To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning.
A double-blind, ...placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed.
Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels.
Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.
A short version of the UTI Guidelines elaborated by the Urinary Tract Infection Working Group of the Health Care Office of the European Association of Urology is presented. The topics include ...classification, diagnosis, treatment and follow-up of uncomplicated UTI, UTI in children, UTI in diabetes mellitus, renal insufficiency, renal transplant recipients and immunosuppression, complicated UTI due to urological disorders, sepsis syndrome, urosepsis, urethritis, prostatitis, epididymitis, orchitis and principles of perioperative prophylaxis in urology.
Abstract Introduction Dual kidney transplantation (DKT), using extended criteria donor (ECD) grafts not suitable for single kidney transplantation (SKT), has been suggested to expand the kidney donor ...pool. Herein, we reviewed the long-term outcomes of DKT to assess its results versus a control group of 179 ECD SKTs. The allocation policy was based on a Remuzzi score obtained from a pretransplant biopsy. Materials and methods We analyzed SKT in 179 (31.8%) and DKT in 41 (7.3%) of 563 cadaveric transplants from 2000 to 2008. Patients with DKT versus SKT showed mean recipient ages of 54 versus 51 years. We performed 17 ipsilateral and 24 bilateral DKT. The mean score was 2.78 for SKT and 4.3/4.6 for DKT. Results Delayed graft function requiring dialysis occurred in 23 (56.1%) DKT and 70 (39.1%) SKT recipients. Primary nonfunction was observed in 1 (2.4%) DKT and 7 (3.9%) SKT recipients respectively. One DKT patient underwent monolateral transplantectomy. In the DKT versus SKT group, patient survivals were 92% versus 95%, 89% versus 93%, and 89 versus 91% at 12, 36, and 60 months, respectively ( P = .3). Graft survivals were 100% versus 94%, 95% versus 90%, and 89% versus 78% at 12, 36, and 60 months, respectively ( P < .001). We observed a lower incidence of chronic allograft nephropathy ( P = .01) and a higher incidence of surgical adverse events ( P = .04) in DKT. Conclusions ECD graft survival using DKT provided better results compared with SKT, despite the use of organs from higher-risk donors. At 5 years follow-up, DKT was a safe strategy to face the organ shortage. To optimize the use of available kidneys, the criteria for DKT require further refinement and standardization. Preimplantation evaluation must maximize transplant success and protect recipients from receiving organs at increased risk of premature failure.
Abstract Introduction The number of overweight and obese patients undergoing renal transplantation has increased dramatically over the past two decades. Studies on graft survival and ...posttransplantation complications have often yielded conflicting results. Some authors have reported similar results for graft and patient survivals between obese and normal weight patients, but with a marginally increased rate of postoperative complications. In contrast, other reports note higher percentage of graft losses as well as increased mortality. In our study, we analyzed early- and long-term outcomes among obese versus nonobese kidney transplant recipients. Patients and Methods Between January 2000 and December 2008, we performed 563 cadaveric kidney transplantations. Recipients were classified in 1 of 5 groups based on their body mass index (BMI) at the time of transplantation: group A (n = 68; BMI < 18.5); group B (n = 310; 18.6 < BMI < 24.9); group C (n = 143; 25 < BMI < 29.9); group D (n = 32; 30 < BMI < 34.9); and group E (n = 10; BMI ≥ 35). The comparative analysis included patient and graft survivals, postoperative complications, onset of delayed graft function (DGF), acute rejection episodes, hospital stay, and serum creatinine values in the first 3 years posttransplantation. Results At a mean follow-up of 53 months (range, 3–112 months), DGF was observed in 20 patients in group A (29.4%), 82 in group B (26.4%), 43 in group C (30%), 16 in group D (50%), and 4 in group E (40%). Nevertheless, obese patients (groups D and E) showed higher mean serum creatinine values and worse renal function at 6 months ( P = .001), 1 year ( P < .001), and 3 years ( P = .001). Moreover, they were at increased risk of an acute rejection episode ( P = .01) and more susceptible to cardiovascular and metabolic complications ( P = .01). Morbidly obese patients displayed a higher incidence of postsurgical complications ( P = .002). There were no differences in the incidences of chronic allograft nephropathy (CAN) or infectious complications. Despite the differences in morbidity among the 5 groups, we failed to observe significant differences in patient or graft survivals at 6, 12, 36, or 60 months. Conclusion Our findings suggested that obese patients should not be discriminated against simply based on the BMI. At our center, obese (BMI >35) transplantation candidates undergo a thorough cardiac evaluation, as well as pulmonary, endocrine, and nutritional counseling seeking to minimize medical and surgical complications and improve survival and quality of life.
Background: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in ...elderly patients. Patients and methods: Patients with metastatic prostate cancer, progressive after primary hormonal therapy, were randomised to receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day or hydrocortisone alone until disease progression. Centres could choose to add aminoglutethimide 1000 mg/day to hydrocortisone as second-line hormone therapy (HT) for all their patients. Randomisation was stratified by centre. Further chemotherapy was allowed after progression. The primary end point was progression-free survival (PFS). The final analysis was performed on a total of 414 patients. Reported results were all based on intention-to-treat analyses. All progressions and responses were reviewed by an independent panel. Results: PFS was significantly prolonged in the VRL plus HT arm compared with the HT alone arm, according to the statistical hypothesis of the protocol (P=0.055 in the two-sided log-rank test with a pre-specified significance level of 10%). The 6-month PFS rates were 33.2% versus 22.8%, and the median durations of PFS were 3.7 versus 2.8 months. In the multivariate Cox analysis, which included age, Karnofsky performance status (PS), haemoglobin, alkaline phosphatase at study entry and number of prior hormonal treatments, the P value was decreased to 0.005. The prostate-specific antigen (PSA) response rate (≥50% decline sustained for at least 6 weeks) was significantly higher for VRL plus HT compared with HT (30.1% versus 19.2%; P=0.01). Clinical benefit, defined as a decrease in pain intensity or analgesic consumption or an improvement of Karnofsky PS for at least 9 weeks, and at least stable assessment in the other two, was also more frequently observed in patients who received VRL plus HT versus HT alone (30.6% and 19.2%; P=0.008). There was no statistical difference in overall survival. Forty-three per cent of patients in the HT arm received at least one line of further chemotherapy after progression, compared with 28% of patients in the VRL-based arm. Aminoglutethimide did not seem to result in better efficacy for either arm. VRL plus HT was well tolerated, with a median administered relative dose intensity of 90%; grade 4 neutropenia occurred in 6.5% of patients and non-haematological toxicity was rare. Conclusions: The combination of VRL and hydrocortisone compared with hydrocortisone alone resulted in improved clinical benefit, PFS and PSA response rate. This therapeutic gain is similar to that previously reported with mitoxantrone in combination with low-dose corticosteroids. There was no gain in survival; however, the combination is well tolerated in this elderly group of patients, who often present cardiac co-morbidities, and therefore offers an active and safe therapeutic option for patients with hormone-refractory prostate cancer.
Dendritic cells (DCs) are potent antigen-presenting cells responsible for the activation and functional polarization of specific T cells. In patients with renal cell carcinoma (RCC) and other ...cancers, coordinate DC and T cell defects have been reported. In particular, DC and T cell functional subsets that are not conducive to tumor clearance are hypothesized to predominate in patients with advanced-stage disease. Two major peripheral blood DC subsets have been identified in humans: myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) that are believed to mediate contrasting effects on cancer immunity.
Given the lack of information regarding DC subsets in patients with RCC, in the present study we have investigated the comparative frequencies and activation states of mDC and pDC in peripheral blood, cancer tissues and lymph nodes of patients with RCC using flow cytometry and immunohistochemistry. Three monoclonal antibodies (mAbs) reactive against specific DC subsets (BDCA-2 or BDCA-4 for pDC and BDCA-1 and BDCA-3 which represent two distinct subsets of mDC, mDC1 and mDC2, respectively) were employed. We observed a significant reduction of both DC subsets in the peripheral blood of patients as compared to normal donors. Similarly, both mDC and pDC were recruited in large numbers into RCC tumor tissues, where they displayed an immature phenotype (DC-LAMP
−) and appeared unable to differentiate into mature DC (CD83
+) that were competent to migrate to draining lymph nodes.
However, we were readily able to generate
ex vivo mDC from RCC patients. These DC stimulated robust anti-tumor CTL
in vitro and would be envisioned for use in DC-based vaccines applied in patients with RCC whose existing immune system is judged dysfunctional, anergic or prone to undergo apoptosis.
Abstract Background The objective of this study was to evaluate differences in outcomes of allograft nephrectomies performed by extracapsular versus intracapsular techniques. Methods From 1993 to ...2010, we performed 89 allograft nephrectomies, including 57 by extracapsular techniques and 32 by intracapsular, chosen according to feasibility at the beginning of the surgery. Fisher exact test and logistic regression were used for statistical analysis. Survival estimates after allograft nephrectomy were calculated according to the Kaplan-Meier method. Results After a mean graft survival of 49.7 months, the indications for transplant nephrectomy were chronic rejection (39.3%), acute rejection (22.5%), infection/sepsis (19.1%), gross hematuria (6.7%), renal vein thrombosis (6.7%), renal artery thrombosis (3.4%), and graft rupture (2.3%). Mean operative time, blood loss, transfusions, and complications were similar between the extracapsular and intracapsular groups. The only difference in surgical aspects between the 2 groups was the mean hospital stay, which was longer for the extracapsular group (13.8 vs 7.6 days; P = .01), a result that was confirmed by multivariate analysis (odds ratio, 1.05; 95% confidence interval, 1.0–1.1; P = .03). Conclusions Our experience showed no significant advantages in favor of the intracapsular technique except for a shorter length of hospital stay than after the extracapsular procedure.
Abstract Introduction Ischemia-reperfusion injury (IRI) causes a high rate of delayed graft function (DGF), the most frequent complication in the immediate postoperative period after cadaveric donor ...kidney transplantation. Herein we evaluated the impact of donor and recipient characteristics on DGF development in terms of the incidence of acute rejection episodes, hospital stay, renal function, and long-term graft and patient survivals. Materials and Methods Between February 1998 and July 2011, 761 patients underwent cadaveric donor kidney transplantations. DGF was defined as the need for dialysis in the first week. Patients were subdivided according to initial graft function as immediate graft function (IGF) or DGF. Results DGF observed in 241 patients (31.6%) was associated independently with expanded criteria donors, extended cold ischemia time, Karpinsky histological score, and prior dialysis duration both univariate and multivariate analysis. The incidence of acute rejection episodes was 18.1% among the DGF group versus 1.3% in the IGF group ( P < .01). DGF significantly reduced both graft and patient survivals at 6, 12, 36, and 60 months. Conclusion DGF was responsible for a longer hospital stay, worse early and long-term renal function, a higher incidence of acute rejection episodes as well as reduced graft and patient survivals.
Precision medicine has the ambition to improve treatment response and clinical outcomes through patient stratification and holds great potential for the treatment of mental disorders. However, ...several important factors are needed to transform current practice into a precision psychiatry framework. Most important are 1) the generation of accessible large real-world training and test data including genomic data integrated from multiple sources, 2) the development and validation of advanced analytical tools for stratification and prediction, and 3) the development of clinically useful management platforms for patient monitoring that can be integrated into health care systems in real-life settings. This narrative review summarizes strategies for obtaining the key elements—well-powered samples from large biobanks integrated with electronic health records and health registry data using novel artificial intelligence algorithms—to predict outcomes in severe mental disorders and translate these models into clinical management and treatment approaches. Key elements are massive mental health data and novel artificial intelligence algorithms. For the clinical translation of these strategies, we discuss a precision medicine platform for improved management of mental disorders. We use cases to illustrate how precision medicine interventions could be brought into psychiatry to improve the clinical outcomes of mental disorders.
Abstract Introduction Renal transplantation in patients older than 60 years has long been regarded with skepticism owing to the increased risk of complications although, as compared with dialysis ...treatment, a graft seems to improve not only the quality of life but also long-term patient survival. This study sought to analyze the impact of recipient age older than 60 years on patient and graft outcomes. Materials and Methods We retrospectively investigated the outcomes of 761 kidney transplant recipients from cadaveric donors performed between February 1998 and July 2011. While 69 subjects were at least 60 years of age (group A), 692 were younger than 60 years (group B) at the time of transplantation. Result Mean follow-up was 60.1 ± 38.5 months. Delayed graft function (DGF) requiring dialysis was observed in 36 group A (52.1%) and 205 group B (29.6%) subjects ( P = .001). However, there were also significant differences between group A and group B in terms of mean donor age (60.3 vs 44.6 years; P < .001) and mean donor estimated creatinine clearance (57.8 vs 83.4 mL/min; P < .001). There were no significant differences in death-censored graft survival between the two groups, but elderly patients experienced worse survival ( P = .0005). The most common causes of patient death were myocardial infarction, other cardiovascular complications, and tumors. Conclusion Kidney transplantation is a good option for elderly recipients with end-stage renal disease, providing long graft survival and a good quality of life, although these patients are more likely to develop cancer or cardiovascular disease. Our findings suggested that older patients should not be excluded a priori from transplantation, but meticulous screening for cancer and heart disease should be always be performed to improve outcomes.
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