Prognostic significance of Ki-67 immunostaining in nonmetastatic renal cell carcinoma.

PURPOSE: Fresh tissue samples from nonmetastatic renal cell carcinoma (RCC) patients were analyzed by Ki-67 immunostaining to determine the prognostic significance of this tumor-biologic parameter. MATERIALS AND METHODS: In a prospective study, Ki-67 immunostaining was performed on frozen sections of histologically proven node-negative RCC from 58 patients operated on between 1986 and 1988 to examine the method's prognostic value and its association with other clinicopathologic parameters such as tumor stage (pT) and grade (G). RESULTS: The percentage of Ki-67-positive cells (ie, the proliferation rate [PR]) of all 58 RCC tumors ranged between 1% and 23%, while normal renal tissue exhibited PRs up to 2% only. In almost all cases, the highest PRs were observed in the peripheral zone of malignant tissue close to the normal renal tissue. PR did not correlate with pT, whereas a strongly significant correlation was observed between PR and G, as well as recurrence rate. Twenty-three of 58 patients (39.6%) developed tumor recurrence. Disease-free survival was strongly associated with PR. In a multivariate analysis, G and PR were independent prognostic markers. CONCLUSION: The tumor-specific PR obtained by Ki-67 labeling seems to be an independent marker to describe the proliferative activity and aggressiveness of individual tumors. This new tumor-biologic marker detects RCC patients at high risk for recurrent disease, especially in those cases with identical pT and G.

[Electrostimulation in therapy of postoperative urinary incontinence. Therapeutic value for quality of life]. / Die Elektrostimulation in der Therapie der postoperativen Harninkontinenz. Therapeutischer Nutzen unter Berücksichtigung der Lebensqualität.

Worldwide use of electrical stimulation for therapy of postoperative incontinence is based on a few prospective randomized controlled studies. We present a three-arm prospective randomized study evaluating physiotherapeutic pelvic floor training alone and in combination with transanal or perineal electrical stimulation. The study compared specific continence training (CT) and a combination of CT with transanal or perineal electrostimulation. The groups included 60 patients each and were analyzed with regard to self-assessment, objective characteristics of incontinence, standard quality of life questionnaire (QLQ-C 30), and recorded data of the stimulation device. The patients participated in a specific inpatient rehabilitation program and were assessed at the time of admittance, upon discharge, and again after 3 months. Significant improvement could be achieved in every group concerning urinary incontinence and quality of life. Additional use of electrical stimulation was significantly superior to physiotherapeutic training alone. However, these results could only be detected in a highly compliant subgroup. Analysis of device data indicated a high score of errors and lack of patient compliance. Perineal electrical stimulation was better accepted than transanal and showed less side effects and better outcome in the characteristics of incontinence. Improvement in the quality of life was mostly achieved during the weeks of inpatient rehabilitation. Electrical stimulation could not improve quality of life items. Electrical stimulation is an efficient instrument for treatment of postoperative high-grade incontinence, however, only with sufficient patient compliance.

[Structure and process quality of inpatient urologic rehabilitation]. / Struktur- und Prozessqualität der stationären urologischen Rehabilitation.

Inpatient rehabilitation and "Anschlussheilbehandlung" (rehabilitation soon after operation or acute intervention) are effective and economic for long-term improvement of urologic patients. Only therapy guided by urologic specialists during rehabilitation and afterwards guarantees the possibility of excellent results. Especially QOL and functional deficits are improved markedly by urologic rehabilitation. Therefore, inpatient urologic rehabilitation should be initiated more often in the future.

Metastatic renal cell carcinoma (RCC): spontaneous regression, long-term survival and late recurrence.

We report 4 cases of metastatic renal cell carcinoma (RCC) with long-term survival either following radical nephrectomy alone or in combination with radio- or hormonal therapy. Two patients with lymph node metastases showed a long-term survival of 12 or more years following radical tumour nephrectomy (with lymphadenectomy) and radiotherapy. One of them exhibited a histologically proven tumour recurrence nearly 12 years after primary surgical treatment and died shortly later; the other one is still without any evidence of metastatic disease. Two other patients exhibited spontaneous regression of pulmonary metastases: one regression occurred after radical tumour nephrectomy alone, the other one after successful primary hormonal treatment and subsequent radical tumour nephrectomy. The following important aspects are emphasized: 1. Renal cell carcinoma is a very unpredictable tumour. Once the diagnosis of renal cell carcinoma is proved, a patient can never be considered cured. 2. Although adjuvant palliative nephrectomy has produced contradictory results in several reports, radical tumour nephrectomy either alone or in combination with other adjuvant therapies such as radiotherapy, hormonal or immunological treatment, can be worthwhile. Cases with long-term survival and spontaneous regression of distant metastases are proof of this. Besides, if carefully selected, the mortality rate of different adjuvant therapies is not significantly higher in patients with metastatic disease than in patients without metastases. The world literature on this subject is reviewed.

[The modular image analysis computer for assessment of prognosis in testicular tumors]. / Der Modular Image Analysis Computer in der Prognoseerfassung bei Hodentumoren.

Since 1981 a total of 107 patients with non-seminomatous germ cell tumors of the testis (NSGCT) in clinical stage I were assigned to a "wait and see" protocol. At a median follow-up of 40 months (4-100) thirty seven pts. (35%) relapsed with 84% of these within the first year. Employing the Hedley-technique out of 50 primary tumor-tissues available nuclear suspensions were obtained, staining according to the DNA-Feulgen-procedure and evaluated by the modular image analysis computer (MIAC, Leitz, FRG). In 67% hyperpentaploidy was found in the cases with progression while only 23% exhibited a greater than 5c-rate in the NED-group. With logistic regression achieving a p-value of 0.0296 hyperpentaploidy has to be considered a significant prognosticator in NSGCT/CS I.

Stage I seminoma of the testis. Adjuvant radiotherapy or surveillance?

Lately the role of radiotherapy in stage I seminoma of the testis has been questioned by some authors who reported on a "surveillance" strategy for these patients. Since 1980, 124 patients with seminoma of the testis have been referred to this institution; 97 of 116 patients analysed presented with stage I disease and 10 of these had elevated levels of beta HCG. A total of 64 patients were given radiotherapy after orchiectomy and 33 entered a surveillance protocol. After a median follow-up of 48 months, 3 patients in the surveillance group relapsed after 5, 13 and 49 months and 2 of the irradiated patients did so after 25 and 33 months. Elevation of beta HCG was not significant because none of these patients showed progression. A low rate of progression and excellent survival are associated with standard treatment (orchiectomy and radiotherapy) and good results have been achieved with chemotherapy in cases of relapse. A surveillance policy is not recommended in stage I seminoma because of its slower growth compared with non-seminomatous germ cell tumours (NSGCT), the absence of a specific tumour marker, the 10% risk of occult metastases and the 3-fold higher progression rate compared with irradiated patients. We suggest the use of a reduced dosage and radiation field.

Effects of cytokines on growth in vitro of primary human renal cell carcinoma.

In clinical trials different haematopoietic active cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) have been proven to alleviate myelosuppressive side effects of intensive chemotherapy in different non-urological malignancies. On the other hand, these cytokines can directly stimulate the proliferation of cells originating from some non-urological tumours. To clarify the impact of these cytokines on the proliferative behaviour of human renal cell carcinoma (RCC), 29 previously untreated RCC tumours were prepared for culturing in vitro using the cell cluster technique. The success rate for growth in vitro was 82.8% (24/29). The malignant renal cells were treated with different cytokines (GM-CSF, G-CSF and interleukin-3) in different dosages. Cell number and proliferation rates detected by immunostaining were used for treatment evaluation. A dosage-dependent stimulation of cell growth could not be observed compared to untreated cells. From the data presented in this study, proliferative stimulation of RCC by administering colony-stimulating factors in clinical trials cannot be assumed.

In vitro sensitivity testing of human renal cell carcinoma with cytostatic agents and interferon alpha-2a.

Samples of 38 human renal cell carcinomas (RCC) were subjected to routine histopathological examination but also to in vitro sensitivity testing with mitomycin C, vinblastine and interferon Alpha-2a at various concentrations corresponding to serum titers recommended to be effective in vivo, employing a monolayer assay. Extending earlier in vitro studies, both tumor cell kill rates (TCKR) and proliferation rates (PR) were assessed. Following in vitro preparation the tumor cell cultures were simultaneously exposed to the anticancer drugs listed above. The proliferation rates were determined immunocytochemically using the monoclonal antibody Ki-67. Nine (23.7%) of the tumors investigated revealed temporary and limited response with respect to either TCKR or PR. Improvement of this percentage could only be obtained by increasing drug concentration to titers with toxicity intolerable for in vivo administration. The in vivo data presented correspond to clinical temporary and limited remissions in patients with metastatic RCC ranging up to 25%.

Efficient pathway for early detection of prostate cancer concluded from a 5-year prospective study.

In a prospective study the statistical characteristics of digital rectal examination (DRE), transrectal ultrasound (TRUS), and serologic determination of prostate-specific antigen (PSA) were assessed in 1230 patients aged over 40 years. The sensitivity, specificity, and positive and negative predictive values were determined to be 80.3%, 69.7%, 58.9%, and 86.7%, respectively, for DRE; 76.5%, 62.3%, 52.3%, and 83.1%, respectively, for TRUS; and 87.9%, 49.6%, 48.5%, and 88.3%, respectively, for PSA (normal level, 4 ng/ml). The data clearly demonstrate the nonsuitability of each single measure for reliable early detection of prostatic carcinoma. Connection of the parameters in all possible combinations under various conditions demonstrated the superiority of the test "DRE and PSA > 4 ng/ml" over DRE as the "gold standard" and all other options. The use of this approach as the first-line raster of an algorithm (outlined herein) would allow the detection of prostatic malignancy with a specificity of 86.5% and a positive predictive value of 74.0%. Supplementing this screen with short-term controls in cases in which only one parameter is positive ("DRE or PSA > 4 ng/ml") might enable the detection of almost all patients with prostate cancer. TRUS did not provide any additional information.