Lymph node metastasis in intermediate-risk penile squamous cell cancer: a two-centre experience.

BACKGROUND: The risk of lymph node (LN) metastasis in G2T1 penile cancer has been previously reported as 0-50% and is classified as "intermediate" in the European Association of Urology (EAU) guidelines. The management of impalpable regional nodes in this cohort of patients remains contentious and varies among treatment centres depending on tumour factors and local resources. OBJECTIVES: To establish the risk of LN metastasis in G2T1 disease. DESIGN, SETTINGS, AND PARTICIPANTS: We interrogated the databases of two referral centres for penile cancer. MEASUREMENTS: Out of 902 patients, 117 (13%) patients were identified with G2T1 cancers. Those with palpable inguinal nodes (cN1) underwent early inguinal LN dissection (iLND). Those with clinically node negative (cN0) inguinal basins were either observed or surgically staged with iLND or by dynamic sentinel LN biopsy (DSLNB). Median follow-up was 44 mo, with minimum follow-up of 6 mo. RESULTS AND LIMITATIONS: Fifteen of 117 (13%) patients with G2T1 cancer had LN metastasis at initial staging or during follow-up. Six of 12 (50%) cN1 patients had histologically proven LN metastasis on iLND. One hundred five patients were cN0 at presentation. Ten cN0 patients had prophylactic iLND, none of which yielded LN metastasis; 5 of 64 (8%) cN0 patients who had DSLNB had tumour-positive LNs, and 4 of 31 (13%) cN0 patients who were observed developed LN metastasis during follow-up. In cN0 patients, the risk of LN metastasis at initial staging or during surveillance was 9%. CONCLUSIONS: We consider that in cN0 patients with G2T1 penile cancer, the risk of developing metastases during surveillance warrants surgical and potentially curative staging. However, the morbidity of prophylactic bilateral iLND is too great to justify a detection rate of 9%. Less morbid alternatives such as DSLNB are advisable in G2T1 disease.

The effect of serotonin and serotonin antagonists on bladder cancer cell proliferation.

OBJECTIVE: To investigate the role of serotonin (5-hydroxytryptamine, 5HT) and its antagonists in the proliferation of high-grade bladder cancer cells (HT1376), as high-grade bladder cancer has a rapid rate of progression, invasion and recurrence, and 5HT antagonists inhibit the growth of the prostate cancer cell line (PC3). MATERIALS AND METHODS: HT1376 (human grade III transitional cell carcinoma) cells were incubated with either 5HT or 5HT antagonists (5HT(1A), 5HT(1B), 5HT(1D), 5HT(2), 5HT(3) and 5HT(4)). After 72 h, cell viability was assessed using the crystal violet assay. The presence of 5HT receptor subtypes on HT1376 cells and sections of human bladder cancer tissue was determined by immunohistochemistry and Western blot analysis. RESULTS: 5HT caused a dose-dependent increase in the proliferation of HT1376 cells. The maximum increase in cell proliferation (12%; 12 samples, P < 0.001) was at 10(-8)m as compared to the control at 72 h. At 10(-4)m, 5HT(1A) antagonist (NAN-190 hydrobromide) and 5HT(1B) antagonist (SB224289 hydrochloride) had a 10% (12 samples, P < 0.001) and 93% (12, P < 0.001) inhibitory effect on HT1376 cell growth, respectively, compared to the control at 72 h. There was immunostaining for 5HT(1A) and 5HT(1B) receptors in HT1376 cells and malignant bladder tissue, confirming the presence of these two receptor subtypes. Western blot analysis showed the presence of 5HT(1A) and 5HT(1B) receptor proteins with bands of 46 kDa and 43 kDa, respectively. CONCLUSION: 5HT(1A) and to a greater extent 5HT(1B) antagonists significantly inhibit bladder cancer cell growth. This effect is probably mediated via the 5HT(1A) and 5HT(1B) receptors. These results highlight the potential use of 5HT(1A) and 5HT(1B) antagonists in the treatment of bladder cancer.