A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder.

Background: S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder. Patients and methods: Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1 mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1 mg or 2 mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety. Results: S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1 mg (100%) and 2 mg (80.0%) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6%), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3% and the disease control rate was 56.3%. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2% of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both peptides was longer than that of those with CTL induction to no or one peptide. Conclusion: S-288310 was well-tolerated and effectively induced peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder. Trial registration ID: JapicCTI-090980.

Slow Progression of Aortic Calcification Is a Potential Benefit of Pre-emptive Kidney Transplantation.

PURPOSE: Pre-emptive kidney transplantation (PKT) is expected to improve graft and cardiovascular event-free survival compared with standard kidney transplantation. Aortic calcification is reported to be closely associated with renal dysfunction and cardiovascular events; however, its implication in PKT recipients remains incompletely explored. This aim of this study was to evaluate whether PKT confers a protective effect on aortic calcification, renal function, graft survival, and cardiovascular event-free survival. METHODS: One hundred adult patients who underwent renal transplantation between January 1996 and March 2016 at Hirosaki University Hospital and Oyokyo Kidney Research Institute were included. Among them, 19 underwent PKT and 81 patients underwent pretransplant dialysis. We retrospectively compared pretransplant and post-transplant aortic calcification index (ACI), renal function (estimated glomerular filtration rate [eGFR]), and graft and cardiovascular event-free survivals between the 2 groups. RESULTS: The median age of this cohort was 45 years. Preoperative ACI was significantly lower in PKT recipients. There were no significant differences between the 2 groups regarding postoperative eGFR, graft survival, and cardiovascular event-free survival. However, the ACI progression rate (ΔACI/y) was significantly lower in PKT recipients than in those who underwent pretransplant dialysis. Higher ACI was significantly associated with poor cardiovascular event-free survival. CONCLUSIONS: PKT is beneficial in that it contributes to the slow progression of after transplantation. Although we could not observe significant differences in graft and cardiovascular event-free survivals between the 2 groups, slow progression of aortic calcification showed a potential to decrease cardiovascular events in PKT recipients during long-term follow-up.

Partial Cystectomy of Paraganglioma of the Urinary Bladder Before Living Kidney Transplantation: Case Report.

BACKGROUND: Paraganglioma (extra-adrenal pheochromocytoma) of the bladder is a very rare disease, accounting for 0.06% of all bladder tumors. Optimal management of bladder paraganglioma before kidney transplantation is unknown. We report a case of partial cystectomy for urinary bladder paraganglioma before living kidney transplantation. CASE PRESENTATION: A 59-year-old man with a 27-year history of hemodialysis was referred to our department for further examination of a bladder tumor detected during pre-transplantation testing. Cystoscopy revealed a submucosal tumor on the right side of the bladder. The patient experienced a hypertensive crisis during transurethral resection of the bladder tumor. Endocrinologic and pathologic examinations confirmed the diagnosis of paraganglioma in the urinary bladder. A partial cystectomy was performed before kidney transplantation. Nine months after partial cystectomy, the patient underwent AB0-incompatible living kidney transplantation from his spouse. No disease recurrence or graft rejection was observed 12 months after the transplantation. CONCLUSIONS: To our knowledge, this is the 1st report on the management of paraganglioma in the urinary bladder before living kidney transplantation. Kidney transplantation after partial cystectomy is an option that may be considered in patients with paraganglioma of the urinary bladder, with careful observations of bladder function and vesicoureteral reflux to the grafts.

Condyloma Acuminata of the Urethra in a Male Renal Transplant Recipient: A Case Report.

BACKGROUND: Condyloma acuminatum (CA) is a common sexually transmitted disease associated with human papilloma virus (HPV). CA occurring in the urethra is rare and has not been reported in male renal transplant recipients. In addition, despite immunosuppressive conditions and increased risk of HPV-related malignant neoplasms in transplant recipients, HPV testing in male transplant recipients has been uncommon. Here we report a case of urethral CA in a male deceased donor renal transplantation recipient and discuss the importance of HPV testing in male transplant recipients. CASE PRESENTATION: A 33-year-old male deceased donor renal transplant recipient presented with miction pain 5 years after the transplantation. He reported repeated urinary tract infections with no sexual contact since the renal transplantation. Multiple papillary tumors in his penile urethra were detected by cystoscopy, and a biopsy sample was pathologically diagnosed with CA. Transurethral tumor resection was performed, and the tumors were completely resected. Additional HPV risk type screening with a urethral smear sample showed the prevalence of low-risk HPV. Although tacrolimus was switched to everolimus and imiquimod cream was administered, the tumors recurred 6 months after the resection, and a second resection was performed. No further recurrence has been observed for 1 year to date. CONCLUSION: As the urethral CA was possibly related to immunosuppressive conditions and a risk for HPV-related malignant neoplasm, the case required careful diagnosis, including HPV risk type. The methodology of sampling for HPV testing in men has not been established. This case suggests the necessity for further discussion about HPV testing in male transplant recipients.

Safety and Effectiveness of Marginal Donor in Living Kidney Transplantation.

BACKGROUND: We evaluated the safety and feasibility of living kidney transplantation from marginal donors. PATIENTS AND METHODS: Between June 2006 and March 2015, we performed 61 living related renal transplantations at two renal transplantation centers. Marginal donors were defined as those who were older than 70 years or who had hypertension, reduced renal function, body mass index greater than 30 kg/m(2), or mildly impaired glucose tolerance. We retrospectively compared renal function and graft survival between marginal and standard living donor kidney transplantations. To evaluate renal function, creatinine clearance (CCr) was preoperatively used for donors, and estimated glomerular filtration rate (eGFR) was postoperatively used for donors and recipients. RESULTS: Among 61 donors, 14 (23%) met the marginal criteria, the major reason being hypertension (91%). The mean age tended to be higher in the marginal group. Preoperative eGFR was significantly lower in the marginal group, whereas postoperative renal function decline ratio at two years was not significantly different between the groups (67% vs 67%, P = .960). Five-year graft survival rates were not significantly different between the two groups. However, recipient eGFR 1 year after kidney transplantation was lower in the marginal group than in the standard group (44 ± 8 vs 55 ± 9 in eGFR, P = .003). CONCLUSIONS: No significant differences were observed between the groups regarding donor renal function. Careful marginal donor selection can be safe and feasible for donors and recipients of living kidney transplantation; however, it may have a negative impact on recipient renal function.

Influence of 1 year of androgen deprivation therapy on lipid and glucose metabolism and fat accumulation in Japanese patients with prostate cancer.

BACKGROUND: We prospectively examined influence of androgen deprivation therapy (ADT) on lipid and glucose metabolisms in Japanese patients with prostate cancer. METHODS: Patients with prostate cancer who were hormone-naive and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight, abdominal circumference and blood testing associated with lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat before and after 1 year of ADT. ADT was limited to a luteinizing hormone-releasing hormone (LHRH) agonist with or without bicalutamide. RESULTS: Of 218 patients registered, data were available from 177 patients who completed 1 year of ADT. Of these, CT was performed before and after 1 year of ADT in 88 patients. Median age was 75 years (range, 49-85 years). Median PSA before ADT was 16.7 ng ml(-1) (range, 0.3-3316). Clinical stage was B (54.2%), C (23.2%) and D (20.9%). Mean increases in body weight and abdominal circumference after 1 year of ADT were 2.9 and 3.0%, respectively. Mean increases in total, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were 10.6, 14.3, 7.8 and 16.2%, respectively. Mean increases in fasting blood sugar and hemoglobin A1c (HbA1c) were 3.9 and 2.7%, respectively. Lipid alterations were noted in patients without comorbidities, whereas changes in HbA1c were noted in patients with diabetes mellitus at baseline. These lipid and glucose alterations were prominent in the early ADT period. Both visceral and subcutaneous fat, as measured by CT, increased by >20%. The increase in subcutaneous fat was significantly greater than that in visceral fat (P=0.028). CONCLUSIONS: One year of ADT significantly changed lipid and glucose metabolism in Japanese patients with prostate cancer. Patient characteristics or comorbidities at baseline may be associated with ADT-induced metabolic changes.

Lymphovascular invasion is significantly associated with biochemical relapse after radical prostatectomy even in patients with pT2N0 negative resection margin.

BACKGROUND: The significance of lymphovascular invasion (LVI) remains controversial, and the association of LVI with biochemical relapse was investigated in men treated with radical prostatectomy according to pathological results. METHODS: Data from 1268 patients undergoing radical prostatectomy between 2000 and 2009 were retrospectively reviewed. Clinicopathological variables were compared between LVI-negative and LVI-positive patients. Multivariate analyses by Cox proportional hazard model and Kaplan-Meier method were performed to identify risk factors for biochemical relapse in all patients, patients with pT2N0 and pT2N0 negative resection margin (RM). RESULTS: LVI information was available in 1160 cases, and LVI was seen in 121 cases (10.4%). Clinicopathological variables were significantly worse in LVI-positive patients than in LVI-negative patients. On multivariate analyses, PSA⩾10 ng ml(-1), pathological Gleason score ⩾8, pathological T stage ⩾3, lymph node metastasis, positive RM and LVI were independent predictors for biochemical relapse in all patients. In patients with pT2N0, PSA⩾10 ng ml(-1), pathological Gleason score ⩾8, positive RM and LVI were independent predictors for biochemical relapse. In patients with pT2N0 negative RM, LVI and pathological Gleason score ⩾8 were independent predictors for biochemical relapse (LVI; hazard ratio 3.809, 95% confidence interval 1.900-7.635, P-value<0.001, Gleason score ⩾8; hazard ratio 2.189, 95% confidence interval 1.199-3.999, P-value=0.011). With a median follow-up of 50 months, 5-year biochemical relapse-free survival in patients with pT2N0 negative RM was 95.7% in those with negative LVI in comparison to 85.3% in those with positive LVI (P<0.001, log rank). CONCLUSIONS: LVI was consistently a significant predictor for biochemical relapse after radical prostatectomy in not only all patients but also in patients with pT2N0 and pT2N0 negative RM. These results strongly support the significance of LVI as a predictor for biochemical relapse.

[The effects of interferon-alpha on oxygen radical production by human neutrophils].

This study was done to determine if the production and metabolism of reactive oxygen species from human neutrophils were modulated by the treatment of interferon-alpha (IFN-alpha). Luminol-dependent Chemiluminescence (LmCL) responses were inhibited by a high concentration of IFN-alpha (more than 1 x 10(4) IU/ml) when opsonized zymosan (OZ) and phorbol 12-myristate 13-acetate (PMA) were used as stimulants. However, these responses were increased by 1 x 10(3) IU/ml of IFN-alpha with Ca(2+)-ionophore A23187 stimulation. Lucigenin-dependent Chemiluminescence (LgCL) responses were inhibited by all concentrations. These findings suggest the possibility that IFN-alpha inhibits activation of protein kinase C (PKC), whereas the resulting effect might be due to the inhibition of myeloperoxidese (MPO) degranulation. Preincubation of human neutrophils with IFN-alpha for 30, 60 or 120 minutes and subsequent stimulation with OZ, PMA and Ca(2+)-ionophore A23187 caused an increase LgCL responses, while inhibiting LmCL responses. These findings suggest that preincubation of human neutrophils with a high concentration of IFN-alpha might enhance the NADPH-oxidase activity, although a relative increase of LgCL was due to the inhibition MPO degranulation.

[Sarcomatoid renal cell carcinoma: a case report].

A 75-year-old male presented to our hospital with a complaint of macroscopic hematuria. Laboratory examinations in peripheral blood showed slight anemia and the increase of acute phase reactants (c-reactive protein, immunosuppressive acidic protein, alpha 2-globulin). Abdominal enhanced computerized tomography revealed a huge tumor with calcification at the upper pole of the right kidney. Magnetic resonance imaging (MRI) showed a low intensity mass at the upper portion of the right kidney on T2-weighted sequences. The right radical nephrectomy was performed and the histopathological diagnosis was sarcomatoid renal cell carcinoma because of positive immunohistochemical staining for vimentin and negative for cytokeratin. Because sarcomatoid type has a highly malignant behavior and poor prognosis among renal cell carcinomas, an adjuvant treatment which is effective in controlling the disease is awaited.

[Rapid ACTH test to judge recovery of adrenal function in patients with Cushing's syndrome].

BACKGROUND: Steroid hormone replacement and recovery of adrenal function after unilateral adrenalectomy were studied in 12 patients with Cushing's syndrome due to adenocortical adenoma. PATIENTS AND METHOD: The patients were 3 males and 9 females aged 19 to 61 years old (mean 34.3 years old). Recovery of adrenal function was judged by plasma cortisol level and rapid ACTH test peridocally. RESULTS: Plasma cortisol level was 13.7 to 20.8 micrograms/dl without diurnal rythme before adrenalectomy. Average replacement period with low dose hydrocortisone was 15 +/- 9.2 months after adrenalectomy. Plasma ACTH and cortisol concentration was recovered to normal range after 3.4 +/- 2.9 months and 12.2 +/- 8.2 after adrenalectomy, respectively. Plasma ACTH concentration was recovered to normal range earlier than plasma cortisol level in all patients. Sufficient response of plasma cortisol concentration in rapid ACTH test was seen a little later than recovery of plasma cortisol level. CONCLUSION: Present data suggest that it is insufficient to judge recovery of adrenal function only by the rise of plasma ACTH and/or cortisol concentrations. Therefore rapid ACTH test is useful to judge sufficient recovery of adrenal function during and after steroid hormone replacement.

[Rhabdomyosarcoma of the bladder: a case report].

A 15-year-old man with the chief complaint of general fatigue was referred to our hospital on November 11, 1993. Bilateral percutaneous nephrostomy was performed for postrenal anuria. X-ray examinations revealed a huge intrapelvic tumor, and it was histopathologically diagnosed as rhabdomyosarcoma by transrectal needle biopsy. He was initially treated with combination chemotherapy regimen of vincristine, actinomycin-D and cyclophosphamide (VAC therapy). Pelvic exenteration was performed on December 15, 1993. Histopathological findings were alveolar rhabdomyosarcoma with degenerative change and partial necrosis. After the operation, he was given two course of VAC therapy. In May, 1994, brain metastasis occurred, so 4 courses of VAC therapy were administered. For a very short period, neurological symptoms improved, but he died of pneumonia on November 15, 1994.

Laser and serum opsonic activity.

The purpose of this study was to investigate the effects of low level laser (LLL: GaA1As diode laser; 830 nm) on serum opsonic activity, which was assessed by neutrophil-associated chemiluminescence (CL) response to zymosan opsonized with sera irradiated in vitro with various doses of LLL. We used both lucigenin-dependent CL (LgCL) for superoxide (O2-) detection and luminol-dependent CL (LmCL) which detects myeloperoxidase (MPO)-dependent formation of hypochlorous acid in combination with MPO inhibitor, sodium azide (NaN3). When serum opsonic activity was assessed by LgCl, NaN3, markedly enhanced the responses, suggesting that O2- is accumulated due to the MPO blockade, leading to the excitation of LgCl. However, LLL-irradiation had no effects on serum opsonic activity. On the other hand, when serum opsonic activity was assessed by LmCl, NaN3, strongly inhibited the response. The effects of LLL at different output powers were characterized by similar values, but significantly higher values were observed at the highest dose tested (60 mW for 1 min) in the absence of NaN3. Since this enhancement effect disappeared with NaN3, it was suggested that high dose LLL-irradiation probably activated the opsonic activity by facilitating neutrophils to degranulate MPO. However, lower doses used for therapeutic purposes had no effects at any output powers tested.

Outcome comparison of ABO-incompatible kidney transplantation with low-dose rituximab and ABO-compatible kidney transplantation: a single-center experience.

BACKGROUND: The development of immunosuppressive techniques has helped overcome the ABO incompatibility barrier. However, the outcomes of ABO-incompatible (ABOi) kidney transplantation remain a controversial issue with the advent of the anti-CD20 chimeric antibody rituximab. Herein, we report the outcomes of ABOi kidney transplantation with low-dose rituximab. PATIENTS AND METHODS: Between June 2006 and April 2013, 42 patients underwent living-related kidney transplantation at our hospital. The patients were divided into 2 groups: ABO-compatible (ABOc; n = 29) and ABOi kidney transplants using low-dose rituximab (100 mg/m(2)) without splenectomy (n = 13). The basic immunosuppression regimen (calcineurin inhibitor [CNI], mycophenolate mofetil [MMF], and steroids) was the same for both groups, except for the use of rituximab and therapeutic apheresis in the ABOi group. We compared post-transplantation renal function, incidents of virus infection, episodes of rejection, and graft survival between the 2 groups. RESULTS: In our hospital, 30% of recipients received ABOi kidney transplants. The estimated glomerular filtration rate (eGFR) did not differ between the groups. Rejection episodes confirmed by biopsy in the ABOc and ABOi groups were 8 (28%) and 4 (31%) patients (P = .833), acute antibody-mediated rejection was observed in 1 (3.5%) and 2 (15%) patients (P = .165), and virus infection was observed in 14 (48%) and 3 (23%) patients (P = .252), respectively. The 5-year patient survival rate was 100% in both groups, and the 5-year graft survival rates were 95% for ABOc and 100% for ABOi transplants (P = .527). CONCLUSIONS: These results suggest that the outcomes of ABOi kidney transplantation with low-dose rituximab are similar to those of ABOc kidney transplantation. Further study is necessary to address the efficacy and safety of ABOi kidney transplantation.

Post-transplant renal function and cardiovascular events are closely associated with the aortic calcification index in renal transplant recipients.

INTRODUCTION: The aortic calcification index (ACI) is reported to be closely associated with renal dysfunction and cardiovascular events; however, its implication in renal transplant recipients has not been well examined. In this study, we investigated the relationship between pretransplant ACI, ACI progression, post-transplant renal function, and post-transplant cardiovascular events in renal transplant recipients. PATIENTS AND METHODS: The study from June 1996 to Jan 2012 included 61 renal transplant recipients (living donors, 47; cadaveric donors, 14). The median follow-up period was 60 months. ACI was quantitatively measured on abdominal computed tomography. The relationship between age, dialysis period, estimated glomerular filtration rate (eGFR), and pre- and post-transplant ACI was longitudinally evaluated. Risk factors for post-transplant ACI progression were determined by logistic regression analysis. Patient background and the incidence of post-transplant cardiovascular events were also assessed. RESULTS: The pretransplant ACI (median 4.2%) significantly correlated with age at transplant, dialysis period, and diabetes mellitus. ACI gradually increased up to 2.8 times at 10 years after transplantation. Post-transplant eGFR significantly correlated with ACI progression in patients with chronic kidney disease of stage ≥ 3. Logistic regression analyses showed that age at transplantation, post-transplant period, cadaveric donors, and post-transplant chronic kidney disease stage 3 were risk factors for post-transplant ACI progression. The pretransplant ACI was higher (median 66%) in 3 patients who experienced post-transplant cardiovascular events. CONCLUSIONS: ACI progression closely correlates with age and post-transplant renal function. A high pretransplant ACI is a risk factor for post-transplant cardiovascular events in renal transplant recipients.

BK virus-associated urothelial carcinoma of a ureter graft in a renal transplant recipient: a case report.

BACKGROUND: Urothelial carcinomas of ureter grafts in renal transplant patients are rare. Here we report our experience with a case of BK virus-associated urothelial carcinoma in a ureter graft. CASE REPORT: A 47-year-old man developed chronic renal failure secondary to diabetes mellitus and started maintenance hemodialysis in September 2007. Two months later, the patient received a renal transplant from his 70-year-old mother. The patient developed BK virus-associated nephropathy 1 year after transplantation and presented with a decline in renal function and hydronephrosis in the transplanted kidney 4 years 6 months after transplantation. Cystoscopy and retrograde pyelography revealed an irregular filling defect in the ureter graft. Cytologic diagnosis of his urine revealed a high-grade urothelial carcinoma. Computerized tomography showed a cT2 ureteral tumor and no involvement of other organs. The patient subsequently underwent a transplant nephroureterectomy with bladder cuff resection. Histopathologic findings revealed a high-grade urothelial carcinoma, pT2, in the ureter graft with SV40-positive staining. The patient was closely observed without adjuvant chemotherapy therapy and remained disease free 1 year after surgery. Renal transplant recipients with BK virus infection are at high risk of developing urologic malignancies. Close attention is necessary to diagnose post-transplantation urologica malignancies as early as possible.

Renal cell carcinoma detected by preoperative kidney transplant donor examination: a case report.

A 37-year-old man undertook preoperative examination for donor nephrectomy for living kidney transplantation. Computerized tomography revealed a small renal mass (1.9 cm in diameter) with contrast enhancement on his left kidney. We couldn't exclude malignant potential for the small mass. Laparoscopic left partial nephrectomy without renal artery clamp was successfully carried out to obtain pathologic diagnosis while preserving his renal function and priority as a donor. He was judged to be an inappropriate donor candidate owing to the histopathologic report suggesting clear cell carcinoma. The patient has been followed for 27 months without any evidence of recurrence.

Impact of body mass index on clinicopathological outcome and biochemical recurrence after radical prostatectomy.

BACKGROUND: Accumulating evidence suggests that obesity is associated with tumor progression in prostate cancer (PCa) patients after radical prostatectomy (RP). We conducted a retrospective multicenter study to determine the effect of body mass index (BMI) on the clinicopathological characteristics and biochemical recurrence of PCa in Japanese men who underwent RP. METHODS: The medical records of 1257 men with PCa treated by RP without neoadjuvant therapy at four medical institutes between 2001 and 2009 were retrospectively reviewed. Patients were categorized into four groups using the World Health Organization (WHO) BMI classification and BMI quartiles. Associations of the various BMI categories with clinicopathological characteristics and biochemical recurrences were statistically evaluated. Biochemical recurrence was defined as a PSA level of >0.2 ng ml(-1). RESULTS: Of the 1257 patients, 230 (18.3%) experienced biochemical recurrence during the median follow-up period of 49 months. The median BMI was 23.8 kg m(-2), and 1.4% patients were underweight, 65.4% were of normal weight, 30.9% were overweight and 2.4% were obese (WHO classification). Preoperative PSA levels and PSA density (PSAD) tended to decrease as BMI increased. Pathological characteristics did not differ significantly among BMI categories. As per the WHO classification and quartile categories, biochemical recurrence rate was comparable among the BMI groups. After adjusting for other pre- and postoperative covariables, multivariate Cox proportional hazards analysis revealed that a high BMI did not have an independent impact on biochemical recurrence-free survival. CONCLUSIONS: Underweight Japanese PCa patients treated by RP had higher preoperative PSA levels and PSAD. High BMI was not associated with adverse pathological findings or increased biochemical recurrence rate in Japanese PCa patients treated with RP. Racial differences may exist in the relationship between obesity and outcomes of RP in PCa patients.

Safety and effectiveness of neoadjuvant luteinizing hormone-releasing hormone agonist plus low-dose estramustine phosphate in high-risk prostate cancer: a prospective single-arm study.

BACKGROUND: Radical prostatectomy (RP) has limited cancer control potential for the patient with high-risk prostate cancer (Pca). We prospectively examined the efficacy and safety of neoadjuvant therapy with luteinizing hormone-releasing hormone (LHRH) agonist + low-dose estramustine phosphate (EMP) (LHRH+EMP) followed by RP. METHODS: High-risk Pca was defined by the D'Amico stratification system. A total of 142 patients with high-risk Pca were enrolled in this trial from September 2005 to March 2011. The LHRH+EMP therapy included administration of LHRH agonist and 280 mg day(-1) EMP for 6 months before RP. Pathological cancer-free (pT0) rate on the surgical specimen was the primary end point. Secondary end points were PSA-free survival and toxicity. RESULTS: The average patient age was 67.4 years (interquartile range (IQR) 72, 65) and the median initial PSA level was 14.80 ng ml(-1) (IQR 26.22, 7.13). The median Gleason score was 9 (IQR 9, 7) and 97 patients (68.3%) had clinical stage T2c or T3. All patients completed 6 months of LHRH+EMP neoadjuvant therapy with no delays in RP. Seven patients (4.9%) achieved pT0. Surgical margins were negative in 125 patients (87.0%). At a median follow-up period of 34.9 months, PSA-free survival was 84.3%. No serious adverse events were reported during the study and there were no toxicity-related deaths. CONCLUSIONS: Six months of LHRH+EMP neoadjuvant therapy followed by RP is safe and oncological outcomes are acceptable. Although this study was a single-arm trial with a relatively short follow-up, this treatment may have a potential to improve PSA-free survival in high-risk Pca patients. Further clinical trials are warranted.

Minimum incision endoscopic radical cystectomy in patients with malignant tumors of the urinary bladder: clinical and oncological outcomes at a single institution.

AIMS: The objectives of this study were to investigate the clinical and oncological outcomes of patients with malignant tumors of the urinary bladder undergoing minimum incision endoscopic radical cystectomy (MIE-RC). METHODS: Between August 2005 and June 2011, 130 consecutive patients at Hirosaki University Hospital underwent MIE-RC and bilateral lymphadenectomy for malignant tumors of the urinary bladder. We retrospectively studied all 130 patients. MIE-RC was performed through a 7-cm suprapubic midline incision. A 30° laparoscope was conveniently positioned on the head side of the patients, for precise observation and monitoring. RESULTS: The median operative time for all procedures, including MIE-RC, bilateral pelvic lymphadenectomy and urinary diversion was 266 min. The median estimated blood loss was 1260 mL. None of the patients had positive surgical margins. The post-operative median follow-up period was 32.8 months. The 5-year overall and disease-free survival rates were 91.6% and 87.0%, respectively. CONCLUSIONS: Our experience with MIE-RC appears to be favorable with acceptable operative and oncological outcomes.

A switch from conventional twice-daily tacrolimus to once-daily extended-release tacrolimus in stable kidney transplant recipients.

BACKGROUND: Extended-release tacrolimus (TAC-ER) was developed to provide a more convenient treatment compliance and improve safety by avoiding toxic peak levels. We prospectively evaluated the safety and effectiveness of a 1:1 dose switch from twice-daily tacrolimus to once-daily TAC-ER in stable kidney transplant recipients and assessed their satisfaction with the regimen. PATIENTS AND METHODS: Tacrolimus was switched to TAC-ER (1:1 dose) in 12 kidney transplant recipients with stable renal function from March 2010 to August 2011. The posttransplantation follow-up period was 7.6 ± 4.3 years (range 1.5-13.2 years). No patient had diabetes mellitus in this group. We evaluated the tacrolimus trough levels, serum creatinine, potassium, glucose, glycohemoglobin (HbA1c), and urine protein concentrations once a month from 6 months prior to 1 year after switching. A satisfaction survey for TAC-ER treatment was performed 3 months after the switch. The questionnaire included administration compliance questions such as "forget to take less often," "easy to carry," "easy to store," and "general satisfaction." RESULTS: After the switch to TAC-ER, we observed a quick and sustained 25% decrease in TAC trough levels from 4.8 ± 1.0 to 3.6 ± 0.8 (P = .0002). No significant differences in serum creatinine, potassium, glucose, HbA1c, or urine protein concentration were observed during the 14.6 ± 2.6 months' follow-up period. No recipient experienced acute rejection. The satisfaction survey demonstrated that the stable kidney transplant recipients were satisfied with the switch. CONCLUSIONS: A switch from twice-daily tacrolimus to once-daily TAC-ER (1:1 dose) was safe and effective. TAC-ER can improve treatment compliance in stable kidney transplant recipients.