Tumour Seeding in the Tract of Percutaneous Renal Tumour Biopsy: A Report on Seven Cases from a UK Tertiary Referral Centre.

The role of percutaneous renal tumour biopsy (RTB) in the management of radiological indeterminate renal masses is long established. Patients with small renal masses who have biopsy-proven renal cell carcinoma (RCC) may be offered surgery, ablative therapy, or active surveillance, and RTB can provide diagnostic tissue from patients with metastatic disease who might benefit from systemic therapy. Current guidelines suggest that tumour seeding along the needle tract is anecdotal, but several cases have been reported recently, although some have been associated with lack of a coaxial sheath. We report on seven patients who underwent surgical resection of RCC in our tertiary referral institution following diagnostic RTB between 2014 and 2017 for whom RTB tract seeding by tumour was identified on histological examination of the resection specimen. One of these patients subsequently developed local tumour recurrence at the site of the previous biopsy.

The incidence of chronic scrotal pain after vasectomy: a prospective audit.

OBJECTIVE: To assess the extent of scrotal pain in men before and after vasectomy, to produce accurate data for the benefit of men considering this procedure, and hence improved informed consent about the outcomes, as chronic scrotal pain after vasectomy is a poorly quantified clinical problem. PATIENTS AND METHODS: Between November 2004 and January 2006 nine surgeons carried out vasectomies in 625 men (mean age 39.9 years, sd 5.6) under local anaesthesia. A questionnaire was devised to establish the presence of any scrotal or testicular pain, and to characterize this discomfort; 6 months after the procedure a modified version of the same questionnaire was administered. RESULTS: In all, 593 (94.7%) men returned the preoperative questionnaires and were entered into the study; 488 (82.2%) of these completed the follow-up questionnaire, giving a mean (sd) follow-up of 6.8 (1.6) months. In all, 65 men reported new-onset scrotal pain at 7 months (14.7%). The mean visual analogue score for this pain was 3.4/10. Four men (0.9%) in the responding group described pain after vasectomy as 'quite severe and noticeably affecting their quality of life'. CONCLUSION: At 7 months after vasectomy about 15% of previously asymptomatic men have some degree of scrotal discomfort. These early data indicate that chronic scrotal pain after vasectomy is a genuine entity, but a longer-term follow-up in this group will be important to allow further evaluation of how this pain develops with time.

Up-regulation of endothelial delta-like 4 expression correlates with vessel maturation in bladder cancer.

PURPOSE: Angiogenesis and vascular endothelial growth factor (VEGF) expression are associated with a poor outcome in bladder cancer. To understand more about the mechanisms, we studied the role of delta-like 4 (DLL4), an endothelial-specific ligand of the Notch signaling pathway, in bladder cancer angiogenesis. EXPERIMENTAL DESIGN: The expression of DLL4, CD34, and VEGF were studied in a cohort of 60 bladder tumors and 10 normal samples using quantitative PCR. In situ hybridization was used to study the pattern of DLL4 expression in 22 tumor and 9 normal samples. Serial sections were also stained for CD34 and alpha-smooth muscle actin (alpha-SMA) using conventional immunohistochemistry. RESULTS: The expression of DLL4 was significantly up-regulated in superficial (P < 0.01) and invasive (P < 0.05) bladder cancers. DLL4 expression significantly correlated with CD34 (P < 0.001) and VEGF (P < 0.001) expression. The in situ hybridization studies showed that DLL4 was highly expressed within bladder tumor vasculature. Additionally, DLL4 expression significantly correlated with vessel maturation as judged by periendothelial cell expression of alpha-SMA, 98.7% of DLL4-positive tumor vessels coexpressed alpha-SMA, compared with 64.5% of DLL4-negative tumor vessels (P < 0.001). High DLL4 expression may have prognostic value in superficial and invasive bladder. CONCLUSION: DLL4 expression is associated with vascular differentiation in bladder cancer; thus, targeting DLL4 may be a novel antiangiogenic therapy.

Open partial nephrectomy: outcomes from two UK centres.

OBJECTIVE: To define the current achievable outcomes from open partial nephrectomy (OPN) in the UK at a time when other treatments for small kidney tumours are increasingly being advocated. Current knowledge of the effectiveness of OPN is limited by the fact that published data are almost exclusively derived from a very few centres of established world renown. PATIENTS AND METHODS: We retrospectively reviewed 100 consecutive planned OPNs in 90 patients at two UK centres; 93 operations were for suspected cancer. The median (range) tumour size was 3.8 (1.2-9) cm. In all, 42 OPNs were imperative for patients with a single kidney (14), synchronous bilateral tumours (20), or renal impairment alone (eight). In 42 patients with a tumour of < or = 4 cm and a normal contralateral kidney the decision to do OPN was considered elective. There were 10 additional operations in seven patients with Von Hippel-Lindau (VHL) disease. In all, 21 OPNs were in the context of a single kidney. RESULTS: In all, 95 OPNs were successfully completed; one operation was abandoned and there were four nephrectomies, including two for bleeding, one for a positive margin on frozen-section analysis, and one for multifocal tumours. The median warm/cold ischaemia time was 20/33 min. The intraoperative/early complication rate was 36%, including a major complication rate of 11% and re-operation rate for primary bleeding of 3%. Of 36 complications, 30 (83%) were in 23 patients with either an imperative indication or VHL. Complications were more common in the imperative/VHL group (59%) than in the elective/other group (12%). Renal function was preserved in 80 of 100 (80%) OPNs overall. Creatinine levels returned to baseline in 11 of 21 (50%) patients with renal impairment before OPN and in 12 of 20 (60%) with a single kidney, whilst five of 21 (24%) with a single kidney needed dialysis after OPN. The median (range) stay after surgery was 6 (3-50) nights. A malignant diagnosis was confirmed in 76 of 93 (82%) specimens on final histopathology. There were 11 of 100 (11%) positive margins, one managed by immediate conversion to nephrectomy and the remaining 10 managed expectantly. After a median (range) follow-up of 24 (1-69) months there were no deaths from kidney cancer, but three patients had local recurrences and two others had developed metastatic recurrence. CONCLUSION: OPN is complex surgery, especially in the imperative setting, but very good results are achievable outside established centres of world renown. It provides good cancer control in the short term with low renal morbidity. These results may act as a reference point in the UK by which to compare results of new treatments for kidney cancer.

Up-regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function.

The Notch signaling pathway and the delta-like 4 ligand (DLL4) play key roles in embryonic vascular development. Many of the pathways involved in embryonic vascular development also play important roles in tumor angiogenesis. In this study, we assessed the expression of DLL4 in primary renal cancer and investigated the biological function of DLL4 in primary endothelial cells. Using real-time quantitative PCR and in situ hybridization, we showed that the expression of DLL4 was up-regulated within the vasculature of clear cell-renal cell carcinoma almost 9-fold more than normal kidney and was correlated with the expression of vascular endothelial growth factor (VEGF). The expression of DLL4 in endothelial cells was up-regulated by VEGF and basic fibroblast growth factor synergistically, and by hypoxia through hypoxia-inducible factor 1alpha. Down-regulation of DLL4 expression with RNA interference led to decreased expression of HEY1 and EphrinB2, and the inhibition of endothelial cell proliferation, migration, and network formation, all of which are important processes in tumor angiogenesis. The inhibition of proliferation occurred via the induction of cell cycle arrest in G0-G1 by increased expression of p21 and decreased phosphorylation of retinoblastoma. We conclude that an optimal window of the DLL4 expression is essential for tumor angiogenesis and that selective modulation of the DLL4 expression within human tumors may represent a potential novel antiangiogenic therapy.