市川 智彦

BACKGROUND/AIM: Photodynamic diagnosis (PDD)-assisted transurethral resection of a bladder tumor (PDD-TURBT) in a patient receiving 5-aminolevulinic acid improved the detection of micro- and flat lesions of the bladder. This study used real-world data in Japan to examine the diagnostic accuracy of PDD-assisted targeted biopsies and white-light (WL) random biopsies and reevaluated the necessity of random biopsies. PATIENTS AND METHODS: A total of 133 patients diagnosed with bladder cancer who underwent TURBT from April 2020 to March 2022 were included in the study. Biopsy specimens obtained from 407 flat lesions or normal-like lesions, excluding biopsies from elevated lesions and TUR specimens, were used to analyze diagnostic accuracy in PDD and WL findings. RESULTS: The respective sensitivities, specificities, and negative predictive values of PDD vs. WL findings were 81.4% vs. 54.0% (p=0.0039), 70.4% vs. 81.4% (p=0.0012), and 96.4% vs. 90.6% (p=0.0144), indicating that PDD was useful for a diagnosis of exclusion. Combining the PDD and WL findings improved the detection of malignant flat lesions. Ten (PDD-positive and WL-negative) specimens from 9 patients were diagnosed as malignant. The results of PDD-assisted targeted biopsy provided an accurate assessment of the risk classification for recurrence and progression of non-muscle invasive bladder cancer (NMIBC) as defined by the Japanese Urological Association (JUA) guidelines. CONCLUSION: For NMIBC treatment, a more accurate diagnosis is important for postoperative treatment decisions. PDD-assisted targeted biopsy may be necessary and sufficient for diagnosis of flat lesions in patients with bladder cancer for treatment decision making based on JUA risk classification.

Abstract Objectives In this study, we aimed to implement and evaluate a Web-based partnership support program to enhance the QoL of male patients undergoing infertility treatment. We conducted a pilot study involving 41 infertile couples from September to October of 2021. We used a quasi-experimental design (pre-test and post-test with comparison) involving purposive sampling. A subgroup analysis was conducted to determine which demographics of the participants would benefit from the program. Results Thirty-four participants (mean age 37.3 years; duration of infertility treatment 14.5 months) were included in the final analysis (follow-up rate 82.9%). Although there was no significant increase in the participants’ QoL under the Web-based partnership support program, the assisted reproductive technology group (P = 0.03), the no medical history group (P = 0.032), and the with experience of changing hospital group (P = 0.027) showed a significant increase in the relational subscale scores of the QoL before and after the program. The majority of the participants (n = 29; 85.3%) expressed satisfaction with the support program. Participation in the Web-based partnership support program may improve the QoL of some men undergoing infertility treatment. Trial registration Retrospectively registered at the University Hospital Medical Information Network on 26 January 2023 (ID: UMIN0000 000050153).

BACKGROUND: The surgical and endocrinological outcomes of single-port laparoscopic partial adrenalectomy for patients with aldosterone-producing adenomas are unknown. Precise diagnosis of intra-adrenal aldosterone activity and a precise surgical procedure may improve outcomes. In this study, we aimed to determine the surgical and endocrinological outcomes of single-port laparoscopic partial adrenalectomy with preoperative segmental selective adrenal venous sampling and intraoperative high-resolution laparoscopic ultrasound in patients with unilateral aldosterone-producing adenomas. We identified 53 patients with partial adrenalectomy and 29 patients with laparoscopic total adrenalectomy. Single-port surgery was performed for 37 and 19 patients, respectively. METHODS: A single-center, retrospective cohort study. All patients with unilateral aldosterone-producing adenomas diagnosed by selective adrenal venous sampling and treated surgically between January 2012 and February 2015 were included. Follow-up with biochemical and clinical assessments was set at 1 year after surgery for short-term outcomes and was performed every 3 months after surgery. RESULTS: We identified 53 patients with partial adrenalectomy and 29 patients with laparoscopic total adrenalectomy. Single-port surgery was performed for 37 and 19 patients, respectively. Single-port surgery was associated with shorter operative and laparoscopic times (odds ratio, 0.14; 95% confidence interval, 0.039-0.49; P = .002 and odds ratio, 0.13; 95% confidence interval, 0.032-0.57; P = .006, respectively). All single-port and multi-port partial adrenalectomy cases showed complete short-term (median 1 year) biochemical success, and 92.9% (26 of 28 patients) who underwent single-port partial adrenalectomy and 100% (13 of 13 patients) who underwent multi-port partial adrenalectomy showed complete long-term (median 5.5 years) biochemical success. No complications were observed with single-port adrenalectomy. CONCLUSION: Single-port partial adrenalectomy is feasible after selective adrenal venous sampling for unilateral aldosterone-producing adenomas, with shorter operative and laparoscopic times and a high rate of complete biochemical success.

OBJECTIVES: To determine candidates for extended pelvic lymph node dissection using a novel nomogram to assess the risk of lymph node invasion in Japanese prostate cancer patients in the robotic era. METHODS: A total of 538 patients who underwent robot-assisted radical prostatectomy with extended pelvic lymph node dissection in three hospitals were retrospectively analyzed. Medical records were reviewed uniformly and the following data collected: prostate-specific antigen, age, clinical T stage, primary and secondary Gleason score at prostate biopsy, and percentage of positive core numbers. Finally, data from 434 patients were used for developing the nomogram and data from 104 patients were used for external validation. RESULTS: Lymph node invasion was detected in 47 (11%) and 16 (15%) patients in the development and validation set, respectively. Based on multivariate analysis, prostate-specific antigen, clinical T stage ≥3, primary Gleason score, grade group 5, and percentage of positive cores were selected as variables to incorporate into the nomogram. The area under the curve values were 0.781 for the internal and 0.908 for the external validation, respectively. CONCLUSIONS: The present nomogram can help urologists identify candidates for extended pelvic lymph node dissection concomitant with robot-assisted radical prostatectomy among patients with prostate cancer.

背景:デュシェンヌ/ベッカー型筋ジストロフィー(DMD/BMD)はともにX染色体上のジストロフィン遺伝子変異を原因とする遺伝性疾患だが,DMDはフレームシフト/ナンセンス変異により若年発症し進行が速い。出生前/着床前診断の対象となりうるためBMDとの鑑別は重要である。症例:11歳女児,ジストロフィン遺伝子のサザンブロット解析でin-frame欠失を認め,BMD保因者であることが示唆された。29歳時,挙児希望にて周産期遺伝カウンセリング目的に来院。MLPA再解析でout-of-frame欠失を認め,DMD保因者であることが示唆された。考察:遺伝子解析方法により欠失領域の判定が異なる結果となった症例を経験した。解析方法の進歩によって,過去の検査結果や解釈が変化することがある。結論:欠失領域の判定は筋ジストロフィーのタイプに直接関係する。周産期遺伝カウンセリングにおいては注意が必要である。(著者抄録)

INTRODUCTION: Combination therapy using immuno-oncology drugs with tyrosine kinase inhibitors is increasingly important in the therapeutic strategy for metastatic renal cell carcinomas. Here, we report a case of metastatic renal cell carcinoma that was successfully treated with deferred cytoreductive nephrectomy following lenvatinib plus pembrolizumab combination therapy. CASE PRESENTATION: A 49-year-old man was referred to our hospital with a diagnosis of advanced right kidney cancer with multiple lung metastases (cT3aN0M1). The size of the primary tumor was so huge that it exceeded 20 cm in diameter, pushing the liver and intestines to the left. After administration of lenvatinib and pembrolizumab combination as first-line treatment, all the metastatic lung lesions disappeared, and the primary lesion shrank significantly. Robot-assisted radical nephrectomy was successfully performed, resulting in complete surgical remission. CONCLUSION: Deferred cytoreductive nephrectomy following a lenvatinib plus pembrolizumab combination is a useful therapeutic strategy for achieving complete remission of metastatic renal cell carcinomas.

Machine learning technology is expected to support diagnosis and prognosis prediction in medicine. We used machine learning to construct a new prognostic prediction model for prostate cancer patients based on longitudinal data obtained from age at diagnosis, peripheral blood and urine tests of 340 prostate cancer patients. Random survival forest (RSF) and survival tree were used for machine learning. In the time-series prognostic prediction model for metastatic prostate cancer patients, the RSF model showed better prediction accuracy than the conventional Cox proportional hazards model for almost all time periods of progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS). Based on the RSF model, we created a clinically applicable prognostic prediction model using survival trees for OS and CSS by combining the values of lactate dehydrogenase (LDH) before starting treatment and alkaline phosphatase (ALP) at 120 days after treatment. Machine learning provides useful information for predicting the prognosis of metastatic prostate cancer prior to treatment intervention by considering the nonlinear and combined impacts of multiple features. The addition of data after the start of treatment would allow for more precise prognostic risk assessment of patients and would be beneficial for subsequent treatment selection.

AIM: During infertility treatment, distress increases and the quality of life declines in both men and women over time. Thus, both men and women need equal support and care. In this study, we aimed to explore the effectiveness of a web-based partnership support program in preventing quality of life deterioration and reducing emotional distress in men undergoing infertility treatment. METHODS: We conducted a non-randomized controlled trial involving 151 infertile couples in Japan from January to April of 2022. The program consisted of couple discussion, information provision for couple cooperation, and communication techniques. We used a quasi-experimental design (non-equivalence two groups pre-test and post-test with comparison) involving purposive sampling. Data were collected using the FertiQoL tool and Distress scales. Analyses were conducted by a two-way factorial analysis of variance using SPSS software. RESULTS: Data for the analysis were included for the intervention group (n = 58) and the control group (n = 62) (valid response rate 79.5%). There were no significant interaction effects between program and time in the FertiQoL and Distress scales. However, there were significant interaction effects between program and time in the Relational (p < .001) and Social (p = .044) subscales. Subgroup analysis showed that in the non-assisted reproductive technologies group, deterioration in the quality of life was more effectively prevented in the intervention group than in the control group. CONCLUSIONS: The web-based partnership support program appeared to be effective in preventing the deterioration of the quality of life of only men undergoing non-assisted reproductive technology treatment.

The L-type amino acid transporter (LAT) family contains four members, LAT1~4, which are important amino acid transporters. They mainly transport specific amino acids through cell membranes, provide nutrients to cells, and are involved in a variety of metabolic pathways. They regulate the mTOR signaling pathway which has been found to be strongly linked to cancer in recent years. However, in the field of prostate cancer (PCa), the LAT family is still in the nascent stage of research, and the importance of LATs in the diagnosis and treatment of prostate cancer is still unknown. Therefore, this article aims to report the role of LATs in prostate cancer and their clinical significance and application. LATs promote the progression of prostate cancer by increasing amino acid uptake, activating the mammalian target of rapamycin (mTOR) pathway and downstream signals, mediating castration-resistance, promoting tumor angiogenesis, and enhancing chemotherapy resistance. The importance of LATs as diagnostic and therapeutic targets for prostate cancer was emphasized and the latest research results were introduced. In addition, we introduced selective LAT1 inhibitors, including JPH203 and OKY034, which showed excellent inhibitory effects on the proliferation of various tumor cells. This is the future direction of amino acid transporter targeting therapy drugs.

Some researchers have found that preoperative pyuria is a risk factor for recurrence after transurethral resection of high-risk non-muscle invasive bladder cancer. However, to our knowledge, none have clarified the risks associated with pyuria according to bacille Calmette-Guerin (BCG) treatment status. We retrospectively selected patients with high-risk non-muscle invasive bladder cancer according to Japanese Urological Association guidelines. Pyuria was defined as ≥10 white blood cells per high-powered field. We analyzed recurrence-free rates (RFS) in 424 patients who had and had not undergone BCG treatment. The median duration of follow-up was 45.2 months. According to multivariate analysis, postoperative intravesical BCG induction and preoperative pyuria were independent risk factors for intravesical recurrence in the whole study cohort. We found no significant risk factors for recurrence in the BCG-treated group (n = 179). In the non-BCG-treated group (n = 245), patients with pyuria were much more frequently female and more often had T1 disease than patients without pyuria. According to univariate and multivariate analysis, preoperative pyuria is an independent risk factor for intravesical recurrence. There was no significant difference in the severity of pyuria between the BCG and non-BCG-treated groups. Aggressive BCG treatment may need to be considered in patients with high-risk NMIBC and pyuria.

Asymptomatic hydronephrosis following hysterectomy is generally transient. Here, we present the case of a 52-year-old woman who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for benign indications. Computed tomography (CT) to examine bleeding on the second postoperative day incidentally revealed bilateral grade II hydronephrosis. Asymptomatic hydronephrosis was not reevaluated, and gynecological outpatient follow-up was terminated with a normal creatinine level on postoperative day 43. On postoperative day 107, the patient noticed weight gain of 10 kg, decreased urine output, and generalized edema. The serum creatinine level was elevated to 5.4 mg/dL, and CT revealed bilateral grade III hydronephrosis. Urgent bilateral ureteral stenting was performed to treat stenosis of the distal ureters that caused postrenal failure. Ureteroneocystostomy was performed for strict stenosis of the right ureter at 10 months postoperatively. Histological examination of the resected distal ureter showed inflammation and fibrosis. Asymptomatic hydronephrosis developing after hysterectomy progress to delayed postrenal failure.

OBJECTIVES: The purpose of this study was to investigate intraductal carcinoma of the prostate (intraductal carcinoma) and significant cancer (SC) in patients with small tumor volume (<0.5 cm3 ) in prostatectomy specimens. METHODS: Data from 639 patients undergoing radical prostatectomy between April 2006 and December 2017 at Chiba University Hospital and 2 affiliated institutions were retrospectively reviewed. Tumor volume in prostatectomy specimens was measured, and with a tumor volume of less than 0.5 cm3 , the presence of intraductal carcinoma and SC was examined. SC was defined as one that did not meet the definition of pathological insignificant cancer (organ-confined cancer, Grade Group 1, tumor volume < 0.5 cm3 ). The number of patients who met four active surveillance (AS) protocols was also examined. RESULTS: A total of 83 patients with tumor volume < 0.5 cm3 were identified in this study population (SC: 43 patients [52%], intraductal carcinoma: 5 patients [6%]). The median follow-up was 34.6 months (range: 18-57 months). Four (5%) developed biochemical recurrence. The number of positive biopsy cores ≥ 2 was an independent predictor of SC in patients with tumor volume < 0.5 cm3 (hazard ratio: 4.39; 95% confidence interval: 1.67-11.56; p = 0.003). In tumor volume < 0.5 cm3 , tumor volume was significantly correlated with the International Society of Urological Pathology Grade Group (1 vs. 4-5, p = 0.002) and the presence of intraductal carcinoma (p = 0.004). In intraductal carcinoma-positive cases, four of five patients (80%) had the predictor of SC, which was two or more positive biopsy cores. Of the four AS protocols, the criteria for Prostate Cancer Research International: Active Surveillance were met most frequently in 46 cases (55%) of tumor volume less than 0.5 cm3 if targeted biopsy by magnetic resonance imaging was available. CONCLUSION: The results of the present study suggest that intraductal carcinoma was present even in cases with small tumor volumes. Grade Group and intraductal carcinoma showed a positive correlation with tumor volume.

Abstract The Prostate Imaging and Reporting and Data System (PI-RADS) version 2.1 (v2.1) has been reported to have an improved reading agreement rate than the prior version. Our study assessed the PI-RADS v2.1 and tumor location in Japanese prostate cancer patients who underwent radical prostatectomy to determine the predictive efficacy of bi-parametric MRI (bp-MRI) for biochemical recurrence (BCR).Retrospective analysis was done on the clinical data from 299 patients who underwent radical prostatectomy at Chiba University Hospital between 2006 to 2018. The median prostate-specific antigen（PSA）before surgery was 7.6 ng/ml. Preoperative PI-RADS v2.1 categories were 1 - 2 /3 /4/ 5 for 35 /56 /138 /70, respectively. Tumor localization at the preoperative MRI was 107 in the transition zone (TZ) and 192 in the peripheral zone (PZ). The duration of BCR-free survival was significantly shortened in the PZ group (p = 0.01). Preoperative PI-RADS category 5, radiological tumor localization, pathological seminal vesicle invasion, and Grade group ≥ 3 of the total prostatectomy specimens were independent prognostic factors of BCR. The four risk factors have the potential to significantly stratify patients and predict prognoses.Radiological tumor localization and PI-RADSv2.1 category using bp-MRI may predict the BCR following radical prostatectomy.

Amino acid transporters are responsible for the uptake of amino acids, critical for cell proliferation. L-type amino acid transporters play a major role in the uptake of essential amino acids. L-type amino acid transporter 1 (LAT1) exerts its functional properties by forming a dimer with 4F2hc. Utilizing this cancer-specificity, research on diagnostic imaging and therapeutic agents for malignant tumors targeting LAT1 progresses in various fields. In hormone-sensitive prostate cancer, the up-regulation of L-type amino acid transporter 3 (LAT3) through the androgen receptor (AR) has been identified. On the other hand, in castration-resistant prostate cancer, the negative regulation of LAT1 through AR has been determined. Furthermore, 4F2hc: a binding partner of LAT1, was identified as the specific downstream target of Androgen Receptor Splice Variant 7: AR-V7. LAT1 has been suggested to contribute to acquiring castration resistance in prostate cancer, making LAT1 a completely different therapeutic target from anti-androgens and taxanes. Increased expression of LAT1 has also been found in renal and bladder cancers, suggesting a contribution to acquiring malignancy and progression. In Japan, clinical trials of LAT1 inhibitors for solid tumors are in progress, and clinical applications are now underway. This article will summarize the relationship between LAT1 and urological malignancies.

(1) Objective: Our study investigated the prognostic value of tumor volume and location in prostate cancer patients who received radical prostatectomy (RP). (2) Methods: The prognostic significance of tumor volume and location, together with other clinical factors, was studied using 557 patients who received RP. (3) Results: The receiver operating characteristic (ROC) curve identified the optimal cutoff value of tumor volume as 2.8 cc for predicting biochemical recurrence (BCR). Cox regression analysis revealed that a tumor in the posterior area (p = 0.031), peripheral zone (p = 0.0472), and tumor volume ≥ 2.8 cc (p &lt; 0.0001) were predictive factors in univariate analysis. After multivariate analysis, tumor volume ≥ 2.8 cc (p = 0.0225) was an independent predictive factor for BCR. Among them, a novel risk model was established using tumor volume and location in the posterior area and peripheral zone. The progression-free survival (PFS) of patients who met the three criteria (unfavorable group) was significantly worse than other groups (p ≤ 0.001). Furthermore, multivariate analysis showed that the unfavorable risk was an independent prognostic factor for BCR. The prognostic significance of our risk model was observed in low- to intermediate-risk patients, although it was not observed in high-risk patients. (4) Conclusion: Tumor volume (≥2.8 cc) and localization (posterior/peripheral zone) may be a novel prognostic factor in patients undergoing RP.

OBJECTIVE: Novel androgen receptor axis-targeted agents (ARATAs) have been developed for mCRPC and improved overall survival (OS). Here, we aimed to find predictors who will receive the greatest benefits from ARATAs. METHODS: We previously performed a multicenter study to identify prognostic factors for metastatic hormone-sensitive prostate cancer (mHSPC, n = 148) and mCRPC (n = 99), and showed that the bone scan index (BSI) was one of the significant prognostic factors for 3-year OS (PROSTAT-BSI study). mHSPC progressed to mCRPC (n = 101), for which 69 patients were treated with (n = 39) or without ARATAs (n = 30, prior to the approval of ARATAs). The 69 patients were divided into two groups according to patient factors, and these cohorts were further divided into two subgroups by usage of ARATAs. OS was compared between subgroups in each group. RESULTS: The predictors were age (<71.4 years), serum levels of C-reactive protein (≥0.16 ng/ml) and alkaline phosphatase (≥548 U/L), time to PSA progression after ADT (<8.9 months), the lowest PSA level (≥1 ng/ml) after ADT, and the rate of PSA decline 3 months after ADT (<0.987), whereas hemoglobin levels, PSA before ADT, Gleason scores, existence of visceral metastases, and BSI were not. CONCLUSIONS: The present study identified predictors for the effectiveness of ARATAs. The number of bone metastases (≒BSI), existence of visceral metastases, and Gleason scores, which were identified as high-risk factors in the LATITUDE study and disease volume in CHAARTED criteria, did not appear to be useful for predicting effectiveness from ARATAs.

Carbon-ion radiotherapy (CIRT) is a high-dose intensive treatment, whose safety and efficacy have been proven for prostate cancer. This study aims to evaluate the outcomes of CIRT in elderly patients with prostate cancer. Patients aged 75 years or above at the initiation of CIRT were designated as the elderly group, and younger than 75 years as the young group. The overall survival (OS), disease-specific survival (DSS), biochemical control rate (BCR), biochemical relapse-free survival (BRFS), and adverse events were compared between the elderly and young patients with high-risk prostate cancer treated with CIRT. The elderly group comprised 173 of 927 patients treated for high-risk prostate cancer between April 2000 and May 2018. The overall median age was 69 (range: 45–92) years. The median follow-up period was 91.9 (range: 12.6–232.3) months. The 10-year OS, DSS, BCR, and BRFS rates in the young and elderly groups were 86.9%/71.5%, 96.6%/96.8%, 76.8%/88.1%, and 68.6%/64.3%, respectively. The OS (p &lt; 0.001) was longer in the younger group and the BCR was better in the elderly group (p = 0.008). The DSS and BRFS did not differ significantly between the two groups. The rates of adverse events between the two groups did not differ significantly and no patient had an adverse event of Grade 4 or higher during the study period. CIRT may be as effective and safe in elderly patients as the treatment for high-risk prostate cancer.