Lower pretreatment serum testosterone level predicts poor prognosis in the patients with metastatic hormone-sensitive prostate cancer undergoing androgen deprivation therapy.

OBJECTIVE: This study aimed to reveal the association between pretreatment serum testosterone levels and prognosis in patients with metastatic hormone-sensitive prostate cancer treated with androgen deprivation therapy. METHODS: A total of 91 patients were included in this retrospective study. Clinical data were obtained through chart review. Multivariate cox proportional hazards analyses addressed the impact of variables on castration-resistant prostate cancer-free and overall survivals. RESULTS: During a median follow-up of 41.7 months, 61 (67%) and 49 (54%) patients developed castration-resistant prostate cancer and died, respectively. The median castration-resistant prostate cancer-free and overall survivals were 15.5 and 59.9 months, respectively. The cutoff value for discriminating between low- and high-testosterone levels was determined as 450 ng/dl by calculating the receiver operating characteristic curve. Patients in the low-testosterone group (n = 37) had a significantly higher body mass index, worse comorbidities represented by the higher Charlson comorbidity index and higher serum lactate dehydrogenase levels, than those in the high-testosterone group (n = 54). Castration-resistant prostate cancer free and overall survivals were significantly shorter in the low-testosterone group than in the high-testosterone group (P = 0.021 and P < 0.001, respectively). Multivariate analysis identified testosterone level of <450 ng/dl as an independent factor predicting development of castration-resistant prostate cancer (hazard ratio 2.28, P = 0.007), along with high-volume disease and Gleason score 9-10. Similarly, testosterone level of <450 ng/dl was independently associated with shorter overall survival (hazard ratio 2.84, P = 0.006), along with higher Charlson comorbidity index, visceral metastasis and higher alkaline phosphatase level. CONCLUSIONS: Lower baseline serum testosterone levels predict poor prognosis in patients with metastatic hormone-sensitive prostate cancer.

Solitary Fibrous Tumor in the Retroperitoneal Space Arising from the Diaphragm.

BACKGROUND/AIM: We present a case of solitary fibrous tumor, arising from the diaphragm in the retroperitoneal space, that was resected with robotic assistance. CASE REPORT: An 85-year-old female patient was referred to our hospital for evaluation of a suspected right renal tumor. Abdominal contrast-enhanced computed tomography revealed a tumor (maximum diameter, 36 mm) protruding from the superior pole of the right kidney. The patient was scheduled for robot-assisted, retroperitoneoscopic, partial nephrectomy based on a preoperative diagnosis of renal cell carcinoma. Intraoperative findings revealed that the tumor originated from the diaphragm and had no continuity with the renal parenchyma. Pathological examination revealed a solitary fibrous tumor. CONCLUSION: Solitary fibrous tumors are rare soft-tissue neoplasms with a distinct molecular feature of the fusion of nerve growth factor-inducible A gene-binding protein 2 with signal transducer and activator of transcription 6 gene (NAB2::STAT6). We believe that this is the first reported case of a solitary fibrous tumor arising from the diaphragm in the retroperitoneal space.

Geriatric 8 and Vulnerable Elders Survey-13 predict length of hospital stay and postoperative complications in Japanese patients undergoing urological surgery.

INTRODUCTION: The Geriatric 8 (G8) and Vulnerable Elders Survey-13 (VES-13) are established screening tools for assessing vulnerability in older patients. Here we investigated their usefulness as predictors of length of hospital stay and postoperative complications in Japanese patients undergoing urological surgery. MATERIALS AND METHODS: This study included 643 patients who underwent urological surgery (74% were for malignancy) at our institute from 2017 to 2020. G8 and VES-13 scores were routinely recorded upon admission. These indices and other clinical data were obtained through chart review. The correlation between G8 group (high, >14; intermediate, 11-14; low, <11) or VES-13 group (normal, <3; high, ≥3) and length of total hospital stay (LOS), postoperative hospital stay (pLOS), and postoperative complications including delirium were analyzed. RESULTS: The median patient age was 69 years. A total of 44%, 45%, and 11% of patients were classified into high, intermediate, and low G8 groups, respectively, while 77% and 23% were classified into normal and high VES-13 groups, respectively. Univariate analyses revealed that low G8 scores were associated with prolonged LOS (vs. intermediate, odds ratio [OR] 2.87, P < 0.001; vs. high, OR 3.87, P < 0.001), prolonged pLOS (vs. intermediate, OR 2.37, P = 0.005; vs. high, OR 3.06, P < 0.001), and delirium (vs. intermediate, OR 3.23, P = 0.007; vs. high, OR 5.38, P < 0.001), and high VES-13 scores were associated with prolonged LOS (OR 2.85, P < 0.001), prolonged pLOS (OR 2.97, P < 0.001), and Clavien-Dindo grade ≥ 2 complications (OR 1.74, P = 0.044), and delirium (OR 3.18, P = 0.001). Furthermore, multivariate analyses revealed that low G8 and high VES-13 scores were independent factors which predicted prolonged LOS (low G8; vs. intermediate, OR 2.96, P < 0.001; vs. high, OR 3.94, P < 0.001; high VES-13; OR 2.98, P < 0.001) and prolonged pLOS (low G8; vs. intermediate, OR 2.41, P = 0.008; vs. high, OR 3.18, P = 0.002; high VES-13; OR 3.47, P < 0.001), respectively. DISCUSSION: The G8 and VES-13 may be effective tools for predicting prolonged LOS/pLOS and postoperative complications in Japanese patients who undergo urological surgery.

Local advanced adrenocortical cancer with a long-term recurrence-free survival treated with complete surgical excision and adjuvant therapy with a very low-dose mitotane.

INTRODUCTION: Adrenocortical cancer is a rare tumor with high malignant potential, often resulting in recurrence and poor survival even after complete excision. Thus, adjuvant therapy needs to be considered despite its unestablished effectiveness. CASE PRESENTATION: We report a 70-year-old man presented with a huge adrenal mass extending into the right liver lobe. He underwent right adrenalectomy concurrent with right nephrectomy and right hemihepatectomy for curative intent. He was given a very low-dose mitotane (0.5 g/day) adjuvant therapy to be alive without any signs of recurrence for 90 months after surgery without unwanted toxicity. CONCLUSION: A long-term and very low dose of adjuvant mitotane could be an option for a patient with complete surgical resection in an expectation to prevent microscopic residual disease from recurrence.

Plasmacytoid urothelial carcinoma of renal pelvis with positive zinc finger E-box-binding homeobox 1: a case report.

BACKGROUND: The tumor transformation mechanism of a plasmacytoid urothelial carcinoma remains unexplained. We describe the case of a plasmacytoid urothelial carcinoma of the renal pelvis in which the expression of zinc finger E-box-binding homeobox 1 (ZEB1), a key nuclear transcription factor in an epithelial-mesenchymal transition, is involved in tumor transformation. CASE PRESENTATION: The patient had a left nephrectomy with the clinical diagnosis of left pelvic renal cancer. The resected specimen showed that the tumor surface comprised a noninvasive papillary urothelial carcinoma with the carcinoma in situ, and the invasive area comprised a plasmacytoid urothelial carcinoma characterized by the presence of single dyscohesive malignant cells that resembled plasma cells in a loose myxoid stroma. The noninvasive urothelial carcinoma was positive for cytokeratin and E-cadherin, and negative for vimentin and ZEB1. In contrast, the invasive plasmacytoid urothelial carcinoma was positive for cytokeratin and also vimentin and ZEB1, and negative for E-cadherin. Additionally, this component was immunoreactive for CD138 and CD38 that are immunohistochemical markers for plasma cells. CONCLUSION: We suggest that ZEB1 is involved in the plasmacytoid transformation by repressing the E-cadherin in a plasmacytoid urothelial carcinoma.

5-Fluorouracil-based adjuvant chemotherapy improves the clinical outcomes of patients with lymphovascular invasion of upper urinary tract cancer and low expression of dihydropyrimidine dehydrogenase.

Lymphovascular invasion (LVI) by urothelial carcinoma of the upper urinary tract (UC-UUT) is associated with an unfavorable prognosis. However, a high proportion of patients with UC-UUT are unable to receive the recommended doses of cisplatin-based adjuvant chemotherapy due to advanced age or renal dysfunction resulting from nephroureterectomy. Tegafur-uracil is an oral form of 5-fluorouracil whose efficacy is influenced by the activities of enzymes associated with its metabolism, such as dihydropyrimidine dehydrogenase (DPD), orotatephosphoribosyltransferase (OPRT) and thymidylate synthase (TS). The aim of the present study was to investigate the efficacy of adjuvant 5-fluorouracil chemotherapy for UC-UUT with LVI, and to assess the expression of enzymes associated with 5-fluorouracil metabolism as promising biomarkers of therapy efficacy. The present study retrospectively investigated 52 cases of UC-UUT. Following nephroureterectomy, tegafur-uracil was administered to 15 out of 30 patients with LVI who were not eligible for cisplatin-based adjuvant chemotherapy. Levels of DPD, OPRT and TS expression in tumor specimens were determined by reverse transcription-quantitative polymerase chain reaction, and their associations with the efficacy of adjuvant 5-fluorouracil chemotherapy were analyzed. The levels of DPD, OPRT and TS expression were not associated with pathological factors or outcome, although a higher expression of TS was associated with a poorer outcome. Adjuvant 5-fluorouracil chemotherapy significantly improved the outcome of patients with lower DPD expression. However, the levels of OPRT and TS expression did not influence therapeutic efficacy. Adjuvant 5-fluorouracil chemotherapy appears to be effective for lymphovascular-invasive UC-UUT in patients with lower DPD expression.

Immunohistochemical expressionof sodium-dependent glucose transporter - 2 (SGLT-2) in clear cell renal carcinoma: possible prognostic implications

ABSTRACT Purpose: Glucose is a major energy resource for tumor cell survival and growth, and its influx into cells is mainly carried out by facilitative glucose transporters (GLUTs). Sodium - dependent glucose transporters (SGLTs) have been highlighted as playing important roles in diabetic treatment. However, their potential roles in cancer remain unclear. We examined expression patterns of SGLTs in tumor tissues together with conventional pathological variables to determine prognostic significance in patients with renal cell carcinoma (RCC). Materials and Methods: Nephrectomy specimens were obtained from 68 patients. GLUT - 1, - 2 and SGLT - 1, - 2 expression in tumor and adjacent normal tissues were analyzed by immunohistochemical staining, and intensity was quantified using an image analyzer. Results: The four glucose transporters evaluated were broadly distributed in tumor tissues as well as throughout the normal parenchyma. There was no significant correlation between transporter expression and conventional pathological variables. However, increased SGLT - 2 expression was significantly associated with shorter overall survival (p < 0.01), regardless of metastatic status. Conclusions: We propose possible prognostic significance of SGLT - 2 expression in human RCC. Given that glucose is a major energy resource for tumor cells and that glucose transport is largely mediated by SGLT, SGLT - 2 may serve as a possible therapeutic target in RCC.

Feeling of incomplete emptying with little post-void residual in patients with lower urinary tract symptoms: Clinical implications and treatment outcomes.

OBJECTIVE: The aim of the present study was to examine the clinical features and implications of a feeling of incomplete emptying despite little post-void residual (PVR), because it remains unclear why patients are bothered by such an undefined feeling. METHODS: Data were collected prospectively from 173 consecutive patients (135 men, 38 women) with a complaint of a feeling of incomplete emptying with PVR <50 mL at an initial visit. The International Prostate Symptom Score (IPSS), quality of life (QoL) score, overactive bladder symptom score (OABSS), prostate volume, and PVR were determined. Subjective symptoms were re-evaluated after 8 weeks of medication for co-occurring urinary symptoms. RESULTS: Most patients presented with high scores for a feeling of incomplete emptying, determined by Item 1 on the IPSS. The score for a feeling of incomplete emptying was positively correlated with all IPSS-related scores. Men with a feeling of incomplete emptying more often had co-occurring voiding symptoms with higher scores than women. Significant symptom relief was achieved for a feeling of incomplete emptying as well as voiding and storage symptoms after treatment. In men, there was a positive correlation between the extent of symptom relief of a feeling of incomplete emptying and voiding symptoms. CONCLUSIONS: A feeling of incomplete emptying with little PVR is frequently observed in routine clinical practice in both men and women, along with voiding and storage symptoms. This feeling was simultaneously improved by medications for co-occurring urinary symptoms.

Immunohistochemical expressionof sodium-dependent glucose transporter - 2 (SGLT-2) in clear cell renal carcinoma: possible prognostic implications.

PURPOSE: Glucose is a major energy resource for tumor cell survival and growth, and its influx into cells is mainly carried out by facilitative glucose transporters (GLUTs). Sodium - dependent glucose transporters (SGLTs) have been highlighted as playing important roles in diabetic treatment. However, their potential roles in cancer remain unclear. We examined expression patterns of SGLTs in tumor tissues together with conventional pathological variables to determine prognostic significance in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: Nephrectomy specimens were obtained from 68 patients. GLUT - 1, - 2 and SGLT - 1, - 2 expression in tumor and adjacent normal tissues were analyzed by immunohistochemical staining, and intensity was quantified using an image analyzer. RESULTS: The four glucose transporters evaluated were broadly distributed in tumor tissues as well as throughout the normal parenchyma. There was no significant correlation between transporter expression and conventional pathological variables. However, increased SGLT - 2 expression was significantly associated with shorter overall survival (p < 0.01), regardless of metastatic status. CONCLUSIONS: We propose possible prognostic significance of SGLT - 2 expression in human RCC. Given that glucose is a major energy resource for tumor cells and that glucose transport is largely mediated by SGLT, SGLT - 2 may serve as a possible therapeutic target in RCC.

Elevated serum levels of cardiovascular biomarkers are associated with progression of renal cancer.

Objective: Renal cell carcinoma (RCC) is a hypervascular tumour due to high constitutive production of vascular endothelial growth factor (VEGF), which is activated by hypoxia-inducible factor (HIF). Elevated levels of cardiovascular peptides, including brain natriuretic peptide (BNP), have been reported in patients with cancer, regardless of whether they have overt cardiovascular disease. Furthermore, it has been demonstrated that hypoxia stimulates BNP production by an HIF-dependent manner. However, the clinical implications of such cardiovascular peptides in patients with RCC have not been assessed. Methods: In patients with clear cell RCC who underwent nephrectomy, we investigated the relationship between the serum level of BNP or N-terminal pro-BNP (NT-proBNP) and various clinicopathological characteristics, including serum VEGF and expression of BNP and HIF-2 alpha in the primary tumour. Results: Elevated preoperative serum levels of BNP, NT-proBNP and VEGF, as well as increased tumour expression of HIF-2 alpha, were associated with a worse performance status, local invasion, distant metastasis and shorter overall survival. HIF-2 alpha expression showed a positive correlation with the preoperative serum VEGF level, while there was no relation between the serum levels of BNP/NT-proBNP and VEGF or tumour expression of HIF-2 alpha. BNP expression was very low in both tumour tissues and normal kidney tissues. Serum levels of BNP, NT-proBNP and VEGF all decreased significantly after nephrectomy. Conclusions: Our findings suggested that the preoperative serum levels of BNP and NT-proBNP are markers of tumour progression, as well as indicators of subclinical functional and structural myocardial damage in patients with advanced RCC.

Significance of sarcopenia as a prognostic factor for metastatic urothelial carcinoma patients treated with systemic chemotherapy.

BACKGROUND: Recently, numerous studies have reported an association between sarcopenia and poor outcomes in various kinds of malignancies. We investigated whether sarcopenia predicts the survival of patients with metastatic urothelial carcinoma who underwent systemic chemotherapy. METHODS: We reviewed 87 metastatic urothelial carcinoma patients who underwent chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin for cisplatin-unfit patients) between 2007 and 2015. A computed tomography scan prior to chemotherapy was used for evaluating sarcopenia, and we measured three cross-sectional areas of skeletal muscle at the third lumbar vertebra and calculated the skeletal muscle index (SMI), the paraspinal muscle index (PSMI), and the total psoas area (TPA) of each patient. Predictive values of survival were assessed using Cox regression analysis. RESULTS: The median overall survival (OS) was 16 months (95% CI 13.5-18). Although SMI alone was not a significant predictor of shorter OS (P = 0.117) in univariate analysis, SMI stratified by the value of the body mass index (BMI) was a significant predictor of shorter OS in univariate analysis (P = 0.037) and was also an independent predictor of shorter OS in multivariate analysis (P = 0.026). PSMI and TPA were not significant prognostic factors even when stratified by BMI (P = 0.294 and 0.448), respectively. CONCLUSION: Neither PSMI nor TPA could substitute SMI as a predictor for poor outcomes in metastatic urothelial carcinoma patients treated with systemic chemotherapy in our study. SMI stratified by BMI is a useful predictor of prognosis in these patients.

[Diagnostic Impact of 3D-CT with Retrograde Pyelography for Ureteropelvic Junction Obstruction : A Case Report].

A 26-year-old woman presented to our hospital with right costovertebral angle (CVA) pain. Ultrasonographyand computed tomography(CT) scan indicated right hydronephrosis, and MAG3 renogram showed an obstructed pattern in the right kidney. Enhanced CT scan revealed an ureteropelvic junction obstruction (UPJO) with an aberrant vessel. To clarifythe ureteropelvic junction (UPJ) structure in detail, we utilized 3D-CT with retrograde pyelography (RP), which further revealed the true pinhole ureteral stricture of UPJ unaffected bythe aberrant vessel.

Case of hydrocele testis caused by vaginalitis, a rare manifestation of immunoglobulin G4-related disease.

We report an extremely rare manifestation of immunoglobulin G4-related disease, presented with hydrocele testis. A planned hydrocelectomy was converted to a high orchiectomy because of bloody fluid, suggestive of paratesticular malignancy. The histopathology showed vaginalitis, which was finally diagnosed as immunoglobulin G4-related disease. To the best of our knowledge, this is the first report of immunoglobulin G4-related disease representing hydrocele testis.

Performance characteristics of prostate-specific antigen density and biopsy core details to predict oncological outcome in patients with intermediate to high-risk prostate cancer underwent robot-assisted radical prostatectomy.

BACKGROUND: Many urologic surgeons refer to biopsy core details for decision making in cases of localized prostate cancer (PCa) to determine whether an extended resection and/or lymph node dissection should be performed. Furthermore, recent reports emphasize the predictive value of prostate-specific antigen density (PSAD) for further risk stratification, not only for low-risk PCa, but also for intermediate- and high-risk PCa. This study focused on these parameters and compared respective predictive impact on oncologic outcomes in Japanese PCa patients. METHODS: Two-hundred and fifty patients with intermediate- and high-risk PCa according to the National Comprehensive Cancer Network (NCCN) classification, that underwent robot-assisted radical prostatectomy at a single institution, and with observation periods of longer than 6 months were enrolled. None of the patients received hormonal treatments including antiandrogens, luteinizing hormone-releasing hormone analogues, or 5-alpha reductase inhibitors preoperatively. PSAD and biopsy core details, including the percentage of positive cores and the maximum percentage of cancer extent in each positive core, were analyzed in association with unfavorable pathologic results of prostatectomy specimens, and further with biochemical recurrence. The cut-off values of potential predictive factors were set through receiver-operating characteristic curve analyses. RESULTS: In the entire cohort, a higher PSAD, the percentage of positive cores, and maximum percentage of cancer extent in each positive core were independently associated with advanced tumor stage ≥ pT3 and an increased index tumor volume > 0.718 ml. NCCN classification showed an association with a tumor stage ≥ pT3 and a Gleason score ≥8, and the attribution of biochemical recurrence was also sustained. In each NCCN risk group, these preoperative factors showed various associations with unfavorable pathological results. In the intermediate-risk group, the percentage of positive cores showed an independent predictive value for biochemical recurrence. In the high-risk group, PSAD showed an independent predictive value. CONCLUSIONS: PSAD and biopsy core details have different performance characteristics for the prediction of oncologic outcomes in each NCCN risk group. Despite the need for further confirmation of the results with a larger cohort and longer observation, these factors are important as preoperative predictors in addition to the NCCN classification for a urologic surgeon to choose a surgical strategy.

Extravasation of Urine Associated with Bilateral Complete Ureteral Duplication, Vesicoureteral Reflux and Benign Prostatic Hyperplasia.

We report a rare case of extravasation of urine, which may be associated with bilateral complete ureteral duplication, vesicoureteral reflux (VUR), and benign prostatic hyperplasia (BPH). A 71-year-old male presented with a complaint of right abdominal pain. An extravasation of urine was noted, and was improved by indwelling urethral catheterization. Transurethral resection of the prostate and the endoscopic subureteral injection of dextanomer/hyaluronic acid were performed for the treatment of BPH and VUR, respectively. The post-surgery recovery was successful.