Kagenori Ito

Objectives: To evaluate perioperative safety, pathological outcomes, and oncological outcomes of en bloc resection of bladder tumor (ERBT) in a large multicenter real‐world cohort. Methods: We retrospectively analyzed 668 patients who underwent ERBT at five institutions. Perioperative and pathological outcomes were assessed in the overall cohort. Recurrence‐free survival (RFS) was evaluated in patients with pathologically confirmed non‐muscle‐invasive bladder cancer (NMIBC) without a history of upper tract urothelial carcinoma ( n = 551). Clinicopathological prognosticators of recurrence were identified using Cox proportional hazards regression. Results: The median age was 73 years, and the median maximum tumor diameter was 15 mm. The median operative time and postoperative catheterization period were 48 min and 3 days, respectively. Perioperative complications occurred in 60 patients (9.0%), including eight (1.2%) with Clavien–Dindo Grade III or higher complications. Detrusor muscle was identified in 77.2% of evaluable specimens. Final pathology showed pTa, pT1, pTis, and pT2 disease in 377 (56.4%), 239 (35.8%), 16 (2.4%), and 25 patients (3.7%), respectively. With a median follow‐up of 42 months, the estimated 1‐, 2‐, and 5‐year RFS rates were 80.9%, 73.2%, and 57.1%, respectively. RFS did not differ significantly between pTa and pT1 disease (log‐rank p = 0.39). Patients presenting with recurrent tumors had a significantly higher risk of subsequent intravesical recurrence than those with primary tumors (HR 2.06, 95% CI 1.38–3.07; p < 0.001). Conclusions: ERBT demonstrated favorable perioperative safety and acceptable oncological outcomes in this large multicenter cohort. Post‐ERBT recurrence remained strongly influenced by prior recurrence history, highlighting the importance of risk‐adapted postoperative management.

Recent genetic analyses have revealed that bilateral pheochromocytoma (PCC) is more frequently associated with hereditary syndromes, such as von Hippel-Lindau (VHL) disease and multiple endocrine neoplasia type 2 (MEN2), than previously recognized. Although bilateral adrenalectomy has traditionally been considered the standard treatment for bilateral PCC, it inevitably results in permanent adrenal insufficiency, requiring lifelong steroid replacement and increasing the risk of adrenal crisis. As an alternative strategy, adrenal-sparing surgery has been proposed to preserve adrenal function; however, concerns remain regarding the risk of tumor recurrence in the remnant adrenal tissue. We report four cases of bilateral PCC treated with adrenal-sparing surgery at The Jikei University Hospitals. Adrenal-sparing surgery was successfully attempted in all patients, and all avoided long-term steroid dependence. Genetic testing confirmed VHL disease in one patient in the overall cohort. Based on family history and clinical features, VHL disease was suspected in one additional patient, and MEN2 was suspected in two patients. Based on our experience and a review of the literature, adrenal-sparing surgery allows preservation of adrenal function and can eliminate the need for postoperative steroid replacement in many patients with bilateral PCC. Although the risk of recurrence in the residual adrenal gland may be higher than that after total adrenalectomy, recurrence at other sites and overall mortality appear comparable between the two surgical approaches. Therefore, adrenal-sparing surgery represents a valuable surgical option in carefully selected patients. Furthermore, recent studies have identified pathogenic mutations in several genes associated with bilateral PCC, with incidence and prognosis varying according to genetic background. Gene mutations are more likely in younger patients, those with tumors ≥5 cm, paragangliomas (PGLs), norepinephrine-secreting tumors lacking epinephrine production, and individuals with known hereditary syndromes, who also exhibit a higher risk of recurrence. Accordingly, current guidelines recommend lifelong surveillance and individualized management based on genetic and clinical factors.

Prostate cancer (PCa) exhibits a unique propensity to metastasize to bone, where it predominantly generates osteoblastic lesions. The formation of these lesions is a complex and dynamic process driven by reciprocal interactions between tumor cells and the bone microenvironment. Emerging evidence indicates that extracellular vesicles (EVs) play pivotal roles in the establishment of metastatic colonies and disease progression, as well as in local tumor–bone interactions. Through their diverse cargos, including proteins, lipids, and non-coding RNAs, EVs mediate bidirectional communication that regulates osteoclastogenesis, osteoblast activation, and osteocyte function, ultimately reshaping the bone niche to favor tumor growth. Importantly, EVs exhibit dual and context-dependent functions, acting either as promoters or suppressors of malignancy depending on the cellular source and microenvironmental context. These insights highlight EVs not only as mechanistic drivers of PCa bone metastases but also as promising therapeutic targets. Approaches aimed at modulating EV biogenesis, eliminating deleterious EVs, or harnessing EVs as drug delivery vehicles hold significant potential for advancing treatment strategies against PCa bone metastases.

Background: Bladder cancer is one of the most prevalent malignancies, and the mechanisms underlying its progression and the role of the tumor microenvironment (TME) are unclear. Recent advancements in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) enable detailed analysis of the cellular heterogeneity, gene expression, and cell–cell interactions in bladder diseases. Methodology: We conducted a comprehensive search for recent articles that have investigated bladder diseases using scRNA-seq and ST. Results: scRNA-seq and ST have led to significant discoveries in bladder disease research. These technologies have enabled the identification of multiple molecular subtypes within individual tumors and of the mechanisms of treatment resistance. Additionally, molecular differences based on gender have been explored, explaining the heterogeneity of the incidence and progression of bladder cancer. These findings deepen our understanding of the pathology of bladder diseases and highlight the transformative potential of scRNA-seq and ST in identifying novel biomarkers and therapeutic targets. Conclusions: Integrating scRNA-seq and ST has considerably enhanced our understanding of tumor heterogeneity and the tumor microenvironment within tissues. These insights may lead to the development of personalized therapies and the improvement of patient outcomes. Several challenges, such as technical limitations and access difficulties, need to be addressed for the future clinical application of these technologies.

The incidence of prostate cancer (PCa) has increased worldwide in recent years along with the recommendation for prostate-specific antigen testing, and mortality has been declining owing to advances in fragmented and simplified access to treatment care. However, GLOBOCAN (Global Cancer Observatory) data show that this result is not true for all countries. It has been reported that the degree of PCa progression at diagnosis and survival rates differ among racial groups. Based on various comparisons between Caucasians and Asians, it was inferred that survival rates were higher in Asians despite the higher degree of progression at diagnosis, suggesting a better prognosis for life compared with Caucasians. The survey among Asian countries did not reveal any obvious differences among Asian subregions; rather, it inferred that the impact of the level of development among the countries was significant. The development of healthcare systems and medical care could improve PCa survival in developing countries.

Microfluidics is applied in biotechnology research via the creation of microfluidic channels and reaction vessels. Filters are considered to be able to simulate microfluidics. A typical example is the cell culture insert, which comprises two vessels connected by a filter. Cell culture inserts have been used for years to study cell-to-cell communication. These systems generally have a bucket-in-bucket structure and are hereafter referred to as a vertical-type co-culture plate (VTCP). However, VTCPs have several disadvantages, such as the inability to simultaneously observe samples in both containers and the inability of cell-to-cell communication through the filters at high cell densities. In this study, we developed a novel horizontal-type co-culture plate (HTCP) to overcome these disadvantages and confirm its performance. In addition, we clarified the migration characteristics of substances secreted from cells in horizontal co-culture vessels. It is generally assumed that less material is exchanged between the horizontal vessels. However, the extracellular vesicle (EV) transfer was found to be twice as high when using HTCP. Other merits include control of the degree of co-culture via the placement of cells. We believe that this novel HTCP container will facilitate research on cell-to-cell communication in various fields.

Objective: To evaluate the risk factors of perioperative hemodynamic instability in pheochromocytoma, we conducted a systematic search of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-analysis. Methods: In April 2021, we systematically searched PubMed, the Cochrane library, and Scopus for relevant studies on the risk factors of perioperative hemodynamic instability of adrenalectomy in patients with pheochromocytoma, and we subjected the findings from those studies to formal meta-analysis. Results: Our systematic review identified 14 studies involving 1725 patients, of which nine studies with 967 patients were eligible for meta-analysis. The results of meta-analysis showed that tumor size (odds ratio (OR): 1.14 for each increased cm, 95% confidence interval (CI) 1.03–1.26, z = 2.57) and urinary norepinephrine (OR, 1.51: 95% CI 1.26–1.81; z = 4.50) were most closely associated with the occurrence of perioperative hemodynamic instability. Conclusion: These findings suggest that tumor size and urinary norepinephrine are important predictors and risk factors for perioperative hemodynamic instability in adrenalectomy for pheochromocytoma. Such findings may be of value to surgeons and anesthesiologists when considering or preparing for this procedure.

Targeting extracellular vesicle (EV) secretion can have potential clinical implications for cancer therapy, however the precise regulatory mechanisms of EV secretion are not fully understood. Recently, we have shown a novel pathway of EV biogenesis in PCa cell lines, PC3 and PC3M. However, as the characteristics of EVs are divergent even among PCa cell lines, we hypothesized that other pathways or common regulatory pathways of EV biogenesis still exist. Here, we performed quantitative high‐throughput screening to determine the key regulatory genes involved in EV biogenesis in 22Rv1 cells, which secrete a different type of EVs. In total, 1728 miRNAs were screened and miR‐1908 was selected as the potential miRNA regulating EV biogenesis in 22Rv1 cells. Subsequently, we investigated target genes of miR‐1908 using siRNA screening and identified that spermidine synthase (SRM) was the key regulator of EV secretion in 22Rv1 cells. Attenuation of SRM expression significantly inhibited secretion of EVs in 22Rv1 cells, and overexpression of SRM was confirmed in PCa tissues. Furthermore, we found that the number of endosome compartments was increased in cellular cytoplasm after knockdown of the SRM gene. In conclusion, our results showed that miR‐1908‐mediated regulation of SRM can control secretion of EVs in PCa. In addition, these data suggested that the EV secretion pathway was dependent on cellular characteristics.

MicroRNA-based screening identifies the novel regulators of EV secretion from cancer cells.