Recently, novel molecular targeted agents markedly changed the treatment of renal cell carcinoma (RCC), with promising results. However, there is little understanding of how these agents affect immune cell populations in RCC, an immunogenic tumor. Therefore, we investigated the changes in the peripheral blood immune cells in 58 RCC patients during the first 4 weeks of treatment with sorafenib, sunitinib, everolimus, or temsirolimus and evaluated whether these changes were associated with clinical outcomes. The immunological parameters were the proportion of type-1 (Th1) and type-2 (Th2) T cells, regulatory T cells (Treg), mature dendritic cells, and the neutrophil-to-lymphocyte ratio (NLR). The changes in these immune cells varied with the agents and the clinical response, dichotomized by the median progression-free survival (PFS) time (PFS-short or PFS-long). A significant decrease in the Th1/Th2 ratio was seen after sunitinib treatment only in the PFS-short group, suggesting a shift toward Th2 that down-regulates host immunity. The NLRs indicative of the balance between host immunity and cancer-related inflammation were consistently lower in the PFS-long group than in the PFS-short group, suggesting that lower NLR is associated with better clinical response. Only sunitinib decreased NLR remarkably regardless of PFS status, which may favor anti-tumor immunity. When patients were dichotomized by the cutoff values, Th1/Th2 ratio was not associated with PFS in any targeted therapy, while lower pre-treatment NLR was associated with longer PFS in each targeted therapy. In addition, in RCC patients given sequential targeted therapy, those with a lower baseline NLR survived significantly longer compared with the counterparts. Moreover, those whose baseline NLR was sustained low during the initial therapy survived the longest. Our results suggest the diverse changes in host immune cells in RCC patients during targeted therapy. The changes in NLR during the early phase of targeted therapy may be a powerful discriminator of who will benefit from the subsequent treatment.

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Abbreviations & Acronyms DLST = drug-lymphocyte stimulation test DTX = docetaxel EMP = estramustine phosphate GA = goserelin acetate GnRHa = gonadotropinreleasing hormone analog LA = leuprorelin acetate PLA = polylactic acid PLGA = polylactic and glycolic acids PSA = prostate-specific antigen SI = stimulation index SpO2 = pulse oximetry Abstract: Gonadotropin-releasing hormone analog depots have been widely used for a variety of diseases including prostate cancer, breast cancer, endometriosis, uterine leiomyomas, and central precocious puberty. Most of the side/adverse effects of gonadotropin-releasing hormone analog depots, such as leuprorelin acetate depot, are related to hypotestosteronism in males. Anaphylaxis to gonadotropin-releasing hormone analog depot is extremely rare. We present the first case report of a Japanese man who developed anaphylaxis to leuprorelin acetate depot during the treatment of metastatic prostate cancer and recovered successfully by conservative treatment. A drug-lymphocyte stimulation test showed that not only leuprorelin acetate itself, but also its vehicle polylactic and glycolic acids, might be responsible for the anaphylaxis to leuprorelin acetate depot. Because anaphylaxis can be lethal, the present case suggests that one should bear in mind the possibility of anaphylaxis in all patients who receive gonadotropin-releasing hormone analog depot and monitor such patients carefully.

Objectives: To assess the relationship between the surgical procedure of robot-assisted radical prostatectomy (RARP) and urinary continence recovery by reviewing the video database.Methods: Video and data about men diagnosed with prostate cancer and underwent RARP were extracted and reviewed. Preserved urethral length (PUL) was semi-quantitatively measured using the lateral width of a 16-Fr urethral balloon catheter while cutting the urethra on a video screen. In addition, by reviewing intraoperative RARP video database, other surgical skill outcomes were also collected. Kaplan-Meier analysis with log-rank test was used to compare the urinary continence recovery rate, stratified by the PUL. Univariate and multivariate analyses were performed using the Cox proportional hazards model, and p-values of <0.05 were considered significant. Results:The number of patients included in this study was 213. In univariate analysis, a PUL of ≥16 mm, a body mass index of <23.1 kg/m 2 and a resected prostate volume of <44.3 g were statistically significant factors that influenced urinary continence recovery [hazard ratio (HR) 1.58, p = 0.036; HR 0.67, p = 0.021; and HR 0.58, p = 0.005, respectively]. Those factors also remained statistically significant in the multivariate analysis (HR 1.87, p = 0.022; HR 0.54, p = 0.001; and HR 0.57, p = 0.005, respectively). One year post-operatively, the recovery rate from urinary continence was 79.0% for patients with a PUL of ≥16 mm and 66.5% for patients with a PUL of <16 mm. Conclusion:These results suggest that patients with longer PUL in RARP have a significantly higher rate of post-operative urinary continence recovery.

Background: It is extremely important to understand the local anatomy prior to performing appropriate and efficient robot-assisted partial nephrectomies (RAPNs).Methods: We developed a personalized three-dimensional printed kidney model of square-block type to enhance our knowledge and understanding on the underlying anatomy during RAPN, and we consequently applied this model to six initial cases of RAPN.Results: The mean warm ischemic time was 18 minutes and the mean estimated blood loss was 59 mL.Only one patient presented with a minor complication, whereas all six patients included in this study were surgical margin negative. Conclusions:We believe that this cost-effective model helped us in understanding the underlying local anatomy and facilitating an increased efficiency in the related surgery. Further studies are required to validate our preliminary results.

PurposeTo determine if switching from one brand of the α1-adrenoceptor antagonist naftopidil (Avishot™) to another brand (Flivas™) under the same conditions causes the same changes in lower urinary tract symptoms (LUTS) and quality of life (QOL) as the perceived placebo effect, and if ambient temperature as a nonspecific factor is related to those changes in benign prostatic hyperplasia (BPH) patients.Patients and methodsA retrospective study was carried out on 217 BPH patients who had received Avishot™ for more than 6 months and then were switched to Flivas™ at the same dose and timing. The two drugs contain the same principal ingredient and display the same pharmacokinetic properties. The International Prostate Symptom Score (IPSS), QOL score, and average monthly ambient temperature at the patients’ residence area from the Automated Meteorological Data Acquisition System in Japan were used for the evaluation.ResultsA significant change in urinary storage symptoms (P = 0.006), and especially in nighttime frequency (P< 0.001), was observed by switching drugs, suggesting the perceived placebo effect. There was significant improvement of daytime frequency (P< 0.05), nighttime frequency (P< 0.001), storage symptoms (P< 0.001), and total IPSS (P< 0.05) when the magnitude of ambient temperature change from before and 3 months after switching drugs was higher than 10°C, while no significant improvement was noted in any of the parameters examined when the same was lower than 10°C.ConclusionThe present study showed the nonspecific effect of magnitude of ambient temperature change was involved in the perceived placebo effect on LUTS, especially on storage symptoms, by switching drugs. The nonspecific effect on LUTS with BPH needs to be considered when evaluating subjective treatment efficacy of drugs for LUTS with BPH in routine clinical practice. The present study supports the lifestyle advice “avoid exposing the lower body to cold temperature” or “keep warm when it is cold” for LUTS with BPH.

We retrospectively compared the post-transplantation graft survival and the donor's estimated glomerular filtration rates (eGFRs) following living donor kidney transplantations (LDKTs) involving medically complex living donors (MCLDs) (the elderly and patients with obesity, hypertension, diabetes mellitus, or reduced renal function) and standard living donors (SLDs). The clinical data on patients who underwent LDKTs at our institution from 2006-2019, including 192 SLDs and 99 MCLDs, were evaluated. Regarding recipients, the log-rank test and multivariable Cox proportional hazards analyses showed a higher incidence of overall and death-censored graft loss in the recipients who received kidneys from MCLDs (Hazard ratio = 2.16 and 3.25, P = 0.015 and 0.004, respectively), after adjusting for recipient-related variables including age, sex, duration of dialysis, ABO compatibility, and donor-specific antibody positivity. Regarding donors, a linear mixed model showed significantly lower postdonation eGFRs (À2.25 ml/min/1.73 m 2 , P = 0.048) at baseline in MCLDs than SLDs, but comparable change (difference = 0.01 ml/min/1.73 m 2 / year, P = 0.97). In conclusion, although kidneys from MCLDs are associated with impaired graft survival, the donation did not adversely affect the MCLDs' renal health in at least the short-term. LDKTs involving carefully selected MCLDs would be an acceptable alternative for recipients with no SLDs.

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