Metabolic changes with degarelix vs leuprolide plus bicalutamide in patients with prostate cancer: a randomized clinical study.

PURPOSE: In a mouse model, degarelix generated the least metabolic consequences via low follicle-stimulating hormone (FSH) levels compared with orchiectomy and leuprolide after 4 months of androgen deprivation therapy (ADT). Here, we comparatively investigated the influence of ADT with degarelix or leuprolide on the development of metabolic syndrome in patients with prostate cancer (PCa). METHODS: Patients with hormone-naive PCa were recruited. Eligible patients were randomized (1:1) to monthly degarelix or monthly leuprolide for 6 months. Key trial variables were monitored monthly. The primary endpoint was changes in fasting blood sugar (FBS). Secondary endpoints were changes in body weight, abdominal circumference, lipid profiles, and hemoglobin A1c (HbA1c) and FSH levels. Computed tomography was performed to measure subcutaneous and visceral fat areas before and after 6 months of ADT. Data were analyzed using the χ2 test, Student's t test, and analysis of variance. RESULTS: From the 100 patients registered, 85 completed the trial (degarelix: 40 patients; leuprolide: 45 patients). Mean increases in FBS did not differ between the two arms. Similarly, there were no differences between the arms in mean increases in body weight, abdominal circumference, lipid profiles, HbA1c, or subcutaneous and visceral fat areas. Follicle-stimulating hormone levels were significantly lower in the degarelix arm than in the leuprolide arm (p < 0.05). CONCLUSIONS: Lipid and glucose metabolism did not differ significantly between the arms, while FSH levels were significantly lower in the degarelix arm.

Massive Renal Replacement Lipomatosis With Foci of Xanthogranulomatous Pyelonephritis in a Horseshoe Kidney.

Renal replacement lipomatosis (RRL) is a rare condition that occurs at the end of the spectrum of renal tissue replacement by fat. Xanthogranulomatous pyelonephritis (XGP) is a granulomatous inflammation characterized by destruction of renal parenchyma and replacement by lipid-laden macrophages. We present the case of a 75-year-old man who complained of severe anemia 34 years after right nephrolithotomy. Computed tomography revealed a huge low-density mass with renal parenchyma atrophy on the right side of horseshoe kidney. Right nephrectomy was performed. Pathological diagnosis was RRL with XGP. This is the first report of RRL with XGP in a horseshoe kidney.

The augmented representation of the cost-effectiveness acceptability curve for economic evaluation of health technology.

New schemes on the cost-effectiveness acceptability curve (CEAC) were developed, which can make the CEAC augmented to be more informative regarding the types of acceptance and statistical inference. Theoretical approaches have been undertaken to address two questions: 1) how the area under the curve (AUC) can be zoned by different types of acceptance displayed on the incremental cost-effectiveness plane, and 2) how the accepted dataset of incremental cost-effectiveness ratios (ICERs), which are generated by simulation runs, can be statistically associated with a threshold of ICER for acceptance. To address the first question, the AUC of a typically sigmoid-shaped CEAC was divided into three zones according to the three segmentations of the scattered plots accepted at South-east, North-east and South-west quadrants on the incremental cost-effectiveness plane. A solution for the second question was "a new CEAC of the mean" (mCEAC), which is defined by plotting a pair of the mean and its occurrence probability of ICER accepted at North-east quadrant on the incremental cost-effectiveness plane. All those schemes were graphically illustrated based on hypothetical examples using the bootstrapping simulation. Our new schemes on CEAC will provide decision makers with useful information on cost-effectiveness assessment beyond the standard presentation of CEAC.

Laparoscopic management of complicated urachal remnants in adults.

OBJECTIVES: The traditional surgical approach for removing a urachal remnant is via a large transverse or midline infraumbilical incision. We review our experience with laparoscopic urachal cyst excision and report the efficacy and outcomes of this approach as a less morbid, minimally invasive alternative. METHODS: Between August 2005 and March 2009, eight patients with a mean age of 26 years who had symptomatic urachal cysts underwent laparoscopic radical excision of the urachal remnant. Using three ports, the urachal remnant was dissected from the umbilicus to the bladder dome and then removed intact via the umbilicus. Umbilicoplasty was performed by a plastic surgeon. We retrospectively reviewed the perioperative records to assess morbidity and outcomes. RESULTS: All eight operations were completed successfully. No intraoperative or postoperative complications were reported at a mean follow-up of 3.2 years. Mean operative time was 147.5 min including umbilicoplasty. Pathological evaluation confirmed a benign urachal remnant in each case. There have been no recurrences of symptoms nor postoperative complications during follow-up. Mean time to full recovery, defined as return to normal life without pain, was 16 days. The patients with bladder cuff resection had a delayed full convalescence (25 vs. 13 days) due to a minimum degree of dysuria. CONCLUSION: A laparoscopic approach with the removal of urachal remnants via the umbilicus appears to be a safe and effective alternative with better cosmesis when compared to an open approach.

Cell-penetrating D-isomer peptides of p53 C-terminus: long-term inhibitory effect on the growth of bladder cancer.

OBJECTIVES: To investigate whether a single application of the membrane-permeable D-isomer of the p53 C-terminus connected with a retro-inverso version of the NH(2)-terminal 20-amino acid peptide of the influenza virus hemagglutinin-2 protein (riHA2) inhibited the growth of bladder cancer cells. The transduction of p53 using poly-arginine is useful for targeting and suppressing the growth of bladder cancer cells. However, the protein's intracellular half-life is short, and repeated application is necessary to achieve an anti-tumor effect. METHODS: The p53 carboxyl-terminal peptides covalently coupled with cell-penetrating peptides were synthesized with D- or L-amino acids. Moreover, the peptides were connected with riHA2 by a disulfide bridge. Human bladder cancer cell lines were incubated with each peptide and cell viability was assessed with the WST assay. Apoptotic cells were confirmed by Hoechst and active capase-3 staining. The p53 peptides were injected into severe combined immunodeficiency disease mice transplanted with J82 cells to investigate their anti-tumor effect on bladder tumors. A survival curve was plotted using the Kaplan-Meier method. RESULTS: A single application of cell-penetrating D-isomer peptides of the p53 C-terminus connected with riHA2 (d11R-p53C'-riHA2 and dFHV-p53C'-riHA2) inhibited the growth and induced the apoptosis of bladder cancer cells. The tumor-bearing mice treated only with vehicle had a mean survival time of 12 days, whereas treatment with d11R-p53C'-riHA2 resulted in a long-term survival rate of 50%. CONCLUSIONS: Peptide transduction therapy using the D-isomer p53 C-terminal peptide with riHA2 may be an innovative method for the treatment of bladder cancer.