Anastasios Zervas

The prevalence of bcl-2, p53, and ki-67 immunoreactivity in transitional cell bladder carcinomas and their clinicopathologic correlates

The aim of this study was to investigate the expression of bcl-2, p53 oncoproteins, and Ki-67 antigen in a series of transitional cell bladder carcinomas and its relation to the traditional prognostic indicators and patients survival. One hundred six cases with transitional cell carcinoma (TCC) were examined for detection of bcl-2, p53 proteins, and Ki-67 antigen (MIB1 antibody). Bcl-2 immunohistochemical positivity was observed in 52% of TCCs and in 57% of low-grade and 44% of high-grade TCCs. Bcl-2 was also detected in normal urothelium and dysplastic lesions with basal cell expression, and negative staining was observed in carcinomas in situ. Tumor stage showed a significant inverse correlation with overall bcl-2 positivity. The loss of bcl-2 protein expression in higher-stage TCCs was statistically significant (Pt = .01). p53 protein was overexpressed in 50% of TCCs and more frequently in invasive and in carcinomas in situ than in superficial TCCs (Pt = .03). In contrast, detection of p53 was not observed in normal and dysplastic urothelium. p53 positivity was related to the degree of differentiation and to the stage of the disease (Pf = .01 and Pt = .03, respectively). Concerning Ki-67 antigen, its expression was found in 57.5% of TCCs. There was a strong overall correlation of Ki-67 with tumor stage (Pt = .002) and grade (Pf = .002). Univariate statistical analysis showed that the expression of p53 and Ki-67 was significantly correlated to poor prognosis (P = .02, P = .02, respectively). On multivariate analysis, none of these markers but only stage and grade were significantly correlated to prognosis (P = .02, P = .02, respectively). These findings suggest that overexpression of bcl-2 protein may be an early event in tumorigenesis. Tumors with loss of bcl-2 positivity and overexpression of p53 and Ki-67 had an unfavorable prognosis; however, in multivariate analysis, they had no independent prognostic value.

Nitric oxide synthase and xanthine oxidase activities in the spermatic vein of patients with varicocele : A potential role for nitric oxide and peroxynitrite in sperm dysfunction

PURPOSE The oxidative and reductive stresses within the varicocele veins were estimated. Nitric oxide synthase and xanthine oxidase activities, as well as nitric oxide, S-nitrosothiols and superoxide release within the spermatic vein in patients with varicocele, and the role of the noxious oxidant peroxynitrite formed from nitric oxide and superoxide in sperm dysfunction were determined. MATERIALS AND METHODS Whole blood samples were drawn from a peripheral vein and a dilated varicocele vein before ligation. Nitric oxide synthase, xanthine oxidase, nitric oxide and peroxynitrite were measured by novel spectro-fluorophotometric methods. S-nitrosothiols were estimated by a luminol-chemiluminescence method. Serum and red blood cell antioxidant capacity was determined by a chemiluminescence reaction. RESULTS Serum nitric oxide synthase and xanthine oxidase activities, as well as nitric oxide, peroxynitrite and S-nitrosothiol levels were greater in the spermatic vein compared to the peripheral vein. Serum antioxidant capacity was greater in varicocele veins compared to peripheral veins. In contrast, the antioxidant capacity of red blood cells was less in the varicocele veins, which was consistent with an increased rate of peroxynitrite production. CONCLUSIONS Our data suggest a high oxidative stress due to the release of nitric oxide synthase and xanthine oxidase within the dilated spermatic vein. The reaction resulted in dramatic formation of nitric oxide, peroxynitrite and S-nitrosothiols, which are biologically active. Formation of peroxynitrite from the reaction of nitric oxide with superoxide could be a causative factor for impaired sperm function in patients with varicocele.

Oral estramustine and oral etoposide for hormone-refractory prostate cancer

OBJECTIVES Estramustine and etoposide have been shown to inhibit the growth of prostate cancer cells in experimental models. An in vivo synergism of the two agents, when administered to patients with metastatic prostate cancer refractory to hormone therapy, has been reported. To confirm these results, we administered this combination to a large number of patients with hormone-refractory prostate cancer (HRPC). METHODS Fifty-six patients with metastatic HRPC were treated with oral estramustine 140 mg three times a day and oral etoposide 50 mg/m2/day for 21 days. Therapy was discontinued for 7 days and the cycle was then repeated. Therapy was continued until evidence of disease progression or unacceptable toxicity occurred. To control for the possible interference of an antiandrogen withdrawal effect, all patients discontinued antiandrogen therapy and were not enrolled in the study unless there was evidence of disease progression. RESULTS Forty-five percent of 33 patients with measurable soft tissue disease demonstrated an objective response, which included five complete and ten partial responses. Among 52 patients with osseous disease 17% showed improvement and 50% showed stability of bone scan. Thirty patients (58%) demonstrated a decrease of more than 50% in pretreatment prostate-specific antigen (PSA) levels. The median survival of all patients was 13 months. Good pretreatment performance status, measurable disease response, improvement or stability of bone scan, and PSA response were important predictors of longer survival. CONCLUSIONS We conclude that the combination of estramustine and etoposide is an active and well-tolerated oral regimen in HRPC.

Short- and long-term complications of open radical prostatectomy according to the Clavien classification system.

To assess the use of the Clavien classification system in documenting the complications related to open retropubic radical prostatectomy (RRP).

Evaluation of overexpression of p53 tumor suppressor protein in superficial and invasive transitional cell bladder cancer: Comparison with dna ploidy

OBJECTIVES p53 tumor suppressor gene is considered to play a significant role in carcinogenesis. Mutations in the p53 are the most frequent genetic abnormalities encountered in human malignancies. Our aim was to investigate the expression of p53 oncoprotein in superficial and invasive transitional cell bladder cancer (TCC) as well as its correlation with established prognostic factors, such as histologic grade, tumor stage, DNA content, and survival. METHODS Forty-five patients with superficial TCC (Ta-T1) and 42 with invasive TCC (T2-T4) were included in our study. Material from transurethral biopsy was examined using an immunohistochemical method and the monoclonal antibody Pab 1801. RESULTS p53 tumor suppressor protein was overexpressed in 48.3% of TCC cases and more frequently in invasive than superficial TCCs (P = 0.03) and undetectable in the tumor adjacent to normal tissue. p53 positivity was related to the degree of differentiation and with the stage of the disease of invasive TCCs (P = 0.03 and P = 0.004, respectively), whereas no statistical significance was documented for superficial TCCs. Moreover, p53 overexpression demonstrated a statistical significance with DNA ploidy in superficial Ta-T1 tumors (P = 0.04) and was suggestive in invasive T2-T4 tumors (P = 0.08). There was no correlation of recurrence related to p53-positive superficial tumors (P = 0.29). Patients with p53-positive invasive TCCs showed statistically significant worse survival (P = 0.007), but in multivariate analysis, p53 positivity is not independently related to poor overall survival (P = 0.30). When we combined ploidy and p53 status, we realized that the subset of patients with aneuploidy and p53 positivity had the worst prognosis (P = 0.008). CONCLUSIONS The results suggest the involvement of p53 protein as a late event in bladder carcinogenesis. p53 does not seem to be a prognostic marker for recurrences of superficial tumors and is not independently related to survival. The aneuploidy of tumors correlates with the p53 positivity in bladder cancer. The combined expression of aneuploidy and p53 positivity in invasive tumors has strong association with the survival of patients.

Expression of transforming growth factor β in renal cell carcinoma and matched non-involved renal tissue

TGFβ1 is one of several cytokines produced by proximal tubular and renal cancer cells. Previous studies have been mainly focused on determining plasma or serum TGFβ levels, its effect on RCC cultures, and the expression of TGFβ mRNA. Cancerous and autologous normal kidney samples were obtained from 24 patients treated by radical nephrectomy. TGFβ1 expression was determined using a semi quantitative Western blot analysis and immunohistochemistry. Blot densities and immunohistochemical expression intensities in normal and neoplastic tissue were compared, and subsequently correlated to tumor stage, histological type and nuclear grade. All tissue samples examined expressed TGFβ1; mean tumor to non-involved kidney spot density ratio correlated with advancing stage and higher nuclear grade. The overexpression of TGFβ1 in certain RCCs may partially explain their resistance to the growth suppression action of TGFβ. The correlation with tumor stage and grade indicates a possible role in the development of metastatic potential as well as in host’s immune response modulation.

Neoadjuvant Cisplatin and Interferon-α2B in the Treatment and Organ Preservation of Penile Carcinoma

We investigated the antitumor activity and toxicity of cisplatin and interferon-alpha 2B as the primary treatment of penile carcinoma. A total of 13 consecutive patients with nonmetastatic, histologically confirmed invasive squamous cell carcinoma of the penis underwent treatment consisting of 20 mg./m.2 cisplatin intravenously and 5 x 10(6) mu./m.2 interferon-alpha 2B subcutaneously daily for 5 consecutive days. An equivalent dose of interferon was then administered subcutaneously every 2 days for 3 weeks and the regimen was repeated at 28-day intervals. Of 12 evaluable patients 9 responded: 4 achieved a pathologically confirmed complete remission of 38+, 21+, 10 and 7 months in duration (2 with relapse were treated with local therapy and remain with no evidence of disease), and 5 achieved a partial response, underwent surgical removal of residual disease and remained disease-free for 14+ to 24+ months. The most significant toxicities were anemia in 5 patients and reversible renal impairment in 3 but no patient had neutropenic fever or required platelet transfusion. We conclude that primary treatment with cisplatin and interferon-alpha 2B induced responses in 75% of 12 patients with penile carcinoma and allowed for a less radical operation than originally scheduled. A larger number of patients and longer followup will be required to confirm these encouraging preliminary results.

Spontaneous Perforation of the Ureter: Clinical Presentation and Endourologic Management

BACKGROUND AND PURPOSE Spontaneous perforation of the upper ureter is a rare condition that poses diagnostic and therapeutic problems. We report on five cases from three institutions and discuss the literature. PATIENTS AND METHODS Five patients presented with renal colic and the imaging modalities used to assess them showed extravasation of urine. RESULTS The cause of spontaneous perforation of the ureter was a ureteral stone in one case and was unknown in four cases. In all cases, a Double-J ureteral stent was inserted under fluoroscopy. Urinoma was percutaneously drained in only one patient. Repeat imaging showed normal renal function and morphology in all patients. CONCLUSION Spontaneous perforation of the ureter should be suspected after renal colic. Endourologic treatment offers excellent results, even for the management of acute complications.

Enucleoresection for the Elective Treatment of Small Renal Cell Carcinoma: Can It Be the Treatment of Choice?

Background: We present our findings in a series of T1 renal cell carcinomas (RCC) treated with excision of the tumor surrounded by a minimal layer of grossly normal parenchyma. Patients and Methods: A total of 43 patients who underwent elective nephron-sparing surgery performed with enucleoresection were studied retrospectively. None of the patients had preoperative or intraoperative suspicion of positive nodes and were free from distant metastases before surgery (N0, M0). Patients status was last evaluated in January 2006. Results: Median age was 58.7 years (35-78). Median tumor size was 3.3 cm (1.5-7). There were no major complications such as bleeding and urinary leakage/ urinoma requiring re-operation. Pathological stage was pT1a in 38 (89%), pT1b in 4 (9%) and pT3a in 1 (2%) patient. Median followup was 32 months (6-89). A total of 5 patients with RCC had died as of January 2006. Overall, 3 (6.9%) patients had disease progression, of whom 2 (4.6%) were local recurrence, 1 alone and 1 associated with distant metastases. The overall cancer-specific survival was 95.4%, and the overall progression-free survival was 93%. Conclusions: Enucleoresection reproduces the results of partial and radical nephrectomy with minimal morbidity. It is a safe and acceptable approach for elective nephronsparing surgery.

Non-endothelial KDR/flk-1 expression is associated with increased survival of patients with urothelial bladder carcinomas.

Aims:  To investigate the immunohistochemical expression of KDR/flk‐1 in a series of 114 urothelial bladder carcinomas in relation to clinicopathological parameters, Ki67, p53 and Bcl‐2 protein expression and patient survival. KDR/flk‐1 is a high‐affinity tyrosine kinase receptor for vascular endothelial growth factor (VEGF), on vascular endothelium. However, there is increasing evidence that KDR/flk‐1 is also expressed by normal non‐endothelial and tumour cells.