The lymphocyte-to-monocyte ratio as a significant inflammatory marker associated with survival of patients with metastatic renal cell carcinoma treated using nivolumab plus ipilimumab therapy.

BACKGROUND: Nivolumab plus ipilimumab (NIVO + IPI) is the first-line treatment for patients with metastatic renal cell carcinoma (mRCC). While approximately 40% of patients treated with NIVO + IPI achieve a durable response, 20% develop primary resistance with severe consequences. Therefore, there is a clinical need for criteria to select patients suitable for NIVO + IPI therapy to optimize its therapeutic efficacy. Accordingly, our aim was to evaluate the association between candidate biomarkers measured before treatment initiation and survival. METHODS: This was a multi-institutional, retrospective, cohort study of 183 patients with mRCC treated with systematic therapies between August 2015 and July 2023. Of these, 112 received NIVO + IPI as first-line therapy: mean age, 68 years; men, 83.0% (n = 93), and clear cell histology, 80.4% (n = 90). Univariable and multivariable analyses were used to evaluate associations between biomarkers and survival. RESULTS: On univariate analysis, high C-reactive protein and systemic index, a high neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio, and a low lymphocyte-to-monocyte ratio (LMR) were associated with shorter overall survival (OS). On multivariable analysis, a LMR ≤ 3 was retained as an independent factor associated to shorter OS with the highest accuracy (C-index, 0.656; hazard ratio, 7.042; 95% confidence interval, 2.0-25.0; p = 0.002). CONCLUSION: A low LMR may identify patients who would be candidate for NIVO + IPI therapy for mRCC.

Impact of trough abiraterone level on adverse events in patients with prostate cancer treated with abiraterone acetate.

PURPOSE: We assessed the impact of plasma trough concentrations of abiraterone (ABI) and its metabolite Δ4-abiraterone (D4A) and related polymorphisms on adverse events (AEs) in patients with metastatic prostate cancer who received abiraterone acetate (AA). METHODS: This prospective study enrolled patients with advanced prostate cancer treated with AA between 2016 and 2021. Plasma trough concentrations of ABI and D4A were measured using high-performance liquid chromatography. The impact of HSD3B1 rs1047303, SRD5A2 rs523349, and cytochrome P450 family 3A member 4 rs2242480 polymorphisms on plasma concentrations of ABI and D4A and the incidence of AEs were also assessed. RESULTS: In 68 patients treated with AA, the median ABI and D4A concentrations were 18.1 and 0.94 ng/mL, respectively. The high plasma trough concentration of ABI (≥ 20.6 ng/mL) was significantly associated with the presence of any AE and its independent risk factor based on multivariable analysis (odds ratio, 7.20; 95% confidence interval (CI): 2.20-23.49). Additionally, a high plasma trough concentration of ABI was an independent risk factor of time to withdraw AA (hazard ratio, 4.89; 95% CI: 1.66-14.38). The risk alleles of three polymorphisms were not statistically associated with the ABI and D4A concentrations and the incidence of AEs. CONCLUSIONS: The plasma trough concentration of ABI is associated with the presence of AEs and treatment failure after AA administration. ABI concentration monitoring may be useful in patients with prostate cancer who received AA.

Real clinical outcomes of nivolumab plus ipilimumab for renal cell carcinoma in patients over 75 years old.

BACKGROUND: Although nivolumab plus ipilimumab is the standard treatment for metastatic renal cell carcinoma (RCC), its efficacy and safety in older patients remain unclear. Therefore, this study aimed to assess the clinical outcomes of nivolumab plus ipilimumab for metastatic RCC in patients aged ≥ 75 years. METHODS: We enrolled 120 patients with metastatic RCC treated with nivolumab plus ipilimumab from August 2015 to January 2023. Objective response rates (ORRs) were compared between patients aged < 75 and ≥ 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events were compared between the groups. Adverse events were evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1. RESULTS: Among the patients, 57 and 63 were classified as intermediate and poor risk, respectively, and one could not be classified. The median follow-up duration after the initiation of treatment was 16 months. The patient characteristics between the groups, except for age, were not significantly different. Intergroup differences in ORR (42% vs. 40%; p = 0.818), PFS (HR: 0.820, 95% CI 0.455-1.479; p = 0.510), and median OS (HR: 1.492, 95% CI 0.737-3.020; p = 0.267) were not significant. The incidence of adverse events (50% vs. 67%; p = 0.111) and nivolumab plus ipilimumab discontinuation due to adverse events was not significantly different between the groups (14% vs. 13%; p = 0.877). CONCLUSIONS: The effectiveness of nivolumab plus ipilimumab was comparable between patients with metastatic RCC aged < 75 and those ≥ 75 years with respect to their ORRs, PFS, OS, and adverse event rates.

Impact of germline HLA genotypes on clinical outcomes in patients with urothelial cancer treated with pembrolizumab.

Human leukocyte antigen class I (HLA-I) genotypes are suggested to influence the cancer response to checkpoint blockade immunotherapy. This study assessed the impact of germline HLA genotypes on clinical outcomes in patients with chemoresistant advanced urothelial cancer (UC) treated with pembrolizumab. Zygosity, supertypes, evolutionary divergency, and specific alleles of germline HLA-I and -II were evaluated using the Luminex technique in 108 patients with chemoresistant metastatic or locally advanced UC treated with pembrolizumab. Among the 108 patients, 69 died and 83 showed radiographic progression during follow-up. Homozygous for at least one HLA-I locus, absence of the HLA-A03 supertype, and high HLA-I evolutionary divergence were associated with a radiographic response, but were not associated with survival outcomes. Patients with the HLA-DQB1*03:01 allele had significantly lower disease control rates than patients without the allele (17.4% vs. 53.8%, p = 0.002); its presence was also an independent risk factor for progressive disease (hazard ratio 4.35, 95% confidence interval 1.03-18.46). Furthermore, patients with the HLA-DQB1*03:01 allele had significantly worse progression-free survival than patients without the allele (median progression-free survival 3.1 vs. 4.8 months, p = 0.035). There was no significant relationship between any HLA status and the incidence of severe adverse events. Several germline HLA genotypes, especially HLA-DQB1*03:01, may be associated with radiographic progression. However, their impact on treatment response is limited, and germline HLA genotypes was not independently associated with survival outcomes. Further prospective studies are needed to confirm the relationship between germline HLA genotypes and clinical outcomes in patients with chemoresistant advanced UC treated with pembrolizumab.

Factors influencing warm ischemia time in robot-assisted partial nephrectomy change depending on the surgeon's experience.

INTRODUCTION: Warm ischemia time (WIT) is a primary concern for robot-assisted laparoscopic partial nephrectomy (RALPN) patients because longer WIT is significantly associated with postoperative deteriorating kidney function. Tumor complexity, determined by the RENAL nephrometry score (RENAL score), can help predict surgical outcomes, but it is unclear what RENAL score and clinical factors affect WIT. This study explored the clinical factors predicting long WIT in experienced surgeon to RALPN. MATERIALS AND METHODS: In our institute, 174 RALPNs were performed between November 2013 and February 2021, of which 114 were performed by a single surgeon and included in this study. Clinical staging and the total RENAL score were determined based on preoperative CT scans. The cases were divided into three groups based on experience: period 1: 1-38, period 2: 39-76, and period 3: 77-114. The clinical factors associated with longer WIT were analyzed per period. RESULTS: The overall median tumor diameter was 32 mm, and one patient had a positive surgical margin, but there were no cancer-related deaths. In total, there were 18 complications (15.8%). Periods 2 and 3 had larger tumor diameters (p < 0.01) and worse preoperative kidney function (p = 0.029) than period 1. A RENAL L-component score of 3 was associated with longer WIT in period 3 (odds ratio: 3.900; 95% confidence interval: 1.004-15.276; p = 0.044), but the tumor diameter and the total RENAL score were not. CONCLUSIONS: A large tumor in the central lesion indicated by the RENAL L-component score was associated with increased WIT in RALPN.

Specific Gut Microbial Environment in Lard Diet-Induced Prostate Cancer Development and Progression.

Lard diet (LD) is a risk factor for prostate cancer (PCa) development and progression. Two immunocompetent mouse models fed with isocaloric specific fat diets (LD) enriched in saturated and monounsaturated fatty acid (SMFA), showed significanftly enhanced PCa progression with weight gain compared with a fish oil diet (FOD). High gut microbial divergency resulted from difference in diets, and the abundance of several bacterial species, such as in the orders Clostridiales and Lactobacillales, was markedly altered in the feces of LD- or FOD-fed mice. The proportion of the order Lactobacillales in the gut was negatively involved in SMFA-induced body weight gain and PCa progression. We found the modulation of lipid metabolism and cholesterol biosynthesis pathways with three and seven commonly up- and downregulated genes in PCa tissues, and some of them correlated with the abundance of the order Lactobacillales in mouse gut. The expression of sphingosine 1-phosphate receptor 2, which is associated with the order Lactobacillales and cancer progression in mouse models, was inversely associated with aggressive phenotype and weight gain in patients with PCa using the NCBI Gene Expression Omnibus database. Therefore, SMFA may promote PCa progression with the abundance of specific gut microbial species and overexpression of lipogenic genes in PCa. Therapeutics with alteration of gut microbiota and candidate genes involved in diet-induced PCa progression may be attractive in PCa.

[A Case of Renal Anastomosing Hemangioma].

A 65-year-old man was found to have a 1.7 cm right renal mass by follow-up abdominal computed tomography for left total nephrectomy after a traffic accident. The renal mass progressed slowly to 2.2 cm in three years and enhanced magnetic resonance imaging revealed marked T2 weighting hyperintensity of the lesion. Although a radiologist (TK) suggested the diagnosis renal anastomosing hemangioma preoperatively, we could not deny the possibility of renal cell carcinoma completely. Therefore, the patient underwent robot-assisted laparoscopic partial nephrectomy. The tumor was successfully removed without any renal arterial clamping or parenchymal excision. Histopathologically, the lesion was composed of capillary-size blood vessels lined by a single layer of endothelial cells, and was diagnosed as a renal anastomosing hemangioma. There were no signs of postoperative recurrence during the 3 month follow-up.

[Successful Re-Administration of Nivolumab in Patient with Metastatic Renal Cell Carcinoma : A Case Report].

A 46-year-old woman was referred to our hospital with a left-sided renal tumor pointed out by ultrasonography at the time of a medical checkup．Computed tomography revealed a mass measuring 88×77×68 mm on the upper pole of the left kidney. She was diagnosed with cT2aN0M0 clear cell renal cell carcinoma. Laparoscopic left nephrectomy was performed uneventfully. Histopathological diagnosis was clear cell renal cell carcinoma, G2, v1, pT2. Four months after surgery, lung metastases appeared, and systemic therapy was given sequentially as follows ; sunitinib for 2 months, nivolumab for 8 months, axitinib for 17 months, and pazopanib for 2 months．However, metastases progressed, and a re-administration of nivolumab was planned. The nivolumab re-treatment resulted in a marked reduction in multiple lung metastases despite the previous failure by nivolumab treatment. There are few reports on the therapeutic effect of re-administration of nivolumab. We report a case of successful treatment by re-administration of nivolumab.

Impact of nuclear YAP1 expression in residual cancer after neoadjuvant chemohormonal therapy with docetaxel for high-risk localized prostate cancer.

BACKGROUND: Although docetaxel-based chemohormonal therapy (CHT) is one of the standard treatments for castration-resistant prostate cancer (CRPC), pertinent biomarkers and precise mechanisms involved in the resistance for CHT for CRPC remain unknown. We investigated the relationship between chemohormonal resistance and the expression of steroid receptors and Hippo pathway proteins using a docetaxel-resistant prostate cancer (PCa) cell line and human PCa tissues in patients who underwent surgery with and without neoadjuvant therapy. METHODS: A docetaxel-resistant subline (22Rv1-DR) was generated to assess Hippo pathway protein expression and the effect of YAP1 inhibition on cellular characteristics. A tissue microarray with 203 cores from 70 high-risk localized PCa tissues was performed to assess steroid receptor and Hippo pathway protein expressions. RESULTS: Nuclear YAP (nYAP) expression was higher in 22RV-1-DR than in parental 22Rv-1 and YAP1 knockdown suppressed cell proliferation of 22Rv1-DR. Steroid receptor and Hippo pathway protein expressions varied among three different neoadjuvant groups, and nYAP1 expression was the highest in the CHT group. The patients with high nYAP in residual cancer after neoadjuvant CHT had a significantly higher biochemical recurrence (BCR) rate than those with low nYAP1. On multivariate analysis, the high nYAP1 was an independent prognostic factor for BCR. CONCLUSIONS: nYAP expression is a potential biomarker in high-risk patients treated with docetaxel-based CHT. Steroid receptors and Hippo pathway proteins may play a role in the chemohormonal resistance in advanced PCa.

Candidate genes involved in the defunctionalization and refunctionalization of the urinary bladder induced by bladder anuria and reperfusion.

AIMS: We develop a novel rabbit urinary diversion model of bladder defunctionalization due to bladder anuria followed by refunctionalization due to urine reperfusion to investigate the molecular biological background. To validate the results, we used reverse transcription-polymerase chain reaction (RT-PCR) to analyze human specimens from defunctionalized bladders in patients receiving dialysis before kidney transplantation. METHODS: Female rabbits were divided into three groups: control, defunctionalized, and refunctionalized. The bilateral ureters were anastomosed to vagina in the defunctionalized and refunctionalized groups at 0 weeks. In the refunctionalized group, the unilateral ureter was reanastomosed to the bladder at 8 weeks. RESULTS: The capacity and compliance of the rabbit bladder in the refunctionalized group were significantly lower than those in the control group at 8 weeks and higher than those in the defunctionalized group at 14 weeks. The significant downregulation of IGFBP2, UPK1B, and CST6 in the defunctionalized group compared with that in the control groups, and the significant downregulation of AGTR2 in the refunctionalized group compared with that in the defunctionalized group in the rabbit bladder-muscle DNA microarray were validated by RT-PCR. Human bladder muscle indicated significant downregulation of UPK1B and CST6 and significant downregulation of IGFBP2 in the defunctionalized group, which is consistent with both rabbit bladder-muscle DNA microarray and rabbit bladder RT-PCR results. CONCLUSIONS: The present study using novel model of bladder defunctionalization followed by refunctionalization indicated the consistent downregulation of UPK1B and CST6 in muscle and the consistent downregulation of IGFBP2 in mucosa in process of bladder defunctionalization, which was validated by human specimens.

Efficacy and safety of nivolumab for renal cell carcinoma in patients over 75 years old from multiple Japanese institutes.

PURPOSE: Despite nivolumab being increasingly used for treating metastatic renal cell carcinoma (mRCC), differing findings have been reported about its efficacy and safety in elderly patients. Thus, this study was aimed at evaluating nivolumab's efficacy and safety for treating mRCC in Japanese patients aged ≥ 75 years. METHODS: From March 2013 to August 2019, 118 mRCC patients (89 men and 29 women) were treated with nivolumab. The objective response rates (ORRs) were compared between patients aged ≥ 75 and < 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were also compared between the two age-groups. RESULTS: The median follow-up duration after nivolumab initiation was 10 months. At the time of nivolumab initiation, 22 and 96 patients were aged ≥ 75 and < 75 years, respectively. Intergroup differences in patient characteristics except for age were not significant. Furthermore, intergroup differences in ORR (14 vs 23%; P = 0.367), PFS (HR 0.74, 95% CI 0.37-1.51; P = 0.414), and median OS (HR 1.29, 95% CI 0.68-2.46; P = 0.433) were not significant. The incidence of nivolumab discontinuation due to AEs was significantly higher in the ≥ 75 years group (27% vs 7%; P = 0.028), although the intergroup difference in the AE incidence rate was not significant (55% vs 43.8%; P = 0.535). CONCLUSIONS: Nivolumab's effectiveness was comparable between the two patient groups, except for early AE-related discontinuation in the ≥ 75 year group.

[Seminal Vesicle Cystadenoma with Concurrent Prostate Cancer : A Case Report].

This case report documents seminal vesicle cystadenoma with concurrent prostate cancer in a 49-yearold man evaluated at follow-up for a high prostate-specific antigen level (12 ng/ml). Transrectal ultrasound-guided prostate biopsy was performed for adenocarcinoma of the prostate (Gleason score 3+4= 7). Staging computed tomography showed a 6.6×5.5×5.0 cm cystic tumorof the seminal vesicle. A possible diagnosis of primary malignant tumor of the seminal vesicle with concurrent organ-confined prostate cancer was considered. However, seminal vesicle tumor biopsy was not performed because the patient underwent open radical prostatectomy with the resection of the seminal vesicle tumor. Histopathologic examination of the seminal vesicle and the prostate revealed cystadenoma (Gleason score 4+3=7) and adenocarcinoma (stage pT2cN0). Neither recurrence of the cystadenoma nor biochemical recurrence of the prostate cancer was observed 5 years and 6 months after the surgery.

[The Initial Results of Robot-Assisted Pyeloplasty in Comparison with Laparoscopic Pyeloplasty for Ureteropelvic Junction Obstruction].

The initial results robot-assisted pyeloplasty (RAP) performed on 6 patients were compared with those of laparoscopic pyeloplasty (LP) for ureteropelvic junction obstruction performed on 26 patients in a Japanese regional center. The median operating time, estimated blood loss, time to oral intake, time to start walking, and hospital stay were not significantly different between the groups. There was no difference in the rate of complications of Clavien-Dindo≥grade III between the two groups. Although the number of entered patients was small, the results indicated that RAP is feasible with favorable outcome.

[Advanced Adrenocortical Carcinoma with Vena Caval Tumor Thrombus Treated with Extended Surgery and Subsequent Chemotherapy].

A 36-year-old female was referred to our hospital for a giant abdominal mass found by ultrasound examination. A computed tomographic scan showed a large retroperitoneal mass measuring 11 cm in diameter suspected to be liver invasion,a right atrial and inferior vena cava (IVC) tumor thrombus with obstruction of hepatic vein junction of IVC,and small lung metastases. She was diagnosed with cT4N0M1 adrenocortical carcinoma (ACC) by a needle biopsy and radiographic examination. Right adrenalectomy and thrombectomy were successfully performed without cardiac arrest and without liver dissection. The operative time was 485 minutes,and the estimated blood loss was 7,533 ml. No major peri- or postoperative complications were observed. For the residual lung mass,a first line combination chemotherapy with etoposide,doxorubicin,cisplatin and mitotane followed by a second line chemotherapy with gemcitabine and capecitabine were administered. She has been alive with disease for 45 months under mitotane treatment against residual lung metastases. In conclusion,extended surgery could be successfully performed for advanced ACC with right atrium and IVC tumor thrombus. Although careful planning is needed for successful surgery,combination therapy with extended surgery and subsequent systematic chemotherapy may provide a substantial benefit in patients with advanced ACC.

[A Case of Penile Pyoderma Gangrenosum Treated with Steroid Administration without Penectomy].

We report a case of idiopathic penile pyoderma gangrenosum that was successfully treated with corticosteroid treatment without penectomy. A 67-year-o1d man with induration and tenderness of the penile shaft visited a local hospital. A penile abscess was suspected on magnetic resonance imaging, and needle biopsy did not reveal malignancy. After the tension of the penile shaft had worsened, he was referred to our hospital where surgical drainage and re-biopsy were performed. Microbiological cultures revealed no growth, and pathological examination revealed no evidence of malignancy. Despite drainage, the abscess recurred on postoperative day 18. With a working diagnosis of penile pyoderma gangrenosum, we initiated prednisolone 30 mg once daily followed by taper and performed a second surgical drainage, leaving the wound open to heal by secondary intention. Wound discharge declined gradually, and no recurrence of abscess has yet been observed. Pyoderma gangrenosum is clinically diagnosed when subcutaneous chronic inflammatory findings are present without concurrent bacterial infection. Corpus cavernosum abscess presenting as the initial symptom of pyoderma gangrenosum is rare. Most cases of recurrent corpus cavernosum abscess eventually result in total penectomy. In this case, we successfully avoided penectomy by suspecting pyoderma gangrenous and initiating prednisolone treatment appropriately.

[METASTATIC Mucinous Tubular and Spindle Cell Carcinoma Treated with Nivolumab Successfully : A Case Report].

A 68-year-old man was referred to our hospital with a right-sided renal tumor identified by ultrasonography at the time of his medical check-up. Computed tomography revealed a well-circumscribed but distorted mass measuring 64×45×57 mm in the right kidney with para-aortic lymph node swelling. Laparoscopic right nephrectomy with para-aortic lymphadenectomy was performed. Histopathological diagnosis was mucinous tubular and spindle cell carcinoma (MTSCC) (pT3a) without lymph node metastasis (pN0). Postoperatively, metastases were identified in the lungs, and the vertebral and iliac bones. The patient was treated with axitinib. The lung nodule progressed and left sacrum metastases appeared even after treatment with axitinib. Therefore, nivolumab was administered as second-line treatment. The metastases in the lungs, as well as vertebral and iliac bone showed complete response to this therapy. MTSCC of the kidney is a rare low-grade renal cell carcinoma without any established systemic therapy for metastatic or unresectable lesions. We report a case of metastatic MTSCC in a patient who showed a favorable response to nivolumab treatment. This is the first report to describe successful treatment of metastatic MTSCC with anti-programmed cell death 1 antibody.

Incidence and location of positive surgical margin among open, laparoscopic and robot-assisted radical prostatectomy in prostate cancer patients: a single institutional analysis.

OBJECTIVE: To evaluate the positive surgical margin rates and locations in radical prostatectomy among three surgical approaches, including open radical prostatectomy, laparoscopic radical prostatectomy and robot-assisted radical prostatectomy. METHODS: We retrospectively reviewed clinical outcomes at our institution of 450 patients who received radical prostatectomy. Multiple surgeons were involved in the three approaches, and a single pathologist conducted the histopathological diagnoses. Positive surgical margin rates and locations among the three approaches were statistically assessed, and the risk factors of positive surgical margin were analyzed. RESULTS: This study included 127, 136 and 187 patients in the open radical prostatectomy, laparoscopic radical prostatectomy and robot-assisted radical prostatectomy groups, respectively. The positive surgical margin rates were 27.6% (open radical prostatectomy), 18.4% (laparoscopic radical prostatectomy) and 13.4% (robot-assisted radical prostatectomy). In propensity score-matched analyses, the positive surgical margin rate in the robot-assisted radical prostatectomy was significantly lower than that in the open radical prostatectomy, whereas there was no significant difference in the positive surgical margin rates between robot-assisted radical prostatectomy and laparoscopic radical prostatectomy. In the multivariable analysis, PSA level at diagnosis and surgical approach (open radical prostatectomy vs robot-assisted radical prostatectomy) were independent risk factors for positive surgical margin. The apex was the most common location of positive surgical margin in the open radical prostatectomy and laparoscopic radical prostatectomy groups, whereas the bladder neck was the most common location in the robot-assisted radical prostatectomy group. The significant difference of positive surgical margin locations continued after the propensity score adjustment. CONCLUSIONS: Robot-assisted radical prostatectomy may potentially achieve the lowest positive surgical margin rate among three surgical approaches. The bladder neck was the most common location of positive surgical margin in robot-assisted radical prostatectomy and apex in open radical prostatectomy and laparoscopic radical prostatectomy. Although robot-assisted radical prostatectomy may contribute to the reduction of positive surgical margin, dissection of the bladder neck requires careful attention to avoid positive surgical margins.

Impact of early changes in serum biomarkers following androgen deprivation therapy on clinical outcomes in metastatic hormone-sensitive prostate cancer.

BACKGROUND: Less evidence is known about the role of early changes in serum biomarker after androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Here we evaluated the impact of pre-treatment prognostic factors and early changes in serum biomarkers on prostate specific antigen (PSA) progression-free and overall survival rates in mHSPC. METHODS: We retrospectively reviewed the medical records of 60 mHSPC patients (median age 72 years) treated with ADT whose laboratory data at baseline and following 12 weeks were available. RESULTS: Forty-four patients (73%) had PSA progression and 27 patients (45.0%) died during a median follow-up of 34 months. The multivariable Cox hazard model demonstrated that a log-transformed baseline PSA level (p = 0.003) and an extent of bone disease (EOD) score of ≥3 (p = 0.004) were statistically associated with an increased risk for PSA progression whereas one unit increase in a log-transformed PSA change (baseline-12 weeks) was associated with a decreased risk for PSA progression (p = 0.004). For overall survival, a high level of alkaline phosphatase (ALP) at 12 weeks was associated with increased risk (p = 0.030) whereas a one-unit increase in the log-transformed PSA change was associated with decreased risk (p = 0.001). CONCLUSIONS: An increased level of PSA at baseline, or an EOD score of ≥3 may be a good predictor of PSA progression, and a high level of ALP at 12 weeks may be a risk predictor of death. A larger decline in PSA at 12 weeks from the baseline was associated with both PSA progression-free and overall survival time. Early changes in serum biomarkers may be useful in predicting poor outcomes in patients with mHSPC who are initially treated with ADT.

Altered miRNA expression in high-fat diet-induced prostate cancer progression.

Recent evidence suggests that a high-fat diet (HFD) plays an important role in prostate carcinogenesis; however, underlying mechanisms largely remain unknown. Here, we investigated microRNA (miRNA) expression changes in murine prostate cancer (PCa) xenografts using two different diets: HFD and control diet. We then assessed the roles and targets of altered miRNAs in HFD-induced PCa progression. We identified 38 up- and 21 downregulated miRNAs in xenografts under HFD conditions using the miRCURY LNA™ microRNA array. The differences in 10 candidate miRNAs were validated using quantitative RT-PCR. We focused on miR-130a because the expression levels were significantly lower in the three PCa cell lines in comparison with benign prostate PINT1B cells. PCa cells cultured in a medium containing HFD mouse serum were associated with significantly higher cell proliferation rates and lower miR-130a expression levels. Further, miR-130a modulated MET expression in PCa cells, and MET was overexpressed in in vitro and in vivo HFD-induced PCa progression models. Moreover, ectopic miR-130a downregulated AR in LNCaP cells and DICER1 in PC-3 and DU145 cells, respectively. In human tissues, as elucidated using laser capture microdissection, the mean miR-130a expression level in cancer epithelium was significantly lower than that in normal epithelium. Furthermore, cytoplasmic MET in PCa tissues was overexpressed in patients with higher body mass index. In conclusion, a substantial number of miRNAs was altered in HFD-induced PCa growth. Specifically, miR-130a was attenuated in HFD-induced PCa progression with MET overexpression. miRNAs thus have implications in the mechanism, prevention and treatment of HFD-induced PCa progression.

De novo renal cell carcinoma in an allograft kidney treated with nephron-sparing surgery: a case report.

The development of primary malignant tumors is a distressing complication of organ transplant. However, the emergence of de novo renal cell carcinoma from a kidney allograft is rare. A 60-year-old man underwent living kidney transplant from a spousal donor. Six years after the transplant surgery, computed tomographic evaluation confirmed the presence of a 2.8-cm-diameter solid mass in the lower pole of the allograft. Partial allograft nephrectomy was performed, and the margin surrounding the normal parenchyma was resected. The serum level of creatinine did not decrease. Here, we report a case of renal cell carcinoma in an allograft kidney that was successfully treated with nephron-sparing surgery.