Microvessel density as a prognostic factor in penile squamous cell carcinoma.

OBJECTIVE: To examine the potential effect of tumor-induced angiogenesis in squamous cell carcinoma of the penis as a possible prognostic factor. PATIENTS AND METHODS: Immunohistochemistry was preformed to detect microvessels in tumor samples of 64 patients with squamous cell carcinoma of the penis. We used a monoclonal mouse antibody directed against CD34 antigen. Only 61 (30 with and 31 without metastasis) patients had good staining properties and were included. After immunostaining, the entire tumor section was scanned microscopically at low power (× 40) to identify hot spots within the tumor and at its periphery. Individual tumor microvessels were then counted under high power (× 200) to obtain a vessel count in a defined area, and the mean of the 3 highest microvessel counts was taken as the microvessel density (MVD). Microvessel counting was performed using a computer-aided image analysis system. The nodal status was based on histopathologic examination or an uneventful follow-up ≥ 2 years. RESULTS: The 5-year overall survival (OAS) was 75% and 30 % for those with high and low peritumoral MVD, respectively (log rank P = 0.01). No difference was noticed within the tumor with regard to high (5-year OAS of 65.03%) and low (5-year OAS of 60.56%) intratumoral MVD (log rank P = 0.99). The mean intratumoral MVD was 32.35 (3.16), 37.94 (3.35), and 62.66 (5.47) in T1, T2, and T3 respectively (ANOVA P = 0.0006), with increasing tendency. The mean peritumoral MVD was 55.91 (5.60), 56.8 (4.00), and 78.86 (8.71), respectively (P = 0.06). No correlation between MVD lymph node status and tumor grade was seen (P > 0.05). CONCLUSION: In our group of patients, a high peritumoral MVD was associated with a better 5-year OAS. However, for a reliable and reproducible assessment of tumor angiogenesis in penile squamous cell carcinoma, validation procedures and quality control protocols are mandatory.

External validation of the proposed T and N categories of squamous cell carcinoma of the penis.

OBJECTIVES: The aim of this study was to validate recently proposed modifications to the current TNM classification of penile squamous cell carcinoma (PSCC) by using data from four German urological centers. METHODS: We identified 89 patients treated for histologically confirmed PSCC between 1996 and 2008 and reclassified them according to the proposed TNM staging revisions. The proposed changes restricted T2 to tumoral invasion of the corpus spongiosum, whereas invasion of the corpus cavernosum was considered as T3. No changes were made to T1 and T4. Furthermore, N1 was limited to unilateral and N2 to bilateral inguinal lymph node involvement regardless of their number. Pelvic lymph node involvement and fixed lymph node were considered as N3 tumors. The range of follow up after initial treatment was 1-142 months (mean 38). RESULTS: Node-negative cases following the current classification were 65.2% (30/46), 48.5% (16/33) and 87.5% (7/8) for T1, T2 and T3, respectively. According to the proposed classification, N0 cases were markedly reduced in the T3 group (55.5%, 10/18) and relatively changed in the T2 group (56.5%, 13/23). T4 patients had no negative disease status. The 3-year disease-specific survival (DSS) rates for the proposed categories were 85.4%, 71.6% and 62.4% for T1, T2 and T3, respectively. For the current categories, the 3-year DSS rates were 85.4%, 66.9% and 100% for T1, T2 and T3, respectively. The 3-year DSS of the current N categories was 78.7%, 51% and 13.3% for N1, N2 and N3, respectively. According to the newly proposed categories, the 3-year DSS was 70%, 50% and 13.3% for N1, N2 and N3, respectively. CONCLUSION: Tumor and nodal staging of the newly proposed TNM classification show a more distinctive survival compared to the current one. However, a multi-institutional validation is still required to further corroborate the proposed modifications.

Histological detection of minimal metastatic disease in inguinal non-sentinel lymph nodes in penile cancer.

UNLABELLED: The aim of this study was to detect lymphatic spread by serial step-section technique in non-sentinel lymph nodes (NSLNs), which were earlier assessed as negative by histological examination. PATIENTS AND METHODS: Inguinal dissection specimens of 13 men with penile cancer were investigated. The LNs were sectioned at multiple levels (150 mum-intervals) and then H&E- and immuno-stained for cytokeratin (Lu-5). RESULTS: 196 LNs of 13 men were examined. In 2 out of 13 patients (15%) previously ranked as pN0, minimal lymph node involvement was detected by serial step sections and both immunohistochemistry and H&E staining. Both patients have had an uneventful follow-up of currently 62 and 16 months. CONCLUSION: Conventional histological examination of NSLNs fails to detect lymphatic spread in penile cancer. Step-section technique at 3 section levels, rather than immunohistochemistry, helps to safely detect minimal metastatic disease. The prognostic relevance is still unclear and has to be investigated in larger cohort studies.

Bicycle riding and erectile dysfunction: a review.

INTRODUCTION: For many years, reports in the literature have implicated bicycle riding as causing increased risk of erectile dysfunction (ED). Perineal compression during cycling has been associated with the development of sexual complications. AIM: To review current literature on the rationale for ED from bicycle riding and outcome of bicycle riding on erectile function and to present available research on preventative measures specifically regarding bicycle riding. METHODS: A systematic comprehensive literature review. RESULTS: There is a significant relationship between cycling-induced perineal compression leading to vascular, endothelial, and neurogenic dysfunction in men and the development of ED. Research on female bicyclists is very limited but indicates the same impairment as in male bicyclists. Preventative measures including use of a properly fitted bicycle, a riding style with a suitable seat position and an appropriate bicycle seat can help prevent impairment of erectile function. CONCLUSIONS: There is a need for further research on safe bicycle and bicycle seat design and investigations that address the underlying mechanisms leading to cycling-related sexual dysfunction in both male and female bicyclists.

Lymphatic spread in squamous cell carcinoma of the penis is independent of elevated lymph vessel density.

OBJECTIVE: To examine the potential effect of tumour-induced lymphangiogenesis in squamous cell carcinoma of the penis as a possible mechanism responsible for lymphatic spread. PATIENTS AND METHODS: Specimens from 65 patients with invasive tumours (31 with and 34 without metastases) were evaluated for lymphatic vessel density (LVD) by the 'hot-spot' method as the density of lymphatic endothelium hyaluronan receptor (LYVE-1)-positive lymphatic vessels per unit area of tissue. LVD was examined in peritumoral, intratumoral and normal tissue areas. The LVD of each tumour in these locations was calculated as the mean of the three highest lymph vessel counts in three to five hot-spots. The nodal status was based on histopathological examination or an uneventful follow-up of >or=2 years. RESULTS: In all patients the mean (SD) peritumoral LVD of 8.05 (3.14)/0.75 mm(2) was significantly higher than for intratumoral and normal tissue, of 4.67 (2.58) and 5.20 (1.87), respectively (P < 0.001). The slightly lower intratumoral LVD than in normal tissue was not significant. The peritumoral LVD was 8.07 (3.29) in metastatic and 8.03 (3.03) in non-metastatic carcinomas. The intratumoral LVD was 5.13 (3.01) in node-positive carcinomas and 4.28 (2.15) in tumours with no lymphatic node metastasis (LNM). Comparing tumours with and without LNM, there was no statistically significant difference between intra- and peritumoral LVD. CONCLUSION: Increased LVD does not significantly affect the lymphatic spread in penile carcinomas, indicating that there must be alternative mechanisms that selectively enable tumour cells to invade lymph vessels and to metastasize into the lymph nodes.

Lymph-node metastases in intermediate-risk squamous cell carcinoma of the penis.

OBJECTIVE: To evaluate the metastatic risk of pT1 G2 squamous cell carcinoma (SCC) of the penis. PATIENTS AND METHODS: We retrospectively reviewed 20 patients with pT1 G2 penile SCC and determined their groin status at first presentation, their nodal status after inguinal lymph node dissection and their follow-up for at least 18 months. RESULTS: Four of the 20 patients had a clinically positive groin; three of these were found to have lymph node metastases. Among the 16 patients with a clinically negative groin, one of five who had surgical lymph node staging had lymph node metastases. During surveillance six of 11 patients developed lymph node metastases. There was lymphovascular invasion in three of 10 patients with lymph node metastases. CONCLUSIONS: As the metastatic risk of pT1 G2 penile SCC was 50% in this series of patients, and 44% in those with an initially negative groin, surgical staging of inguinal lymph nodes is recommended in patients with pT1 G2 penile SCC.