Clinical, pathological, and therapeutic features of newly diagnosed prostate cancer predominantly detected by opportunistic PSA screening: A survey of Shiga Prefecture, Japan.

BACKGROUND: In all the prefectures of Japan, with the exception of Shiga Prefecture, more than half of local governments have an organized prostate-specific antigen (PSA) screening system in place. However, in the Shiga Prefecture, only a single city performed PSA screening over the time period of this survey. The purpose of the present study was to determine the clinical, pathological, and therapeutic features of newly diagnosed prostate cancer in localities where a formally organized screening system was almost entirely absent. METHODS: A multicenter observational study was conducted in the Shiga Prefecture, which has the lowest rate of population-based PSA-screening in Japan. Patients' age, initial PSA, reasons for PSA testing, Gleason score, clinical stage, and primary treatments were surveyed. We stratified patients according to the reasons for PSA measurement, and compared the differences between groups subject to organized versus opportunistic screening. RESULTS: In the 2 years 2012 and 2017, 984 newly diagnosed prostate cancer patients were analyzed. Of these, 954 (97%) were opportunistically tested (i.e., not as part of an organized screening system), with the remaining 29 (3%) measured as part of an organized screening program. Patients in the former group exhibited a higher initial PSA value than in the organized screening group (median: 11.49 vs. 5.67 ng/ml). They also had worse clinical features, including higher Gleason score and TNM stage. More patients in the organized screening group were treated curatively than in the nonorganized screening group in terms of the primary treatment. The results were similar in a subanalysis of the patients of age 50-69 years. CONCLUSIONS: Organized PSA screening contributes to increasing the number of patients diagnosed with early-stage cancer who can be treated curatively.

Nivolumab in patients with unresectable locally advanced or metastatic urothelial carcinoma: CheckMate 275 2-year global and Japanese patient population analyses.

BACKGROUND: Nivolumab has demonstrated antitumor activity and manageable safety in the single-arm, phase II CheckMate 275 study in patients with unresectable locally advanced or metastatic platinum-resistant urothelial carcinoma. We report updated results of the global population and a subanalysis of Japanese patients from this study. METHODS: Patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) confirmed by blinded independent review committee (BIRC) per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included progression-free survival (PFS) by BIRC and overall survival (OS). Safety was also reported. The minimum follow-up was 21 months. RESULTS: Overall, 270 patients were treated with nivolumab globally; 23 patients were Japanese. In the global and Japanese populations, respectively, ORR per BIRC was 20.4% and 21.7%; median PFS was 1.9 (95% confidence interval [CI] 1.9-2.3) and 3.8 months (95% CI 1.9-7.2); and median OS was 8.6 (95% CI 6.1-11.3) and 21.0 months (95% CI 7.2-not reached). The most common any grade treatment-related adverse events were fatigue (18.1%) and diarrhea (12.2%) in the global population; the most common in the Japanese population were diarrhea (26.1%) and pyrexia (13.0%). Grade 3 or 4 treatment-related adverse events occurred in 61 (22.6%) and seven (30.4%) of the global and Japanese patients, respectively. CONCLUSIONS: Nivolumab continues to show antitumor activity and survival in the global population of CheckMate 275. Meaningful clinical benefit was also observed in Japanese patients. No new safety signals were identified.

Genome-wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population.

Through genome-wide association analysis and an independent replication study using a total of 1131 bladder cancer cases and 12 558 non-cancer controls of Japanese populations, we identified a susceptibility locus on chromosome 15q24. SNP rs11543198 was associated with bladder cancer risk with odds ratio (OR) of 1.41 and P-value of 4.03 × 10(-9). Subgroup analysis revealed rs11543198 to have a stronger effect in male smokers with OR of 1.66. SNP rs8041357, which is in complete linkage disequilibrium (r(2) = 1) with rs11543198, was also associated with bladder cancer risk in Europeans (P = 0.045 for an additive and P = 0.025 for a recessive model), despite much lower minor allele frequency in Europeans (3.7%) compared with the Japanese (22.2%). Imputational analysis in this region suggested CYP1A2, which metabolizes tobacco-derived carcinogen, as a causative candidate gene. We also confirmed the association of previously reported loci, namely SLC14A1, APOBEC3A, PSCA and MYC, with bladder cancer. Our finding implies the crucial roles of genetic variations on the chemically associated development of bladder cancer.

Preoperative lipiodol marking and its role on survival and complication rates of CT-guided cryoablation for small renal masses.

BACKGROUND: Partial nephrectomy for small renal masses (SRM) may be useful for preserving renal function, but is technically more difficult than radical nephrectomy. Cryoablation may be performed under local anesthesia. The objective of the present study is to assess the safety and therapeutic efficacy of cryoablation with lipiodol marking for SRM. METHODS: Cryoablation therapy was performed on 42 patients under local anesthesia. Their median age was 74 years (31-91). The median tumor diameter was 21 mm (10-42). Responses to the treatment were evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST) by contrast-enhanced CT. In six patients (14.3%) for whom it was not possible to use contrast medium, plain CT findings were assessed according to Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Twenty-nine (69%) and five (12%) patients achieved complete responses (CR) and partial responses (PR), respectively, while four (10%) and four (10%) patients each had stable disease (SD) and progressive disease (PD) after the first course of therapy. A second course of cryoablation therapy with lipiodol marking was performed on three out of four patients with PD after the first course of therapy, and resulted in a total of 32 patients achieving CR (76%). Four (36.4%) out of 11 patients for whom lipiodol marking was not conducted had PD, whereas none of the 31 patients for whom lipiodol marking was conducted had PD. All grade complications were reported in 11 (24.4%) patients while grade 3 in two (4.4%) patients. 11 (24.4%) A significant difference was observed in postoperative hemorrhagic events in all grades (18% in patients undergoing cryoablation without lipiodol marking vs. 0% in patients undergoing cryoablation without lipiodol marking). CONCLUSIONS: Although further studies involving more patients are needed in order to evaluate long-term results, cryoablation therapy appears to be a useful treatment option for SRM. Preoperative marking with lipiodol was helpful for improving complication and survival rates with cryoablation.

PAX2 promoted prostate cancer cell invasion through transcriptional regulation of HGF in an in vitro model.

Elucidating the mechanism of prostate cancer cell invasion may lead to the identification of novel therapeutic strategies for its treatment. Paired box 2 (PAX2) and hepatocyte growth factor (HGF) proteins are promoters of prostate cancer cell invasion. We found that PAX2 protein activated the HGF gene promoter through histone H3 acetylation and upregulated HGF gene expression. Deletion analysis revealed that the region from -637 to -314 of the HGF gene was indispensable for HGF promoter activation by PAX2. This region contains consensus PAX2 binding sequences and mutations of the sequences attenuated HGF promoter activation. Using an in vitro invasion model, we found that PAX2 and HGF promoted prostate cancer cell invasion in the same pathway. Knockdown of HGF expression attenuated the cells' invasive capacity. Moreover, in tissue samples of human prostate cancers, HGF and PAX2 expression levels were positively correlated. These results suggested that upregulation of HGF gene expression by PAX2 enhanced the invasive properties of prostate cancer cells. The PAX2/HGF pathway in prostate cancer cells may be a novel therapeutic target in prostate cancer patients.

Post-chemotherapy laparoscopic retroperitoneal lymph node dissection is feasible for stage IIA/B non-seminoma germ cell tumors.

OBJECTIVE: To assess the efficacy, outcome and complications of post-chemotherapy laparoscopic retroperitoneal lymph node dissection (L-RPLND) for stage IIA/B testicular germ cell tumor (GCT) patients in comparison with open RPLND (O-RPLND). METHODS: L-RPLND was performed in 14 patients with stage IIA/B non-seminoma GCTs among 154 non-seminoma patients who received RPLND after completion of chemotherapy with tumor marker normalization at our institution between 1998 and 2013. Their outcomes were compared with those of 14 patients with stage IIA/B non-seminoma GCTs treated with O-RPLND during the same period. Clinical parameters were compared between L-RPLND and O-RPLND. RESULTS: There were no significant differences in the background characteristics of the two groups except for follow-up duration (36 months for L-RPLND, 70 months for O-RPLND; p = 0.02). Blood loss during surgery was significantly less for the L-RPLND group than for the O-RPLND group (155 mL for L-RPLND, 700 mL for O-RPLND; p < 0.001). Parameters related to post-operative recovery were significantly better for the L-RPLND group than for the O-RPLND group. Histopathological examination showed no difference between the two groups. Neither group had disease recurrence. CONCLUSION: Post-chemotherapy L-RPLND with a bilateral template and nerve-sparing method was safe, effective, and showed a high preservation rate of antegrade ejaculation with no deterioration of outcomes compared to O-RPLND.

Transvesical laparoscopic surgery for double renal pelvis and ureter with or without ureterocele.

OBJECTIVE: To evaluate the performance of transvesical laparoscopic surgery for patients with complete double pelvis and ureter. METHODS: A total of 10 patients were included in the present study: five had complete double pelvis and ureter with ureterocele (group A), and five did not have ureterocele (group B). Three small incisions of 5 mm were used, without incision in the lower abdomen. In group A patients, the ureterocele wall was resected, and two ureters were sufficiently detached as a combined ureteral complex. Ureterocele on the side of the bladder wall was sutured to the bladder neck, and the bladder wall was strengthened. According to the cross-trigonal technique, ureterocystoneostomy was carried out in two ureters as a combined ureteral complex. In group B patients, two ureters were sufficiently detached, and ureterocystoneostomy was carried out as in group A. RESULTS: In group A, the mean age was 13.4 years (range 2-34 years). The mean operation time was 304.6 min (242-346 min). In group B, the mean age was 16.6 years (range 2-48 years). The mean operation time was 207.8 min (150-249 min). There were no intraoperative and postoperative complications in both study groups. CONCLUSIONS: Transvesical laparoscopic surgery can be safely and effectively used in patients with double pelvis and ureter.

The efficacy of radio-frequency ablation for metastatic lung or liver tumors of male germ cell tumors as an alternative minimally invasive therapy after salvage chemotherapy.

BACKGROUND: The aim of this study was to assess the efficacy of radio-frequency ablation (RFA) for metastatic lung or liver tumors of germ cell tumors (GCTs) after chemotherapy. METHODS: RFA with computed tomography guidance and monitoring was performed in 24 patients with 48 metastatic lung or liver tumors of GCTs. Group A consisted of 9 patients with tumor marker normalization after salvage chemotherapy and group B consisted of 15 patients without tumor marker normalization in spite ofintensive treatment. RESULTS: Out of 48 tumors, 41 tumors in 21 patients were evaluated for the efficacy of the RFA treatment. Of the 41 tumors, successful ablation was achieved in 34 (82.9 %). The patients in group A had significantly better survival than the patients in group B (p = 0.0003). In group A, all 9 patients are still alive with no evidence of disease (NED). Patients with a solitary tumor had significantly better survival than those with multiple tumors (p = 0.0247). In group B, 2 patients are alive with NED, 1 patient is alive with disease, and the remaining 12 patients have died a tumor-related death. Three cases of pneumothorax requiring intubation were observed. CONCLUSIONS: RFA is less invasive than surgery and is an effective treatment option for curative and palliative therapy as an alternative to invasive salvage surgery for post-chemotherapeutic metastatic lung or liver lesions from GCT.

Comparison of diameter-axial-polar nephrometry and RENAL nephrometry score for treatment decision-making in patients with small renal mass.

INTRODUCTION: The aim of this study was to evaluate our institution's experience in performing laparoscopic radical nephrectomy (LRN) and partial nephrectomy (PN) in patients with small renal masses. METHODS: 142 patients with cT1aN0M0 lesions were identified. 68 of these subjects were treated with LRN and 74 were treated with laparoscopic PN (LPN). The clinicopathological characteristics of the two groups of patients, including diameter-axial-polar (DAP) nephrometry and RENAL nephrometry score (RENAL-NS), operative results, and outcomes, were retrospectively analyzed. RESULTS: A multivariate logistic regression analysis for the selection of PN as the treatment showed that tumor size, DAP nephrometry, RENAL-NS and imperative condition were all independent factors. The area under the curve receiver operating characteristics (ROC-AUC) of DAP and RENAL-NS for performing LPN were 0.897 and 0.825, respectively. CONCLUSIONS: Although LRN was performed in patients with a high nephrometry score in this study, open partial nephrectomy (OPN) should be considered for patients with a high nephrometry score in T1a renal cell carcinoma (RCC) because of better functional and similar oncological outcomes. Based on ROC analysis, when DAP is 6 or less, LPN should be considered and when DAP is 7 or more, OPN should be considered.

Initial experience of combined use of photodynamic diagnosis and narrow band imaging for detection of flat urothelial lesion.

BACKGROUND: This preliminary study is the first report to compare photodynamic diagnosis (PDD) with narrow band imaging (NBI) in the same patients with flat urothelial lesions suspicious of carcinoma in situ (CIS) of the bladder. METHODS: Between November 26, 2012 and April 1, 2013, 10 patients underwent transurethral resection of bladder tumor using PDD and NBI simultaneously because of suspicion of CIS. The bladder was mapped first under white light (WL), then under NBI, and subsequently under blue light in odd-numbered patients. The bladder was mapped first under WL, then under blue light, and subsequently under NBI in even-numbered patients. Biopsies were carried out from all suspicious areas, noting whether NBI, PDD or both detected lesions. Random cold cup biopsies from healthy mucosa of bladder were performed from lesions negative on PDD and NBI. RESULTS: The sensitivity and specificity of PDD for detection of CIS and dysplasia were 0.916 and 0.827, respectively. The sensitivity and specificity of NBI for detection of CIS and dysplasia were 0.625 and 0.879. The area under the curve (AUC) for detection of CIS and dysplasia was 0.872 with PDD and 0.752 with NBI. The AUC with combined use of PDD and NBI was 0.918. There was no cancer or dysplasia identified in 43 lesions that were both PDD- and NBI-negative. CONCLUSION: When both PDD and NBI are negative, the possibility of CIS or dysplasia might be very low. The usefulness of the combination of PDD with NBI was suggested in this study.

Percutaneous nephrolithotripsy and antegrade ureterolithotripsy in a 10-month-old infant with urinary stones in both kidney and ureter.

The prevalence of urinary tract stones in the pediatric population is lower than that in adults. Although methods of surgery and medical equipment have developed, medical treatments for urinary tract stones are limited for pediatric cases. We report the case of a 10-month-old male infant with urinary stones in the left kidney and ureter who underwent percutaneous nephrolithotripsy and ureterolithotripsy using antegrade insertion of a ureteroscope through the same nephrostomy tract.

Laparoscopic off-clamp partial nephrectomy using soft coagulation.

OBJECTIVES: To assess the effectiveness of soft coagulation in off-clamp laparoscopic partial nephrectomy. METHODS: A total of 32 patients with renal tumors underwent laparoscopic partial nephrectomy with off-clamp using soft coagulation between May 2012 and September 2013. Tumor resection was carried out using a combination of bipolar forceps and a ball electrode using the soft coagulation system without hilar clamping. The outcomes of these patients were compared with those of 30 patients treated with hilar clamping. RESULTS: This off-clamp procedure was successfully completed in 31 cases. No significant differences were observed in the mean age (60 vs 61 years), sex (male/female; 25/7 vs 20/10), mean RENAL nephrometry score (5.7 vs 5.8), mean body mass index (24.4 vs 23) or tumor size (15 mm vs 16 mm) between the two groups. No significant differences were noted in positive surgical margins (0 vs 0) or blood loss (104 vs 115 cc) as well. In contrast, a significant difference was noted in the total operative time (278 vs 238 min). Serum creatinine percentage changes at 3 months were 6.4 versus 7.3% in the off-clamp and hilum-clamp groups, respectively, which were not significantly different. CONCLUSIONS: Off-clamp laparoscopic partial nephrectomy can be safely carried out by using a soft coagulation technique.

Clinical outcomes and histological findings of patients with advanced metastatic germ cell tumors undergoing post-chemotherapy resection of retroperitoneal lymph nodes and residual extraretroperitoneal masses.

OBJECTIVES: To assess clinical outcomes of patients with advanced germ cell tumor undergoing post-chemotherapy retroperitoneal lymph node dissection with or without extraretroperitoneal mass resection. METHODS: Between 1998 and 2013, 175 retroperitoneal lymph node dissections for advanced metastatic germ cell tumors were carried out at Kyoto Prefectural University of Medicine, Kyoto, Japan. Of patients receiving retroperitoneal lymph node dissections, 156 underwent post-chemotherapy retroperitoneal lymph node dissection with or without extraretroperitoneal mass resection as first surgery after completion of chemotherapy. Of these 156 patients, 47 underwent both post-chemotherapy retroperitoneal lymph node dissection and extraretroperitoneal mass resection. RESULTS: The histological findings were necrosis in 59.6%, teratoma in 31.4% and viable cancer in 9.0% at retroperitoneal lymph node. At extraretroperitoneal mass resection, necrosis was present in 59.6%, teratoma in 31.9% and viable cancer in 8.5%. Overall histological discordance between retroperitoneal lymph node and extraretroperitoneal mass was found in 31.9%. Five-year disease-free survival stratified by retroperitoneal lymph node histology in 156 patients was 91.3% for necrosis, 78.7% for teratoma and 63.5% for viable cancer (log-rank, P = 0.009). Antegrade ejaculation was preserved in 80.9%. In the worst histology of post-chemotherapy retroperitoneal lymph node dissection or extraretroperitoneal mass resection in 156 patients, 5-year disease-free survival was 93.2% for necrosis, 79.0% for teratoma and 63.4% for viable cancer (log-rank, P < 0.001). Independent prognostic factors for disease-free survival were presence of viable cancer in retroperitoneal lymph node histology and salvage chemotherapy. CONCLUSION: The presence of viable cancer at the retroperitoneal lymph node is an independent predictor of disease recurrence. In approximately one-third of cases, there is a histological discordance between retroperitoneal lymph node and extraretroperitoneal mass. Resection of residual retroperitoneal lymph node and extraretroperitoneal masses remains an important procedure in the management of advanced germ cell tumors.

Salvage combined chemotherapy with paclitaxel, ifosfamide and nedaplatin for patients with advanced germ cell tumors.

OBJECTIVES: To investigate the efficacy of combined regimen with paclitaxel, ifosfamide and nedaplatin as salvage chemotherapy in patients with cisplatin-refractory or multiple relapsed germ cell tumors. METHODS: A total of 65 patients refractory to cisplatin-based chemotherapy or with relapse after induction or salvage chemotherapy received paclitaxel 210 mg/m(2) on day 1, ifosfamide 1.2 g/m(2) on days 2-6 and nedaplatin 100 mg/m(2) on day 2 of a 3-week cycle. The primary and secondary end-points were the response rate and overall survival, respectively. RESULTS: Paclitaxel, ifosfamide and nedaplatin therapy was carried out as second-line therapy in 17 patients, third-line in 31 and fourth-line or later in 17. Patients were pretreated with a median of six cycles of platinum-based chemotherapy (range 3-15 cycles). The overall response rate was 62.9%, including one patient with complete response and 38 with partial response. Serum tumor marker levels normalized in 35 (56.5%) patients. Overall survival at a median follow up of 34 months was 59.3%, and median time to progression was 12 months. Multivariate analysis showed that serum tumor marker normalization was the only independent predictor of better progression-free survival and overall survival. Grade 3/4 of neutropenia, anemia and thrombocytopenia was observed in 96.9%, in 81.5%, and in 90.8% of patients, respectively. CONCLUSION: Paclitaxel, ifosfamide and nedaplatin chemotherapy appears to be effective when used as first or second salvage treatment in advanced relapsed germ cell tumors. Even after fourth-line therapy, patients with serum tumor marker normalization might have a chance for a cure.

Fifteen-second skin icing using a frozen gel pack is effective for reducing goserelin injection pain.

OBJECTIVE: The efficacy of skin icing to reduce the pain of goserelin injection has been reported. We investigated the optimal icing time with a frozen gel pack and its effectiveness. METHODS: Abdominal skin temperatures of 49 healthy volunteers were measured after application of the frozen gel pack for 10, 15 and 30 s, and it was decided that a 15-second icing was adequate. For 55 consecutive patients who received goserelin (10.8 mg) injection, pain was evaluated employing a visual analog scale (VAS). The first injection was administered routinely. A second injection was administered after skin icing in 27 of 55 patients who wanted to try icing. At the time of the third injection, all patient decided whether they were to receive icing or the routine method. RESULTS: After icing, VAS scores decreased in 20 of 27 patients. At the third injection, 18 patients requested icing. CONCLUSION: When a patient complains of injection pain, the icing method should be considered for pain reduction.

Long-term outcome of hand-assisted laparoscopic radical nephrectomy for T1 renal cell carcinoma.

OBJECTIVES: To investigate the long-term outcomes of hand-assisted laparoscopic radical nephrectomy compared with those of open nephrectomy. METHODS: Hand-assisted laparoscopic radical nephrectomy was carried out in 132 patients with T1 renal cell carcinoma (between November 1999 and November 2008). Their outcomes were compared with those of 61 patients treated with open nephrectomy. The durations of follow up were 6-121 months (median 65 months) and 7-146 months (median 84 months) in the hand-assisted laparoscopic radical nephrectomy and open nephrectomy groups, respectively. RESULTS: The 7-year recurrence-free rates were 88.5 and 85.6% in the hand-assisted laparoscopic radical nephrectomy and open nephrectomy groups, respectively, showing no significant difference between the two groups. The 7-year cancer-specific survival rates were 92.3 and 91.4% in the hand-assisted laparoscopic radical nephrectomy and open nephrectomy groups, respectively, showing no significant difference between the two groups. Also, the 10-year recurrence-free rates were 85.4 and 78.1% in the hand-assisted laparoscopic radical nephrectomy and open nephrectomy groups, respectively. When changes in the recurrence-free rate were analyzed using the Kaplan-Meier method, no significant difference was observed between the two groups. The 10-year cancer-specific survival rates were 91.8 and 87.9% for hand-assisted laparoscopic radical nephrectomy and open nephrectomy, respectively, showing no significant difference between the groups. CONCLUSIONS: Hand-assisted laparoscopic radical nephrectomy might be comparable with open nephrectomy with regard to long-term cancer control.

Percutaneous transluminal renal angioplasty remarkably improved severe hypertension and renal function in a patient with renal artery stenosis and postrenal kidney failure.

A 69-year-old man was admitted to our hospital with severe hypertension and rapidly worsening renal function. He presented with a 10-year history of chronic renal failure caused by bilateral ureteral obstruction due to retroperitoneal fibrosis. Magnetic resonance angiography and Doppler ultrasonography suggested severe right renal artery stenosis (RAS). Renal angiography revealed 99% stenosis at the ostium of the right renal artery. We performed percutaneous transluminal renal angioplasty (PTRA) with the support of intravascular ultrasound to decrease the amount of contrast agent needed. In addition, to prevent distal atheroembolism, a distal protection device was used. The procedure was completed without any adverse effects. After PTRA, renal function and blood pressure improved remarkably and remained stable for one year. PTRA for RAS remains controversial, especially in patients with renal insufficiency. Use of new devices should be considered to decrease catheterization-related adverse effects.

Preliminary study of the safety of acrinol in probe-based confocal laser endomicroscopy during transurethral resection of bladder tumors.

We previously reported that probe-based confocal laser endomicroscopy using acrinol can depict cancerous nuclei. The objective of this study was to confirm the safety of acrinol in patients. For all seven patients, '50 ml' of a 0.1% acrinol and '1 ml' of 10% fluorescein in 99 ml of normal saline were introduced into the bladder. The laser probe adhered to the suspicious lesion from the working channel of the cystoscope. The patients underwent mucosal biopsy and transurethral resection after observation. Adverse events were noted during a valuation using common terminology criteria for adverse events version 4.0. Confocal laser endomicroscopy detected the nuclei of cancer cells in all seven patients. No adverse event was observed in any of the seven patients. Confocal laser endomicroscopy using acrinol as a novel dye can help visualize the cancerous nuclei of bladder urothelial carcinoma during cystoscopy without severe adverse events.

Negative association between loneliness and healthy state among rural residents in Japan: a cross-sectional single region population-based survey.

Objective: Loneliness is an important health problem in rural areas of Japan because of its ageing and declining population. Therefore, we investigated the association between loneliness and health. Materials and Methods: Self-administered questionnaires were distributed to rural adult residents. The Japanese 3-item versions of the UCLA Loneliness Scale, self-rated health (SRH), and objective health status (whether the respondents had a physical and/or mental illness) were used. We defined a UCLA score of four points or more as loneliness, an SRH of four points or more as a subjective healthy state, and no physical or mental illness as an objective healthy state. The association was adjusted for sociodemographic data, lifestyle habits, and isolation risk using logistic regression analysis. Results: The five-year population decline rate in the target areas was 10.2 to 12.3%. Of the 2,700 participants, there were 1,211 male and 1,489 female respondents, with an average age of 65.4 years. Moreover, 358 (13.6%) were living alone, and 829 (31.5%) were living in couple-only households. Among the participants, 1,395 (53.2%) experienced loneliness, 1,751 (65.7%) had good self-rated health, and 1,587 (60.8%) had objective health status. Loneliness was negatively associated with good SRH (OR=0.56, CI=0.45-0.70) and objective health status (OR=0.57, CI=0.46-0.71) after adjusting for sociodemographic data, lifestyle habits, and the risk of isolation. Statistically significant confounding factors for subjective and/or objective health status were employment, not smoking, obesity, exercise, having a family doctor, having an above-average number of teeth, and the ability to leave home. Conclusion: In an ageing and declining population, loneliness is an independent factor affecting the health status of rural residents and is not limited to older adults. Therefore, measures to reduce it are needed.

Population­based prostate­specific antigen screening for prostate cancer may have an indirect effect on early detection through opportunistic testing in Kusatsu City, Shiga, Japan.

Prostate cancer is the most common genitourinary cancer in men. Population-based serum prostate-specific antigen (PSA) testing is used to screen men for the early detection of asymptomatic prostate cancer. The present study compared the features of patients with prostate cancer in Kusatsu City, the only municipality in Shiga Prefecture of Japan to implement organized PSA screening, with those in other municipalities. The target population for organized PSA screening by mail invitation was men ≥50 years. Patients were pathologically diagnosed via prostate biopsy because of elevated serum PSA. This multicenter observational study was subsequently conducted in 14 hospitals. The following information was extracted from patient records: age, reason for PSA testing, initial PSA level, Gleason score, clinical stage, and place of residence. Risk classification was defined as low, intermediate, high, and advanced. Each patient was stratified according to their city/town. A total of 984 patients diagnosed with prostate cancer in Shiga in 2012 and 2017 were analyzed, of which 955 (97%) were opportunistically tested, with the remaining 29 (3%) assessed by organized screening. In Kusatsu, 93 patients were diagnosed, of whom 26 (28%) were detected by organized screening. By contrast, only three of 891 patients (0.3%) were detected by organized screening in other municipalities. Of patients in Kusatsu, cases identified by opportunistic testing had a higher initial PSA value (P=0.010) than those identified by organized screening. However, patients detected through opportunistic testing in Kusatsu City were younger (P=0.034), had a lower PSA value (P=0.001), and improved risk classification (P<0.001) than those in other municipalities. It was concluded that more patients were diagnosed with early-stage cancer by organized PSA screening. Furthermore, population-based PSA screening in Kusatsu City may have indirectly affected early detection, even by opportunistic testing.