Prostate-specific antigen (PSA) decline with apalutamide therapy is associated with longer survival and improved outcomes in individuals with metastatic prostate cancer: a plain language summary of the TITAN study.

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC). A total of 1052 participants with mCSPC were included in the TITAN study. Treatment with apalutamide was compared with treatment with placebo. All participants received androgen deprivation therapy (or ADT), which is a type of hormone therapy that has been part of the main treatment for mCSPC for many years. The results showed that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT. Apalutamide plus ADT also controlled the growth of the cancer for a longer length of time compared with placebo plus ADT. Additionally, participants who received apalutamide plus ADT experienced a greater reduction in the blood levels of prostate-specific antigen (or PSA), called a deep PSA decline, compared with those who received placebo plus ADT. An additional (or post hoc) analysis was carried out to understand whether a decrease in blood PSA levels, in response to treatment, was associated with improved outcomes, including longer survival time. WHAT WERE THE RESULTS OF THE ADDITIONAL ANALYSIS?: In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes. WHAT DO THESE RESULTS MEAN FOR INDIVIDUALS WITH MCSPC?: These results demonstrate that individuals with mCSPC can benefit from treatment with apalutamide plus ADT. The association seen between deep PSA decline and the longer survival time and improved outcomes highlights how PSA measurements can be used to help monitor cancer disease evolution in response to treatment. Monitoring PSA levels will assist doctors and other healthcare professionals to understand how effectively a treatment is working for a patient and to tailor their treatment approach to improve PSA decline.

Perioperative and short-term outcomes of Retzius-sparing robot-assisted laparoscopic radical prostatectomy stratified by gland size.

OBJECTIVE: To investigate the effect of preoperative prostate volume (PV) on the perioperative, continence and early oncological outcomes among patients treated with Retzius-sparing robot-assisted laparoscopic radical prostatectomy (RS-RALP). PATIENTS AND METHODS: This is a retrospective analysis of 294 patients with organ-confined prostate cancer treated with RS-RALP in a high-volume centre from November 2012 to February 2015. Patients were divided into three groups based on their transrectal ultrasonography estimated PV as follows: group 1, <40 mL (231 patients); group 2, 40-60 mL (47); group 3, >60 mL (16). Perioperative, oncological, and continence outcomes were compared between the three groups. RESULTS: The median [interquartile range (IQR)] PV for each group was; 26.1 (22-31) mL, 45.9 (41-50) mL, and 70 (68-85) mL. Blood loss was higher in group 3 compared to groups 2 and 1; at a median (IQR) of 475 (312-575) mL, 200 (150-400) mL, and 250 (150-400) mL, respectively (P = 0.001). The intraoperative transfusion rate was higher in group 3 patients (P = 0.004), while the complication rate did not differ (P = 0.05). The console time was slightly higher but was not statistically significant in group 3 compared to groups 2 and 1; at a mean (sd) of 100 (35) min, 92 (34.4) min, and 93 (24.8) min, respectively (P = 0.70). Biochemical recurrence and the continence rate did not differ between the three groups (P = 0.89 and P = 0.25, respectively). CONCLUSION: RS-RALP is oncologically and functionally equivalent for all prostate sizes but technically demanding for larger prostates. We therefore recommend that surgeons initiate their RS-RALP technique with smaller prostates.

Inhibition of dipeptidyl peptidase IV protects tacrolimus-induced kidney injury.

Accumulating evidence shows that a gut-released hormone, the glucagon-like peptide-1 (GLP-1), has not only a glucose-lowering effect but also a renoprotective effect against kidney injury. In this study, we investigated whether a dipeptidyl peptidase (DPP) IV inhibitor has a protective effect against tacrolimus-induced renal injury. Rats were treated with tacrolimus (1.5 mg/kg, subcutaneously) and the DPP IV inhibitor MK0626 (10 or 20 mg/kg, oral gavage) for 4 weeks. MK0626 treatment attenuated tacrolimus-induced renal dysfunction, tubulointerstitial fibrosis, and arteriolopathy. Moreover, these improvements were accompanied by a reduction in oxidative stress and apoptosis. MK0626 treatment increased the blood level of GLP-1 and the level of its receptor in tissue sections but did not alter the levels of other DPP IV substrates, such as neuropeptide Y and the stromal cell-derived factor-1. These data suggest that DPP IV inhibition has an important role in the renoprotection against tacrolimus-induced nephrotoxicity via antioxidative and antiapoptotic effects and preservation of the GLP-1 system.

Number of positive preoperative biopsy cores is a predictor of positive surgical margins (PSM) in small prostates after robot-assisted radical prostatectomy (RARP).

OBJECTIVE: To determine the impact of prostate size on positive surgical margin (PSM) rates after robot-assisted radical prostatectomy (RARP) and the preoperative factors associated with PSM. PATIENTS AND METHODS: In all, 1229 men underwent RARP by a single surgeon, from 2005 to August of 2013. Excluded were patients who had transurethral resection of the prostate, neoadjuvant therapy, clinically advanced cancer, and the first 200 performed cases (to reduce the effect of learning curve). Included were 815 patients who were then divided into three prostate size groups: <31 g (group 1), 31-45 g (group 2), >45 g (group 3). Multivariate analysis determined predictors of PSM and biochemical recurrence (BCR). RESULTS: Console time and blood loss increased with increasing prostate size. There were more high-grade tumours in group 1 (group 1 vs group 2 and group 3, 33.9% vs 25.1% and 25.6%, P = 0.003 and P = 0.005). PSM rates were higher in prostates of <45 g with preoperative PSA levels of >20 ng/dL, Gleason score ≥7, T3 tumour, and ≥3 positive biopsy cores. In group 1, preoperative stage T3 [odds ratio (OR) 3.94, P = 0.020] and ≥3 positive biopsy cores (OR 2.52, P = 0.043) were predictive of PSM, while a PSA level of >20 ng/dL predicted the occurrence of BCR (OR 5.34, P = 0.021). No preoperative factors predicted PSM or BCR for groups 2 and 3. CONCLUSION: A preoperative biopsy with ≥3 positive cores in men with small prostates predicts PSM after RARP. In small prostates with PSM, a PSA level of >20 ng/dL is a predictor of BCR. These factors should guide the choice of therapy and indicate the need for closer postoperative follow-up.

Clinical significance of the ratio between FOXP3 positive regulatory T cell and interleukin-17 secreting cell in renal allograft biopsies with acute T-cell-mediated rejection.

The aim of this study is to investigate the clinical significance of the ratio between interleukin-17 (IL-17) secreting cell and FOXP3-positive regulatory T cell (FOXP3(+) Treg) infiltration in renal allograft tissues with acute T-cell-mediated rejection (ATCMR). Fifty-six patients with biopsy-proven ATCMR were included. Infiltration of FOXP3(+) Treg and IL-17-secreting cells was evaluated with immunostaining for FOXP3 or IL-17 on the biopsy specimens, and the patients were divided into the FOXP3 high group (Log FOXP3/IL-17 > 0·45) or the IL-17 high group (Log FOXP3/IL-17 < 0·45). We compared the allograft function, severity of tissue injury, and clinical outcome between the two groups. In the IL-17 high group, allograft function was significantly decreased compared with the FOXP3 high group (P < 0·05). The severity of interstitial and tubular injury in the IL-17 high group was higher than the FOXP3 high group (P < 0·05). The proportions of steroid-resistant rejection, incomplete recovery and recurrent ATCMR were higher in the IL-17 high group than in the FOXP3 high group (all indicators, P < 0·05). The IL-17 high group showed lower 1-year (54% versus 90%, P < 0·05) and 5-year (38% versus 85%, P < 0·05) allograft survival rates compared with the FOXP3 high group. Multivariate analysis revealed that the FOXP3/IL-17 ratio was a significant predictor for allograft outcome. The FOXP3/IL-17 ratio is a useful indicator for representing the severity of tissue injury, allograft dysfunction and for predicting the clinical outcome of ATCMR.

Pain relieving effect of music on patients during transrectal ultrasonography: A pilot study.

BACKGROUND: Patient discomfort is often inevitable during transrectal ultrasonography (TRUS), a widely used modality for evaluating benign prostate hyperplasia/lower urinary tract symptoms. Music has been suggested as a method of pain relief during urologic procedures. In this study, we investigated the effect of music on pain relief during TRUS. METHODS: In a pilot study conducted from March to June 2019, pain scores of 316 patients who underwent TRUS with or without music were quantified using the visual analog scale (VAS). One-to-one propensity score matching was performed by matching the subjects between the groups. Patients with hemorrhoids of grade ≥ III were excluded (n = 4). RESULTS: Among the 312 patients included in the study (VAS score = 3.3 ± 2.4), 177 listened to music during the procedure. There were significant differences in age, prostate-specific antigen, prostate volume, International Prostate Symptom Score symptom/life score, and VAS score between the music (+) and music (-) groups. After adjusting for relevant variables, VAS scores were significantly lower in male patients aged ≥65.0 years who underwent music intervention than in those who did not (1.5 ± 1.4 vs. 3.0 ± 1.4, p = 0.002). CONCLUSION: Age was negatively associated with pain during TRUS, and music had a relieving effect on pain in patients aged ≥65.0 years. Our findings may help improve the quality of examinations in urologic outpatient offices.

Characterization of liver disease and lipid metabolism in the Niemann-Pick C1 mouse.

Niemann-Pick type C1 (NPC1) disease is an autosomal-recessive cholesterol-storage disorder characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. The NPC1 gene is expressed in every tissue of the body, with liver expressing the highest amounts of NPC1 mRNA and protein. A number of studies have now indicated that the NPC1 protein regulates the transport of cholesterol from late endosomes/lysosomes to other cellular compartments involved in maintaining intracellular cholesterol homeostasis. The present study characterizes liver disease and lipid metabolism in NPC1 mice at 35 days of age before the development of weight loss and neurological symptoms. At this age, homozygous affected (NPC1(-/-)) mice were characterized with mild hepatomegaly, an elevation of liver enzymes, and an accumulation of liver cholesterol approximately four times that measured in normal (NPC1(+/+)) mice. In contrast, heterozygous (NPC1(+/-)) mice were without hepatomegaly and an elevation of liver enzymes, but the livers had a significant accumulation of triacylglycerol. With respect to apolipoprotein and lipoprotein metabolism, the results indicated only minor alterations in NPC1(-/-) mouse serum. Finally, compared to NPC1(+/+) mouse livers, the amount and processing of SREBP-1 and -2 proteins were significantly increased in NPC1(-/-) mouse livers, suggesting a relative deficiency of cholesterol at the metabolically active pool of cholesterol located at the endoplasmic reticulum. The results from this study further support the hypothesis that an accumulation of lipoprotein-derived cholesterol within late endosomes/lysosomes, in addition to altered intracellular cholesterol homeostasis, has a key role in the biochemical and cellular pathophysiology associated with NPC1 liver disease.