Charles Mangan

Elevated serum cathepsin B1-like activity in women with neoplastic disease

Abstract Activities of selected hydrolytic enzymes were assessed in blind-coded sera of 121 women with invasive cancer of various organs. Acetylglucosaminidase, β-glucuronidase, and alkaline phosphatases were not markedly elevated above controls. In contrast, cathepsin B1-like (CB1) activity in sera before therapy averaged 45-fold greater than that of 56 normal controls ( P P P

Para-aortic nodal metastases in early cervical carcinoma: long-term survival following extended-field radiotherapy.

From 1960 to 1979 there were a total of 14 patients followed at the University of Pennsylvania with early cervical carcinoma who had histologically documented metastases to the para-aortic nodes and who were treated with extended-field radiotherapy. Thirteen of these patients were stage IB and one was stage IIA. All patients underwent exploratory laparotomy and lymph node dissection, followed by extended-field radiotherapy. Six patients are alive with NED for greater than 5 years; one patient is alive with NED at 3 years. An additional patient is now alive and well almost 3 years from a biopsy documented recurrence treated with chemotherapy, and 6 years from initial diagnosis. Thus 8 of 14 patients have enjoyed a long-term survival. Five patients experienced severe treatment-related morbidity. Two had long-term survival, two died of disease, and one died of radiation complications with NED on autopsy. Each of the six patients that died of disease had recurrences at distant sites. One also had a pelvic recurrence. These patients appear to have a prognosis quite different from that of patients with locally advanced cervical cancer metastatic to the para-aortic nodes and deserve aggressive treatment. The need for adjuvant systemic therapy is stressed.

The “problem” radical hysterectomy

This is a study of 243 radical hysterectomy and pelvic lymphadenectomy procedures performed for gynecologic malignancy. The term problem radical hysterectomy was applied to those patients with one of the following conditions: (1) recent cervical conization (within 21 days). (2) previous total or supravaginal hysterectomy, (3) pregnancy, or (4) previous pelvic radiation. There were 88 patients in theses categories. One hundred and fifty-five patients had none of these predisposing problems which might influence operative or postoperative complications. There were two deaths (0.82 per cent). There was no statistically significant difference in operative injuries to the bladder, ureters, or rectum or in the mean operative time and mean blood loss across the categories. However, there was a statistically significant difference across the categories in postoperative complicatons, both major and minor. The greatest incidence of such complications occurred in patients who had previous radiation therapy and the second greatest incidence was in patients who had recent cervical conization. Pregnant patients had the least number of complications.

Estradiol binding by human endometrial tissue

Estrogen binding in endometrial tissue of various hormonal conditions was compared by a quantitative dextran-coated charcoal assay. The amount of [ 3 H]E 2 bound to cytosol in vitro was expressed as fmole/ μ g DNA and fmole/mg protein. The highest values were obtained for proliferative endometrium (1.95 ± 0.45; 244.06 ± 38.99). Endometrium from patients on oral contraceptives had low levels of estrogen receptor, which was slightly higher than that of atrophic endometrium. Various endometrial lesions were examined. The most consistent results were found for areas of hyperplastic endometrium (1.51 ± 0.41; 138.88 ± 3.43). Seventeen cases of endometrial adenocarcinoma plus one case of endocervical adenosquamous carcinoma can be divided into three groups. One-third showed no detectable estrogen binding, one group of seven patients showed low values, and a third group of five patients had high concentrations of estrogen receptors.

Flow cytometric DNA analysis as a diagnostic aid for cervical condyloma and cancer

Flow cytometric DNA analysis data (FCDA) were obtained from 324 samples provided through the Gynecology‐Oncology Clinic. These samples consisted of 294 combined endoectocervical and vaginal smears and 30 peritoneal washings. Using a conventional scheme for G0/G1, S + G2/M and the coefficient of variation with computer correction for the cell‐cycle kinetics, it was possible to assign a diagnostic Class, I, II, III or V similar to that used by the Cytology Laboratory. These data were then compared with the histopathologic and colposcopic diagnoses. The correlation between FCDA and cytologic results were essentially similar to the previous data obtained from only endocervical sampling.14 The most interesting finding in this study was the recognition of an FCDA pattern showing a higher DNA content in the G0/G1 and the early S regions in 70 of 94 (74.5%) of samples from patients with condyloma acuminata. All condyloma samples were diagnosed either by cytologic, histopathologic, or colposcopic examination, or a combination of two or three. All biopsy specimens were then reviewed by one pathologist to verify any discrepancies. The relationship of this pattern to the viral etiology of this disease is discussed with the three methods of diagnosis and electron microscopic observations. It is suggested that, based on this study, FCDA analysis of pap smears may also be useful in determining the presence of condyloma in a gynecology clinic. The potential value of FCDA analysis from peritoneal washings for the diagnosis of gynecologic cancer can not be ascertained in this preliminary investigation because of insufficient samples.

Phase II trial of galactitol 1,2:5,6-dianhydro (NSC 132313) in the treatment of advanced gynecologic malignancies: A gynecologic oncology group study

Dianhydrogalactitol was administered intravenously to patients with advanced or recurrent gynecologic malignancies on a weekly schedule. The initial dosage was 60 mg/m2 with escalation to 75 mg/m2 if there were no adverse effects. Forty-two patients with ovarian epithelial adenocarcinoma (OEA) and forty-one patients with squamous carcinoma of the cervix (SCC) were entered into this study. Of these, 39 patients with OEA and 36 with SCC were evaluable for toxicity and response. Seven patients (19.4%) with SCC had an objective response, while six patients (15.4%) with OEA had an objective response. Adverse effects were frequent but tolerable. There were no drug-related deaths, and only two patients suffered life-threatening hematologic toxicity. Myelosuppression was observed more frequently among the patients with OEA. A higher percentage of OEA patients had received prior chemotherapy. The level of activity and frequency of adverse effects observed at this dose schedule warrant further studies of this drug in these two tumors.

Flow cytometric DNA and 5′‐nucleotide phosphodiesterase in endometrium

One hundred endometrium specimens have been studied with flow cytometry for DNA analysis (FCDA) and a proliferative enzyme marker, 5′‐nucleotide phosphodiesterase (5′‐NPD). FCDA data showed that aneuploidy was present in only 5 of 40 cancer specimens. However, with corrected histograms, a higher DNA value was observed in the G2/M (6%) of all cancer compared with noncancer specimens (4%). Thus, FCDA can be a useful diagnostic aid for endometrial cancer. The determination of 5′‐NPD was done with a quenching method based on the use of 5′‐(5‐iodo‐3‐indoxyl)‐thymidine phosphodiester as a substrate and 4′,6‐diamidino‐2‐phenylindole for DNA. This method could qualitatively define which population of the cell cycle had a higher enzyme level and also quantitatively gave the enzyme units per cell. It was found that 12.5% of all cancer specimens had 5′‐NPD activity in the G0/G1 cells and 87.5% in the S and/ or G2/M cells, whereas in the noncancer specimens 5′‐NPD was found in 28.5% of the G0/C1 cells and 71.5% of the specimens had 5′‐NPD in the S and/or G2/M cells. Furthermore, the concentration of 5′‐NPD was found to be five times higher in the G2/M cells of the cancer specimens than that in the noncancer specimens. However, in the hyperplasia specimens, the activity was only two times higher in the same cell cycle fraction than in the normal specimens. The results of this investigation provided for the first time evidence that this exonuclease activity alters in the cell cycle fractions and that a decrease in the enzyme activity in G0/G1 cells and an increase in G2/M cells may be a useful marker for neoplastic development in human endometrial cancer.

Six years' experience with screening of a diethylstilbestrol-exposed population

The physician population delivering obstetric care in Philadelphia between 1950 and 1970 was contacted to ascertain their use of diethylstilbesterol (DES) during pregnancy. Of the 31.8% of the physicians who responded to the questionnaire, 71.8% used DES during pregnancy and 12.7% desired assistance in review of their records. During the 6 years from the initial survey, 830 young women exposed to DES in utero were periodically screened for cervicovaginal abnormalities and clear cell adenocarcinoma. Of these 830 patients 61.7% were found to have cervicovaginal abnormalities, and 65.9% of the patients showed either adenosis or evidence of the prior existence of vaginal adenosis. Eight patients were treated for clear cell adenocarcinoma. Two cases were detected while asymptomatic. Seven of the patients are living with no evidence of cancer, and two of these have survived over 5 years.

Evaluation of a one-parameter flow analysis of cervical samples for gynecology cancer screening

A total of 246 endocervical samples were collected for Papanicolaou staining and one-parameter flow cytometric DNA analysis (FCDA) using 4,6-diamidino-2-phenylindole as a DNA stain. Typical histograms derived from FCDA analysis were designated class I, II, III, and V. Two groups of patients were studied: 135 women referred for colposcopy (COLPO), and 79 women exposed to diethylstilbestrol (DES). The remaining 32 samples were evaluated and found unsatisfactory. In the colposcopy group FCDA assigned 38 patients normal, 62 mild to moderate dysplasia, 33 moderate to severe dysplasia, and 2 carcinoma in situ and invasive carcinoma. Agreement of Pap smear and FCDA occurred in 56, 59, 72, and 100%, respectively. In the diethylstilbestrol group 57 patients were normal and 12 had mild to moderate dysplasia according to Pap diagnosis. Agreement between FCDA and Pap diagnosis were 45 and 58%, respectively. However, FCDA did not falsely assign severe dysplasia or carcinoma in situ to any DES patient. This preliminary study based on FCDA appears to clearly differentiate patients with normal Pap smears from those patients with invasive cancer.

Zinc sulfate: an adjuvant to wound healing in patients undergoing radical vulvectomy.

Abstract The average postoperative stay for 45 patients undergoing radical vulvectomy with femoral and inguinal lymphadenectomy was 37 days. Five patients were treated with oral zinc sulfate for at least 7 days prior to surgery. The incidence of wound infection was decreased, and the average postoperative stay was reduced to 18 days.