BCG treatment in Tis of the urinary bladder, results of the EORTC Protocol 30861. EORTC GU Group.
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Adult↗
Biomedical subjects
G Jakse
Publications and source records attributed to G Jakse.
[Systemic chemotherapy of urothelial cancer].
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Antineoplastic Agents↗
Expression of the insulin like growth factor-binding protein 3 (IGFBP-3) gene is increased in human renal carcinomas.
After we had established that the IGFBP-3 gene is expressed in normal human kidney we examined renal adenocarcinoma tissue for alterations of the expression of this gene. For this purpose we prepared poly(A)+ RNA from normal kidney tissue and adjacent renal adenocarcinoma of 18 adult patients and compared the levels of IGFBP-3 mRNA by Northern analysis in both samples. The mean content by densitometry was markedly increased in the carcinoma tissues; in 17 of 18 patients the carcinoma contained significantly more IGFBP-3 mRNA than the normal kidney sample. The highest mRNA levels were found in patients with N2 and N3 lymph node extensions. Comparative Southern analysis of paired samples of four of these patients did not reveal amplification of the gene as the cause of these increased mRNA levels. In one patient, however, we identified a restriction fragment length polymorphism (RFLP) present in normal and malignant cellular DNA. This suggests a participation of the IGFBP-3 gene in the development of human renal cell cancer.
Aged↗
pT1 bladder cancer.
pT1 bladder tumors invade the lamina propria and are more aggressive biologically than superficial pTa or in situ carcinomas (Tis). Among patients with pT1 tumors treated by transurethral resection (TUR), 30% develop a muscle-invasive neoplasm within 3-5 years, but intravesical chemotherapy or BCG reduce progression rates to 20 and 14%, respectively. Tumor variables favoring progression include multiple, recurrent pT1 tumors, high grade (G3), solid configuration and associated Tis. Many pT1 tumors can be managed conservatively, but patients failing an adequate trial (3-6 months) of TUR and intravesical therapy are best treated by cystectomy.
Humans↗
[Systemic chemotherapy of urothelial carcinoma].
Systemic chemotherapy is used mainly in patients in whom metastases develop after successful local therapy. It is also used for inductive and adjuvant treatment, mostly still in clinical trials. At present cisplatin and methotrexate are the most effective drugs. Polychemotherapy protocols including cisplatin and methotrexate are more effective than those with neither of these two drugs. The complete remission rate in patients with metastatic tumors is about 10-20%. The relapse rate is about 60%. Long-lasting remissions are now being seen for the first time. A significant advantage of polychemotherapy over monochemotherapy has not been definitely proven. Inductive chemotherapy destroys locally advanced bladder tumors in about 30% of cases. It has not so for been shown whether this has a positive influence on the length of survival. Adjuvant chemotherapy has also yielded no results confirming that chemotherapy following cystectomy results in prolonged tumor-free survival. We cannot yet say whether subgroups it has not yet been possible to define will profit from it. The rate and severity of side-effects are dose-dependent, and their occurrence is determined by many factors. Especially in older patients, age-related disease has to be taken into consideration; to what extent the dose reduction needed may result in a significant lower remission rate is not known.
Antineoplastic Agents↗
Modulation of pro-epidermal growth factor, pro-transforming growth factor alpha and epidermal growth factor receptor gene expression in human renal carcinomas.
We have analyzed the expression of the genes for the precursors of epidermal growth factor (pro-EGF) and transforming growth factor alpha (proTGF-alpha) as well as for the EGF receptor in tissue specimens of a large number of adult patients with renal cell carcinoma. Since normal kidney tissue was available from the same patients we could directly compare the expression of these genes in tumors with that in adjacent normal renal tissue. Our experiments reveal underexpression of the proEGF gene in all tumors analyzed (21 of 21) and overexpression of the genes for proTGF-alpha (33 of 33 analyzed) and EGF receptor (22 of 23 analyzed) in tumor samples, when compared with normal kidney tissue. The expression of the proTGF-alpha gene appeared to depend on grade and differentiation of the tumor, since well differentiated tumors (grade 1) expressed more proTGF-alpha mRNA than the adjacent normal tissue but significantly less than poorly differentiated tumors (grade 2 or 3), which are the most aggressive ones. In none of these tissue specimens did we find, by Southern analysis, amplification of the proTGF-alpha or EGF receptor gene. Therefore, overexpression of these genes must be due to another effect, perhaps an alteration of their mRNA turnover. Although the EGF receptor gene (c-erbB1) is overexpressed in nearly all carcinomas analyzed, there was no linear coexpression with the proTGF-alpha gene. In contrast, transcription of the proEGF gene was completely turned off in tumor tissue. Although we have found by restriction fragment length polymorphism analysis, in one of three tumor samples, evidence for a somatic mutation within the proEGF gene, we do not know yet, due to the limited number of Southern analyses, whether this somatic mutation is causally involved in the decrease of proEGF mRNA expression and, hence, is representative of renal cell carcinoma. To our knowledge, this is the first observation on primary tumor tissue in humans that upon malignant transformation the gene for a polypeptide growth factor gene is underexpressed.
Blotting, Northern↗
Evaluation of tumor response in patients with bladder cancer undergoing combined radiotherapy and chemotherapy.
The value of non-invasive methods to evaluate the tumor response in locally advanced bladder cancer has to be established. 34 patients with locally advanced bladder cancer were treated by combined radiotherapy and chemotherapy. The response of the local tumor was assessed by biopsy, deep transurethral resection, partial cystectomy or cystectomy and computerized tomography scan. Persistent tumor or complete response could be diagnosed by computerized tomography scan in 76% of the patients.
Aged↗
The T1 bladder tumor.
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Combined Modality Therapy↗
Evaluation of tumor response and prognostic factors in patients with bladder cancer undergoing combined radiotherapy and chemotherapy.
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Combined Modality Therapy↗
Concurrent adriamycin and radiotherapy in locally advanced bladder cancer.
A prospective 2-phase study was performed on 24 patients with locally advanced transitional cell carcinoma of the urinary bladder to evaluate the toxicity of integrated treatment with Adriamycin 10 mg/m2 (group A) or 20 mg/m2 (group B) and hyperfractionated, accelerated radiotherapy. Local and systemic toxicity with Adriamycin 10 mg/m2 was significantly lower than with 20 mg/m2. Complete tumour remission was achieved in 18 patients (6 of 8 patients in group A and 12 of 16 in group B). In 12 cases the treatment could be stopped after the first series.
Carcinoma, Transitional Cell↗
Combined percutaneous and transurethral approach to stenoses of the ureteral meatus after transurethral resection for bladder tumor.
A stenosis of the ureteral meatus may result from transurethral resection (TUR) for bladder tumor. Open reconstructive surgery is not recommended because of possible tumor implantation. Preservation of the renal function is the main goal, particularly when chemotherapy with nephrotoxic drugs is planned. Moreover, the patency of the vesicoureteral junction has to be preserved to allow regular inspection of the upper urinary tract for urothelial tumor. The first measure is decompression by nephrostomy. After antegrade cannulation of the stenotic ureteral meatus, a ureteral stent is left for several weeks prior to transurethral meatotomy, which is also followed by stenting for 6 weeks. The retrograde approach will fail more frequently. Sixteen ureteral meatal stenoses were treated in 11 patients. The vesicoureteral junction was permanently restored in about 50%, even when it had not only been injured by one or several TURs, but also by the preceding radio- and chemotherapy.
Aged↗
Complications of Bacillus Calmette-Guerin immunotherapy: review of 2602 patients and comparison of chemotherapy complications.
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Antineoplastic Agents↗
Cystectomy: the treatment of choice in patients with carcinoma in situ of the urinary bladder?
Patients (n = 46) with carcinoma in situ (Tis) of the urinary bladder were treated by intravesical chemotherapy. The complete remission rate was 75%. After a mean interval of 17 months recurrent tumours were diagnosed in 47%. Radical cystectomy with urethrectomy was performed in eight patients. Distal ureterectomy and uretercystoneostomy was done in six patients because of a distal ureteric tumour. Based on this group of 46 patients and the current literature, the following criteria are essential in indicating cystectomy: (1) micro-invasion; (2) persistent Tis after adequate intravesical treatment; (3) progressive tumour; (4) Tis of ureter and/or prostate; (5) tumour recurrence at more advanced stage.
Administration, Intravesical↗
Intravesical instillation of BCG in carcinoma in situ of the urinary bladder. EORTC protocol 30861. EORTC-GU Group.
This is a report of an ongoing phase II study which should elucidate some of the open questions which still remain in the most effective treatment of CIS by BCG. As indicated by the preliminary results on side effects the number of instillations or reducing the dosage (as toxic reaction to BCG could be possibly reduced by changing already shown by Dr. Pagano in this meeting), as far as there is equal efficacy. Prognostic factors in patients with intravesical BCG have yet to be defined. A recent publication by Torrence demonstrated that granulomatous cystitis or PPD skin test are of no or borderline significance (Torrence et al., 1988). They are not considered as a prognostic indicator for the individual patient. Although the number of patients (14) evaluated by immunohistological techniques is small, we do hope that the information about the local immune response will give more insight in the mode of action of BCG as well as indicate possibly a good prognostic factor.
Administration, Intravesical↗
Hormone receptors in renal cancer: an overview.
The current literature concerning hormone receptors in renal cell cancer is reviewed. Our own results of histochemical determination of estrogen receptors by means of monoclonal antibodies are presented. Based on the studies that have been reviewed and the differing results of the receptor assays, we conclude that there is a very limited basis to apply hormone therapy in renal cell cancer. However, the new immunohisto-chemical methods should be used to resolve the question about the hormone dependency of renal carcinoma.
Antibodies, Monoclonal↗
Antiproliferative effect of Hu-interferon-gamma in 674V and J82 bladder carcinoma cell lines.
Hu-IFN-gamma was evaluated in regard to the antiproliferative effect on J82 and 647V bladder cancer cell lines. In addition, the IFN-receptors were determined. There was a significant growth inhibition of J82 as well as 647V at low dose Hu-IFN-g (1 U/ml). The growth inhibition was significantly higher in 647V than in J82. The binding assay for 125J-Hu-IFN-g revealed 870 and 3,000 binding sites for 647V and J82, respectively, indicating that the antiproliferative effect of Hu-IFN-g may not depend on the absolute amount of IFN-receptors, in the two cell lines tested.
Carcinoma↗
Interactions between bladder tumor cells as tumor spheroids from the cell line J82 and human endothelial cells in vitro.
Multicellular tumor spheroids (MCTS) are a reliable model of nonvascularized tumor cell aggregates showing a well defined three-dimensional growth pattern and are comparable with small metastatic cancer cell complexes in blood circulation. In the present study we have established a co-culture system of multicellular bladder tumor spheroids with human endothelial cells on extracellular matrix (ECM) in order to investigate morphological and proliferative changes of endothelial and tumor cells within a defined time of cell-cell interaction. The MCTS--endothelial cell--extracellular matrix complex was observed within coculture periods from 1/2 to seven days. Morphological changes (light microscopy, scanning and electron microscopy) indicated that MCTS are not influenced by cocultured endothelial cells. The tumor cells invaded into the ECM after degradation of endothelial cells in the center of the contact zone. Endothelial cells, however, showed degenerative changes as well as a complex reaction in their proliferation activities. We could recognize an initial increase of proliferation of endothelial cells next to the MCTS. Later on, endothelial cells next to invading tumor cells showed changes in morphological polarity. The model system used has the advantage of using human tumor tissue. It distinguishes between basic cellular mechanisms like adherence, migration, DNA synthesis and proliferation in the study of the contact of tumor cells and vascular endothelial cells as an important event in hematogenous tumor spread.
Cell Communication↗
The value of sonography in the diagnosis and follow-up of patients with blunt renal trauma.
Eighty-eight patients with blunt renal trauma were examined sonographically. Rupture of the kidney was diagnosed in 41 patients and contusion of the kidney in 45. The correlation between operative findings, sonography and urography showed positive sonographic findings to be correct in all patients with rupture of the kidney. In 4 patients with normal sonograms, the diagnosis of a contusion was based on the urographic results. Three patients underwent angiography. An intimal lesion was seen in 2 and a tear of the renal artery in 1. The results of our investigation suggest that sonography should be applied in the first place in the evaluation of blunt renal trauma. It is the investigation of choice during follow-up after surgical as well as conservative therapy.
Adolescent↗