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About 1 month after the first TUR, NBI cold-cup biopsies were taken from areas suspicious for urothelial cancer at the end of an extensive white-light second TUR protocol including: (i) resection of the scar of the primary tumour; (ii) resection of any overt or suspected urothelial lesions; and (iii) six random cold-cup biopsies of healthy mucosa. RESULTSIn 2008, 47 consecutive patients were recruited after giving written consent (median age 62 years, range 49-83, 39 men and eight women). Nine patients (19%) had macroscopic or microscopic high-grade NMI urothelial cancer, whereas one was reassessed as having muscle-invasive disease at the white-light second TUR plus the six random biopsies. NBI biopsies were taken in 40 of the 47 patients and detected six more patients with high-grade cancerous tissue (13%). In all 16 of the 47 patients (34%) were found to have residual/recurrent cancer using our extensive protocol of second TUR followed by NBI biopsies. CONCLUSIONSAdding NBI biopsies at the end of an extensive second TUR protocol in patients with newly diagnosed high-grade NMIBC can lead to the identification of patients with otherwise missed high-grade residual/ recurrent urothelial carcinoma. KEYWORDSurinary bladder, neoplasm, cystoscopy, recurrence, diagnostic imaging Study Type -Diagnostic (case series) Level of Evidence 4 OBJECTIVETo determine if narrow-band imaging (NBI) can be used to detect high-grade cancerous lesions missed with the white light at the time of a second transurethral resection (TUR) of high-grade non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODSConsecutive patients with newly diagnosed high-grade NMIBC were enrolled in a prospective observational study. Patients with incomplete resection or absence of muscle tissue in the specimen were excluded.

Natural killer (NK) cells, effector lymphocytes of the innate immunity, have been shown to be altered in several cancers, both at tissue and peripheral levels. We have shown that in Non-Small Cell Lung Cancer (NSCLC) and colon cancer, tumour associated circulating NK (TA-NK) and tumour infiltrating NK (TI-NK) exhibit pro-angiogenic phenotype/functions. However, there is still a lack of knowledge concerning the phenotype of peripheral blood (PB) NK (pNK) cells in prostate cancer (PCa). Here, we phenotypically and functionally characterized pNK from PCa patients (PCa TA-NKs) and investigated their interactions with endothelial cells and monocytes/macrophages. NK cell subset distribution in PB of PCa patients was investigated, by multicolor flow cytometry, for surface antigens expression. Protein arrays were performed to characterize the secretome on FACS-sorted pNK cells. Conditioned media (CM) from FACS-sorted PCa pTA-NKs were used to determine their ability to induce pro-inflammatory/pro-angiogenic phenotype/functions in endothelial cells, monocytes, and macrophages. CM from three different PCa (PC-3, DU-145, LNCaP) cell lines, were used to assess their effects on human NK cell polarization in vitro, by multicolor flow cytometry. We found that PCa pTA-NKs acquire the CD56brightCD9+CD49a+CXCR4+ phenotype, increased the expression of markers of exhaustion (PD-1, TIM-3) and are impaired in their degranulation capabilities. Similar effects were observed on healthy donor-derived pNK cells, exposed to conditioned media of three different PCa cell lines, together with increased production of pro-inflammatory chemokines/chemokine receptors CXCR4, CXCL8, CXCL12, reduced production of TNFα, IFNγ and Granzyme-B. PCa TA-NKs released factors able to support inflammatory angiogenesis in an in vitro model and increased the expression of CXCL8, ICAM-1, and VCAM-1 mRNA in endothelial cells. Secretome analysis revealed the ability of PCa TA-NKs to release pro-inflammatory cytokines/chemokines involved in monocyte recruitment and M2-like polarization. Finally, CMs from PCa pTA-NKs recruit THP-1 and peripheral blood CD14+ monocyte and polarize THP-1 and peripheral blood CD14+ monocyte-derived macrophage towards M2-like/TAM macrophages. Our results show that PCa pTA-NKs acquire properties related to the pro-inflammatory angiogenesis in endothelial cells, recruit monocytes and polarize macrophage to an M2-like type phenotype. Our data provides a rationale for a potential use of pNK profiling in PCa patients.

TURis offers the patient the same results as monopolar technology guaranteeing maximum safety without increasing the incidence of urethral strictures.

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