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Biomedical subjects

H W Herr

Publications and source records attributed to H W Herr.

At least 145 records · Page 8Linked to original sources
PubMed1988

Anticarcinoma activity of rhodamine 123 against a murine renal adenocarcinoma.

The mitochondria of carcinoma cells retain the permeant cationic compound rhodamine 123 longer than the mitochondria of normal epithelial cells. The possibility of exploiting this difference in the chemotherapy of a murine renal adenocarcinoma was investigated. Rhodamine 123 exhibited anticarcinoma activity in mice and this activity was potentiated by 2-deoxyglucose and methylglyoxal bis(guanylhydrazone), a chemotherapeutic agent that is toxic to mitochondria. Prolonged retention of rhodamine 123 by renal tumor cells compared with normal renal epithelial cells was demonstrated by flow cytometry, perhaps explaining its antitumor activity. A combination of both mitochondrial toxins, rhodamine 123 and methylglyoxal bis(guanylhydrazone) produced the longest survival and had the greatest antitumor effect.

Adenocarcinoma↗
PubMed1988

Bladder cancer: pelvic lymphadenectomy revisited.

The value of pelvic lymphadenectomy in patients undergoing cystectomy for bladder cancer is controversial. While perhaps 1-2 percent of all patients may be cured after excision of positive nodes, the overall contribution of this procedure to survival is minimal. Pelvic lymphadenectomy is however becoming more valuable for staging and therapy in combination with more effective systemic chemotherapy and its role in the overall management of patients with invasive bladder cancer is presently being redefined.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for advanced transitional cell carcinoma of the urothelium.

Of 92 patients who received methotrexate, vinblastine, doxorubicin and cisplatin complete and partial remissions were observed in 69 +/- 10 per cent of 83 adequately treated measurable and evaluable patients with advanced stages (N+M0 and N0M+) transitional cell urothelial cancer. Complete remission was achieved in 37 +/- 10 per cent of the patients clinically, pathologically and after surgical resection of residual disease. With 17 of 31 complete responders (55 per cent) surviving for 26+ to 49+ months, the estimated probability of survival at 2 and 3 years was 71 and 55 per cent, respectively. Partial remission occurred in 31 +/- 10 per cent of the patients, while 8 per cent had a minor response and 23 per cent had progression with median survivals of 11, 11 and 7 months, respectively. Whereas all metastatic sites responded, including the bone and liver, complete tumor regression was observed more frequently with nodal, pulmonary and local-regional lesions. Brain metastases occurred within 6 to 42 months in 18 per cent of the responders, half of whom never had systemic relapse. Of the remaining 9 patients 2 with nontransitional cell histological tumors did not respond, 5 (5 per cent) were inadequately treated and 2 were excluded from response data because of inevaluable disease parameters but they were free of disease at 16+ and 31+ months. Toxicity was significant, with 20 per cent of the patients experiencing nadir sepsis, 4 per cent a drug-related death, 31 per cent +1 renal toxicity and 41 per cent +1 mucositis. The applications and advantages of the newly proposed international response criteria for bladder cancer are discussed in reference to 25 patients who underwent surgical re-staging, indicating that the disease was understaged clinically in 24 per cent (T less than P), as well as in reference to attainment of true (pathological) complete remission and to other urothelial tract trials. While this therapy seems to have limited antitumor activity against nontransitional cell histological cancer, stage Tis disease and later development of de novo lesions, the regimen is efficacious in selected patients with advanced urothelial tract transitional cell carcinoma.

Adult↗
PubMed1988

Neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) effect on the primary bladder lesion.

Of 50 patients with bladder cancer given 1 to 5 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin in a pilot phase I and II study 63 per cent of 41 with pure transitional cell stage T2-4 lesions responded. While significant downstaging occurred by transurethral resection of the bladder in 70 per cent and by cytology in 60 per cent of the patients, the final T response rate by all noninvasive clinical staging procedures, including sonography and computerized tomography, revealed complete remission in 24 per cent and partial remission in 39 per cent. Of 30 patients who underwent pathological staging 33 per cent achieved stage P0 and 17 per cent stage Tis disease or P less than T. Despite extensive re-evaluation by transurethral resection of the bladder and other noninvasive staging procedures, a clinical staging error (T versus P) of 38 per cent was observed. Of the other 9 patients 4 with mixed nontransitional cell histological findings at presentation never achieved complete remission, although 3 had resolution of all transitional cell elements and 5 (10 per cent) were inevaluable. The toxicity of the regimen was generally acceptable but 6 per cent of the patients required hospitalization for neutropenic fever. While this active regimen can clinically (T) and pathologically (P) induce downstaging in a significant number of patients with primary bladder tumors, this pilot study has raised serious questions concerning the design of future nonrandomized and randomized neoadjuvant studies.

Adult↗
PubMed1988

Neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for extravesical urinary tract tumors.

A total of 11 patients with stage T2-4N0M0 extravesical tumors (prostate, prostatic urethra, urethra and ureter) received 1 to 4 cycles of neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin. Of 10 evaluable patients 4 (40 per cent) had downstaging to T0 disease with a clinical complete remission observed in 3 of 5 (60 per cent) with transitional cell tumors of the prostate and prostatic urethra. Four patients with urethral tumors of mixed or nontransitional histology failed to achieve a complete remission. The disease was staged pathologically in 4 patients: 1 had a partial remission and 3 had progression (all 4 had residual disease). Because therapy with methotrexate, vinblastine, doxorubicin and cisplatin induced only significant tumor regression of transitional cell elements of extravesical tumors and because it was ineffective against mixed histological tumors and in preventing new stage Tis lesions, surgical resection of such lesions is required.

Aged↗
PubMed1988

Bacillus Calmette-Guérin therapy alters the progression of superficial bladder cancer.

The effectiveness of BCG in preventing disease progression in patients with superficial bladder cancer is evaluated. Long-term follow-up of high-risk patients treated in a previously reported randomized control trial of intravesical plus percutaneous BCG shows that progression occurred in 41/43 (95%) of control and 23/43 (53%) of BCG-treated patients. Muscle invasive and/or metastatic disease occurred with equal frequency in the two groups, but was significantly delayed by BCG treatment (P = .012). Cystectomies were required in 18/43 (42%) control and 11/43 (26%) BCG-treated patients. Median time to cystectomy was 8 months for control v 24 months for BCG-treated patients. Based on initial treatment, survival was improved by BCG therapy (P = .032) (median follow-up 6 years). These results suggest that in high-risk patients intravesical BCG can delay disease progression, prolong the period of bladder preservation, and increase overall survival.

Administration, Intravesical↗
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

Quality of life measurement in testicular cancer patients.

The linear-analogue self-assessment (LASA) technique was used to assess acute toxicity and other pertinent attributes relative to quality of life (QL) in patients with advanced testicular cancer who were entered into chemotherapy trials with either velban, Actinomycin-D, bleomycin, cisplatin, and cytoxan (VAB-6), etoposide and cisplatin (EP), or both regimens. Results showed significantly less nausea, vomiting, mucositis, and a earlier return to normal physical activity with EP versus VAB-6. The LASA method appears to be a valid measure of acute toxicity to chemotherapy in testicular cancer patients and provides objective QL information for patients entered into prospective clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
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

Strategies for the management of recurrent and advanced urologic cancers. Quality of life.

The goal of any treatment strategy for cancer is to improve not only patient survival but also quality of that survival. Quality of life (QL) involves individual perceptions (physical, mental, social) which are particularly germane to management of recurrent and advanced urologic cancers. Cancer therapy ideally equally documents a patient's QL as well as tumor response and survival. The QL is best achieved by optimal therapy, defined as appropriate treatment of those patients who need it and avoiding unnecessary or overtreatment of those patients who are not expected to obtain significant benefit. Specific goals of management of urologic neoplasms should strive to eradicate all existing and/or palliate symptomatic disease with the least possible morbidity while attempting to preserve function. Some examples of positive advances in this regard include reduction of therapeutic burden in good-risk patients with germ cell neoplasms; preservation of bladder and sexual function in childhood, adolescent and adult pelvic sarcomas with initial chemoradiotherapy programs and conservative surgery; improved responses of metastatic bladder cancer with combination chemotherapy; pelvic nerve-sparing techniques to preserve sexual potency and continent external or internal urinary diversions should total cystectomy become necessary; prevent or delay cystectomy with intravesical therapy in high-risk patients with polychronotopic superficial bladder tumors and ureteropyeloscopic management (rather than nephroureterectomy) of selected upper tract urothelial tumors. On the negative side, no appreciable value can yet be ascribed to nephrectomy, adjunct radiation or chemotherapy, hormonal or immunotherapy for advanced locoregional or metastatic renal cell carcinoma, aggressive radiation or chemotherapy for nodal metastases from bladder or prostate cancer or hormonal and/or chemotherapy of the asymptomatic patient with metastatic prostatic cancer. Future treatment strategies will improve tumor responses that now prove refractory but they should not be applied at the expense of QL as assessed by the patient. Valid methods for objective measurements of QL need to be devised and incorporated into multimodality curative and palliative clinical trials.

Adolescent↗