5.3% in the low-dose group (n = 5) and 51.8 +/- 20.3% in the high-dose group (n = 6). Tumor growth was significantly inhibited after 1 and 2 weeks in the ethanol groups compared with the control group (n = 3). After 3 weeks, there was a tendency for tumor regrowth in the low-dose group, but growth inhibition was maintained in the high-dose group. Histological examination showed tumor degeneration and necrosis with feeding vessel obstruction in the acute phase. CONCLUSIONS: Local injection of dehydrated ethanol regressed tumors of prostatic carcinoma cells in nude mice, with the degeneration of tumor cells and occlusion of feeding vessels.

[Survey on the current status of delivered informed consent for renal replacement therapy among patients with end-stage renal disease].

We conducted a survey on the adequacy of delivered informed consent (IC) among patients with end-stage renal disease (ESRD) regarding the information provided on renal replacement therapies (RRT): Hemodialysis (HD), peritoneal dialysis (PD), and renal transplantation (RTx). A self-assessment style of questionnaire entitled "Informed consent for the selection of dialysis therapy modality" was prepared for evaluation, and the adequacy of IC was scored by 5 grades ranging from "excellent" to "bad". The questionnaire was sent to all the JSDT registered facilities (n=3484), and 480 centers replied (13.8%). Among these, 407 centers had patients introduced onto some form of RRT modality in the last 12 months. As to the adequacy of delivered IC for each modality, "excellent and good" status was reported as follows: 80.8% in HD, 49.8% in PD, and 32.5% in RTx, respectively. The major reason for "poor and bad" IC adequacy in PD and RTx, was "not available in the facility". By analyzing the facilities stratified by the clinical experiences of each modality in the past, poorly delivered IC for PD and RTx was revealed in centers lacking experience. Delivered information about RRT to ESRD patients may be biased in Japan. The findings of this study suggested that a lack of medical experience of the modality contributes to insufficient IC.

T-cell mediated induction of allogeneic endothelial cell chemokine expression.

BACKGROUND: The goal of the current study was to test the ability of T cells to stimulate allogeneic endothelial cells to express chemokines, particularly the T-cell recruiting factors monokine induced by interferon-gamma (Mig) and inducible protein (IP)-10. METHODS: Lymph node cells from C57BL/6 (H-2b) recipients of C3H (H-2k) skin grafts or from naïve mice were added to monolayers of C3H-derived endothelial cell line 2F-2B. After 5 or 24 hr, the lymph node cells were removed, and RNA was prepared from the endothelial cells and tested by ribonuclease protection assay or Northern blot hybridization for endothelial cell expression of chemokines. RESULTS: Alloantigen-primed T cells induced endothelial cell expression of regulated on activation normal T-cell expressed and secreted (RANTES), IP-10, Mig, monocyte chemotactic protein-1, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta within 5 hr of coculture. In vitro chemotaxis assays demonstrated the production of T-cell chemoattractants by the endothelial cells. With the exception of low levels of monocyte chemotactic protein-1 and RANTES, culture with naïve C57BL/6 lymph node T cells did not induce endothelial cell chemokine expression. Alloantigen-primed CD4 T cells induced endothelial expression of IP-10 and RANTES but none of the other chemokines tested, whereas primed CD8 T cells induced all of the chemokines tested. Expression of IP-10 and Mig was not induced when alloantigen-primed T cells from interferon-gamma deficient recipients of C3H skin grafts were cultured with the endothelial cells. This expression was blocked by addition of intercellular adhesion molecule-1 or lymphocyte function-associated antigen-1 specific antibodies to the cultures. CONCLUSIONS These results demonstrate the ability of alloantigen-primed CD8 T cells to quickly and directly stimulate endothelial cells to express and produce chemokines, including those recruiting T cells.

Caspase-8 gene therapy using the human telomerase reverse transcriptase promoter for malignant glioma cells.

Telomerase is a distinctive candidate for targeted gene therapy of malignant gliomas, because the vast majority of malignant gliomas express telomerase activity while normal brain tissues do not. Recently, we developed a telomerase-specific expression system of caspase-8 gene using the promoter of the human telomerase reverse transcriptase (hTERT) gene. However, the transcriptional activity of hTERT-181 promoter (a 181-base pair [bp] region upstream of the transcription start site) was relatively lower in malignant glioma cells than in other tumors such as prostate cancer cells. To establish the hTERT/caspase-8 construct as a novel therapy for malignant gliomas, we need to increase the transcriptional activity of the hTERT promoter in malignant glioma cells. In the present study, we demonstrate that the transcriptional activity of hTERT-378 promoter (a 378-bp region) was 2- to 40-fold higher in hTERT-positive malignant glioma cells (A172, GB-1, T98G, U87-MG, U251-MG, and U373-MG) than that of hTERT-181. We further demonstrate that by using the hTERT-378/caspase-8 construct, apoptosis was restricted to malignant glioma cells, and was not seen in astrocytes or fibroblasts lacking hTERT. Moreover, the growth of subcutaneously established U373-MG tumors in mice was significantly inhibited by seven daily intratumoral injections of hTERT-378/caspase-8 construct and its inhibitory effect persisted during 3 additional weeks without additional treatment. These results suggest that the telomerase-specific expression of caspase-8 under hTERT-378 promoter is a novel targeting approach for the treatment of telomerase-positive malignant gliomas.