Importance of Management of Lifestyle-Related Diseases After Kidney Donation to Living Donors.

BACKGROUND: Living kidney transplant donors are classified as stage 3 chronic kidney disease after kidney donation. For this reason, we provide daily lifestyle guidance, such as blood pressure and weight management before surgery, and dietary counseling focused on salt restriction. We emphasize providing lifestyle guidance after kidney donation. METHOD: At Osaka Medical and Pharmaceutical University Hospital, living kidney donors are scheduled for their first postoperative visit 1 month after kidney donation, followed by regular checkups every 6 months after that, starting 3 months after the initial visit. When living kidney donors come to the Renal Replacement Therapy Selection Outpatient Clinic before kidney transplantation, we provide sufficient explanations of the potential risks that may arise after kidney donation and ensure that they understand the importance of regular postoperative checkups. Apart from cases where patients reside far away, and we ask another hospital to provide postoperative follow-up, we can achieve regular checkups for almost all cases. RESULTS: Eighty-four living kidney transplant donors are being followed up at Osaka Medical and Pharmaceutical University Hospital. The average age is 59.8 ± 11.8 years, showing a trend of aging. Among the donors under follow-up, 7 developed hyperlipidemia, 2 developed hypertension, and 1 developed diabetes as new-onset lifestyle diseases after kidney donation. CONCLUSION: The ability to empathize with and support the anxieties associated with kidney donation and build a strong relationship of trust with the donors has become a significant factor in achieving a high rate of regular checkups after kidney donation. As a result, it has led to early detection and intervention for donor diseases, contributing to the maintenance of their health. Managing lifestyle-related diseases after kidney donation is essential for living kidney donors.

Pattern of expression of microRNA in patients with radiation induced bladder injury.

INTRODUCTION: Bladder cancer (BC) is sensitive to radiation treatment and a subset of patient experiences radiation induced injuries including shrinkage of bladder due to bladder fibrosis. METHODS: Using a micro-RNA (miRNA) array comparing patient's samples with, or without radiation induced injuries, we have checked the clustering of miRNA expression. RESULTS: Hsa-miR-130a, hsa-miR-200c, hsa-miR-141, and hsa-miR-96 were found to be highly expressed (>50 times) in patients with fibrotic bladder shrinkage (FBS) compared to those with intact bladder (IB) function. In patients with FBS, hsa-miR-6835, hsa-miR-4675, hsa-miR-371a, and hsa-miR-6885 were detected to have lesser than half expression to IB patients. We have analyzed the significance of these genes in relation to overall survival of 409 BC patients retrieved from TCGA data set. We have run combined survival analysis of mean expression of these four miRNAs highly expressed in FBS patients. 175 patients with high expression had longer median survival of 98.47 months than 23.73 months in 233 patients with low expression (HR: 0.53; 0.39 - 0.72, logrank P value: 7.3e-0.5). Combination analysis of all 8 genes including hsa-miR-6835, hsa-miR-4675, hsa-miR-371a, and hsa-miR-6885 showed the same HR for OS. Target scanning for these miRNAs matched specific cytokines known as an early biomarker to develop radiation induced fibrosis. CONCLUSIONS: BC patients with fibrotic radiation injury have specific miRNA expression profile targeting pro-fibrotic cytokines and these miRNAs possibly renders to favorable survival.

Nephron-sparing ureteroscopic surgery vs. radical nephroureterectomy: comparable survival-outcomes in upper tract urothelial carcinoma.

PURPOSE: This study investigates the utility of ureteroscopic surgery (URS) as an alternative to radical nephroureterectomy (RNU) in managing upper tract urothelial carcinoma (UTUC), with a focus on survival outcomes and re-evaluation of current the European Association of Urology guidelines criteria. METHODS: We conducted a retrospective, multi-institutional review of 143 UTUC patients treated with URS (n = 35) or RNU (n = 108). Clinicopathological factors were analyzed, and survival outcomes were assessed using Kaplan-Meier analysis and Cox proportional-hazards models. RESULTS: The median follow-up period was 27 months. Overall survival (OS) and radiographic progression-free survival (rPFS) were comparable between the URS and RNU groups (OS: HR 2.42, 95% CI 0.63-9.28, P = 0.0579; rPFS: HR 1.82, 95% CI 0.60-5.47, P = 0.1641). URS conferred superior renal function preservation. In patients characterized by factors such as radiographically invisible lesions, negative cytology, pTa stage, low-grade tumors, and multiple lesions, the OS outcomes with URS were comparable to those with RNU as follows: radiographically invisible lesions (P = 0.5768), negative cytology (P = 0.7626), pTa stage (P = 0.6694), low-grade tumors (P = 0.9870), and multiple lesions (P = 0.8586). CONCLUSION: URS offers survival outcomes similar to RNU, along with better renal function preservation, especially in low-risk UTUC patients. These findings underscore the urgency of re-evaluating the current EAU guidelines and encourage further research into determining the ideal patient selection for URS in UTUC treatment.

Factors affecting insulation failure in reusable surgical devices.

The purpose of this study was to investigate the associated factors of insulation failure (IF) in reusable endoscopic instruments. The insulation coating of reusable endoscopic instruments underwent routine visual checks, hand washing to remove visible stains, and mechanized sterilization. We recorded the cleaning number and usage period of all instruments. The instruments were tested for IF using a detector. IF was found in eight of 69 devices (11.6%). Examining by clinical specialty, we found IF in 4 of 28 gastrointestinal (14.3%), 3 of 20 gynecological (15.0%), 1 of 12 urological (8.3%), and none of the nine thoracic devices. The median distance from the tip to the damaged part was 5 cm (3-5 cm). In the IF and the intact groups, the period of use [7 years (6-8) versus 7 years (4-8), P = 0.90] and the number of cleanings [281 (261-323) versus 261 (179-320), P = 0.27] were not significantly different. The IF group included products of three different companies; however, six of the eight (75.0%) were from the same company. Cleaning methods and usage period have a lower impact on IF. The use of reusable forceps as a monopolar device was found to pose a higher risk, requiring regular assessments.

Pulmonary artery occlusion post immunotherapy for hilar node-positive lung cancer.

We present the case of a patient who developed pulmonary artery occlusion following immune-checkpoint inhibitor (ICI) therapy for non-small cell lung cancer. A 69-year-old man with squamous cell carcinoma (yc-T1cN0M0), initially diagnosed at c-stage IVA (T3N1M1b), in the upper lobe of the left lung, was scheduled to undergo salvage lung resection after ICI therapy. However, he exhibited an occlusion of the lingular pulmonary artery near the clinically metastatic hilar lymph node. To avoid severe adhesions, the patient underwent successful wedge resection without dividing pulmonary vessels and was discharged without complications. Surgeons should be prepared for pulmonary artery changes following ICI therapy.

Optimal Time Point for Evaluation of Response to Pembrolizumab Treatment in Japanese Patients With Metastatic Urothelial Carcinoma.

BACKGROUND/AIM: The duration of pembrolizumab use in actual daily practice might be shorter than that in clinical trials because termination of pembrolizumab therapy is at the discretion of the physician. We retrospectively reviewed the response to pembrolizumab in Japanese patients with metastatic urothelial carcinoma (mUC) in relation to the time to response (TTR). PATIENTS AND METHODS: The records of 165 patients treated with pembrolizumab for mUC were retrospectively analyzed. Response was evaluated at 2, 4, 6 and 8 months. TTR along with time to best response were analyzed. Phase II-III clinical trials were also reviewed to compare the TTR and time to best overall response. RESULTS: The median patient age was 70 years. The objective response rate in the total cohort was 27.1% (42 out of 155 patients). Median TTR was 2.4 months and the time to best response was 3.1 months. Radiological evaluation at each time point significantly predicted overall survival (OS). Considering the evaluation of response at 2, 4, 6 and 8 months, the response at later time points tended to predict OS better. Multivariate analysis showed that the evaluation of response at 8 months (hazard ratio=1.91, 95% confidence interval=1.16-3.16 months; p<0.01) and best response during the treatment (hazard ratio=1.69, 95% confidence interval=1.17-2.44; p<0.01) independently predicted improved OS. CONCLUSION: Given that response when evaluated at a later point during pembrolizumab treatment more favorably reflected improved survival than when assessed earlier, physicians may be encouraged to wait until at least the termination of pembrolizumab treatment to determine the best response.

Tissue Distribution of Cisplatin by Intra-arterial Infusion Route in Comparison to Systemic Route: Implication to Therapy for Node-positive Bladder Cancer.

BACKGROUND/AIM: In clinical practice, platinum-based systemic chemotherapy works to shrink pelvic lymph nodes. Intra-arterial (IA) bolus infusion may result in more favorable results than systemic chemotherapy. In the present study, we investigated the distribution of cisplatin administrated by IA infusion in varying organs, specifically focusing on the node tissue, in comparison with the intravenous (IV) route. MATERIALS AND METHODS: Under anesthesia, cisplatin 0.42 mg/body was administrated by IA or IV infusion in rats to mimic a balloon-occluded arterial infusion model used in clinical practice. The kidney, bladder, lymphatic tissue, and peripheral blood were extracted to analyze the amount of cisplatin by inductively coupled plasma-mass spectrometry. RESULTS: Concertation of cisplatin by IA infusion was higher than that by the IV route in the peripheral blood and kidney. IA infusion led to a significantly high concentration of cisplatin in the bladder compared to IV infusion (1.3±0.452 vs. 0.2 ppb/mg ± 0.055, p=0.050). Furthermore, the IA method led to an extremely high concentration of cisplatin in the lymphatic tissue compared to the IV method (0.1±0.036 vs. 13.3±5.36, p=0.048). CONCLUSION: High cisplatin accumulation in the lymphatic tissue and bladder by IA administration may have a potential role for treating patients with node-positive bladder cancer.

Unplanned hemodialysis initiation and low geriatric nutritional risk index scores are associated with end-stage renal disease outcomes.

Patients with end-stage renal disease (ESRD) have a low nutritional status and a high mortality risk. The geriatric nutritional risk index (GNRI) is a predictive marker of malnutrition. However, the association between unplanned hemodialysis (HD) and GNRI with mortality remains unclear. In total, 162 patients underwent HD at our hospital. They were divided into two groups: those with unplanned initiation with a central venous catheter (CVC; n = 62) and those with planned initiation with prepared vascular access (n = 100). There were no significant differences in sex, age, malignant tumor, hypertension, and vascular disease, while there were significant differences in the times from the first visit to HD initiation (zero vs. six times, p < 0.001) and days between the first visit and HD initiation (5 vs. 175 days, p < 0.001). The CVC insertion group had significantly lower GNRI scores at initiation (85.7 vs. 99.0, p < 0.001). The adjusted hazard ratios were 4.002 and 3.018 for the GNRI scores and frequency, respectively. The 3-year survival rate was significantly lower in the CVC + low GNRI group (p < 0.0001). The GNRI after 1 month was significantly inferior in the CVC insertion group. Inadequate general management due to late referral to the nephrology department is a risk factor for patients with ESRD.

Prognostic value of the fluctuation in the neutrophil-lymphocyte ratio at 6 weeks of pembrolizumab treatment is specific to the clinical response in metastatic urothelial carcinoma.

PURPOSE: Most patients with metastatic urothelial carcinoma experience no objective response to pembrolizumab and have poor overall survival (OS). Here, we investigated the prognostic value of fluctuation in the neutrophil-lymphocyte ratio (NLR) at 6 weeks of pembrolizumab treatment, focusing on its association with the achievement of objective response. MATERIALS AND METHODS: The clinical records of 177 metastatic urothelial carcinoma patients treated with pembrolizumab were retrospectively analyzed. RESULTS: The median age was 72 years, and the median OS was 14 months. The objective response rate in the total cohort was 26.5% (47 of 177 patients). Multivariable analysis showed that objective response achievement (hazard ratio 0.3 [95% confidence interval 0.15-0.59], P < 0.001) and decline in NLR from that at baseline at 6 weeks of treatment (0.54 [0.34-0.88], P = 0.013) were independent prognostic factors for improved OS. For 47 (26.5%) patients who achieved an objective response, OS was similar regardless of NLR fluctuation at 6 weeks of treatment (P = 0.723). Intriguingly, of the 130 (73.5%) patients with no objective response, those who showed a decreased NLR at 6 weeks of pembrolizumab treatment (57 patients) from that at baseline had significantly longer OS than those with elevated NLR (73 patients) (14 vs. 6 months, P = 0.007). CONCLUSIONS: The fluctuation in NLR from that at baseline at 6 weeks of pembrolizumab treatment may be useful for patients without an objective response. This could potentially aid decision-making for post pembrolizumab therapies.

Efficacy of pembrolizumab and comprehensive CD274/PD-L1 profiles in patients previously treated with chemoradiation therapy as radical treatment in bladder cancer.

BACKGROUND: Chemoradiation therapy (CRT) has been increasingly reported as a possible alternative to total cystectomy (TC) for localized bladder cancer (BC). Pembrolizumab is the standard of care for platinum-refractory metastatic urothelial carcinoma, although it is unknown whether the efficacy of pembrolizumab in patients previously treated with curative CRT varies from the results of benchmark trials. METHODS: We retrospectively assessed whether the survival benefit of pembrolizumab differs between patients previously treated with TC or CRT as radical treatment. A total of 212 patient records were collected for a logistic regression propensity score model. An independent dataset with next-generation sequencing (n=289) and PD-L1 Combined Positive Score (CPS: n=266) was analyzed to assess whether CRT-recurrent tumor harbors distinct CD274/PD-L1 profiles. RESULTS: Propensity score matching was performed using putative clinical factors, from which 30 patients in each arm were identified as pair-matched groups. There was no significant difference in overall survival from the initiation of pembrolizumab (p=0.80) and objective response rate (p=0.59) between CRT and TC treatment groups. In the independent 289 BC cohort, 22 samples (7.6%) were collected as CRT-recurrent tumors. There was no significant difference in CD274 mRNA expression level between CRT-naïve and CRT-recurrent tumors. The compositions of CD274 isoforms were comparable among all isoforms detected from RNAseq between CRT-naïve (n=267) and CRT-recurrent (n=22) tumors. No actionable exonic mutation in CD274 was detected in CRT-recurrent tumors. PD-L1 CPS was positively correlated with CD274 mRNA expression level, and PD-L1 CPS was comparable between CRT-naïve and CRT-recurrent tumors. CONCLUSIONS: The efficacy of pembrolizumab for patients previously treated with CRT was similar to those treated with TC. The enhanced tumor regression by combining programmed cell death protein 1/PD-L1 inhibitor and CRT might be expected only in the concurrent administration.

Salvage Surgery for Bronchopleural Fistula Due to Durvalumab and Chemoradiation.

Herein we describe a case of salvage lobectomy for a bronchopleural fistula secondary to durvalumab after chemoradiotherapy in initially unresectable non-small cell lung cancer. A 75-year-old man with adenocarcinoma, c-stage IIIB (T4N2M0) in the upper lobe of the right lung, received durvalumab after chemoradiotherapy. Fourteen months after durvalumab was discontinued, pneumonitis developed followed by peripheral bronchopleural fistula, and he unavoidably underwent salvage right upper lobectomy. The postoperative course was uneventful, and air leakage ceased. After chemoradiotherapy and durvalumab, refractory air leakage may develop that may require salvage surgery.

Taurodeoxycholic acid and valine reverse obesity-associated augmented alloimmune responses and prolong allograft survival.

Obesity initiates a chronic inflammatory network linked to perioperative complications and increased acute rejection rates in organ transplantation. Bariatric surgery is the most effective treatment of obesity recommended for morbidly obese transplant recipients. Here, we delineated the effects of obesity and bariatric surgery on alloimmunity and transplant outcomes in diet-induced obese (DIO) mice. Allograft survival was significantly shorter in DIO-mice. When performing sleeve gastrectomies (SGx) prior to transplantation, we found attenuated T cell-derived alloimmune responses resulting in prolonged allograft survival. Administering taurodeoxycholic acid (TDCA) and valine, metabolites depleted in DIO-mice and restored through SGx, prolonged graft survival in DIO-mice comparable with SGx an dampened Th1 and Th17 alloimmune responses while Treg frequencies and CD4+ T cell-derived IL-10 production were augmented. Moreover, in recipient animals treated with TDCA/valine, levels of donor-specific antibodies had been reduced. Mechanistically, TDCA/valine restrained inflammatory M1-macrophage polarization through TGR5 that compromised cAMP signaling and inhibited macrophage-derived T cell activation. Consistently, administering a TGR5 agonist to DIO-mice prolonged allograft survival. Overall, we provide novel insights into obesity-induced inflammation and its impact on alloimmunity. Furthermore, we introduce TDCA/valine as a noninvasive alternative treatment for obese transplant patients.

Hemodialysis Initiation in Oldest-Old Patients: A Case Series.

With an increase in the number of older adults worldwide, the oldest-old population, defined as individuals over the age of 90, is also growing. Japan is now facing the problem of a "super-aged society" in which over 21% of the population is aged over 65. The oldest-old constituted 1.8% (2.31 million) of the Japanese population in 2019. Such individuals have special health-care needs. In cases of acute or chronic (or both) renal failure in the oldest-old, it becomes difficult to decide whether dialysis should be initiated. The issue is controversial, and there is some debate on whether dialysis should be avoided in elderly people because of their frailty or if it should be initiated to enable them to spend their remaining years with their families by improving their quality of life. Herein, we describe our experience in 4 cases of hemodialysis initiated in patients over the age of 90. In our experience, dialysis enabled them to spend the rest of their lives with their families, which could not have been possible without it. Although further studies are needed, we concluded that oldest-old individuals in good general health could be eligible for and benefit from hemodialysis.

Increased BUB1B/BUBR1 expression contributes to aberrant DNA repair activity leading to resistance to DNA-damaging agents.

There has been accumulating evidence for the clinical benefit of chemoradiation therapy (CRT), whereas mechanisms in CRT-recurrent clones derived from the primary tumor are still elusive. Herein, we identified an aberrant BUB1B/BUBR1 expression in CRT-recurrent clones in bladder cancer (BC) by comprehensive proteomic analysis. CRT-recurrent BC cells exhibited a cell-cycle-independent upregulation of BUB1B/BUBR1 expression rendering an enhanced DNA repair activity in response to DNA double-strand breaks (DSBs). With DNA repair analyses employing the CRISPR/cas9 system, we revealed that cells with aberrant BUB1B/BUBR1 expression dominantly exploit mutagenic nonhomologous end joining (NHEJ). We further found that phosphorylated ATM interacts with BUB1B/BUBR1 after ionizing radiation (IR) treatment, and the resistance to DSBs by increased BUB1B/BUBR1 depends on the functional ATM. In vivo, tumor growth of CRT-resistant T24R cells was abrogated by ATM inhibition using AZD0156. A dataset analysis identified FOXM1 as a putative BUB1B/BUBR1-targeting transcription factor causing its increased expression. These data collectively suggest a redundant role of BUB1B/BUBR1 underlying mutagenic NHEJ in an ATM-dependent manner, aside from the canonical activity of BUB1B/BUBR1 on the G2/M checkpoint, and offer novel clues to overcome CRT resistance.

Risk Classification for Overall Survival by the Neutrophil-Lymphocyte Ratio and the Number of Metastatic Sites in Patients Treated with Pembrolizumab-A Multicenter Collaborative Study in Japan.

Pembrolizumab has emerged as the new standard of care in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas the optimal risk stratification to predict survival outcomes is still controversial. We examined a risk model for overall survival (OS) in mUC treated with pembrolizumab using our multi-institutional dataset (212 patients). The median age was 72 years old. Median OS from the initiation of pembrolizumab treatment was 11.7 months. The objective response rate (ORR) was 26.4%. On multivariate analysis, multiple metastatic sites and an NLR > 3.50 at the initiation of pembrolizumab treatment were identified as independent predictors for OS. We next developed a risk model using those two predictors. Patients without any factors were assigned to the favorable-risk group (26.5%). Patients with either factor and both factors were assigned to the intermediate-risk group (44.3%), and poor-risk group (29.2%), respectively. Kaplan-Meier curves showed clear discrimination of OS among the risk groups (p < 0.001). The ORR in each group was 35.7% in the favorable-risk group, 27.7% in the intermediate-risk group, and 17.7% in the poor-risk group. Given that the model can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice.

Restored TDCA and valine levels imitate the effects of bariatric surgery.

Background: Obesity is widespread and linked to various co-morbidities. Bariatric surgery has been identified as the only effective treatment, promoting sustained weight loss and the remission of co-morbidities. Methods: Metabolic profiling was performed on diet-induced obese (DIO) mice, lean mice, and DIO mice that underwent sleeve gastrectomies (SGx). In addition, mice were subjected to intraperitoneal (i.p.) injections with taurodeoxycholic acid (TDCA) and valine. Indirect calorimetry was performed to assess food intake and energy expenditure. Expression of appetite-regulating hormones was assessed through quantification of isolated RNA from dissected hypothalamus tissue. Subsequently, i.p. injections with a melanin-concentrating hormone (MCH) antagonist and intrathecal administration of MCH were performed and weight loss was monitored. Results: Mass spectrometric metabolomic profiling revealed significantly reduced systemic levels of TDCA and L-valine in DIO mice. TDCA and L-valine levels were restored after SGx in both human and mice to levels comparable with lean controls. Systemic treatment with TDCA and valine induced a profound weight loss analogous to effects observed after SGx. Utilizing indirect calorimetry, we confirmed reduced food intake as causal for TDCA/valine-mediated weight loss via a central inhibition of the MCH. Conclusions: In summary, we identified restored TDCA/valine levels as an underlying mechanism of SGx-derived effects on weight loss. Of translational relevance, TDCA and L-valine are presented as novel agents promoting weight loss while reversing obesity-associated metabolic disorders. Funding: This work has been supported in part by a grant from NIH (UO-1 A1 132898 to S.G.T., DP and MA). M.Q. was supported by the IFB Integrated Research and Treatment Centre Adiposity Diseases (Leipzig, Germany) and the German Research Foundation (QU 420/1-1). J.I. was supported by the Biomedical Education Program (BMEP) of the German Academic Exchange Service (DAAD). T.H. (HE 7457/1-1) and F.K. (KR 4362/1-1) were supported by the German Research Foundation (DFG). H.R.C.B. was supported the Swiss Society of Cardiac Surgery. Y.N. was supported by the Chinese Scholarship Council (201606370196) and Central South University. H.U., T.M. and R.M. were supported by the Osaka Medical Foundation. C.S.F. was supported by the German Research Foundation (DFG, SFB738, B3).

Construction of a computational mechanical model of bronchi for practical simulation of the optimal positive intrathoracic pressure conditions during general thoracic surgery.

BACKGROUND: Thoracic CO2 insufflation with positive intrathoracic pressure is usually effective during thoracoscopic surgery, however, lung collapse is sometimes insufficient. We hypothesized that inappropriate bronchial collapse might cause this unsuccessful lung collapse. OBJECTIVE: The objective of this study was to construct a computational mechanical model of bronchi for practical simulation to discover the optimal conditions of positive intrathoracic pressure during thoracoscopic surgery. METHODS: Micro-focus high-resolution X-ray computed tomography measurements of lungs from just-slaughtered swine were extracted, and the three-dimensional geometries of the bronchi under pressurized and depressurized conditions were measured accurately. The mechanical properties of the bronchus were also measured. Computational fluid dynamics (CFD) and computational structural mechanics (CSM) analyses were conducted. RESULTS: The CSM results indicated that the present structural model could simulate bronchial occlusion. The CFD results showed that airflows from pressed lung alveoli might cause low-internal-pressure regions when suddenly or heterogeneously pushed airflow was injected from a small branching bronchus to a large bronchus. A preliminary computational mechanical model of bronchi was constructed. CONCLUSIONS: We demonstrated the performance of the mechanical model of bronchi in rough simulations of bronchial occlusions. However, this model should be verified further using human data to facilitate its introduction to clinical use.

Spontaneous pneumothorax during nintedanib therapy in patients with systemic sclerosis-associated interstitial lung disease.

Interstitial lung disease (ILD) is a common complication of systemic sclerosis (SSc). Nintedanib, an antifibrotic drug, has recently been approved for treating SSc-ILD. Although there have been no reports suggesting the development of pneumothorax with nintedanib use, its safety in patients with impaired lung function is unclear. We observed the development of refractory spontaneous pneumothorax during nintedanib therapy in two patients with SSc-ILD and impaired lung function. Nintedanib use for SSc-ILD, an extensive disease, may therefore increase the risk of pneumothorax. In addition, pneumothorax is more likely to be refractory in these cases; initiation of nintedanib treatment and follow-up should be considered carefully.

Distinct effect of body mass index by sex as a prognostic factor in localized renal cell carcinoma treated with nephrectomy ~ data from a multi-institutional study in Japan ~.

BACKGROUND: We assessed the prognostic value of body mass index (BMI) in Asian patients with localized RCC who underwent nephrectomy. METHODS: A total of 665 patients who underwent nephrectomy for localized RCC were enrolled in the present study and divided into the two BMI groups: i.e., BMI < 25 in 463 (69.6%) and BMI > 25 in 202 (30.4%) patients. RESULTS: In total, there were 482 (72.5%) males and 183 (27.5%) females. Five-year cancer-specific survival (CSS) rates were significantly higher in increased BMI than the lower BMI group (97.1 and 92.5%: P = 0.007). When stratified by sex, significantly longer CSS in higher BMI was confirmed in males (5-year CSS of 92.7% in BMI < 25 and 98.1% in BMI > 25, p = 0.005), while there was no difference in CSS between BMI groups for female patients. Multivariable analysis exhibited that higher BMI was an independent predictor for favorable CSS in male (cox model: p = 0.041, Fine & Gray regression model: p = 0.014), but not in the female. Subgroup analysis for CSS revealed that favorable CSS with higher BMI was observed in patient subgroups of age < 65 (p = 0.019), clear cell histology (p = 0.018), and tumor size > 4 cm, p = 0.020) as well as male (p = 0.020). CONCLUSION: Our findings collected from the multi-institutional Japanese dataset demonstrated longer survival in patients with higher BMI than lower BMI for non-metastatic RCC treated with nephrectomy. Intriguingly, this finding was restricted to males, but not to females.

Early Prostate-Specific Antigen (PSA) Change at Four Weeks of the First-Line Treatment Using Abiraterone and Enzalutamide Could Predict Early/Primary Resistance in Metastatic Castration-Resistant Prostate Cancer.

The identification of early or primary resistance to androgen signaling inhibitors (ASIs) is of great value for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the predictive value of prostate-specific antigen (PSA) response at dour weeks of first-line ASIs treatment for mCRPC patients. A total of 254 patients treated with ASIs (abiraterone acetate: AA and enzalutamide: Enz) at the first-line treatment are retrospectively analyzed. Patients are stratified according to the achievement of >30% PSA decline at 4 and 12 weeks from the treatment initiation. At four weeks of the treatment, 157 patients (61.8%) achieved >30% PSA decline from the baseline. Thereafter, 177 patients (69.7%) achieved >30% PSA decline at 12 weeks of the treatment. A multivariate analysis exhibits >30% PSA decline at four weeks as an independent predictor for overall survival (OS). We note that 30 of 97 (30.9%) patients who did not achieve >30% PSA decline at four weeks consequently achieved >30% PSA decline at 12 weeks, and had a comparable favorable three years OS rate as the 147 patients achieving >30% PSA decline at both 4 and 12 weeks. To identify the variables that discriminate the patient survival in 97 patients without achieving >30% PSA decline at four weeks, a multivariate analysis is performed. The duration of androgen deprivation therapy before CRPC ≤ 12 months and Eastern Cooperative Oncology Group Performance Status ≥ 1 are identified as independent predictors for shorter OS for those patients. These data offer a concept of early treatment switch after four weeks of first-line ASIs when not observing >30% PSA decline at four weeks-particularly in patients with a modest effect of ADT and poor performance status.