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Background: To investigate variations in diagnostic performance of photodynamic diagnosis (PDD) according to surgical experience., Methods: Data were extracted from patients having pT1 or lower primary tumors that underwent PDD-assisted transurethral resection of bladder tumors (TURBT) with orally 5-amibolevulinic acid at our institute. Surgical experience was categorized by urological experience (first-year and second-year) and PDD experience (<10, 10-19, and ≥20 cases). Sensitivity, specificity, and accuracy rates were calculated based on PDD or white light (WL) findings and pathologic diagnosis. The bladder neck, trigone, and prostatic urethra were defined as areas with a high probability of tangential effect., Results: A total of 108 patients and 343 specimens were extracted. The second-year surgeons had significantly higher accuracy rates than first-year surgeons (81.5 % vs. 69.0 %, p = 0.013), while PDD experience did not significantly affect accuracy rates (76.5, 75.5, and 69.0 %). In addition, the accuracy rate was also significantly lower in tangential effect areas (59.6 % vs. 80.8 %). Multivariate analysis identified urological experience as a significant factor improving accuracy rate (odds ratio [OR] 2.14) while tangential effects substantially reduced accuracy rate (OR 0.37). Notably, combining both PDD and WL resulted in a sensitivity exceeding 94 %, even in first-year urology residents and tangential effect areas., Conclusions: Urological experience had a greater impact on diagnostic performance of PDD compared to PDD experience. The combination of PDD and WL findings may improve sensitivity and reduce the possibility of missed diagnoses for less experienced urology residents., Competing Interests: Declaration of competing interest We confirm no conflicts of interest related to the article., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The tumor microenvironment (TME) modulates therapeutic response and prognosis in patients with bladder cancer (BC). The roles of two phospholipase D (PLD) isoforms, PLD1 and PLD2 (hydrolysis of phosphatidylcholine to phosphatidic acid), in cancer cells have been well-studied in numerous cancer types, but their roles in the TME remain unclear. We used a mouse BC Pld2-KO carcinogenesis model and global transcriptomic analysis to reveal that PLD2 was significantly involved in BC progression through immunosuppressive pathways in the TME. We therefore focused on PLD2 and tumor-associated macrophages (TAMs), which were increased in Pld2-KO mice and further associated with poor prognoses in BC patients. In vitro, we found that Pld2-KO mouse TAMs had significantly enhanced proliferation, correlating closely with increased interleukin-1β (IL-1β) production. These results indicate that PLD2 suppresses BC progression by regulation of IL-1β secretion from TAMs in the TME, suggesting that PLD2 could serve as a potential therapeutic target for modifying the TME in BC., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Combination therapy of nivolumab and ipilimumab (NIVO + IPI) for metastatic renal cell carcinoma (mRCC) has shown efficacy, but approximately 20% of patients experience disease progression in the early stages of treatment. No useful biomarkers have been reported to date. Therefore, it is desirable to identify biomarkers to predict treatment responses in advance. We examined the tumor microenvironment (TME)-related gene expression in mRCC patients treated with NIVO + IPI, between the response and non-response groups, using tumor tissues, before administering NIVO + IPI. In TME-related genes, TNFSF9 expression was identified as a candidate for the predictive biomarker. Its expression discriminated between the response and non-response groups with 88.89% sensitivity and 87.50% specificity (AUC = 0.9444). We further analyzed the roles of TNFSF9 in TME using bioinformatics from The Cancer Genome Atlas (TCGA) cohort. An adaptive immune response was activated in the TNFSF9 -high-expression tumors. Indeed, T follicular helper cells, plasma B cells, and tumor-infiltrating CD8 + T cells were increased in the tumors, which indicates the promotion of humoral immunity due to enhanced T-B interactions. However, as the number of regulatory T cells (Treg) increased in the tumors, the percentage of dysfunctional T cells also increased. This suggests that not only PD-1 but also CTLA-4 inhibition may have suppressed Treg activation and improved the therapeutic effect in the TNFSF9 high-expression tumors. Therefore, TNFSF9 may predict the therapeutic efficacy of NIVO + IPI for mRCC and allow more appropriate patient selection., Competing Interests: Chia-Ling Wu and Yi-Hua Jan were employed by ACT Genomics, Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Case 1 : A 75-year-old man was emergently admitted to our hospital with a complaint of continuous bleeding from the ileal conduit. The conduit was constructed by a total pelvic resection for sigmoid colon cancer that invaded the urinary bladder 24 years ago. Swollen cutaneous mucosa was seen around the ileal conduit, but no obvious bleeding spot was observed. The contrast-enhanced computed tomographic (CT) scan and 3D visualization revealed varices extending to the abdominal wall. Percutaneous transhepatic embolization successfully stopped the bleeding, but it was needed again after two years. Case 2 : A 72-yearold man with a history of open cystectomy and ileal conduit for bladder cancer came to our hospital two years after the surgery, complaining of continuous bleeding from the conduit. The skin around the stoma site was discolored purple, but no obvious bleeding site or bloody urine was observed. The CT scan similar to Case 1 revealed varices in the ileal conduit, and percutaneous transhepatic embolization successfully stopped the bleeding, but it was needed again after five months. After that, three months passed without recurrence.

Postoperative femoral nerve palsy (FNP) is a rare complication associated with urologic surgery. Inappropriate use of retractors, use of lithotomy position, and prolonged surgery that lead to the femoral nerve compression have been reported as risk factors for FNP. Here, we report two cases of FNP after pelvic surgery. Case 1: A 47-year-old woman underwent ureterocystoneostomy for a giant ureterocele. On the first postoperative day, she developed muscle weakness and paresthesia in the left lower leg. An orthopedic surgeon diagnosed her with FNP associated with the surgery. Case 2: An 82-year-old woman underwent radical cystectomy for invasive bladder cancer. On the second postoperative day, she developed extension deficit in the left lower leg and was diagnosed with an iatrogenic FNP. Although this complication is infrequent, at onset, it leads to difficulty in walking and gait disturbance in the patient. As a result, it greatly reduces the patient's postoperative quality of life. Therefore, preventive measures should be taken to reduce the risk of this postsurgical nerve injury, such as appropriate placement of retractors and proper patient positioning during the operation.