Variant spectrum of von Hippel-Lindau disease and its genomic heterogeneity in Japan.

Von Hippel-Lindau (VHL) disease is an autosomal dominant, inherited syndrome with variants in the VHL gene, causing predisposition to multi-organ neoplasms with vessel abnormality. Germline variants in VHL can be detected in 80-90% of patients clinically diagnosed with VHL disease. Here, we summarize the results of genetic tests for 206 Japanese VHL families, and elucidate the molecular mechanisms of VHL disease, especially in variant-negative unsolved cases. Of the 206 families, genetic diagnosis was positive in 175 families (85%), including 134 families (65%) diagnosed by exon sequencing (15 novel variants) and 41 (20%) diagnosed by multiplex ligation-dependent probe amplification (MLPA) (one novel variant). The deleterious variants were significantly enriched in VHL disease Type 1. Interestingly, five synonymous or non-synonymous variants within exon 2 caused exon 2 skipping, which is the first report of exon 2 skipping caused by several missense variants. Whole genome and target deep sequencing analysis were performed for 22 unsolved cases with no variant identified and found three cases with VHL mosaicism (variant allele frequency: 2.5-22%), one with mobile element insertion in the VHL promoter region, and two with a pathogenic variant of BAP1 or SDHB. The variants associated with VHL disease are heterogeneous, and for more accuracy of the genetic diagnosis of VHL disease, comprehensive genome and DNA/RNA analyses are required to detect VHL mosaicism, complicated structure variants and other related gene variants.

Cutibacterium acnes invades prostate epithelial cells to induce BRCAness as a possible pathogen of prostate cancer.

BACKGROUND: Abundant evidence suggests that chronic inflammation is linked to prostate cancer and that infection is a possible cause of prostate cancer. METHODS: To identify microbiota or pathogens associated with prostate cancer, we investigated the transcriptomes of 20 human prostate cancer tissues. We performed de novo assembly of nonhuman sequences from RNA-seq data. RESULTS: We identified four bacteria as candidate microbiota in the prostate, including Moraxella osloensis, Uncultured chroococcidiopsis, Cutibacterium acnes, and Micrococcus luteus. Among these, C. acnes was detected in 19 of 20 prostate cancer tissue samples by immunohistochemistry. We then analyzed the gene expression profiles of prostate epithelial cells infected in vitro with C. acnes and found significant changes in homologous recombination (HR) and the Fanconi anemia pathway. Notably, electron microscopy demonstrated that C. acnes invaded prostate epithelial cells and localized in perinuclear vesicles, whereas analysis of γH2AX foci and HR assays demonstrated impaired HR repair. In particular, BRCA2 was significantly downregulated in C. acnes-infected cells. CONCLUSIONS: These findings suggest that C. acnes infection in the prostate could lead to HR deficiency (BRCAness) which promotes DNA double-strand breaks, thereby increasing the risk of cancer development.

Comparative assessment of disease recurrence after transurethral resection of non-muscle-invasive bladder cancer with and without a photodynamic diagnosis using 5-aminolevulinic acid: a propensity score-matching analysis.

BACKGROUND: Among patients with non-muscle-invasive bladder cancer (NMIBC), systematic reviews showed lower recurrence rate in patients treated with photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) than with white-light (WL) TURBT. However, the result is not consistent between clinical trials and the significance of preoperatively available factors in disease recurrence after PDD-TURBT remains unclear. METHODS: The present study retrospectively analyzed 1174 NMIBC patients who underwent TURBT and were followed up for ≥ 6 months. Among 1174 patients, 385 and 789 underwent PDD-TURBT with oral 5-aminolevulinic acid (the PDD group) and WL-TURBT (the WL group), respectively. Recurrence-free survival (RFS) was compared between the PDD and WL groups before and after propensity score matching, and the impact of several baseline parameters on RFS between the 2 groups was investigated after matching. RESULTS: Before propensity score matching, RFS was significantly longer in the PDD group than in the WL group (P = 0.006). After matching, 383 patients were included in both groups, and RFS was significantly longer in the PDD group than in the WL group (P < 0.001). In the cohort after matching, RFS between the two groups was compared in each subgroup classified according to baseline parameters, including age, sex, history of previous or concomitant upper urinary tract urothelial carcinoma, preoperative urinary cytology, tumor multiplicity, and tumor size, and significantly longer RFS was observed in the PDD group in all subgroups, except for the patients with tumors ≥ 30 mm (P = 0.21). CONCLUSION: These results suggest that PDD-TURBT prolongs RFS in NMIBC patients, except for those with tumors ≥ 30 mm.

Differences in oncological benefits from second transurethral resection between white-light initial surgery and photodynamic diagnosis-guided initial surgery for primary high-risk non-muscle invasive bladder cancer.

OBJECTIVES: The aim of this study was to compare clinical outcomes between patients receiving second TUR after initial white-light transurethral resection of bladder tumor (WL-TURBT) and initial photodynamic diagnosis (PDD)-assisted TURBT. METHODS: A total of 1007 patients were divided into four groups based on the treatment pattern: WL-TURBT with second TUR (161 patients, WL-second group) or without second TUR (540 patients, WL-alone group) and PDD-TURBT with second TUR (112 patients, PDD-second group) or without second TUR (194 patients, PDD-alone group). Oncologic outcomes (bladder cancer recurrence, progression, urothelial cancer-specific mortality) and rates of residual tumor and risk stratification of non-muscle-invasive bladder cancer (NMIBC) after second TUR were evaluated. RESULTS: After propensity score-matching 121 patients were included each in the WL-alone and WL-second groups, and 63 patients each in the PDD-alone and PDD-second groups. In the WL group, the second TUR was significantly associated with improved progression-free (p = 0.012) and urothelial cancer-specific free survival (p = 0.011), but not with recurrence-free survival (p = 0.93). Patients initially treated with PDD-TURBT, and with a tumor diameter <30 mm and multifocality had a relatively high benefit from second TUR. The rates of residual tumor and risk stratification of NMIBC did not significantly differ between WL-TURBT and PDD-TURBT groups. CONCLUSIONS: Our findings suggested that a second TUR could be omitted after an initial PDD-TURBT in selected patients with high-risk NMIBC.

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 on Japanese healthcare economics of photodynamic diagnosis-assisted transurethral resection of bladder tumor for non-muscle invasive bladder cancer: A multicenter retrospective cohort study.

OBJECTIVES: Bladder cancer, especially non-muscle invasive bladder cancer (NMIBC), is one of the most costly cancers owing to its long-term management. Photodynamic diagnosis-assisted transurethral resection of bladder tumor (PDD-TURBT) reduces the risk of intravesical recurrence. However, its impact on healthcare economics in Japan remains unclear. We evaluated the comprehensive medical costs of Japanese healthcare economics regarding PDD-TURBT. METHODS: This large-scale, multicenter, retrospective study included a dataset of 1531 patients who were diagnosed with primary NMIBC who underwent initial TURBT between April 2006 and June 2021. A one-to-one propensity-score matching analysis was used for an unbiased comparison based on postTURBT follow-up periods. The total medical costs, including hospitalization, surgical procedures for TURBT and salvage radical cystectomy, adjuvant intravesical therapies, and follow-up examinations, were compared between white light (WL)-TURBT and PDD-TURBT groups. RESULTS: After propensity-score matching, 468 patients each of WL- and PDD-TURBT groups were matched. Total costs were 510 337 128 and 514 659 328 ¥ in WL- and PDD-TURBT groups, respectively. The costs of adjuvant intravesical therapies, follow-up examinations, and salvage radical cystectomy in PDD-TURBT group were equivalent to or lower than those in WL-TURBT group. Furthermore, total costs of high- and highest-risk NMIBC in PDD-TURBT group were either equivalent or lower compared to those in WL-TURBT group. CONCLUSIONS: The total costs associated with PDD-TURBT were higher compared to WL-TURBT, while there is the potential of PDD-TURBT to reduce the burden on healthcare economics in limited cases.

Current status of photodynamic technology for urothelial cancer.

5-Aminolevulinic acid is a new-generation photosensitizer with high tumor specificity. It has been used successfully in the diagnosis, treatment, and screening of urological cancers including bladder cancer; specifically, it has been used in photodynamic diagnosis to detect tumors by illuminating the lesion with a specific wavelength of light to produce fluorescence in the lesion after administration of 5-aminolevulinic acid, in photodynamic therapy, which induces tumor cell death via production of cytotoxic reactive oxygen species, and in photodynamic screening, in which porphyrin excretion in the blood and urine is used as a tumor biomarker after administration of 5-aminolevulinic acid. In addition to these applications in urological cancers, 5-aminolevulinic acid-based photodynamic technology is expected to be used as a novel strategy for a large number of cancer types because it is based on a property of cancer cells known as the Warburg effect, which is a basic biological property that is common across all cancers.

Sarcopenia and the rate of change of the neutrophil/lymphocyte ratio as predictors of pembrolizumab efficacy in advanced urothelial carcinoma.

The objective was to evaluate the usefulness of sarcopenia and the neutrophil/lymphocyte ratio (NLR) as therapeutic efficacy predictors in patients who received pembrolizumab after platinum-based chemotherapy for advanced urothelial carcinoma (aUC). Forty-four patients with aUC were enrolled. Patients' background characteristics and clinical factors, the skeletal muscle index, and the psoas muscle index were evaluated. The NLR before and during treatment was calculated, and the rate of change of NLR was calculated. The median age was 70 years; the follow-up period was 13.2 months. The response rate was 54%. The nonresponding group had significantly more sarcopenia cases (P = 0.007) and a high rate of change of NLR (P = 0.0076). Progression-free survival (PFS) was significantly shorter in the group with sarcopenia (P = 0.002). Both PFS and overall survival were significantly shorter with an NLR rate of change greater than or equal to 1 (P = 0.001 and P = 0.002). On multivariate analysis, the presence of immune-related adverse events [hazard ratio (HR), 0.3723; 95% confidence interval (CI), 0.14-0.97; P = 0.04] and the NLR rate of change (HR, 3.986; 95% CI, 1.01-15.70; P = 0.048) were independent predictors of PFS. Sarcopenia and the rate of change of NLR appear to be useful as predictors of pembrolizumab efficacy in aUC.

Prognostic value of left ventricular mechanical dyssynchrony induced by exercise stress in patients with normal myocardial perfusion single-photon emission computed tomography.

BACKGROUND: Left ventricular mechanical dyssynchrony (LVMD) induced by exercise stress was reported to be clinically useful in detecting multivessel coronary artery diseases. The aim of this study was to compare the prognostic value of LVMD induced by pharmacological stress with that induced by exercise stress. METHODS: We retrospectively examined 918 consecutive patients who underwent exercise (N = 310) or pharmacological stress (N = 608) 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) with normal myocardial perfusion. LVMD was evaluated by phase analysis as the indices of phase bandwidth and phase standard deviation (PSD). RESULTS: During the follow-up period (2.2 ± 1.9 years), 74 major cardiac events (MCEs) occurred (7 cases of cardiac death, 17 cases of heart failure, and 50 cases of coronary intervention). In global patients, the indices of LVMD on rest images were significantly greater in patients with MCEs (bandwidth (°): 51 ± 31 vs 37 ± 21, P = .001, PSD: 14 ± 9 vs 10 ± 6, P = .001). The exercise stress bandwidth was significantly higher in patients with MCEs (62 ± 37° vs 42 ± 21°, P = .026), as was the pharmacological stress bandwidth (57 ± 35° vs 43 ± 24°, P = .006). Multivariate analysis demonstrated the exercise stress bandwidth to be an independent predictor of MCEs (HR 1.017, CI 1.003 to 1.032, P = .019), but the pharmacological stress bandwidth had no influence on MCEs. CONCLUSIONS: LVMD induced by exercise stress was an independent predictor of MCEs in patients with normal perfusion SPECT, whereas that induced by pharmacological stress had no association with further events.

Tadalafil 5 mg Once Daily Improved Each IPSS Subscore, QOL, and Nocturia in Elderly BPH Patients over 70 Years Old in a Real-World Clinical Setting.

OBJECTIVE: No reports have evaluated the treatment effects of tadalafil by age group in a positive, noninterventional observational study of Japanese men. The present study aimed to evaluate the treatment effects of tadalafil by age group in a positive, noninterventional observational study of Japanese men. We therefore divided patients into 2 groups about the age of 70 years and investigated the treatment effects of tadalafil regarding voiding and storage functions by age group. METHODS: Changes from baseline in each parameter (International Prostate Symptom Score [IPSS], quality of life [QOL] score, Overactive Bladder Symptom Score [OABSS], and residual urine volume) at 4, 12, and 24 weeks after initiating tadalafil for benign prostatic hyperplasia (BPH) patients were compared between groups (50-69 years vs. ≥70 years). In addition, side effects of tadalafil were investigated by age group. RESULTS: In the 50-69 years group, significant improvements from baseline were seen in IPSS total and QOL score for all time points. In addition, significant improvements in IPSS storage subscore from baseline were observed at the 4- and 24-week time points. In the ≥70 years group, significant improvements from baseline were seen in IPSS total, IPSS voiding and storage subscores, and QOL score at each time point. CONCLUSIONS: Tadalafil 5 mg once daily appeared effective in clinical settings for elderly BPH patients even over 70 years old.

The impact of the quantitative assessment procedure for coronary artery bypass graft evaluations using high-resolution near-infrared fluorescence angiography.

PURPOSE: Near-infrared angiography (NIR) is used for on-site graft assessment during coronary artery bypass grafting. This study evaluated the results of a quantitative NIR assessment using a new high-resolution NIR device (h-NIR) for graft assessment. METHODS: Forty-three patients were enrolled in our study. Internal thoracic artery (ITA) grafts anastomosed to the left anterior descending artery and examined intraoperatively using h-NIR were included. The ITA grafts were divided into 2 groups for a comparative analysis: patent grafts (P group; n = 37) and failed grafts (F group; n = 6). The graft flow was evaluated by a "quantitative NIR assessment", and the fluorescence luminance intensity (FLI) was measured. Direct observation of the graft and anastomosis with h-NIR was also performed. RESULTS: The FLI was higher in the P group than in the F group. The receiver operating characteristic analysis revealed the following cut-off values for FLIs depending on imaging duration: 21.1% at 1 s, 35.5% at 2 s, 58.4% at 3 s, and 83.3% at 4 s. The sensitivity and specificity for detecting graft failure were 83.3% and 69.8-80.6%, respectively. Furthermore, h-NIR was also able to visualize arterial dissection in ITA grafts. CONCLUSIONS: A quantitative NIR assessment with an h-NIR device can improve the detectability of anastomotic stenosis, and h-NIR successfully detected arterial dissection of grafts.

5-Aminolevulinic acid has the potential to prevent bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis.

OBJECTIVES: To investigate the effects of pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis in rats. METHODS: Male Wistar rats (340-460 g) were pretreated with vehicle or with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (100/157 or 300/471 mg/kg/day, po) once daily for 7 days before cystometry. Saline or cyclophosphamide (150 mg/kg, ip) was administered 2 days before cystometry. Cystometry was performed under urethane anesthesia (0.8 g/kg, ip) via a catheter inserted into the bladder. After cystometry, bladder tissues were collected to perform hematoxylin and eosin staining for pathological evaluation (neutrophil infiltration, edema, and bleeding scores), and for enzyme-linked immunosorbent assay and real-time polymerase chain reaction for investigating tissue levels of myeloperoxidase, and mRNA levels of haem oxygenase-1 as a cytoprotective molecule. RESULTS: Compared to controls, cyclophosphamide induced a shorter intercontraction interval, lower bladder compliance, increased number of non-voiding contractions, and increased pathological scores and myeloperoxidase expression in the bladder. Pretreatment with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate (300/471 mg/kg/day) significantly improved cyclophosphamide-induced intercontraction interval shortening and increases in number of non-voiding contractions and neutrophil infiltration/bleeding scores and enhanced haem oxygenase-1 expression in the bladder. In addition, cyclophosphamide-induced decreases in bladder compliance and increases in myeloperoxidase were not detected with 5-aminolevulinic acid hydrochloride combined with sodium ferrous citrate pretreatment. CONCLUSIONS: Pretreatment with 5-aminolevulinic acid expects protective effects on bladder dysfunction in cyclophosphamide-induced hemorrhagic cystitis by improving inflammatory changes in bladder tissues perhaps via up-regulation of haem oxygenase-1.

Bladder cancer prospective cohort study on high-risk non-muscle invasive bladder cancer after photodynamic diagnosis-assisted transurethral resection of the bladder tumor (BRIGHT study).

OBJECTIVES: Transurethral resection of bladder tumor with photodynamic diagnosis has been reported to result in lower residual tumor and intravesical recurrence rates in non-muscle invasive bladder cancer. We aimed to evaluate the usefulness of photodynamic diagnosis-transurethral resection of bladder tumor combined with oral 5-aminolevulinic acid hydrochloride for high-risk non-muscle invasive bladder cancer. METHODS: High-risk non-muscle invasive bladder cancer patients with an initial photodynamic diagnosis-transurethral resection of bladder tumor (photodynamic diagnosis group) were prospectively registered between 2018 to 2020. High-risk non-muscle invasive bladder cancer cases with a history of initial white-light transurethral resection of bladder tumor (white-light group) were retrospectively registered. Propensity score-matching analysis was used to compare residual tumor rates, and factors that could predict residual tumors at the first transurethral resection of bladder tumor were evaluated. RESULTS: Analyses were conducted with 177 and 306 cases in the photodynamic diagnosis and white-light groups, respectively. The residual tumor rates in the photodynamic diagnosis and white-light groups were 25.7% and 47.3%, respectively. Factor analysis for predicting residual tumors in the photodynamic diagnosis group showed that the residual tumor rate was significantly higher in cases with a current/past smoking history, multiple tumors, and pT1/pTis. When each factor was set as a risk level of 1, cases with a total risk score ≤1 showed a significantly lower residual tumor rate than cases with a total risk score ≥2 (8.3% vs 33.3%, odds ratio 5.46 [1.81-22.28]). CONCLUSIONS: In high-risk non-muscle invasive bladder cancer cases, the odds of a residual tumor after initial photodynamic diagnosis-transurethral resection of bladder tumor were 0.39-fold that of the odds of those after initial white-light transurethral resection of bladder tumor. A risk stratification model could be used to omit the second transurethral resection of bladder tumor in 27% of the cases.

Artificially induced pneumothorax with a Veress needle for cryoablation of renal cell carcinoma.

Thermal ablative techniques are used increasingly to treat renal cell carcinoma (RCC). Percutaneous cryoablation of tumors at the upper pole of the kidney may result in pulmonary damage due to the intervening lung parenchyma. We treated two patients with RCC in the upper pole of the kidney by inducing pneumothorax with a pneumoperitoneum needle before proceeding to percutaneous cryoablation. The procedures, performed under computed tomography (CT) fluoroscopy guidance, resulted in complete tumor necrosis. There was no pulmonary damage.

Efficacy and safety of CT-guided cryoablation after lipiodol marking and embolization for RCC.

PURPOSE: To evaluate the safety and efficacy of CT fluoroscopy-guided percutaneous cryoablation (PCA) after lipiodol marking and embolization (LME) in patients with renal cell carcinoma (RCC). MATERIAL AND METHODS: This study included 29 patients (18 men, 11 women; mean age 69 years, range 22-89 years) with 42 RCCs. They underwent CT fluoroscopy-guided PCA after LME between March 2016 and March 2020. The mean tumor diameter was 21 mm (range 7-50 mm). LME was performed with lipiodol and gelatin particles. PCA was considered successful when the ice ball encapsulated the entire tumor and the margin was sufficient on post-ablation CT scans. RESULTS: LME was successfully performed in 39 of 40 tumors (97.5%). PCA after LME was successful in all 39 of 39 tumors (100%). During the follow-up period (mean 13.9 ± 12.1 months), one of the 39 tumors (2.6%) developed local tumor progression. A significant complication (reversible hypertensive crisis) was encountered in only one of 37 (2.7%) procedures. The mean eGFR was 64.2 ± 26.8 before and 63.3 ± 26.4 after PCA (p = .44). CONCLUSION: LME using iodized oil and gelatin particles to improve visualization of the RCC facilitated tumor localization on unenhanced CT images. PCA after LME might be a safe and effective for treatment in patients with RCC.

Identification of risk factors associated with oral 5-aminolevulinic acid-induced hypotension in photodynamic diagnosis for non-muscle invasive bladder cancer: a multicenter retrospective study.

BACKGROUND: To investigate risk factors for orally administered 5-aminolevulinic acid (ALA)-induced hypotension for bladder cancer patients receiving photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT). METHODS: Patients were categorized into two groups intraoperatively: a hypotensive group (minimum systolic blood pressure (SBP) ≤80 mmHg) and a non-hypotensive group (minimum SBP > 80 mmHg). We examined differences between the hypotensive group and non-hypotensive groups to identify clinical risk of ALA-induced hypotension using multivariate logistic regression analysis and decision tree analysis. RESULTS: Among 282 cases with ALA-PDD-assisted TURBT from three institutions who were screened, 245 patients were included in the final analysis. In total, 156 patients (63.7%) showed any grade of hypotension during ALA-PDD-assisted TURBT. General anesthesia and spinal anesthesia were induced intraoperatively in 113 patients (46.1%) and 132 patients (53.9%), respectively. Median SBP at baseline (before taking ALA) and at the beginning of anesthesia was 127 mmHg (range, 69-186 mmHg) and 124 mmHg (range, 69-186 mmHg), respectively. Median minimum SBP during ALA-PDD-assisted TURBT was 75 mmHg (range, 43-140 mmHg). Multivariate logistic regression analysis revealed that history of hypertension (odds ratio (OR) 7.568, p < 0.05) and general anesthesia (OR 14.435, p < 0.05) as significantly associated with an increased risk of hypotension incidence. Use of calcium antagonist showed significant negative associations with hypotension (OR 0.183, p < 0.05). Decision tree analysis showed presence of general anesthesia, age ≥ 74 years and American Society of Anesthesiologists physical status (ASA-PS) ≥2 as the most important discriminators. CONCLUSIONS: General anesthesia and hypertension were independent risk factors related to ALA-induced hypotension. In contrast, use of calcium antagonists was identified as a factor associated with reduced risk of ALA-induced hypotension.

Evaluation of a rapid one-step PSA test for primary prostate cancer screening.

BACKGROUND: To enhance the convenience and reduce the cost of prostate cancer (PC) screening, a one-step prostate-specific antigen (PSA) test was evaluated in a large population. The PSA SPOT test kit enables rapid detection of human PSA in serum or plasma at or above a cutoff level of 4 ng/mL to aid in the diagnosis of PC. METHODS: PC screening using the PSA SPOT test was offered to male participants in educational public lectures that we conducted in various cities. Test results were reported to participants at the end of the lectures. Blood samples from 1429 men were evaluated. Two independent observers interpreted the tests at 15 and 30 min. The remaining serum samples were subsequently tested using a conventional quantitative assay. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the test were 79.9, 93.0, 65.4, 96.6, and 91.2%, respectively. The sensitivity and specificity of the test changed with variations in the reading time. Quantitative assessment of the intensity of the band was correlated with the PSA value. CONCLUSIONS: PSA testing using this kit can be easily performed. The low cost and speed of the test make it a useful and convenient tool for primary PC screening.

Photodynamic diagnosis and therapy for urothelial carcinoma and prostate cancer: new imaging technology and therapy.

Photodynamic technology using light-sensitive and fluorescent substances has an important role in an accurate diagnosis for a variety of malignancies, including bladder cancer and prostate cancer. Light-sensitive and fluorescent substances accumulate specifically in tumor cells compared to normal tissue, and by light irradiation and excitation at each specific wavelength, tumor lesion, blood flow, lymph node and so on show fluorescence. 5-Aminolevulinic acid (ALA) is converted to protoporphyrin IX (PpIX) into mitochondria. PpIX is excited by blue light, red fluorescence is emitted in the mitochondria. This phenomenon is the mechanism of ALA-mediated photodynamic diagnosis (ALA-PDD). ALA-PDD has made it possible to visualize smaller lesions and flat lesions that were previously difficult to visualize by endoscope using a white-light source. So accurate diagnosis and complete resection become possible during operation. The accumulation of PpIX in the mitochondria also induces direct mitochondrial damage and subsequent cell death by red and green light. This biological reaction is the ALA-mediate photodynamic therapy (ALA-PDT). ALA-PDT has been developed as a modality for minimum invasive cancer treatment that utilizes low-energy light and photosensitizer. Vascular-activated photosensitizer induces rapid tumor ablation by PDT involving direct tumor cell killing as well as damage to the exposed microvasculature. We summarize the clinical outcomes of PDD and PDT for urothelial carcinoma and prostate cancer.

Efficacy of arterial infusion of iodized oil on CT-guided cryoablation for renal cell carcinoma.

PURPOSE: To evaluate the effectiveness of the transarterial infusion of iodized oil and gelatin particles for marking before CT-guided percutaneous cryoablation (PCA) in patients with renal cell carcinoma (RCC). MATERIAL AND METHODS: This study included ten patients (seven men, three women; mean age 53 years) with 13 RCCs between July 2016 and September 2017. The transarterial infusion of iodized oil and gelatin particles was considered successful when iodized oil accumulated in the target area on CT. CT value of the tumor before and after marking was measured and two diagnostic radiologists evaluated the visualization scores by using a five-point scale (5 = excellent to 1 = invisible). RESULTS: Preoperative marking was successful in all 13 tumors; the median visualization score was 5 post-lipiodol marking and 4 at the time of PCA. The mean CT density was 597 ± 371 Hounsfield units (HU) just after marking and 437 ± 234 HU at the time of PCA. All 13 CT-guided PCA procedures were successful. There were no significant complications. During follow-up (median 11.5 ± 7.0 months) there were no local recurrences. CONCLUSION: As the transarterial infusion of iodized oil and gelatin particles improved RCC visualization on CT, its delivery before CT-guided PCA may improve its safety and success rate in patients with RCC.

Near-infrared fluorescent solid material for visualizing indwelling devices implanted for medical use.

BACKGROUND: In clinical practice, various devices are implanted into the body for medical reasons. As X-ray fluoroscopy is necessary to visualize medical devices implanted into the body, the development of a less-invasive visualization method is highly desired. This study aimed to investigate the clinical applicability of our novel solid material that emits near-infrared fluorescence. METHODS: We developed a solid resin material that emits near-infrared fluorescence. This material incorporates a near-infrared fluorescent pigment, with quantum yield ≥ 20 times than that of indocyanine green. It can be sterilized for medical treatment. This resin material is designed to be molded into a catheter and inserted into the body with an endoscope clip. In this preclinical experiment using a swine model, the resin material was embedded into the body of the swine and visualized with a near-infrared fluorescence camera system. RESULTS: Endoscopic clips were placed in the mucosa of the stomach, esophagus, and large intestine, and the indwelling ureteral catheters were successfully visualized by near-infrared fluorescence laparoscopy. CONCLUSIONS: We confirmed the tissue permeability of the fluorescence emitted by our novel near-infrared fluorescent material and the possibility of its clinical application. This material may allow visualization of devices embedded in the body.