Seasonal Changes in Lower Urinary Tract Symptoms in Japanese Men With Benign Prostatic Hyperplasia Treated With α-Blockers

Purpose To investigate whether seasonal changes occurred in lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH). Methods Patients aged 50 years and older with BPH treated with α1-blockers were enrolled. The International Prostate Symptom Score (IPSS), quality of life (QoL) score, maximum and average flow rate, voided volume, and postvoid residual volume were measured in summer and winter. Results A total of 164 patients were enrolled. The total IPSS and QoL index did not show a significant difference between the 2 seasons. When the IPSS was divided into storage symptoms and voiding symptoms, storage symptoms in winter were substantially but nonsignificantly higher than those in summer (P=0.056). Of the 7 individual symptoms in the IPSS, a significant seasonal difference was observed only for nocturia, with a higher score in winter. Moreover, none of the uroflowmetric parameters showed a seasonal change. Voided volume had significant correlations with each symptom (urgency and nocturia) and overall subjective scores (storage, total IPSS, and QoL) exclusively in summer, while this correlation remained only for nocturia in winter. Conclusions As it has generally been assumed that LUTS deteriorate in winter, the present study corroborated that the severity of storage symptoms was higher in winter than in summer, even in patients treated with α1-blockers. In contrast, a seasonal difference was not observed in the uroflowmetric parameters, which may be partly due to the loss of the correlation between subjective and objective measurements of storage symptoms in winter

Increased serum level of soluble interleukin-2 receptor is associated with a worse response of metastatic clear cell renal cell carcinoma to interferon alpha and sequential VEGF-targeting therapy

Abstract Background Renal cell carcinoma (RCC) is a tumor with immunogenic properties. Soluble interleukin-2 receptor (sIL-2R) has a role in T cell activation and may be important for immune regulation in various conditions, including infections, transplantation rejection, autoimmune inflammatory states, and cancer. We investigated the prognostic value of the serum sIL-2R level in patients with metastatic RCC receiving IFN-alpha and vascular endothelial growth factor (VEGF)-targeting therapy. Methods We monitored the serum level of sIL-2R over time and examined phosphorylated Akt expression by the primary tumor in 47 patients with metastatic clear cell RCC (ccRCC) undergoing cytoreductive nephrectomy followed by first-line adjuvant therapy with IFN-alpha plus sequential VEGF-targeting therapy as second- or third-line adjuvant therapy. Results A preoperative increase of the serum level of sIL-2R was correlated with a higher preoperative serum level of programmed cell death 1 (PD-1)-ligand 1 (PD-L1), increased expression of phosphorylated Akt by the primary tumor, and a worse response to IFN-alpha/sequential VEGF-targeting therapy, as well as being an independent prognostic factor for a shorter overall survival time by multivariate analysis. Over time, the serum sIL-2R level largely reflected the tumor response to therapy. Conclusions Monitoring the serum level of sIL-2R may help to predict the biological behavior of ccRCC, its response to IFN-alpha/sequential VEGF-targeting therapy, and the prognosis

Clinically significant association of elevated expression of nuclear factor E2-related factor 2 expression with higher glucose uptake and progression of upper urinary tract cancer

Abstract Background There is growing evidence that the transcription factor nuclear factor E2-related factor 2 (Nrf2) is the major participant in regulating antioxidants and pathways for detoxifying reactive oxygen species (ROS), as well as having a vital role in tumor proliferation, invasion, and chemoresistance. It was also recently reported that Nrf2 supports cell proliferation by promoting metabolic activity. Thus, Nrf2 is involved in progression of cancer. Upper urinary tract urothelial carcinoma (UTUC) is a biologically aggressive tumor with high rates of recurrence and progression, resulting in a poor prognosis. However, the role of Nrf2 in UTUC is largely unknown. Methods In order to study the role of Nrf2 in UTUC from the metabolic perspective, we retrospectively assessed Nrf2 expression in the surgical specimen and the preoperative maximum standard glucose uptake (SUVmax) on [18F]fluorodeoxy-glucose positron emission tomography (18F-FDG-PET) of 107 patients with UTUC who underwent radical nephroureterectomy. Results Increased expression of Nrf2 in the primary lesion was correlated with less differentiated histology, local invasion, and lymph node metastasis, and was also an independent indicator of shorter overall survival according to multivariate analysis. Furthermore, increased expression of Nrf2 was associated with higher preoperative SUVmax by the primary tumor on 18F-FDG-PET, while Nrf2 expression and SUVmax were also significantly correlated in the metastatic lymph nodes. Among the 18 patients with lymph node metastasis at nephroureterectomy who underwent retroperitoneal lymph node dissection and received adjuvant chemotherapy, the patients with higher Nrf2 expression in the primary tumor had worse recurrence-free survival. Conclusions These results suggest that constitutive activation of Nrf2 might be linked with tumor aerobic glycolysis and progression of UTUC, indicating that Nrf2 signaling in the tumor microenvironment promotes progression of UTUC

Docetaxel with or without estramustine for estramustine refractory castration-resistant prostate cancer: a single institution experience

Abstract Background The significance of combination of docetaxel (DTX) with estramustine phosphate (EMP) in castration-resistant prostate cancer (CRPC) patients remains unclear. In this study, we aimed to retrospectively evaluate the efficacy and toxicity of DTX with or without EMP and to elucidate the significance of DTX and EMP combination therapy in Japanese EMP-refractory CRPC patients. Methods To compare the efficacy and toxicity of DTX and EMP, we divided CRPC patients, who were confirmed to be resistant to EMP, into the following two groups: group D (n = 28), which included patients treated with DTX (60 mg/m2, once in every four weeks) alone, and group DE (n = 33), which included patients treated with a combination of DTX (60 mg/m2, once in every four weeks) and EMP (twice daily oral administration at 280 mg). Results Prostate specific antigen (PSA) response (> 50% decline in PSA) was observed in six patients (21%) in group D and eight patients (24%) in group DE. The median time to progression (TTP) was 12.0 months and 6.2 months and the median overall survival (OS) was 26.4 months and 24.3 months in group D and DE, respectively. There was no statistical difference between the two groups in terms of PSA response, TTP, and OS. The incidence of adverse events of grade 3/4 was low in both the groups, and there was no statistical difference between the two groups. Conclusions Although treatment with DTX at 60 mg/m2 was effective and highly tolerated in EMP-refractory Japanese CRPC patients, the DTX and EMP combination therapy might not exhibit any survival benefit for CRPC patients.</p

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

Transperitoneal laparoscopic umbilical resection of urachal remnants: a feasible surgical method

Abstract Background To date, there is no standard established laparoscopic surgical method for managing urachal remnants because of their rarity, and several questions remain unanswered. Are there any problems for considering the operative indications about patients’ factors for example, body mass index and so on? This study aimed to determine the feasible surgical method for managing urachal remnants and presents the operative outcomes of our cases in relation to the findings from the existing literature. Methods We analyzed the data of 16 patients (7 women and 9 men; age range, 19–48 years) who underwent surgery for urachal remnants between January 2013 and March 2019 at our institution. Results In our cases, all urachal remnants were urachal sinuses, and the primary complaints were umbilical pain and pus discharge. Most of these symptoms were controlled using umbilical drainage and oral antibiotic intake; however, incisional drainage was required in two cases. In all cases, we performed a laparoscopic resection of the urachal remnants; one patient underwent an open conversion due to a very thick abdominal wall. Therefore, “peri-umbilical distanse” was proposed as an index to verify the periumbilical abdominal wall thickness. This index may clear the difficulties of the laparoscopic resection of the urachal remnunts. A postoperative complication—local infection that was treated using re-suturing—was observed in one patient. No adverse events occurred in the other cases. Our method was appropriate because it allowed for complete urachal resection with good cosmetic results, i.e., a small and natural scar appearance. Additionally, if bladder injury occurred, bladder re-suturing was easily possible because of the laparoscopic port’s position. Conclusions We present an feasible method for laparoscopic urachal resection. This method may be recommended for young patients with an peri-umbilical distanse of < 2 cm

Additional file 1 of Clinically significant association of elevated expression of nuclear factor E2-related factor 2 expression with higher glucose uptake and progression of upper urinary tract cancer

Figure S1 Association between immunostaining intensity for Nrf2 and expression levels of Nrf2 detected by western blotting and pathological characteristics. (A). The tumors with intense immunostaining of Nrf2 showed increased expression of Nrf2. X–axis is intensity of immunestaining of Nrf2. Y-axis for Nrf2 is a ratio of the optical density for the tumor specimen to that for the corresponding non-neoplastic specimen (set at 1.0) by western blotting. The median value is the central line, the box is the interquartile range, the bars are the full range, and the points are the outliers. (B). Higher immunostaining of Nrf2 was associated with poorer histological grading, local invasion (pT), regional lymph node metastasis (pN), and lymphovascular invasion (LVI). (TIFF 1521 kb