Cystectomy: ureteroileal anastomosis without stenting.
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Biomedical subjects
Publications and source records attributed to T Farsund.
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Since the first ureteral dilatations in experimental dogs were performed, the technique in human has been accepted and improved over the years. Balloon dilatation has been successful, but it has been very difficult or impossible to force the guide wires through long total strictures, especially those localized distally. In order to recanalize very narrow strictures or total occlusions located in the distal ureter, a modified angiographic technique was developed and tested in 12 ureters in 10 patients.
Cytology is an essential and indispensable procedure in the evaluation of patients suspect of harboring a tumor of the lower urinary tract. The interpretation of the cytologic sample is difficult but, in experienced hands, the value of the procedure is significant to the urologist.
The purpose of this study was to investigate the applicability of flow cytometry to human placenta and to challenge the hypothesis that no cell division takes place in the last 4-6 weeks of pregnancy. Relative DNA content in individual placental cells was measured and high-resolution DNA histograms were obtained, based upon measurements of more than 10 000 cells. The fraction of cells with S-phase DNA content was lower in cases of intra-uterine growth retardation. In contrast to the earlier concept based on measurements of total organ content of DNA, this study indicates that cell division in placenta takes place right up to parturition. Small amounts of tissue are sufficient for the analyses which may aid surveillance of both normal and risk pregnancies.
High-resolution flow cytometric measurements of cellular DNA content have been performed in 69 patients with transitional cell carcinomas of the urinary bladder. By selective sampling of cells at cystoscopy, mapping of the whole bladder could easily be performed, including the tumor as well as different areas of the surrounding normal-appearing mucosa. The cell-cycle distribution showed an increasing fraction of cells with S- and G2-phase content parallel to the World Health Organization (WHO) grade of the tumors, ranging from 1.7% S-phase cells in normal subjects to nearly 20% in tumors of WHO grade 3. WHO grade 2 tumors could be divided into two populations: (1) diploid, with a cell-cycle distribution similar to grade 1 tumors and low frequency of infiltration; and (2) aneuploid, with a high rate of infiltration and high fractions of S- and G2-phase cells. Furthermore, the aneuploid tumors could be subdivided into two main classes, one hypertriploid with high frequency of involvement of the surrounding normal appearing mucosa; and one hypotetraploid, with less frequency of such involvement and infiltration. It is concluded that by selective sampling and mapping of the bladder mucosa using flow cytometry, subclassification of this type of tumor can be performed rapidly, giving a reliable measure of the involvement of the bladder in the neoplastic disease and a biologic subclassification based on the type of DNA aberrations.
A method is described by which the effect of intravesical chemotherapy can be monitored. Cytological samples obtained selectively during treatment were used for morphological and flow cytometric studies, and isoantigen (A, B and H) assessment in 2 patients with urothelial cancer. With flow cytometry even small aneuploid populations in the urothelium could be identified. From the histograms the urothelium was seen to contain 2 different cell populations: 1) diploid and 2) aneuploid. The ratio between aneuploid and diploid cells decreased significantly during treatment. Treatment was continued until no evidence of aneuploid cells could be identified in the histograms. Thus, it is demonstrated that intravesical chemotherapy for certain types of bladder cancer can eradicate the aneuploid cell population. A good correlation was found between cytological studies and flow cytometric measurements. Isoantigen assessment was done in the cell suspension used for morphological and flow cytometric studies. Isoantigen assessment also showed loss of antigens after completion of treatment, indicating that the diploid population was not normal biologically. Thus, 3 parameters can be correlated and related also to topography.
A longitudinal study of transitional cell carcinomas of the urinary bladder has been performed in a region of Western Norway. Hematuria and infection were the first symptoms of neoplasia of the urinary bladder, showing marked and reproducible seasonal variations. Most of the tumours showed the first symptom at the end of the year. They also had a higher histological grade (WHO) than those occurring at other times of the year. This indicates that environmental factors dependent on the season may be of importance for the manifestation of malignant growth of the urinary bladder.
DNA aberrations in bladder mucosa have been investigated in altogether 26 patients with aneuploid WHO grade 2 and 3 tumours (transitional cell carcinomas; TCC). In about 1/4 of the patients aneuploid cells were found only in the tumour. Hypotetraploid tumours showed the lowest frequency of involvement of the normal appearing mucosa of the trigone (43%). In hypertriploid tumours the corresponding value was 71%. In altogether 14 of the patients, the same type of aneuploid cells was found in the normal appearing mucosa as in the tumour. This indicates frequent involvement of the whole bladder mucosa in the tumour disease. In about 1/4 of the cases other types of ploidy aberrations were found in the normal appearing mucosa than in the tumour. This is indicative of preneoplastic changes in the mucosa, of which only one type of aberrations is associated with tumour growth. In some cases with multiple tumours of the bladder, all the tumours had the same aneuploid stemline, while in other cases the tumours were of different aneuploid stemlines. This is conformal with other reports of atypia in the surrounding mucosa in TCC and with the concept that recurrence of high grade tumours is the consequence of neoplastic involvement of the whole bladder.
A total of 4 patients with transitional cell carcinoma of the bladder underwent complete mapping of the mucosa and tumors with combined cytologic, histologic and flow cytometric evaluation of the extent of involvement of the neoplastic process. Flow cytometric measurement of the cellular deoxyribonucleic acid content in multiple cell samples taken at cystoscopy showed similar changes in the normal mucosa as in the tumors. These changes consisted of an increased fraction of cells with S-phase deoxyribonucleic acid content in 2 patients with grades 1 and 2 tumors, and the presence of extensive aneuploidy in 2 patients with World Health Organization grades 2 and 3 tumors. While grade 1 and some grade 2 tumors (World Health Organization) are composed only of diploid cells, some of the grade 2 and all grade 3 tumors consist of a mixture of diploid and aneuploid populations. Such aneuploid clones could be identified in normal-appearing mucosa and, thus, be a source of new occurrences. The impression of heterogeneity in histograms from different tumors within the same bladder is assumed to be caused by a variation in the ratio between aneuploid and diploid populations (high ratio in tumor and low in normal-appearing mucosa). This phenomenon may be the reason for variation in grading based on histological studies.
A method is described by which urothelial cells from well defined areas in the urinary bladder mucosa can be obtained. At cystoscopy epithelial cells are aspirated by means of a ureteral catheter. The cells obtained by this selective sampling technique are well suited for morphology and for quantitative single cell measurements by flow cytometry (FCM). In the present study the cell cycle distribution has been measured by FCM. Twenty-five patients (13 males and 12 females) had urothelial cells collected from well defined areas in the mucosa and the DNA content measured from different sites separately. The distribution of bladder mucosa cells in the different parts of the cell cycle (G1, S-phase and G2 + M) is reported. No significant differences were found with regard to sex and age of the patients. Also, a low regional variation was found in the bladder mucosa indicating that the method should enable the discrimination of even small abnormal cell populations in tumour disease. No evidence of polyploidy in the human urothelium was found.
A simple method is described by which epithelial cells can be obtained easily from well defined areas in the human bladder. During cystoscopy under direct vision epithelial cells can be aspirated through a blunt ureteral catheter from selected areas of normal-appearing mucosa and from bladder neoplasms for use in routine cytology studies and quantitative single cell measurements by flow cytometry. With this selective method of collecting cytological material pathological changes not detectable in voided urine or bladder washing specimens can be demonstrated. The method seems especially suited for tracing aneuploid cells in pre-malignant and malignant conditions, with the possibility of mapping the entire bladder mucosa for the extent of pathological changes.
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A survey of the use of flow cytometry for clinical purposes is given. In the last decade the main clinical application of this technique has been measurements of cellular DNA content for estimation of cell cycle distribution and ploidy studies. A large body of data is now available on the presence of aneuploidy in different malignant diseases. By measurements with high resolution, the demonstration of abnormal cellular DNA content in several types of tumors can be of definite diagnostic value when combined with conventional diagnostic procedures. The prognostic significance of different types of DNA aberrations is so far not established. Attempts to monitor cancer treatment by studying altered cell cycle distribution have not been successful, although some applications are of potential value. The main reasons for this are the complexity of tumor tissue as well as difficulties with interpretation of altered cell cycle distribution caused by drug combinations. For further progress in this field more emphasis on other cell constituents than DNA measured by flow cytometry is desirable, either as single or as multiparameter measurements.
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A dose of 0.2 ml propylene glycol (1,2 propanediol) was injected subcutaneously into 12 hairless mice three times a week for three months. Four animals were killed at 1, 2 and 3 months and micro-flow fluorometric histograms of the bladder epithelial cells were made. The proportion of cells in diploid S phase was not much altered, but the proportion of tetraploid S-phase cells was significantly reduced and at three months DNA synthesis in tetraploid cells completely disappeared. The proportion of diploid cells increased, the proportion of tetraploids was slightly reduced and almost all octoploid cells disappeared. The changes are qualitatively similar to those seen after the bladder carcinogen dibutylnitrosamine, and after repeated injections of cyclophosphamide, but quantitatively much less pronounced. They can be explained as a result of cell toxicity whereby propylene glycol kills some bladder epithelial cells and disturbs the mechanism of repeated DNA synthesis. Propylene glycol is thus not a completely harmless solvent and when the kinetic effects of bladder carcinogens dissolved in propylene glycol are studied, the effect of the solvent alone must be accounted for.
A dose of 2 mg cyclophosphamide (Sendoxan, "Pharamcia", Sweden) dissolved in 0.2 ml distilled water was injected intraperitoneally once a week to 12 hairless mice for three months. Four animals were killed at 1, 2 and 3 months and micro-flow fluormetric histograms of the bladder epithelial cells were made. The proportion of cells in diploid S phase remained normal at 1 and 2 months, but increased at 3 months. The proportion of tetraploid S-phase cells fell rapidly and markedly and there were almost no cells in this phase at 1, 2 and 3 months. The proportion of diploid cells increased, the proportion of tetraploids was significantly reduced and the octoploid cells disappeared after 2 months. The changes are similar to those seen after repeated injections of the bladder carcinogen dibutylnitrosamine, but less pronounced. Since cyclophosphamide is a strong alkylating agent it is possible that, in the doses used, it is also a weak carcinogen for hte bladder epithelium. This must be tested in direct, long-term treatment experiments. Bladder cancers in humans receiving cyclophosphamide therapy have been described.
In order to see whether the polyploid cells lining the mouse urinary bladder are formed by nuclear fusion, such epithelium was studied under the light and electron microscope forty-eight hours after an injection of cyclophosphamide when the bladder epithelium regenerates with rapid formation of many diploid, tetraploid and octoploid cells. The probability of seing fusion, if it occurs, ought then to be high. Serial sections of many specimens from four mice revealed no signs of fusion. Thus we found no support for the theory that polyploid cells are formed by nuclear fusion.
The initial effect of a single subcutaneous injection of 0.01 ml of dibutylnitrosamine on the mouse (hr/hr strain) urinary bladder epithelium was a block in DNA synthesis in the diploid cells followed by a regenerative reaction. This did not, however, lead to a subsequent wave of increased DNA synthesis among the tetraploid cells. Later, a new wave of DNA synthesis occurred among the diploid cells, and again there was no subsequent wave of tetraploid DNA synthesis. The total cell number was not affected. These disturbances resulted in periods of reduced numbers of octoploid cells. This effect was unlike that obtained in previously published experiments using cyclophosphamide, which led to considerable hyperplasia, especially of octoploid cells, and no disturbance of tetraploid DNA synthesis. Thus the action of a single dose of dibutylnitrosamine on the epithelial cells in the mouse urinary bladder is very different from that of cyclophosphamide in a single dose, but it is not possible to say whether this has anything to do with the carcinogenicity of the nitrosamine.