Second line treatment of hormone refractory prostatic cancer patients.
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Biomedical subjects
Publications and source records attributed to L G Collste.
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Results of flow cytometry (FCM) examinations of bladder irrigation specimens were compared with those of FCM examinations of cell suspensions from bladder biopsies of 44 urologic patients. The fluorescent dye, acridine orange (AO), was used to stain DNA and RNA differentially and abnormal urothelial cells were identified by their relative content of nucleic acids. Granulocytes and squamous cells could be distinguished from transitional cells in this procedure, and did not interfere with the analyses. Of 28 patients with papillary carcinoma, carcinoma in situ, and invasive carcinoma 27 were identified through FCM examination of irrigation cytology specimens; the one false-negative result was from a low-grade papillary carcinoma. Of 7 patients with papilloma, FCM examinations of irrigation specimens were positive in 4 and negative in 3. Results of FCM studies of biopsy specimens were in good but not complete agreement with those of irrigation specimens. In several cases, irrigation FCM disclosed tumor stemlines that were not identified in biopsy specimens. Discrepancies of this kind seemed most likely due to differences in sampling. Irrigation FCM seems to be a sensitive method for assessing multiple-site bladder tumors, and may be a useful technique for monitoring the course of conservatively managed bladder tumors.
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A new technique for simultaneous multiparameter deoxyribonucleic acid, ribonucleic acid and nuclear size measurements by flow cytometry was applied to the examination of bladder irrigation cytology specimens from 107 urologic patients. The cell samples from patients with bladder carcinoma could be distinguished from normal by 2 features: 1) an increase in the proportion of bladder epithelial cells with more than diploid deoxyribonucleic acid and 2) aneuploid cell peaks. These criteria identified 12 of 13 cases of invasive carcinoma, 24 of 28 cases of carcinoma in situ and 11 of 13 cases of papillary carcinoma. An increased proportion of cells with more than diploid deoxyribonucleic acid or aneuploidy was found in 9 of 14 patients with papilloma and 6 of 19 patients with a history of bladder tumors but no evident disease at present--these were believed owing to increased epithelial proliferative rates or nuclear chromatin abnormalities not visible by light microscopy. None of the 20 patients who had never had bladder tumors was abnormal. While the results in this small clinical trial have been most encouraging an additional descriptor of nuclear chromatin structure is believed necessary to discriminate benign, reactive proliferative epithelium from neoplasm when the latter is near diploid or shedding few cells. Studies to develop such a parameter presently are under way.
An 80-mg dose of adriamycin was given intravesically once a month to 58 patients with superficial transitional cell tumor of the bladder. Complete cytological remission was achieved in all 11 patients with previously untreated, flat carcinoma in situ lesions. In 19 carcinoma in situ patients, who were previously treated by other means, cytological remission occurred in 74%. In T1 and T2 papillary tumor remission occurred in 65 and 20%, respectively. Minor local side effects were observed.
The fraction of cells in S + G2 + mitosis from 54 urothelial tumours was calculated by flow cytometry after acridine orange (AO) staining of cells obtained by bladder irrigation or biopsy. Fluorescence signals emitted by the AO-stained DNA and RNA of each cell were separated optically and measured for 5,000 cells per specimen. The patients were classified by the histology of their tumours and clinical data into 5 diagnostic categories: NED (no evidence of disease, but history of bladder tumour), 3; papilloma, 8; non-invasive papillary carcinoma, 8; carcinoma in situ, 17 and invasive carcinoma, 18. The fraction of cells with DNA values in S + G2 + M of the cell cycle varied between 7 and 57% of the total, with a wide range within each diagnostic category, but no statistically significant differences between the groups. The proportion of cells in S + G2 + M from an individual tumour was not correlated with histologic grade or clinical behaviour. The possibility that some tumour cells with DNA values above G1 level are quiescent cells arrested at S or G2 is discussed.
The reactivity of lymphocytes in lymph nodes draining the site of a transplantable experimental bladder tumor (MBT2 in C3H/HeJ mice) has been measured in a multiparameter flow cytometry system. Acridine orange was used as a nucleic acid probe. This dye intercalates in helical DNA, emitting green (530 nm) fluorescence upon exposure to blue light; it stacks to single-stranded RNA, emitting red (640 nm) fluorescence. The relative magnitude of the increase of lymphocyte DNA and RNA has been evaluated simultaneously in tumor-draining nodes, in nondraining nodes of the same animal, and in untreated control animals. Stimulation of the regional node lymphocytes could be observed after 20 days but not after 10 days. It was uniformly high at 35 days. The transcriptive response (increased proportion of lymphocytes with high RNA) was more pronounced than the proliferative (increased proportion of lymphocytes with more than diploid DNA). The histological changes in the stimulated nodes resembled closely those described by others in human tumor-draining nodes. The described method has the advantage of being simple, rapid, and able to measure a representative part of the whole-cell population.
Lymph node lymphocyte reaction to an explanted, transplantable mouse bladder tumor (MBT-2) was investigated by flow cytometry in animals previously immunized with irradiated tumor cells. Nodal lymphocytes in representative samples from four different lymph node sites were differentially stained for DNA and RNA with the fluorescent dye acridine orange; cell proliferation and the increase in RNA content were measured. Immunization abrogated tumor growth; one immunization reduced tumor take to 25 per cent of the animals, and two immunizations to 14 per cent. Lymphocyte reactivity to the tumor was reflected both by an increase of DNA synthesizing cells and by diploid cells with high RNA. The latter response was more pronounced and thus the more sensitive parameter for measuring immunologic lymph node reactivity. The juxtatumoral node displayed the most pronounced reactivity, but all node sites showed some degree of reaction.
Positive preoperative urine cultures were obtained from 31 of 107 patients who underwent transurethral prostatectomy (TUR). The incidence was 59% among the patients who had had indwelling catheter and 15% in the non-catheterized cases. Of the 76 patients whose urine was sterile before TUR, 24 (32%) became infected in connection with the operation or in the immediate postoperative period. The length of hospital stay after TUR averaged 7.2 days for the patients with sterile urine postoperatively and 10.3 days for those with infected urine, a non-significant difference, partly explained by circumstances other than the infection. The postoperative urinary infections were not associated with serious complications. Postoperative epididymitis occurred in three patients. The mortality was nil.
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