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Biomedical subjects

H W Herr

Publications and source records attributed to H W Herr.

At least 163 records · Page 9Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Conservative management of muscle-infiltrating bladder cancer: prospective experience.

Between May 1979 and July 1983, 217 consecutive patients with documented primary bladder tumors invading muscle were evaluated to determine the fate of patients with conservatively treated muscle-infiltrating bladder cancer. The disease was re-staged by urine cytology, bimanual examination with the patient under anesthesia and transurethral biopsy or resection. Of the 217 patients 172 underwent total or partial cystectomy and 45 (21 per cent, 37 with stage T2, 7 with stage T3a and 1 with stage T4 disease) did not because re-staging showed no residual tumor (stage T0) in 20, carcinoma in situ in 17, stage T1 tumor in 4 and local stage T2 cancer in 4. The median followup was 5.1 years (range 3 to 7 years). Of the 45 patients 30 (65 per cent) are free of tumor or have required transurethral resection and intravesical therapy for recurrent tumors but cystectomy has not been necessary. Of the 15 failures 11 underwent cystectomy 9 to 30 months after re-staging (7 are alive and 4 died of disease) and 4 are alive with metastatic disease (2 with negative bladder biopsies). Re-staging in the 4 patients who died showed stage T0 disease in 2, carcinoma in situ in 1 and stage T2 tumor in 1. The over-all survival rate was 82 per cent (37 of 45) and it was 67 per cent (30 of 45) for patients with a functioning bladder. The data suggest that endoscopic re-staging may identify a subset of patients with limited muscle-infiltrating bladder tumors that can be managed conservatively without immediate cystectomy.

Administration, Intravesical↗

Endocrine and exocrine profiles of men with testicular tumors before orchiectomy.

In 15 patients with germ cell testicular tumors serum hormone profiles and semen analysis before orchiectomy were evaluated to determine the incidence of defective spermatogenesis associated with testicular tumors. Defective spermatogenesis was noted in 10 patients (66 per cent) on the basis of low sperm concentration, motility or semen volume. Of the 10 patients 7 had sperm concentrations less than 10 million per cc. Endocrine abnormalities occurred in 10 patients, the most common of which were elevations in serum human chorionic gonadotropin and estradiol, and a relative decrease in follicle-stimulating hormone. Three patients who presented with subfertile semen analyses were treated with orchiectomy alone. Repeat semen analyses 4 to 12 months after orchiectomy showed improvement in spermatogenesis and 2 patients achieved a normal semen analysis. Endocrine abnormalities and defective spermatogenesis are common in patients with testicular tumors. These abnormalities precede orchiectomy and imply that a primary germ cell defect exists in these patients.

Adolescent↗

Penile cancer: relation of extent of nodal metastasis to survival.

A retrospective review of 199 patients with penile cancer revealed that the extent of inguinal nodal metastasis was related to survival after radical ilioinguinal dissection. Patients with unilateral inguinal nodal involvement had a 56 per cent median 5-year survival rate, whereas those with bilateral inguinal nodal metastasis, extranodal tumor extension or iliac nodal involvement had a 9 per cent median 5-year survival rate.

Humans↗

Residual mass after chemotherapy for seminoma: changing concepts of management.

A residual mass after induction chemotherapy for advanced seminoma may present radiographically and clinically as either retroperitoneal fibrosis or a discrete mass. The former is nonresectable and often it is associated with negative pathological findings, whereas the latter is resectable but frequently it consists of viable seminoma, providing an indication for further therapy.

Antineoplastic Combined Chemotherapy Protocols↗

A prospective randomized trial of maintenance versus nonmaintenance intravesical bacillus Calmette-Guérin therapy of superficial bladder cancer.

Between August 1981 and July 1984, 93 patients with polychronotopic superficial papillary carcinoma (Ta and/or T1), flat carcinoma in situ (Tis), or concomitant superficial papillary and in situ bladder carcinoma were entered into a prospective randomized trial of maintenance v nonmaintenance intravesical bacillus Calmette-Guérin (BCG) therapy. Forty-six patients who received BCG weekly for 6 weeks were compared with 47 patients receiving the six-weekly doses of BCG plus monthly BCG for 2 years. Both groups were evaluated every 3 months by cytology, cystoscopy, and biopsy. A significant reduction in the number of recurrent tumors per patient-month was demonstrated for both groups (P less than .0001); however, the difference in reduction of tumors between the two groups was not significant. Additionally, patients receiving maintenance and nonmaintenance therapy had similar tumor recurrence and progression rates. These results indicate that monthly maintenance BCG does not prevent, delay, or reduce tumor recurrence or progression observed with the 6-week regimen. Maintenance BCG was associated with increased local toxicity, primarily dysuria, frequency, and urgency. Dosage reduction was required in 22 of 47 patients (46.8%). When the data were subjected to multivariate analysis, the presence or absence of tumor following induction BCG and PPD skin test results were found to be significant variables. Controlling for either the presence or absence of tumor following induction BCG, tumor recurrence and progression rates were not significantly different for the two treatment groups. However, the absence of tumor after induction BCG was associated with a longer disease-free duration (P = .00001) and time to progression (P = .095). Patients with a reactive tuberculin skin test before and after induction BCG had significantly less tumor recurrences than patients with different PPD skin tests results (P = .02). Tumor progression was not related to tuberculin skin testing.

BCG Vaccine↗

Intravesical therapy. A critical review.

In order to determine the effectiveness of intravesical therapy for superficial bladder cancer, the author critically reviews current data and the methodology upon which such data are based. Included is a discussion of prophylactic versus therapeutic intravesical therapy, the design of clinical trials for intravesical therapy and endpoints of response, biostatistical considerations, a review of randomized clinical trials, and selection of patients for intravesical therapy.

Administration, Topical↗

Monitoring intravesical bacillus Calmette-Guerin treatment of superficial bladder carcinoma by serial flow cytometry.

Simultaneous urinary flow cytometry, cytologic, and cystoscopic examinations were performed at 3-month intervals for a minimum of 1 year on 29 patients receiving intravesical bacillus Calmette-Guerin (BCG) treatment of superficial bladder carcinoma. Flow cytometry (FCM) and cytology were concordant in 57 of 103 examinations; both FCM and cytology were positive in 38 instances, and carcinoma was confirmed by biopsy in 35 (92.1%). In 16 instances FCM and cytology were negative, but carcinoma was present on biopsy in 5 (31.3%). Three examinations were suspicious by both techniques. The 46 determinations with discordant FCM and cytology were subdivided into pathologically confirmed recurrences (25 instances) and no evidence of pathologic and/or cystoscopic disease (21 instances). In the 25 instances of recurrences, FCM was positive in 18 (72.0%), suspicious in 3 (12.0%), and negative in 4 (16.0%), while cytology was positive in 3 (12.0%), suspicious in 9 (36.0%), and negative in 13 (52.0%). Most patients had a severe BCG-induced inflammatory response that caused an elevation of the hyperdiploid population, believed secondary to epithelial regeneration and proliferation. In the 21 instances without detectable recurrence, hyperploidy led to a relatively high proportion of positive (15) and suspicious (4) results by FCM, but only eight had distinct aneuploid populations. It is possible that this latter group, at least, is harboring occult carcinoma. Conventional cytology in the nonrecurrent group was positive in 1 (4.8%), suspicious in 7 (33.3%), and negative in 13 (61.9%). In those instances when tumor was confirmed by biopsy, the false-negative rate for FCM was 19.7%; the false-negative rate for cytology was 40.9%. Thus, FCM appears to be more sensitive but less specific than conventional cytology, having a lower false-negative but a higher false-positive rate. Although serial FCM provides an objective quantitative measure of aneuploid stemlines and hyperdiploid populations in bladder irrigation specimens and can be helpful in following intravesical BCG therapy for superficial bladder carcinoma, it should still be used with conventional cytology. The greatest difficulty with FCM at present, as with conventional cytology, is in cases of marked inflammation. The results reported here were obtained under the most stringent conditions and represent the minimum level of accuracy. Potential improvements in the technique, with the addition of immunologic or other markers, hold hope of further increasing the accuracy of FCM.

Aged↗

Intermittent endocrine therapy for advanced prostate cancer.

Twenty patients with advanced prostate cancer have been treated with an intermittent endocrine therapy schedule. Hormone therapy (diethylstilbestrol in 19 patients and flutamide in 1 patient) was administered until a clinical response was clearly demonstrated and then it was withheld until symptoms recurred. Prior to treatment 17 of 20 patients had bone pain and positive radionuclide scans, two had asymptomatic pulmonary metastases, and one had symptomatic localized disease. Duration of endocrine therapy prior to withdrawal of all treatment ranged 2 to 70 months (median, 10 months). Disease progression occurred 1 to 24 months (median, 8 months) after interruption of therapy. All patients who relapsed had a rapid clinical response following resumption of endocrine therapy. Nine of ten patients rendered impotent by endocrine therapy resumed sexual activity within 3 months of stopping treatment. This data indicates that satisfactory palliation of advanced prostatic cancer can be achieved in selected patients using intermittent endocrine therapy.

Aged↗

Sequential excision of residual thoracic and retroperitoneal masses after chemotherapy for stage III germ cell tumors.

Twenty-three patients with advanced (Stage III) mixed germ cell tumors underwent laparotomy and thoracotomy or neck dissection for excision of persistent radiographic masses after systemic chemotherapy. In those who received multidrug regimens incorporating high-dose cisplatin, 4 of 15 (27%) harbored persistent tumor in at least one site, 6 of 15 (40%) demonstrated necrotic tumor or fibrosis only in all sites examined, and the remaining 5 of 15 (33%) harbored mature teratoma in at least one area. In patients treated with high-dose platinum chemotherapy regimens 11 of 15 (73%) remain disease-free with a median follow-up period of 29 months (range, 1-58 months). Histologic comparison of tissues resected during thoracotomy and retroperitoneal node dissection indicated that patterns were dissimilar in 8 of 23 patients (35%). These data indicate the favorable impact of combined sequential chemotherapy and surgery in patients with advanced mixed germ cell tumors. In patients with Stage III tumors, persistent radiographic disease after cyclic cisplatin-based chemotherapy is appropriately managed by excision of both thoracic and retroperitoneal deposits.

Adolescent↗