Neoadjuvant chemotherapy with docetaxel and cisplatin in patients with high-risk resectable bladder carcinoma: long term results.

OBJECTIVES: Neoadjuvant chemotherapy has been used to improve outcome after cystectomy or for selection for bladder preservation in patients with bladder cancer. We have shown encouraging results using docetaxel and cisplatin in patients with advanced urothelial cancer. We are reporting the results of a phase II study using this combination as neoadjuvant treatment in patients with muscle invasive bladder cancer. METHODS: Fifty patients were treated with docetaxel and cisplatin at 75 mg/m2 every 3 weeks for 3 cycles prior to cystectomy. Median follow-up was 70.2 months. RESULTS: Chemotherapy was well tolerated. 5-year survival and progression-free survival (PFS) were 51.92% (95% confidence intervals [CI]: 37.76-66.08) and 52.47% (95%CI: 37.99-66.95). Multivariate analysis showed that clinical stage (cT) < or = 3a was associated with improved 5-year survival (86.42% vs. 40.81%, p = 0.027). Forty one patients underwent cystectomy. No tumor was found in 15 cases (36.6%). 5-year survival was 60.34% (95%CI: 52.2-68.48) and PFS was 57.11% (95%CI: 41.29-72.93). Absence of residual tumor was associated with improved 5-year survival (93.33% vs. 40.72%, p = 0.031). CONCLUSIONS: Neoadjuvant chemotherapy with docetaxel and cisplatin is feasible and produced high pathological complete remission rate and excellent outcome in patients with no residual tumor.

Combined treatment with low-dose interferon plus vinblastine is associated with less toxicity than conventional interferon monotherapy in patients with metastatic renal cell carcinoma.

The outcome of treatment of advanced renal cell carcinoma is disappointing. In interferon (IFN)-treated patients, the high incidence of adverse effects causes many patients to withdraw from treatment. This 12-week randomized study compared the incidence of toxicity associated with high-dose IFN monotherapy (15 x 10(6) U thrice weekly) and treatment with the combination of low-dose IFN (5 x 10(6) U thrice weekly) and 6 mg/m2 vinblastine (VBL) every 14 days in 100 consecutive patients. There was no significant difference in response rate between treatment arms (42% IFN vs. 34% IFN + VBL) or between subgroups (by tumor location). Combined treatment was associated with a significantly lower incidence of fever, fatigue, and weight loss but with a higher incidence of leukopenia. There was no significant difference in the incidence of other events. More patients treated with IFN monotherapy required bed rest, and overall treatment costs were 60% higher than for combined treatment. It is concluded that combined treatment with low-dose IFN and VBL, without loss of short-term efficacy, is better tolerated and less expensive than high-dose IFN monotherapy.

p53 protein expression and proliferative activity in imprints of superficial transitional cell carcinoma of the bladder.

OBJECTIVE: To investigate p53 protein expression and proliferative activity in imprints of tumor biopsies from superficial transitional cell carcinoma of the bladder in relation to the histologic grade of malignancy and recurrence status. STUDY DESIGN: The study group consisted of 70 cases of superficial transitional cell carcinoma of the bladder. In order to investigate p53 protein expression and Ki-67 expression, an immunocytochemical avidin-extravidin complex technique was performed using monoclonal antibodies p53 D0-7 and proliferating cells correspondingly. RESULTS: Thirty-seven percent of superficial transitional cell carcinoma cases showed positive expression of p53 protein. No correlation was found between p53 protein expression and grade of malignancy (P = .45). p53 Protein expression was statistically correlated with a high Ki-67 labeling index (LI) (P < .001) and recurrence status (P < .001). Forty-seven percent of cases showed a Ki-67 LI > 25%. No correlation was found between a high Ki-67 LI and grade of malignancy (P = .703). A significant difference in high Ki-67 LI between recurrent and nonrecurrent tumors of the same grade (P < .001) and between recurrent and nonrecurrent tumors was found independently of grade (P < .001). CONCLUSION: These results on cytologic material could provide useful information on the biologic behavior of superficial transitional cell carcinoma of the bladder at the time of diagnosis.

Cushing syndrome as the presenting feature of metastatic Leydig cell tumor of the testis.

We report a patient with a history of orchiectomy for Leydig cell tumor of the testis who developed Cushing syndrome. This syndrome was due to ectopic production of cortisol and was the primary feature of tumor recurrence.

DNA ploidy and p53 protein expression in superficial transitional cell carcinoma of the bladder.

Superficial transitional cell carcinoma of the bladder (STCCB) is a heterogeneous group of neoplasias with an unpredictable clinical course. In recent years many techniques have been used in order to predict the behaviour of these tumours at individual patient level. The aim of this study was to investigate in imprints from tumour biopsies the DNA ploidy and p53 protein expression in a group of 80 STCCB (pTa-pT1) patients in relation to histological grade and recurrence status. The DNA content was studied in Feulgen-stained imprints by the image analysis technique using a SAMBA 2005 analyser. In order to investigate p53 protein expression an avidin-extravidin immunocytochemical technique was used. According to our measurements a strong correlation was observed between recurrence status and DNA ploidy status (P < 0.001). No statistical difference was found in DNA ploidy status and grade of malignancy (P = 0.68). A statistically significant difference was found in p53 protein expression between recurrent and nonrecurrent tumours (P < 0.001). No statistically significant difference was found among tumours of grade I, grade II and grade III (P = 0.42). These results could provide useful information on the potential behaviour of STCCB.

Immunohistochemical expression of transforming growth factor beta 1 and nm-23 H1 antioncogene in prostate cancer: divergent correlation with clinicopathological parameters.

BACKGROUND: Prostate cancer is one of the main causes of morbidity and mortality among men. Several oncogenes and growth factors have been studied in an attempt to explain the molecular basis of carcinogenesis and progress of this carcinoma. In this study we correlated the immunohistochemical expression of antioncogene nm-23 H1 and transforming growth factor beta 1 (TGF-beta 1) with the clinical stage, PSA values, Gleason score and survival in prostate cancer. MATERIALS AND METHODS: Fifty nine patients with prostate cancer were evaluated. PSA measurement, Gleason score determination and clinical staging were recorded for all the patients by the time of initial diagnosis and prior to any treatment. Follow-up ranged from 12 to 40 months. Tissue sections from representative areas of the tumors were immunohistochemically stained for nm-23 H1 and TGF-beta 1. The expression of these markers was correlated with stage, PSA values, Gleason score and survival. RESULTS: There was a negative correlation between nm-23 H1 staining and tumor stage and grade. High grade (Gleason score 8-10) and stage D tumors showed weaker staining than low stage and grade tumors. There was a positive correlation between TGF-beta 1 staining, tumor stage and serum PSA levels. Additionally, TGF-beta 1 proved to be a negative predicting factor for patient survival. In tumors expressing both markers, TGF-beta 1 was the one to determine the aggressiveness of the carcinoma. CONCLUSIONS: nm-23 H1 appears to be a tumor suppressor gene in prostate cancer, while TGF-beta 1 may act as a stimulating agent provoking aggressive behavior and metastasis. Their immunohistochemical staining may constitute complementary information in the evaluation of prostate cancer patients.

Image cytometric DNA analysis and proliferating cell nuclear antigen (PCNA) expression in transitional cell carcinoma of the bladder.

The proliferation rate as determined by Proliferating Cell Nuclear Antigen (PCNA) immunostaining and the DNA ploidy status as measured by static cytometry were studied in 70 transitional cell carcinomas of the bladder (TCCB) in relation to grade, stage, and recurrence. The follow-up period was 2 years. A significant difference was observed in PCNA expression among grades I, II, and III (P < 0.02), between superficial (pTa-pT1) and invasive (pT2-pT4) tumors (p < 0. 04), between recurring and non-recurring tumors (p < 0.001), and between tumors of the same grade with and without recurrence (p < 0. 05). A significant difference was also found in the ploidy pattern among grades I, II, and III (p = 0.002), and between superficial and invasive (p = 0.02) and recurring and non-recurring tumors (p < 0. 01). Finally, the recurrence status seems to be strongly influenced by the proliferation rate and ploidy of TCCB (p < 0.001). Our results suggest that the above-studied parameters may offer useful information on the biological behavior of TCCB.

Docetaxel and cisplatin combination chemotherapy in advanced carcinoma of the urothelium: a multicenter phase II study of the Hellenic Cooperative Oncology Group.

PURPOSE: Both docetaxel and cisplatin have moderate activity in patients with advanced urothelial cancer. We performed a multicenter phase II study in order to assess the efficacy and toxicity of the combination of these two agents in patients with advanced carcinoma of the urothelium. PATIENTS AND METHODS: Sixty-six patients not amenable to curative surgery or irradiation were enrolled onto this cooperative group study and treated on an outpatient basis with docetaxel 75 mg/m2 followed by cisplatin 75 mg/m2, both administered intravenously. Granulocyte-colony stimulating factor was administered subcutaneously at a dose of 5 micrograms/kg daily from day 5 until resolution of neutropenia. The chemotherapy was administered every three weeks for a maximum of six courses in patients without evidence of progressive disease. RESULTS: Thirty-four of sixty-six patients (52%, 95% confidence interval 40%-64%) demonstrated objective responses, with eight achieving clinical complete responses and twenty-six partial responses. A multivariate logistic regression analysis indicated that the patients most likely to respond were those without lung metastasis and without weight loss before treatment. The median duration of response was 6.1 months and the median times to progression and survival for all patients were 5 and 8 months, respectively. Absence of anemia, of liver metastases and of weight loss correlated with longer survival. Grade > or = 3 toxicities included granulocytopenia in 33% of patients, anemia in 14%, diarrhea in 13% and emesis in 7% of patients. CONCLUSION: The combination of docetaxel and cisplatin appeared relatively well tolerated and moderately active in patients with advanced urothelial cancer. The patients most likely to benefit were those without weight loss and without lung or liver metastases.

Static cytometry and neural networks in the discrimination of lower urinary system lesions.

OBJECTIVES: To investigate the potential of morphometry and artificial intelligence tools for the discrimination of benign and malignant lower urinary system lesions. METHODS: The study group included 50 cases of lithiasis, 61 cases of inflammation, 99 cases of benign prostatic hyperplasia, 5 cases of in situ carcinoma, 71 cases of grade I transitional cell carcinoma of the bladder (TCCB), and 184 cases of grade II and grade III TCCB. Images of voided urine smears stained by the Giemsa technique were analyzed by a custom image analysis system. The analysis gave a data set of features from 45,452 cells. A learning vector quantizer (LVQ)-type neural network (NN) was used to discriminate benign from malignant cells on the basis of the extracted morphometric and textural features. The data from 13,636 randomly selected cells were used as a training set and the data from the remaining 31,816 cells made up the test set. Similarly, in an attempt to discriminate at the patient level, 30% of the cases randomly selected were used to train an LVQ NN and the remaining 329 cases were used for the test. RESULTS: The application of the LVQ NN enabled the correct classification of 95.42% of the benign cells and 86.75% of the malignant cells, giving an overall accuracy rate of 90.63%. At the patient level, the LVQ NN enabled the correct classification of 100% of benign cases and 95.6% of malignant cases, giving an overall accuracy rate of 97.57%. CONCLUSIONS: NNs combined with image analysis offer useful information in the discrimination of benign and malignant cells and lesions of the lower urinary system.

Comparing neural networks in the discrimination of benign from malignant lower urinary tract lesions.

OBJECTIVE: To compare the performance of two different neural networks (NNs) in the discrimination of benign and malignant lower urinary tract lesions. MATERIALS AND METHODS: A group of patients was evaluated, comprising 50 cases of lithiasis, 61 of inflammation, 99 of benign prostatic hyperplasia (BPH), five of in situ carcinoma, 71 of grade I transitional cell carcinoma of the bladder (TCCB), and 184 of grade II and grade III TCCB. Images of routinely processed voided urine smears were stained using the Giemsa technique and analysed using an image-analysis system, providing a dataset of 45452 cells. Two NN models of the back propagation (BP) and learning vector quantizer (LVQ) type were used to discriminate benign from malignant cells and lesions, based on morphometric and textural features. The data from 13636 randomly selected cells (30% of the total data) were used as a training set and data from the remaining 31816 cells comprised the test set. Similarly, in an attempt to discriminate patients, 30% of the cases, selected randomly, were used to train a BP and an LVQ NN, with the remaining 329 cases used for the test set. The data used for training and testing were the same for the two kinds of classifiers. RESULTS: The two NNs gave similar results, with an overall accuracy of discrimination of approximately 90.5% at the cellular level and of approximately 97% for individual patients. There were no statistically significant differences between the two NNs at the cellular or patient level. CONCLUSIONS: The use of NNs and image morphometry could increase the diagnostic accuracy of voided urine cytology; despite the different nature of the two classifiers, the results obtained were very similar.

Back propagation neural network in the discrimination of benign from malignant lower urinary tract lesions.

PURPOSE: We investigated the potential value of morphometry and artificial intelligence tools to discriminate between benign and malignant lower urinary tract lesions. MATERIALS AND METHODS: The lesions included lithiasis in 50 cases, inflammation in 61, benign prostatic hyperplasia in 99, carcinoma in situ in 5, and grade I and grades II and III transitional cell carcinoma of the bladder in 71 and 184, respectively. Images of routine processed voided urine smears stained by the Giemsa technique were analyzed using a custom image analysis system, providing a data set of 45,452 cells. A neural net model of the back propagation type was used to discriminate benign from malignant cells based on the extracted morphometric and textural features. Data from 13,636 randomly selected cells (30% of the total data) were used as a training set and the data from the remaining 31,816 cells comprised the test set. In a similar attempt to discriminate at the patient level data on 30% of those randomly selected were used to train a back propagation neural net and data on the remaining 329 were used for testing. RESULTS: Application of the back propagation neural net enabled the correct classification of 95.34% of benign and 86.71% of malignant cells with overall 90.57% accuracy. At the patient level the back propagation neural net enabled the correct classification of 100% of those with benign and 94.51% of those with malignant disease with overall 96.96% accuracy. CONCLUSIONS: The use of neural nets and image morphometry may increase the speed of cytological diagnosis and the diagnostic accuracy of voided urine cytology.

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.

DNA content and proliferation activity in superficial transitional cell carcinoma of the bladder.

The identification of new prognostic parameters in Superficial Transitional Cell Carcinoma of the Bladder (STCCB) is important since conventional methods are often insufficient for prognostic purposes. We studied the proliferation activity and the DNA ploidy status of 60 pTa and pT1 Superficial Transitional Cell Carcinoma of the Bladder in relation to grade and recurrence rate. The proliferative activity was investigated by measuring the PCNA expression in paraffin embedded tissue sections. The DNA content was studied in Feulgen stained imprints by image analysis technique using a SAMBA 2005 analyser. According to our measurements a statistically significant difference was found in PCNA expression among tumors grade I, grade II, grade III (F = 5.43, p < 0.001), between tumors of the same grade with, and without recurrence (p < 0.001); and between recurrent and non-recurrent tumors (T58 = -6.03, p < 0.001). A statistically significant difference was also observed concerning the DNA-index among grade I, grade II and grade III (F = 4.81, p < 0.01), and between recurrent and non-recurrent tumors concerning the DNA DNA ploidy status (DNA-euploid vs. DNA-aneuploid tumors) (X2 = 24.96, p < 0.001). The recurrence status is also strongly influenced by the proliferation rate and the DNA ploidy status of tumors (X23 = 41.19, p < 0.001). No cases recurrence were found in the group of DNA-euploid tumors with PCNA. expression lower than 30%, in contrast a very high percentage of recurrence in patients with DNA-aneuploid tumors with PCNA expression higher than 30%. Although a small proportion of cases could not be included in me previous categories, STCCB may be classified in to main groups concerning the risk of recurrence. In keeping with this view of proliferation rate and DNA ploidy status could provide useful information, on the potential malignancy of Superficial Transitional Cell Carcinoma of the Bladder. However further studies are required to establish the clinical utility of these parameters.

Primary renal lymphoma: a clinical and radiological study.

PURPOSE: We assessed the incidence, clinical and radiological features, and prognosis of patients with renal lymphoma. MATERIALS AND METHODS: We studied 210 patients with symptoms, signs and and radiological findings suggestive of renal cell carcinoma. RESULTS: Final diagnosis in 6 of 210 patients (3%) was primary renal lymphoma. Radiological features were similar to those of renal cell carcinoma. Five of the 6 patients had an International Prognostic Index score of greater than 1. Despite appropriate chemotherapy, only 2 patients remain with complete remission. CONCLUSIONS: Primary renal lymphoma is unusual but not rare. The relatively poor prognosis in our patients could be attributed to the adverse prognostic factors associated with aggressive nodal lymphomas.

Efficacy of eight serially measured markers for diagnosis of prostatic carcinoma.

In this study we measured eight different tumor markers (PSA, PAP, TPA, CEA, Ca 50, Ca 19-9, Ca 125 and Ca 15-3) in 39 patients with prostatic adenocarcinoma and in 90 patients with benign prostatic hyperplasia. We then calculated the sensitivity and specificity for each tumor marker separately and found that only PSA, when we consider as normal value 10 ng/ml, has a sufficiently high sensitivity and specificity. Our conclusion is that only PSA can be used for diagnostic purposes in conjunction with other diagnostic modalities.

Effect of drugs on crystal adhesion to injured urothelium.

The normal urothelium is covered by a glycosaminoglycan (GAG) layer which acts as a barrier to the adhesion of crystals. Destruction of the GAG layer increases the number of adhered crystals, and it is therefore assumed that it promotes crystal growth and stone formation. Intravesical instillation of pentosanpolysulfate, an exogenous glycosaminoglycan, after destruction of this layer reduces the adhesion of crystals to the urothelium. Intramuscular administration of carbenoxolone sodium following the experimental destruction of the GAG layer increases the rate of healing of the layer and reduces the number of adhered crystals.

The effect of pentosanpolysulphate and carbenoxolone on bacterial adherence to the injured urothelium.

The effect of the glycosaminoglycan (GAG) layer on the adherence of Escherichia coli to the bladder urothelium of rats has been studied. The study was performed by destroying the GAG layer and the changes were observed using the electron microscope. Bacterial adherence to the bladder with a destroyed GAG layer was much higher than to the normal bladder. Following the destruction of the GAG layer, the instillation of sodium pentosanpolysulphate significantly reduced the adhesion of bacteria. Prophylactic intramuscular administration of carbenoxolone increased the speed of regeneration of the destroyed GAG layer.

[Association of a rare form of testicular ectopia, a persistent Müllerian duct syndrome and a supernumerary ectopic epididymis]. / Association d'une forme rare d'ectopie testiculaire, d'un "syndrome de persistance du canal de Müller" et d'un épididyme ectopique surnuméraire.

We report the first case of persistence of the Müllerian duct associated with transverse testicular ectopia and a supernumerary ectopic epididymis in the same hemiscrotum. The patient is a thirty-year-old man with azoospermia. Uterine and Fallopian tube structures were clearly recognizable within the Müllerian remnants. The ectopic supernumerary epididymis was detected at the lower pole of one of the two testicles and had to be removed surgically.