Photodynamic diagnosis-assisted transurethral resection of bladder tumor for high-risk non-muscle invasive bladder cancer improves intravesical recurrence-free survival (BRIGHT study).

OBJECTIVES: In a primary analysis of data from the BRIGHT study (UMIN000035712), photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) using oral 5-aminolevulinic acid hydrochloride reduced residual tumors in high-risk non-muscle invasive bladder cancer (NMIBC). We aimed to evaluate the effectiveness of PDD-TURBT for intravesical recurrence after a second transurethral resection for high-risk NMIBC. METHODS: High-risk NMIBC patients initially treated with PDD-TURBT (PDD group) were prospectively registered between 2018 and 2020. High-risk patients with NMIBC who were initially treated with white-light TURBT (WL group) were retrospectively registered. Intravesical recurrence-free survival after the second transurethral resection was compared between the PDD and WL groups using propensity score matching analysis. RESULTS: In total, 177 patients were enrolled in the PDD group, and 306 patients were registered in the WL group. After propensity score matching (146 cases in each group), intravesical recurrence within 1 year was significantly less frequent in the PDD group than in the WL group (p = 0.004; hazard ratio [HR] 0.44, 95% confidence interval [CI]: 0.25-0.77). In subgroup analysis, PDD-TURBT showed a particularly high efficacy in reducing intravesical recurrence within 1 year, especially in cases of tumors measuring less than 3 cm (p = 0.003; HR 0.31, 95% CI: 0.14-0.67), absence of residual tumor at second transurethral resection (p = 0.020; HR 0.37, 95% CI: 0.16-0.86), and no postoperative intravesical Bacillus Calmette-Guérin therapy (p < 0.001; HR 0.27, 95% CI: 0.13-0.58). CONCLUSIONS: PDD-TURBT may reduce short-term intravesical recurrence in patients with high-risk NMIBC.

Impact of Nerve-Sparing Status on Positive Surgical Margin Location and Biochemical Recurrence in Patients with Prostate Cancer Post Radical Prostatectomy.

PURPOSE: This study was designed to assess the relationship between nerve-sparing (NS) status, positive surgical margin (PSM) location, and biochemical recurrence (BCR) based on a multicenter, radical prostatectomy (RP) database. METHODS: We retrospectively reviewed data from 726 patients who underwent RP without any neoadjuvant or adjuvant treatment between 2010 and 2014. We statistically assessed the impact of NS sides on PSM location and BCR. RESULTS: PSM rates were 21.9% in the 726 patients studied, 13.2% in patients with ≤pT2, and 46.8% in patients with ≥pT3. Regarding PSM locations, the anterior-apex (AA) was the most common site for PSM (43.3%). After adjusting for confounding factors, bilateral nerve sparing (BNS) had a significantly higher odds ratio of PSM than the absence of NS did (odds ratio [OR] 3.04, 95% confidence interval [CI] 1.85-4.99). In the UNS RP in patients with ≤pT2, non-AA PSM on the non-NS side was significantly higher than that on the NS side (92.9% vs. 45.5%, p = 0.009). In all patients, 5.8% experienced BCR during a median follow-up of 43.5 months. PSM was significantly associated with BCR-free survival in patients with ≤pT2 (p = 0.013), but not in patients with ≥pT3 (p = 0.185). Non-AA PSM at the non-NS side was an independent risk factor for BCR (hazard ratio [HR] 2.56, 95% confidence interval [CI] 1.12-5.85), whereas AA PSMs, including NS/non-NS sides and non-AA PSM at the NS side, were not associated with BCR-free survival. CONCLUSIONS: Avoidance of non-AA PSM on the non-NS side may be rather important for maintaining BCR-free survival after RP.

Robot-assisted partial nephrectomy versus standard laparoscopic partial nephrectomy for renal hilar tumor: A prospective multi-institutional study.

OBJECTIVE: To investigate whether robot-assisted partial nephrectomy compared with laparoscopic partial nephrectomy is effective for renal hilar tumor removal. METHODS: This was a prospective, multicenter, single-arm, open-label trial with a 2-year enrollment period. A total of 22 academic hospitals in Japan participated in the present study. Comparison with historical control values from reported studies of laparoscopic partial nephrectomy was carried out. The warm ischemia time and positive surgical margin rate were set as primary perioperative and oncological outcomes. In the historical control group, these were 27.7 min and 13%, respectively. RESULTS: The analysis population included 105 participants. The mean warm ischemia time was 20.2 (95% confidence interval 16.7-21.8; P < 0.0001 vs 27.7). Two of 103 participants (1.9%) had a positive surgical margin (95% confidence interval 0.5-6.8%). Both results satisfy the prespecified decision criteria for the superiority of robot-assisted partial nephrectomy over the historical control of laparoscopic partial nephrectomy. Resected weight and preoperative estimated glomerular filtration rate were predictive factors of functional loss of the partially nephrectomized kidney after robot-assisted partial nephrectomy. CONCLUSION: Robot-assisted partial nephrectomy for clinical T1 renal hilar tumors results in shorter warm ischemia time than and comparable positive surgical margin rate to those reported for laparoscopic partial nephrectomy.

[Ganglioneuroma with calcification mimicking adrenal tumor: a case report].

A 28-year-old woman was referred to our hospital complaining of upper abdominal discomfort. The patient had been receiving medical treatment for hypertension. Computed tomography revealed a 30 mm solid tumor with calcification in the left adrenal gland and a 8 mm nodule in the right adrenal gland. Endocrinological examinations revealed no activity of either adrenal mass. The left adrenal tumor was extirpated, because malignancy of the tumor was not ruled out. Histopathological examination proved that the tumor was ganglioneuroma arising from the extra-adrenal retroperitoneum.

Prospective study of combined treatment with interferon-alpha and active vitamin D3 for Japanese patients with metastatic renal cell carcinoma.

OBJECTIVES: To assess the safety and efficacy of combined therapy with interferon-alpha (INF-alpha) and active vitamin D(3) for metastatic renal cell carcinoma (RCC). METHODS: Sixteen patients with metastatic RCC were enrolled in this prospective study. All received oral alfacalcidol (1 microg once daily) and INF-alpha (Sumiferon; 3 million units, three times a week). The primary endpoint was the response rate (defined as complete + partial remission). Secondary endpoints were cancer-specific survival and toxicity. The median follow-up period was 17 months (range: 5-49 months). RESULTS: The median age of the patients was 68 years (range: 41-73 years). The sites of metastases were: lung in 13 patients, bone in one, lung and bone in one, and lung, bone, and lymph nodes in one. Four patients (25%) had a partial response (PR), 10 patients (62.5%) showed no change (NC), and two patients (12.5%) had progressive disease (PD). The median cancer-specific survival time was 45 months. One patient had to discontinue vitamin D(3) because of hypercalcemia. Kaplan-Meier survival analysis revealed that metastasis at the time of initial diagnosis and older than average age were significant predictors of poor survival (P < 0.05). CONCLUSIONS: Combined treatment with INF-alpha and active vitamin D(3) has shown to be safe and effective for metastatic RCC patients.

Can atorvastatin with metformin change the natural history of prostate cancer as characterized by molecular, metabolomic, imaging and pathological variables? A randomized controlled trial protocol.

BACKGROUND: Atorvastatin and metformin are known energy restricting mimetic agents that act synergistically to produce molecular and metabolic changes in advanced prostate cancer (PCa). This trial seeks to determine whether these drugs favourably alter selected parameters in men with clinically-localized, aggressive PCa. METHODS/DESIGN: This prospective phase II randomized, controlled window trial is recruiting men with clinically significant PCa, confirmed by biopsy following multiparametric MRI and intending to undergo radical prostatectomy. Ethical approval was granted by the Royal Brisbane and Women's Hospital Human and The University of Queensland Medical Research Ethics Committees. Participants are being randomized into four groups: metformin with placebo; atorvastatin with placebo; metformin with atorvastatin; or placebo alone. Capsules are consumed for 8weeks, a duration selected as the most appropriate period in which histological and biochemical changes may be observed while allowing prompt treatment with curative intent of clinically significant PCa. At recruitment and prior to RP, participants provide blood, urine and seminal fluid. A subset of participants will undergo 7Tesla magnetic resonance spectroscopy to compare metabolites in-vivo with those in seminal fluid and biopsied tissue. The primary end point is biochemical evolution, defined using biomarkers (serum prostate specific antigen; PCA3 and citrate in seminal fluid and prostatic tissue). Standard pathological assessment will be undertaken. DISCUSSION: This study is designed to assess the potential synergistic action of metformin and atorvastatin on PCa tumour biology. The results may determine simple methods of tumour modulation to reduce disease progression.

Polyinosinic-polycytidylic acid induces the expression of GRO-alpha in BEAS-2B cells.

Growth-related oncogene protein-alpha (GRO-alpha)/CXCLl is a chemokine that activates neutrophils and plays an important role in inflammatory reactions. Polyinosinic-polycytidylic acid (poly IC) is a synthetic double-stranded RNA (dsRNA), which is a ligand for Toll-like receptor-3. Poly IC mimics viral infection when applied to cells and induces inflammatory and immune responses. In the present study, we found the induction of GRO-alpha in BEAS-2B bronchial epithelial cells treated with poly IC. Pretreatment of cells with 2-aminopurine, an inhibitor for dsRNA-dependent protein kinase (PKR), inhibited the expression of GRO-alpha-induced by poly IC. Overexpression of interferon-regulatory factor-3 (IRF-3) or retinoic-acid inducible gene-I (RIG-I) enhanced the induction of GRO-alpha by poly IC. PKR, IRF-3, and RIG-I may be involved in the poly IC-induced expression of GRO-alpha in BEAS-2B cells. Airway viral infection may elicit GRO-alpha expression in the bronchial epithelium, which may be implicated in inflammatory and immune reactions.

Listeria monocytogenes induces the expression of retinoic acid-inducible gene-I.

Retinoic acid-inducible gene-I (RIG-I) is considered to play a role in innate immunity against virus infections. We showed by immunohistochemical study that RIG-I expression is upregulated in vivo in hepatic Kupffer cells and in splenic reticular cells of mice infected with Listeria monocytogenes. Both heat-killed L. monocytogenes and live L. monocytogenes induced the expression of RIG-I in cultured RAW264.7 murine macrophage-like cells in vitro. RIG-I may also be involved in innate immunity against Listeria infection.

Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant.

PURPOSE: The glutathione peroxidase 1 gene (GPX1) and the manganese superoxide dismutase gene (MnSOD) encode the main antioxidant enzymes that detoxify endogenous reactive oxygen species involved in carcinogenesis. Polymorphisms of GPX1 and MnSOD genes, and the risk of transitional cell cancer of the bladder were tested. MATERIALS AND METHODS: Genotypes of the leucine (Leu) to proline (Pro) polymorphism at codon 198 of GPX1, the alanine (Ala) to Valine (Val) polymorphism in exon 2 and the isoleucine to threonine polymorphism at codon 56 of MnSOD were determined by a polymerase chain reaction-restriction fragment length polymorphism technique in 213 patients and 209 normal controls. RESULTS: There was a significant difference in GPX1 genotype frequency between the case and control groups (p = 0.001). The adjusted OR for bladder cancer was 2.63 for the Pro/Leu genotype compared with the Pro/Pro genotype (95% CI 1.45 to 4.75, p = 0.001). Compared with the Pro/Pro genotype the Pro/Leu genotype was significantly associated with advanced tumor stage (Ta-1 vs T2-4, OR 2.58, 95% CI 1.07 to 6.18, p = 0.034) but not with tumor grade. Analysis of the MnSOD polymorphism provided no significant results. However, in men with at least 1 Ala MnSOD allele the risk associated with the Pro/Leu GPX1 genotype increased up to 6.31 (95% CI 1.28 to 31.24, p = 0.024). CONCLUSIONS: The GPX1 Pro/Leu genotype may significantly increase the risk of bladder cancer and the increased risk may be modified by the Ala-9Val MnSOD polymorphism. The GPX1 genotype may further affect the disease status of bladder cancer.