D. Chopin

Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study.

PURPOSEnTo evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study.nnnPATIENTS AND METHODSn4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center.nnnRESULTSnThe UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients.nnnCONCLUSIONnThis study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.

Laparoscopic radical nephrectomy for T1 renal cancer: the gold standard? A comparison of laparoscopic vs open nephrectomy

To evaluate the complication rate and clinical follow‐up of patients treated for T1 renal cancer by open or laparoscopic nephrectomy at the same institution, as this approach appears to be attractive for treating small renal cancers.

Outcome and complications of radical prostatectomy in patients with PSA <10 ng/ml: comparison between the retropubic, perineal and laparoscopic approach

The objective of this work was to evaluate the oncological outcomes and complications of prostate cancer patients with prostate specific antigen (PSA) <10u2005ng/ml after radical prostatectomy by retropubic, perineal and laparoscopic approach. From 1988 to 2001, 306 patients with PSA <10u2005ng/ml underwent radical prostatectomy by the retropubic, perineal or laparoscopic approach. Mean operative time, complication rates, length of hospital stay, catheterization time and pathological results were reviewed. Kaplan-Meier analysis was used to evaluate the likelihood of biochemical PSA recurrence. There were no statistical differences between the three groups in terms of preoperative characteristics except for PSA levels (5.5, 6.5 and 6.6u2005ng/ml for the retropubic, perineal, and laparoscopic approach, respectively, P<0.05) and for the T1c stage prevalence (50%, 43.1% and 68.4%, P<0.05). Operating time was significatively longer in the laparoscopic approach (266u2005min), whereas transfusion rate (22.1%), bladder catetherization (12.1 days), and length of hospital stay (12.1 days) were higher in the retropubic group (P<0.05). The percentage of medical and surgical complications were 6.9%, 3.1% and 3.4% (P<0.05) and 18.6%, 16.9% and 11.6% (P<0.05) for the retropubic, perineal, and laparoscopic approach, respectively. Pathological staging revealed pT2 in 76.7%, 78.4% and 81.3% for retropubic, perineal and laparoscopic approach, respectively (P<0.05). Positive surgical positive margins were noted in 20.9%, 18.4% and 20.6% (P>0.05). The actuarial 3-year recurrence-free survival rate was 89.3%, 89.2% and 86.2% (P>0.05) for retropubic, perineal and laparoscopic approach, respectively. It can be concluded that in patients with preoperative PSA<10u2005ng/ml, clinical outcome and complication rates were similar, regardless of the choice of surgical approach.

Monoclonal antibodies against transitional cell carcinoma for detection of malignant urothelial cells in bladder washing.

The diagnosis of transitional cell carcinoma by cytological examination of exfoliated urinary cells is important in the early detection and followup of patients with this disease. Proper interpretation requires a skilled pathologist. Accuracy also is influenced by collection methods and nonmalignant pathological conditions of the bladder. An immunocytochemical technique using monoclonal antibodies G4 and E7 successfully identified tumor-associated antigens on the surface of transitional carcinoma cells obtained by bladder washings. The method, which uses immunoperoxidase staining, was compared to conventional Papanicolaou staining of bladder washings from 75 patients with and without transitional cell carcinoma. Patients were divided into 4 groups: group 1 (nontumor control)--15 patients with no pathological condition of the bladder or nonmalignant urological diseases, group 2 (nontransitional cell carcinoma)--19 patients with other urological malignancies, group 3-18 patients with active transitional cell carcinoma and group 4-23 patients with a history of transitional cell carcinoma but no evidence of tumor at the time of the washing. The incidence of positive staining in these groups was 0, 5, 78 and 0 per cent, respectively. The diagnostic value of immunoperoxidase staining was similar to that of Papanicolaou staining in the control group and in patients with high grade transitional cell carcinoma, and provided specific morphological criteria not possible by conventional cytology studies. Interpretation of immunoperoxidase staining was difficult in washings with a large number of inflammatory cells if endogenous peroxidase activity was not blocked properly. The application of the immunoperoxidase staining method for diagnosis of low grade tumor is under further investigation.

Hormone-refractory prostate cancer: a multi-step and multi-event process.

Since the pioneering studies of Huggins in 1941, it has been known that prostate cancer cells, like certain normal epithelial cells, can chronically depend on a critical level of androgenic stimulation for their continuous growth and survival. The entire issue of the development of resistance to androgen ablation therapy for metastatic prostate cancer is based on the fact that a portion of cells can survive without androgen stimulation. The cell mechanism of androgen independent status is unclear. For some authors, a portion of the cells present within a patient with a prostate cancer before therapy is naturally androgen independent (selection hypothesis). However, this hypothesis does not consider gene alteration during prostate cancer natural history and probably hormone-refractory prostate cancer (HRPC) is due to a multi-step and multi-event process. In this literature review, different cell pathways that lead to HRPC are described..

Antibodies to Cultured Tumor Cells Detected in Sera of Renal Cell Carcinoma Patients by a Quantitative Avidin-Biotin Method

Antibodies reacting with the tumor cell line RC-Pa were measured by a quantitative avidin-biotin complex method. Sera of renal cell carcinoma patients, patients with other types of cancer and healthy donors were analyzed. Of 71 sera from renal cell carcinoma patients 67 (94 per cent) were classified as showing renal cell carcinoma, while 32 of 36 sera (89 per cent) from healthy subjects were classified as showing no renal cell carcinoma. Four of 21 serum specimens (19 per cent) from individuals with other than renal cancer were misclassified. Furthermore, sera from renal carcinoma patients immunized with a mixture of autologous tumor cells and Corynebacterium parvum showed a marked increase in reactivity compared to those from patients receiving progesterone. The results indicate that this assay might become useful to detect or monitor renal cell carcinoma.

Prognostic Value of Histologic Subtypes in Renal Cell Carcinoma: A Multicenter Experience

PURPOSEnTo analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience.nnnPATIENTS AND METHODSnFour thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively.nnnRESULTSnClear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001).nnnCONCLUSIONnThe stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.

618 Restoration of functional motor units in a rat model of sphincter injury by muscle precursor cell autografts

BACKGROUNDnUrinary incontinence is a debilitating condition that affects primarily elderly individuals. One major mechanism results from chronic denervation of the striated urethral sphincter with associated fibrosis. The authors investigated the fate of muscle precursor cells (MPC) injected into a model of striated urethral sphincter injury that reproduces the histopathologic changes of sphincter insufficiency.nnnMETHODSnThe striated urethral sphincter of older male rats was damaged by electrocoagulation. MPC were isolated from limb myofiber explants, infected with an adenovirus carrying the transgene encoding beta-galactosidase, and injected into the sphincter of the same animal 37 days after injury. Animals were killed 5 and 30 days after injection for assessment of sphincter function and the formation of motor units.nnnRESULTSnElectrocoagulation resulted in an irreversible destruction of both sphincteric myofibers and nerve endings, with a functional incapacity of the damaged sphincter to sustain an increase in bladder pressure; atrophy and fibrosis developed after 1 month. Injection of MPC resulted in the formation of beta-galactosidase-expressing myotubes in the sphincter that persisted beyond 30 days. The regenerated myotubes carried acetylcholine receptors associated with a nerve ending and were thus considered to form anatomic motor units. Urodynamic studies confirmed the restoration of 41% of sphincter function 1 month after MPC injection.nnnCONCLUSIONSnThe authors showed that MPC isolated from limb muscles of an older animal can recapitulate a myogenic program when injected into an irreversibly injured sphincter. The maturation of MPC activates nerve regeneration and restores functional motor units.

Pretreatment P53 nuclear overexpression as a prognostic marker in superficial bladder cancer treated with bacillus calmette-guérin (BCG)

INTRODUCTIONnAltered p53 gene product correlates with the stage and grade of bladder tumor, but its value as a predictor of BCG response has been disappointing. In order to revisit the prognostic value of pretreatment p53 nuclear overexpression for the BCG response, we studied a large cohort of consecutive patients with superficial bladder cancer treated with BCG.nnnMETHODSnFrom 1988 to 2001, 102 patients with a history of multifocal, recurrent, and/or high-risk papillary transitional cell carcinoma or carcinoma in situ, were treated for the first time with BCG. p53 immunostaining was performed on paraffin-embedded tissues using monoclonal antibody DO7 and an automated immunostainer. Special attention was paid to the conditions of tumor fixation. p53 overexpression was defined as more than 20% tumor cells with p53-stained nuclei.nnnRESULTSnImmunostaining was significantly higher for Ta/T1 G3 +/- Cis (p < 0.001), tumoral substage T1b (p = 0.001), grade 3 (p = 0.0001), and Cis (p = 0.002). Times to recurrence, progression and cancer death were shorter among patients with p53 overexpression (p = 0.03; p < 0.0001; p = 0.0003). In multivariate analysis, p53 overexpression was an independent predictor of recurrence (p = 0.0003) [RR = 0.15; 95%CI, 0.06 to 0.42].nnnCONCLUSIONnPretreatment p53 nuclear overexpression in superficial bladder tumors is associated with a high risk of disease recurrence, progression and cancer death after BCG therapy. Applying antibody DO7 with an automated immunostainer and stringent fixative conditions, p53 nuclear immunostaining yields clinically relevant information and may be a useful tool for selecting patients with superficial bladder cancer who might be resistant to BCG.