George H. Barrows

Pathologic changes associated with androgen deprivation therapy for prostate cancer

Prostate glands exposed to androgen deprivation with leuprolide ± flutamide were evaluated for pathologic changes which might be related to therapy. Comparing pretreatment and posttreatment tissue by visual discrimination using light microscopic study revealed treatment‐related alterations in the size and distribution of neoplastic glands in 60% of cases. Quantitative measurements documented glandular changes in an even greater percentage of cases. Although distinctive, the histologic pattern was not specific for leuprolide/flutamide. The absence of appreciable degeneration and necrosis in tumor cells suggests that this type of androgen deprivation may act through suppression rather than ablation of prostatic cancers. The relationship between treatment‐related histologic effects and initial tumor grade and clinical stage as well as expression of prostate‐specific antigen was studied. Accurate histologic assessment of leuprolide/flutamide‐treated prostate glands should not be a problem so long as specimens are thoroughly examined and drug‐related variations in tumor morphologic features are appreciated.

Fine‐needle aspiration of breast cancer: Relationship of clinical factors to cytology results in 689 primary malignancies

Between 1980 and 1983, 689 women with primary breast cancer at the Royal Infirmary of Edinburgh and associated Hospitals had fine‐needle aspiration biopsies prior to definitive surgery. Clinical factors relating to the success of these aspirations were evaluated. The most significant factor was which physician performed the aspiration. Size of the lesion was also an important variable; however, size difference could not account for the marked variation between different individuals performing the aspiration. There was no difference between node‐positive and node‐negative patients when matched by tumor size. A significantly lower rate of positive aspirations occurred in the 45 to 55 year age group which could not be accounted for by tumor size. Location of the mass was not significant, although there was a persistent lower rate of positive aspirates from the upper inner quadrants. Aspiration cytology was positive or suspicious in 65 percent of patients with primary breast cancer who had clinical diagnoses of benign breast lesions. It is concluded that the most significant variable in the accuracy of breast aspiration biopsy is the size of the lesion and the proficiency of the individual performing the procedure. With a skilled physician, positive aspiration results were obtained in over 80% of breast cancers.

Carboxyhemoglobin levels in patients with flu-like symptoms

Subacute carbon monoxide poisoning is commonly misdiagnosed as an influenza-like viral illness. All patients presenting to the triage nurse at University Hospital with flu-like symptoms during February 1985 were asked to give blood samples for carboxyhemoglobin determination. Fifty-five patients (10% of those eligible) with headache, dizziness, nausea, vomiting, diarrhea, weakness, general malaise, or shortness of breath were enrolled in the study. Carboxyhemoglobin levels ranged from 0 to 21%. Thirteen patients (23.6%) of this self-selected subgroup had carboxyhemoglobin levels greater than or equal to 10%. There was no statistically significant difference in carboxyhemoglobin levels between smokers and nonsmokers. More patients using wood heat had elevated carboxyhemoglobin levels than patients using any other form of heating (P less than .05). No patient with a carboxyhemoglobin level greater than or equal to 10% was diagnosed as having subacute CO poisoning by emergency physicians. Physicians must seek out the possibility of CO toxicity in patients with flu-like illness, particularly in inner-city populations during the heating months. Fundoscopy and COHb levels may be useful in selected cases to correctly diagnose patients and avoid a return to a hazardous environment with potentially fatal consequences.

Comparison of Avitene, Topical Thrombin, and Gelfoam as Sole Hemostatic Agent in Tuboplasties*

Forty-eight virgin guinea pigs were subjected to bilateral sectioning of the uterine horn and cuff type salpingostomy. Avitene, Topical Thrombin, or Gelfoam was used as the sole hemostatic agent in each of three study groups. Bipolar cauterization was used in a control series. These agents were compared with regard to ease of application, degree of adhesion formation, net surface area, and microscopic evaluation of degree of fibrosis and inflammatory reaction. The results revealed no statistically significant differences among the various methods of hemostasis. Data were evaluated by uni- and multivariate analyses. Several trends in the data were noted: the greatest amount of fibrosis was associated with Topical Thrombin and Avitene, and the greatest inflammatory response was associated with Avitene. These agents show no superiority to currently used cautery methods of obtaining hemostasis.

Granular cell myoblastoma arising from the thoracic sympathetic nerve chain

Abstract Granular cell myoblastoma has been of interest both to the clinician and the pathologist for many years. This uncommon tumor presents the usual diagnostic problem of a mass, but the actual diagnosis of granular cell myoblastoma is rarely made prior to biospy. The origin of the tumor from either myoblastic or neural tissue remains controversial. Light and electron microscopic studies of a granular cell myoblastoma uniquely located in the posterior mediastinum and associated with the sympathetic chain support the neural origin of this tumor.

Cytochrome P-450 activity in human leiomyoma and normal myometrium

Variations in cytochrome P-450 levels may influence the responsiveness of uterine and breast tissue as well as carcinomas to endocrine therapy and may be of particular importance with agents such as tamoxifen (Nolvadex) where hydroxylation is known to alter therapeutic activities. Therefore, a sensitive spectrophotometric assay of cytochrome P-450 levels in reproductive tissue microsomes was developed to measure cyclohexane hydroxylase activity. Cyclohexane served as a substrate for several forms of cytochrome P-450. Human uterine leiomyomas (uterine fibroid tumor) contained significantly higher (p less than 0.01) cytochrome P-450 activity than adjacent normal myometrium. Specific activities for both leiomyomas (2.87 +/- 0.26 nmol/min/mg) and normal myometrium (1.60 +/- 0.11 nmol/min/mg) were in the range of those observed for untreated rabbit liver microsomes (1 to 3 nmol/min/mg). The contribution of smooth muscle in the specimen, the phase of the menstrual cycle, and the clinical diagnosis did not influence the level of cytochrome P-450 activity.

Human Liver Neoplasia and Steroid Exposure

This study examines experience with over 250 liver tumors in young women. Most were oral contraceptive related. There were two distinct benign liver tumor types: focal nodular hyperplasia and liver cell adenoma. Six benign liver tumors were examined for estrogen receptors. They did not contain significant quantities of estrogen receptor, supporting experimental studies of an epigenetic origin. Multiple tumors occurred in about 20% of cases but did not change the favorable prognosis associated with benign tumors. The most significant source of morbidity and mortality was spontaneous hemorrhage or rupture. Twenty-three women in this series had hepatocellular carcinoma and the majority of these were associated with prolonged steroid usage. These malignant liver tumors occurred in young females without cirrhosis or other factors known to be associated with hepatic malignancy. Unlike “hepatocellular carcinomas” reported in males taking anabolic androgenic steroids, the tumors in females had a high rate of metastasis to a variety of organs. The risk of liver tumors in oral contraceptive users remains unknown, but must be very small since an estimated 150 million women worldwide and 40 million in the U.S.A. have used oral contraceptives.

Occurrence of a thermostable antigen of ovarian carcinoma in normal tissues and secretions.

Thermostable antigen (TA) occurs in ovarian carcinoma and in certain specialized tissues. High titers of TA were found in nineteen of twenty endocervical extracts but not in myometrium, endometrium, or exocervix. TA was present in all of sixteen cervical mucus samples. Antibodies to perchloric acid extract of bronchus showed cross‐reactivity with TA from ovarian carcinoma and cervix. Immunofluorescence with frozen sections revealed TA to be present in the columnar epithelium of ovarian neoplasms, and endocervical glands, in bronchial seromucous glands and in hepatic bile canaliculi. Immunofluorescence and immunodiffusion were used to test for cancer patient antibodies against TA. All sera tested negative. An immunofluorescence inhibition test for circulating TA also tested negative in sera of ovarian and cervical cancer patients.