Sinan Ekici

Surgical management of renal cell carcinoma with inferior vena cava tumor thrombus

BACKGROUND The successful excision of a renal cell carcinoma (RCC) invading the inferior vena cava (IVC) remains a technical intraoperative challenge and requires a careful preoperative surgical management planning. Although a radical operation remains the mainstay of the therapy for RCC, the optimal management of the patients with RCC causing IVC tumor thrombus remains unresolved. In this study, we reviewed our experience in this group of patients and herein report the results. METHODS Between July 1990 and August 1998, 11 patients with RCC with IVC tumor thrombus underwent surgical treatment. The mean patient age was 54.2 years and the male to female ratio was 1.75. The cephalad extension of the tumor was suprarenal in all cases, being infrahepatic in 6 patients, intrahepatic in 2, and suprahepatic with right atrial extension in 3 patients. All tumors were resected via inferior vena cava isolation and, when necessary, extended hepatic mobilization and Pringle maneuver, with primary or patch closure of vena cavotomy. Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) were used in 3 patients. RESULTS The mortality rate was 9.1% (1 patient was lost on the 11th postoperative day). Complications occurred in 3 patients. The remaining 10 patients (90.9%) could be successfully discharged from hospital. Two of them were lost during follow-up because of tumor progression at the 43rd and 54th postoperative months. The 10-year Kaplan-Meier survival estimate was 71.4%, with a mean follow-up of 4.6 years. The presence of lymph node metastases and perinephric spread seemed to possess an adverse effect on the survival. Although the groups included small numbers of patients, there was no significant difference in survival in regard to the different levels of tumor thrombus extension into the vena cava. CONCLUSIONS Surgical treatment is the preferred approach to patients with RCC and IVC tumor thrombi as it provides markedly better results when compared with the other therapeutical modalities. We believe that complete surgical excision of the tumor and the resulting thrombus with appropriate preoperative staging and a well-planned surgical approach, using CPB and DHCA when necessary, provide an acceptable long-term survival with a good quality of life expectation.

FALSE-POSITIVE RESULTS OF THE NMP22 TEST DUE TO HEMATURIA

PURPOSE The problem with available markers for bladder cancer is their low specificity and low positive predictive value due to false-positive results. False-positive results of the NMP22 nuclear matrix protein test (Matritech, Cambridge, Massachusetts) are usually observed in some clinical categories that are usually associated with hematuria and pyuria. This problem is especially serious in bladder cancer since 85% of patients present with hematuria. We investigated the effect of the degree of hematuria and pyuria on NMP22 results in an experimental model and human subjects. MATERIALS AND METHODS This study was performed in 202 urine samples from 30 healthy individuals (group 1), 20 with symptomatic urinary tract infection (group 2) and 32 with known bladder carcinoma (group 3). In the first group to achieve 0, 10, 100, 1,000 and 5,000 red blood cells per high power field the blood obtained from each patient was added to test tubes at 0.02, 0.2, 2 and 10 microl, respectively. RESULTS In the first group median urinary NMP22 in healthy individuals was 4 units per ml. (range 1.6 to 9.5). When blood was added to the urine sample, the NMP22 increase paralleled the increase in the amount of red blood cells in the sediment. When greater than 2 microl./ml. blood or 1,039.5 red blood cells per high power field (range 278 to 1,438) were added to the urine of a healthy individual, the NMP22 level reached and surpassed the level in patients with bladder carcinoma. The leukocyte count in the urine sediment also had a significant impact on urinary NMP22 in group 2. The degree of hematuria and pyuria did not significantly effect NMP22 in group 3. The sensitivity, specificity, positive and negative predictive values of NMP22 were 78.1%, 66%, 59.5% and 82.5%, respectively. Test sensitivity increased as grade and stage progressed. CONCLUSIONS In an experimental model pyuria and hematuria significantly affected urinary NMP22. The effect of white blood cells was more pronounced than that of red blood cells. The source of NMP22 in isolated hematuria remains to be elucidated. On the other hand, in group 3 the tumor was the main source of NMP22, and urinary erythrocytes and/or leukocytes had a negligible effect.

A novel surveillance protocol for stage I nonseminomatous germ cell testicular tumours.

To report the results of a novel surveillance policy for stage I nonseminomatous germ cell tumours (NSGCTs).

The protective effects of spirulina in cyclophosphamide induced nephrotoxicity and urotoxicity in rats.

OBJECTIVE To evaluate the role of Spirulina, a blue-green algae with antioxidant properties in the protection of cyclophosphamide-induced nephrotoxicity and hemorrhagic cystitis in rats. METHODS The control group (C) was sacrificed 24 hours after being given a single dose of saline intraperitoneally (150 mg/kg) on the seventh day of the experiment. The rats in the second group (CP) were sacrificed 24 hours after being given a single dose of cyclophosphamide, intraperitoneally (150 mg/kg) on the seventh day of the experiment. Spirulina was administered to the third group (SP+CP) orally (1000 mg/kg bw/day) for 7 days and a single dose of cyclophosphamide was injected intraperitoneally (150 mg/kg) on the seventh day of the experiment. At the eighth day of the experiment, malondialdehyde, superoxide dismutase, and catalase levels in renal and urinary bladder tissues were measured. Histomorphology in urinary bladder, apoptosis by caspase 3 immunostaining, and TUNEL assay in kidney were also evaluated. RESULTS Tissue levels of malondialdehyde in the SP+CP group were significantly lower versus CP group (P < .05). Tissue levels of superoxide dismutase and catalase in the SP+CP group were significantly higher vs the CP group (P < .05). The histomorphologic alteration in urinary bladder in the SP+CP group was significantly lower vs that in the CP group. In the kidney, apoptosis in the SP+CP group as shown with TUNEL assay and immunohistochemistry was significantly lower vs that in the CP group (P < .05). CONCLUSION Pretreatment with Spirulina protects the rats from cyclophosphamide-induced nephro-urotoxicity via its antioxidant and anti-apoptotic properties.

Proliferating-cell nuclear antigen (PCNA) as an independent prognostic marker in patients after prostatectomy: a comparison of PCNA and Ki-67

To investigate the prognostic value of prostatic tumour cell proliferation, as measured by Ki‐67 and proliferating cell nuclear antigen (PCNA), and to compare these measures in men at low and high risk for progression of tumour.

The role of the pathologist in the evaluation of radical prostatectomy specimens.

Objective: To compare the difference between the routinely reported pathology records and the results of re‐evaluation of the same radical retropubic prostatectomy (RRP) specimens. Material and Methods: The RRP specimens of 114 patients initially reported by a general pathologist for routine purposes were re‐examined and re‐evaluated blindly with respect to the following parameters: organ confinement; capsular invasion; seminal vesicle invasion; lymph node metastasis; surgical margin positivity; Gleason grade and pathologic stage. Repeat and step sections were performed where necessary. Prostate mapping was done for each patient. Results: A statistically significant discordance between the routine evaluation and the re‐evaluation was observed with regard to capsular invasion, organ confinement, Gleason grade and pathologic stage. In addition to pathologic stage, Gleason grade and surgical margin positivity became significant prognostic factors after the re‐evaluation. Conclusions: RRP specimens should be evaluated by an expert prostate pathologist by submitting whole prostate specimens and should include detailed prostate mapping.

Microstaging of pT1 Transitional Cell Carcinoma of the Bladder

Introduction: Our objective was to evaluate the feasibility and value of microstaging in pT1 transitional cell carcinoma (TCC) of the bladder in a well-defined group of patients treated with transurethral resection (TUR) only. Materials and Methods: The clinical records of 152 patients who underwent TUR for the treatment of primary superficial TCC of the bladder between 1983 and 1997 were reviewed. Patients with primary carcinoma in situ and who received adjuvant intravesical treatments were excluded from study. We subclassified the pT1 tumors into two groups according to muscularis mucosae (MM) invasion (pT1 and pT1b). The recurrence and progression rate of cancers was analyzed according to the stage, grade, multiplicity and tumor size. Mean follow-up was 68 months. Estimation of the cumulative distribution of the disease-free interval in separate groups was calculated according to the Kaplan-Meier method. Multivariate analysis of the data was performed by using Cox regression method. A value of p < 0.05 was taken to be statistically significant with odds ratios. Results: Of the 152 patients, tumor stage was pTa in 62 (40.8%) patients and pT1 in 90 (59.2%) patients. Among those pT1 tumors, MM was identified in 50 (55.5%) of cases (pT1a = 34, pT1b = 16). In the remaining 40 (44.5%) patients, MM could not be assessed. Kaplan-Meier analysis revealed that recurrence and progression were statistically significant for stage, multiplicity and grade of tumor. However, multivariate analysis revealed that stage was the only prognostic factor for recurrence and progression (p = 0.0001). Conclusion: The present study underscores the fact that pT1b tumors have a distinct natural history. If initial conservative treatment is selected, the patients must be followed very cautiously.

Identification of microRNAs differentially expressed in prostatic secretions of patients with prostate cancer

Prostate cancer (PCa) is one of the leading causes of cancer deaths in men. Since there are limited treatment options available for the advanced tumors, there is an urgent need for novel diagnostic tools for PCa. Prostate secretion samples (PSS) from 23 PCa and 25 benign prostate hyperplasia (BPH) patients were obtained from Urology Department of Bagcilar Educational and Research Hospital (Istanbul). MicroRNA (miRNA) profiling of eight PSS (four from BPH, four from PCa patients) was performed using microarray. Four of significantly deregulated miRNAs were further confirmed using quantitative reverse‐transcription PCR (qRT‐PCR). Statistical analysis was performed using Students t‐test. ROC curves were plotted with SPSS‐15.0.

Determination of Prognosis in Patients With Prostate Cancer Treated With Radical Prostatectomy: Prognostic Value of CD44v6 Score

PURPOSE A third of the patients treated with radical prostatectomy experience progression even when tumors are confined pathologically to the prostate. CD44 may be a promising prognostic marker for determining malignant potential. However, there has not been a standard scoring system because of its heterogeneous staining pattern. Thus, we developed an objective scoring system to evaluate reliably CD44v6 (Bender Medsystems, Vienna, Austria) as a prognostic marker for prostate cancer. MATERIALS AND METHODS A total of 22 patients with metastatic stage pT3bN0M0 or any pTN1M0 disease and 18 with nonmetastatic disease less than stage pT3bN0M0 were selected from a well examined group of 114 who underwent radical retropubic prostatectomy. Mean followup was 33 months (range 4 to 78). A combined CD44v6 score was determined by adding the scores of the primary and secondary areas. CD44v6 expression in terms of the CD44v6 score in primary and metastatic tissues was examined. The relationships of CD44v6 expression with pathological stage, progression and PSA-free survival were also evaluated. The prognostic value of the CD44v6 score for progression was analyzed by multivariate analysis. RESULTS Progression in the metastatic group was significantly higher than in the nonmetastatic group (p <0.0001). CD44v6 expression of the primary tumors differed significantly in the 2 groups (p = 0.014). The CD44v6 score in primary tumor tissues inversely correlated with pathological stage (p = 0.004) and progression (p = 0.035), and positively correlated with PSA-free survival (p = 0.041). Furthermore, patients in the nonmetastatic group with a CD44v6 score of greater than 75 (cutoff value) had a significantly better prognosis (log rank test p = 0.0022), while those with a CD44v6 score of less than 75 had a prognosis similar to those in the metastatic group. On multivariate analysis pathological stage and surgical margin positivity were independent factors for progression but the CD44v6 score was not. CONCLUSIONS According to our results the suggested CD44v6 score system is useful. A CD44v6 score of less than 75 may be a predictor of poor prognosis in the nonmetastatic group and this property may have potential application for planning adjuvant therapy.

Comparison of Melatonin and Ozone in the Prevention of Reperfusion Injury Following Unilateral Testicular Torsion in Rats

OBJECTIVE To compare the efficacy of ozone with melatonin, shown as the most powerful antioxidant in attenuation of testicular ischemia/reperfusion injury, in an experimental rat model of testicular torsion/detorsion. METHODS Twenty-four male Wistar rats were divided into 4 groups: sham-operated, torsion/detorsion, torsion/detorsion plus melatonin, and torsion/detorsion plus ozone. Melatonin (10 mg/kg) and ozone (4 mg/kg) were intraperitoneally injected daily beginning 15 minutes before detorsion for the following 7 days. At the seventh day, blood and tissue samples were obtained. Johnsen score, malondialdehyde, inhibin B, glutathione plasma total sulfhydryl group (RSH) levels, and total nitric oxide were studied. RESULTS Torsion/detorsion caused increase in tissue malondialdehyde and total nitric oxide along with a decrease in Johnsen score, tissue and plasma inhibin B, RSH, and glutathione levels. Melatonin prevented the rise in malondialdehyde and total nitric oxide levels and improved Johnsen score, tissue and plasma inhibin B, and tissue glutathione levels, along with a decrease in plasma RSH level. Ozone showed similar results except for the total nitric oxide level. Concomitantly, in contralateral testis, melatonin and ozone induced similar changes for Johnsen score, malondialdehyde, and inhibin B (not significant) and in glutathione (significant). Melatonin decreased the total nitric oxide level in both testes and ozone increased the same parameter. CONCLUSION On different pathways, ozone was comparable with melatonin in the amelioration of ischemia/reperfusion injury. Protective effects of ozone were associated with nitrous oxide. The potential for ozone as a treatment for torsion/detorsion therefore deserves to be further elucidated.