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Biomedical subjects

W F Whitmore

Publications and source records attributed to W F Whitmore.

At least 73 records · Page 4Linked to original sources
PubMed1988

The relative value of cytometry and cytology in the management of bladder cancer: the Memorial Sloan-Kettering Cancer Center experience.

The flow cytometric studies presented herein are based almost entirely on DNA measurements and represent an early application of this diagnostic test. Nevertheless, the MSKCC experience with FCM has demonstrated that it is technically feasible and clinically useful. The sensitivity of FCM is in the range of 80% to 85% overall, and is superior to that of conventional voided or bladder wash cytology. In the absence of inflammation secondary to infection, calculi, or intravesical agents such as BCG, the specificity is greater than 90%. In the presence of inflammation, FCM appears to be less specific than conventional cytology. A potential advantage of FCM over cytology is the quantitative nature of the examination permitting comparisons of sequential examinations. Also, there are refinements in technique that hold promise of increasing the accuracy or clinical usefulness of FCM, eg, the joint measurements of DNA and differentiation antigens defined by monoclonal antibodies. Yet, despite the current and potential advantages of FCM, voided urinary cytology continues to be the procedure of choice for detection and monitoring urothelial carcinoma, not only because of our long experience and better understanding of this test, but because of its proven high specificity, because it is noninvasive, widely available, and may help to detect upper tract or urethral tumors.

Carcinoma, Transitional Cell↗
PubMed1987

Effects of intermittent diethylstilbestrol diphosphate administration on the R3327 rat prostatic carcinoma.

Clinical trials have utilized intermittent diethylstilbestrol diphosphate (DES) therapy in advanced symptomatic prostatic carcinoma to diminish the morbidity of standard endocrine therapy. To determine the effect of intermittent DES administration on the Dunning R3327 rat prostatic adenocarcinoma 60 days following tumor implant, 6 groups were randomly assigned: control (N = 8), castrate (N = 10), high dose DES (N = 8, 1.6 micrograms/ml DES continuously in drinking water), low dose DES (N = 10, 0.4 microgram/ml continuously in drinking water), intermittent high dose DES (N = 10, 1.6 micrograms/ml DES in drinking water for 1 week, then off for 3 weeks), and intermittent low dose DES (N = 10, 0.4 microgram/ml DES for 1 week, then off for 3 weeks). Results indicate that low or high dose DES, and intermittent low or intermittent high dose DES during the week of administration were able to reduce serum testosterone to castrate levels (0.1 ng/ml). After withdrawal of intermittent DES, serum testosterone returned toward control levels (1.0 ng/ml). Initial mean tumor burden between control and treatment groups was not significantly different. All DES exposed rats had a tumor volume at death (range, 15.6-18.3 cm3) smaller than control (mean, 25.4 cm3) or castrate (mean, 40.8 cm3) rats. Despite this significant survival advantage from the time of randomization was achieved only in castrate (median survival, 331 days) or high dose DES (median survival, 359 days) groups compared to control (median survival, 225 days). Similarly, significant prolongation in tumor doubling time was achieved only by rats receiving castration or high dose DES. Intermittent DES administration controls tumor volume but does not provide a survival advantage. In this respect, intermittent DES is inferior to castration.

Animals↗
PubMed1987

The sensitivity of bladder wash flow cytometry, bladder wash cytology, and voided cytology in the detection of bladder carcinoma.

The sensitivity of voided urinary cytology (VUC), bladder wash cytology (BWC), and bladder wash flow cytometry (BWFCM) in detecting cancer was studied in 70 patients with biopsy-proven bladder tumors. There were 11 Grade I papillomas, 14 Grade II TA, 18 Grade II-III TIS, 19 Grade II-III T1, and eight Grade II-III T2 carcinomas. One to five VUCs per patient (mean, 2.63) were obtained within the 24 hours preceding biopsy. At endoscopy a bladder wash specimen was obtained and divided for cytologic and flow cytometric examinations. For all tumor categories combined, the sensitivity for one, two, and three voided cytology examinations per patient was 41%, 41%, and 60%, respectively. The sensitivity of a single BWC was 61%, of a single BWFCM, 83%. Thus, one BWFCM is more sensitive than three VUC (binomial test; P = 0.006); one BWC is more sensitive than two VUC (P = 0.01); and one BWFCM is more sensitive than one BWC (P = 0.003). These findings remain significant when papillomas are excluded from the analysis (P less than or equal to 0.03) and when papillomas and T2 tumors are jointly excluded (P less than or equal to 0.02). Only four of 70 patients (6%) had their cancers detected by VUC and/or BWC rather than BWFCM. In summary, irrigation cytology specimens are more sensitive than voided urinary cytology, and bladder wash flow cytometry is more sensitive than either in diagnosing bladder cancer. Flow cytometry is more sensitive because of the better sampling of bladder irrigation compared with voided urine and because of the measurement technique itself.

Biopsy↗
PubMed1987

The practical use of tumor marker determination in bladder washing specimens. Assessing the urothelium of patients with superficial bladder cancer.

Bladder washing specimens from 81 patients with recurrent multifocal superficial bladder cancer were evaluated for DNA profile by flow cytometry and cell-surface blood group (ABH) antigen reactivity by a modified specific erythrocyte adherence test. The study was conducted in a prospective, blind, nonrandomized fashion. Fifteen patients were treated with transurethral resection (TUR) alone and 66 with TUR and intravesical administration of bacillus Calmette-Guerin weekly for 6 weeks (TUR + BCG). Among the patients treated with TUR only, there was a notably greater rate of tumor recurrence and progression in patients with unfavorable tumor markers (aneuploidy and ABH-negative reactivity) than in those with favorable markers (diploidy and ABH-positive reactivity). The difference was less striking in patients treated with BCG, which reduced the frequency of recurrence or progression at 30 months from 87% to 44% and from 60% to 23%, respectively. This favorable effect of BCG was virtually confined to patients with initially favorable markers and to those whose initially unfavorable markers became favorable during BCG administration. Aneuploidy and negative ABH are phenotypic expressions of undifferentiation that can forecast the potential of the urothelium to form new tumors and predict invasion. To an extent, these markers are independent of the grade and stage of the disease. BCG can induce prognostically favorable conversion of the markers expression. Lack of such conversion indicates lack of response to BCG and should be regarded as evidence of persistent disease even if conventional methods do not reveal it. Therefore, sequential determination of markers is useful in monitoring patients with superficial bladder cancer treated with intravesical BCG.

Adult↗
PubMed1987

Long-term effects of initial therapy.

The long term effects of initial therapy are a combined consequence of the effects of treatment on the cancer and on the host. Local tumor control, whatever its impact on the occurrence of metastasis, is an achievable and worthwhile goal of therapy and the methods for attaining it may have significantly different effects on quality of life. These considerations are grossly illustrated for renal cell, bladder and prostatic cancers.

Kidney Neoplasms↗
PubMed1987

Toxicity of intravesical BCG and its management in patients with superficial bladder tumors.

Toxicity of bacillus Calmette-Guerin (BCG) Pasteur strain, given in a dose of 120 mg once a week for 6 weeks, was retrospectively evaluated in a study of 107 patients with recurrent superficial bladder cancer. Only six patients had no symptoms of toxicity. Severe cystitis (ten patients) was most likely to occur in those with decreased bladder compliance before treatment. Systemic symptoms resembling those of influenza (flu) were severe in six patients. Potentially serious complications occurred in six patients. Overall, toxic reactions were mild and self limited, and toxicity often could be easily managed by a reduction in the BCG dose (17 patients), temporary interruption of treatment (five patients), or cessation (four patients). Late occurrence of bladder granulomas (32 patients) and cystoscopic appearance of significant cystitis (55 patients) did not correlate with posttreatment voiding symptoms, and these changes were temporary and confined to the first 6 months after treatment. There were no cases of late bladder contracture, and none of the patients free of voiding symptoms before treatment had such symptoms afterward. Extravesical granulomas were observed in 37 patients and were the cause of obstruction of the urinary tract in nine. Pretreatment skin reactivity did not correlate with toxicity, and concurrent percutaneous administration of BCG had no effect on toxicity. BCG has a cumulative effect, so increased toxicity is to be expected during long-term administration. BCG toxicity is primarily a response of the cell-mediated immune system, and transient local or systemic infection appears to be important. This fact suggests that immunosuppression is a relative contraindication to BCG use.

Adult↗
PubMed1987

Testicular failure in patients with extragonadal germ cell tumors.

Eight patients with mediastinal or retroperitoneal germ cell tumors who had undergone testicular biopsy or orchiectomy were retrospectively analyzed for primary testicular abnormalities, subfertility, and abnormal sex hormone levels. Testicular tissue was abnormal in all patients, revealing peritubular fibrosis (six), decreased spermatogenesis (eight), interstitial edema (five), Sertoli cells only (one), and Leydig cell hyperplasia (two). Detailed hormone analysis in five patients revealed elevations of luteinizing hormone in four, decreased serum testosterone in two, elevations of estradiol in two, and elevation of human chorionic gonadotropin in one patient. A history of infertility was documented 2 months to 13 years before presentation in four patients and suspected in another. Extragonadal germ cell tumors, like their testicular counterparts are associated with primary germ cell defects, some of which seem to be independent of gonadotropin production by the tumor. In addition, the rather high incidence of antecedent infertility suggests that either a congenital or acquired primary germ cell defect contributes to defective spermatogenesis and the development of cancer in incompletely migrated germ cells.

Adolescent↗
PubMed1987

The sensitivity of flow cytometry compared with conventional cytology in the detection of superficial bladder carcinoma.

Three groups of patients with superficial bladder carcinoma were studied: 110 patients had carcinoma in situ (TIS), 54 had noninvasive papillary transitional cell carcinoma (TA), and 64 had transitional cell carcinoma infiltrating the lamina propria (T1). One to six conventional cytologic examinations per patient (mean 2.8) were obtained during the 24 hour period before biopsy. For all tumor categories combined, the sensitivity was 49%, 54%, 62%, and 66% for one, two, three, and four cytologic examinations per patient, respectively. Cytologic sensitivity varied according to tumor category; it was greater in the TIS and T1 categories than in the TA category. To compare with the cytologic results, a subset of 103 patients had bladder irrigation performed immediately before the biopsy which was subsequently analyzed by flow cytometry. The sensitivity of a single flow cytometric examination for all tumor categories combined was 78%. As with the cytologic examinations, the sensitivity of flow cytometry varied with tumor category; it was greater in TIS and T1 categories than in the TA category. The sensitivity of one flow cytometric examination was superior (binomial test, P less than or equal to 0.05) to that of one or two cytologic examinations for TA tumors and to that of one, two, or three cytologic examinations for TIS, T1, and all tumor categories combined. Only three of 103 patients had their cancers detected by cytologic examination and not by flow cytometry.

Carcinoma in Situ↗
PubMed1987

Flow cytometry of prostate cancer: relationship of DNA content to survival.

Between March 1970 and December 1978 there were 366 patients with prostatic cancer treated by 125I seed implants and pelvic lymph node dissection. All had a minimum of 5 years follow-up. One hundred thirty-three patients had metastatic prostatic cancer in lymph nodes (Stage D1) at the time of lymph node dissection and seed implantation. Ninety-one of the 133 patients were judged to have sufficient metastatic prostatic cancer in their nodal tissue (greater than 50% replacement with tumor) to justify flow cytometric cellular DNA measurements on the involved paraffin-embedded nodal tissue. Nine patients were excluded due to uninterpretable DNA histograms leaving 82 patients for analysis. Forty-nine patients had aneuploid and 33 had diploid tumors. There was no statistical bias between the aneuploid and diploid groups due to age (P = 0.970, chi 2 test), time between diagnosis and implantation (P = 0.217, chi 2 test), number of positive nodes (P = 0.669, two-sample t test of means), or tumor grade (P = 0.332, chi 2 test). Median survival time of the aneuploid and diploid groups was 5.0 and 8.8 years, respectively (P = 0.0109, log rank test). Cox regression analysis confirmed the effect of aneuploidy versus diploidy on survival by controlling for other potentially confounding variables (age, time from diagnosis to implantation, number of positive nodes, and grade). Grade as a predictor of survival did not approach statistical significance in this series of relatively small size (P = 0.116). Thirty-eight of the 82 patients had moderately differentiated neoplasms. Nineteen of these were aneuploid and 19 diploid. The median survival was 5.8 and 9.1 years, respectively, for these grade-matched aneuploid and diploid groups (P = 0.039, log rank test). We conclude that flow cytometric DNA measurements on archived paraffin-embedded tumor in nodal metastases appear to be a strong predictor of survival for Stage DI prostatic cancer.

Aneuploidy↗
PubMed1987

Abnormalities at chromosome region 3p12-14 characterize clear cell renal carcinoma.

In an effort to determine whether or not any characteristic chromosomal abnormalities exist in renal cancer, cytogenetic findings were correlated with tumor histology in nine cases of renal adenocarcinoma. Metaphase preparations adequate for analysis were obtained from cultures harvested between day 3 and day 21. Model chromosome number was diploid in three cases, hypodiploid in three, and hyperdiploid in the remaining three. One clear cell adenocarcinoma failed to reveal any chromosomal abnormality. Two tumors, a tubular/papillary carcinoma and an acinar/papillary carcinoma, showed the clonal abnormalities del(1)(p2l),+2,+7,+8,+12,+13,+16,+17,-21 and t(2;10)(q14-21;q26),+7q,+11q,-18, respectively. Interestingly, five of six clear cell tumors studied had clonal abnormalities affecting the short arm of chromosome #3 in the 3p12-21 region, and in the remaining case, of 15 karyotyped metaphases suitable for interpretation, one showed a deletion in 3p. These data indicate that clear cell carcinoma of the kidney may be associated with a nonrandom chromosomal abnormality involving the 3p12-14 region.

Adult↗
PubMed1987

Fertility status of patients with clinical stage I testis tumors on a surveillance protocol.

A potential benefit of a surveillance protocol for the management of patients with clinical stage I testis tumors is the avoidance of ejaculatory disturbances and infertility resulting from retroperitoneal lymph node dissection, the standard treatment for patients with this stage of disease. To address this issue we evaluated 22 patients with clinical stage I testis tumors on a surveillance protocol with history, physical examination and semen analysis. Previous fertility was unknown or it had not been tested in the majority of the patients (74 per cent). Ten patients (45 per cent) had abnormal spermatogenesis on the basis of a low sperm count or sperm motility. Of 6 patients with oligospermia or azoospermia 3 had recovered normal spermatogenesis when they were re-evaluated 4 to 19 months later. Although in this group of carefully staged cases the incidence of subfertile sperm counts seems to be similar to those with higher stage disease, some patients with abnormal counts clearly recover. The avoidance of retroperitoneal lymph node dissection seems to spare fertility in at least a small percentage of these patients.

Adult↗
PubMed1987

Ureteral carcinoma in situ after successful intravesical therapy for superficial bladder tumors: incidence, possible pathogenesis and management.

A total of 66 patients with multifocal, progressive, flat carcinoma in situ of the bladder responded completely to intravesical bacillus Calmette-Guerin therapy for more than 1 year. Of the patients 19 (29 per cent) had clinical evidence of distal ureteral carcinoma in situ between 13 and 30 months (median 15 months) after bacillus Calmette-Guerin treatment. After evaluation of a positive urinary cytology study failed to reveal recurrent urothelial tumor of the bladder or prostatic urethral mucosa 6 patients underwent distal ureterectomy, 2 underwent nephroureterectomy, and 11 were managed by ureteroscopic resection and fulguration. In patients with carcinoma in situ of the bladder treated successfully with topical therapy the ureters represent a potential site of in situ carcinoma.

Administration, Intravesical↗
PubMed1987

Monitoring endoscopic treatment of superficial bladder carcinoma by postoperative urinary cytology.

Transurethral resection was the only modality of treatment in 39 patients with long-standing, recurrent, superficial bladder carcinoma. Postoperative urinary cytology was performed within 3 days of each endoscopy. Tumor recurrence was defined by the presence of a positive biopsy or visible papillary tumors on followup cystoscopic examination. Tumor recurred in 38 patients (97.4 per cent) and 1 patient (2.6 per cent) has remained free of disease 74 months following transient positive postoperative cytology. Among the 38 recurrences 15 (39.5 per cent) were positive, 3 (7.9 per cent) suspicious and 20 (52.6 per cent) negative at the postoperative cytological examination. The interval to recurrence did not differ significantly among the 3 groups. The failure of a negative postoperative cytology study to predict a durable response to treatment by transurethral resection reflects the polychronotopic nature of superficial bladder tumors in this select patient population and suggests the need for adjuvant therapy.

Carcinoma, Transitional Cell↗
PubMed1987

Monitoring intravesical bacillus Calmette-Guerin treatment of superficial bladder carcinoma by postoperative urinary cytology.

We studied 51 patients with superficial bladder carcinoma who had been treated with transurethral resection of all gross tumor followed by intravesical bacillus Calmette-Guerin weekly for 6 weeks. Within 72 hours of either the first or second quarterly cystoscopic surveillance examination after bacillus Calmette-Guerin therapy, a conventional cytology study was obtained. Of these patients 8 (15.7 per cent) had positive, 9 (17.6 per cent) suspicious and 34 (66.7 per cent) negative postoperative cytology studies. Subsequent tumor recurrence was defined as a positive biopsy or visible papillary tumors on cystoscopic examination. All 8 patients with a positive postoperative cytology study had tumor recurrence at a median interval of 4 months. Of the 9 patients with a suspicious study 7 (77.8 per cent) had recurrent tumor at a median interval of 7 months and 2 (22.2 per cent) had no evidence of disease at 16 and 19 months, respectively. Of the 34 patients with a negative postoperative cytology study 13 (38.2 per cent) had tumor recurrence after a median interval of 4 months and 21 (67.8 per cent) had no evidence of disease after a median of 25 months. The tumor recurrence rate in patients with a positive or suspicious postoperative cytology study was significantly greater than that of patients with a negative study (p equals 0.001, Fisher's exact test). Postoperative cytology appears to be a significant prognostic indicator following transurethral resection and intravesical bacillus Calmette-Guerin treatment of superficial bladder carcinoma.

Administration, Intravesical↗