Immunocytochemical detection of tumor cells in bone marrow and peripheral blood stem cell collections from patients with ovarian cancer.

High-dose chemotherapy (HDC) followed by autologous hematopoietic reconstitution is an experimental treatment option for patients with epithelial ovarian cancer. However, the incidence of occult ovarian tumor cell involvement in autologous bone marrow (BM) or peripheral blood stem cell (PBSC) autografts has not been widely investigated. We used a highly sensitive immunocytochemical (ICC) procedure that detects occult blood-borne tumor micrometastases. We analyzed 24 BM specimens (15 obtained during therapy and 9 harvest samples) and seven PBSC specimens from 22 patients with ovarian cancer. Overall, ICC analysis detected immunostained tumor cells in 10 of 23 evaluable BM specimens (43%) from 9 of 19 patients (47%). One of 9 (11%) harvest samples contained tumor cells. Only one of the 10 ICC-positive BM specimens had tumor cells detected by routine histopathological analysis. ICC-detectable tumor cells were cleared from the marrow of two patients during chemotherapy. None of the seven PBSC specimens contained tumor cells. We conclude that ovarian cancer micrometastases have the potential to contaminate BM, as is also the case in patients with other epithelial malignancies. In the limited number of specimens analyzed, PBSC harvests appeared to provide a less tumor-contaminated source of hematopoietic stem cells for autologous transplantation.

Primary adenocarcinoma of bladder.

Between April 1983 and December 1987, we have treated and followed 16 patients at the University of Southern California for adenocarcinoma of the bladder. In 10 patients, the cancer originated from a nonurachal source; all underwent radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion. The other 6 patients had an apparent urachal origin of their cancer. Half of these patients were treated with radical cystectomy and urinary diversion and half were treated initially with segmental cystectomy. Presenting characteristics (age, sex ratio, and symptoms) were similar for both groups. Three-year adjusted acturial tumor-free survival rates for the two groups were 48 percent and 31 percent, respectively. We advocate an aggressive approach of radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion for all invasive adenocarcinoma of the bladder, regardless of location.

The effect of in utero ethinyl oestradiol exposure on the risk of cryptorchid testis and testicular teratoma in mice.

Epidemiological findings indicate that both cryptorchid testis and testicular germ cell cancer may be a result of high maternal oestrogen levels early in pregnancy. An experiment was conducted with a mouse strain (129 Sv-S1 C P) in which the males are susceptible to testicular teratomas to determine if the frequency of undescended testis and testicular teratoma in male offspring could be increased by administration of ethinyl oestradiol (EE) to pregnant mice before day 13 of gestation. This point in gestation marks the completion of the migration of germ cells to the gonadal ridge in mice and other studies with these mice have shown that the tumours are initiated in this critical time period. EE mixed with corn oil was administered by subcutaneous injection in doses of 0.02 (n = 76) and 0.2 (n = 102) mg kg-1 of body weight on gestational days 11 and 12. These mice were allowed to deliver their offspring and the males were killed at 15 days of age. Since the tumours are present from birth, this amount of time was allowed to permit the tumours to reach sufficient size for easy visual identification. Compared to controls (n = 63), who received corn oil alone, the treated mothers produced offspring who were significantly more likely to have a cryptorchid testis (P = 0.0001) and who had an increased risk, although not significant, of a testicular teratoma.

Pancreatic nesidioblastosis in adults.

Nesidioblastosis, a condition characterized by diffuse islet cell hyperplasia arising from the ductal epithelium, is often associated with hyperinsulinemic hypoglycemia. This is a childhood disease and is rarely found in adults. Only 10 histologically proven cases have been recorded, including 3 new cases described in this article. Most clinical and biochemical features are identical to those of an insulinoma, except the proinsulin-like component of circulating immunoreactive insulin, which is usually within the normal range in nesidioblastosis. Limited observations show that some patients may be managed medically with diazoxide. Patients who remain hypoglycemic despite medical therapy require pancreatectomy, although greater than 90% resection frequently results in insulin dependency and permanent diabetes.

Ambulatory care centers: a unique opportunity for nurse practitioners.

Nurse practitioners continue to struggle to find avenues for professional fulfillment. Urgent care or ambulatory care centers (ACCs) may, because of their need to respond to consumer demands for more comprehensive services, offer nurse practitioners a unique opportunity to establish productive primary care practices based on the concepts of total patient care. A model for such a practice has operated successfully since 1983, establishing that both professional and business success can result from the collaborative efforts of nurse practitioners and physicians in an ACC setting.

Unsuspected prostatic adenocarcinoma in patients who have undergone radical cystoprostatectomy for transitional cell carcinoma of the bladder.

In 45 of 165 male cystectomy patients with bladder cancer (27 per cent) incidental adenocarcinoma of the prostate was found during the diagnostic evaluation or histological examination of the cystoprostatectomy specimens. Of the patients 37 had stage A1 or A2 and 8 had stage C or D1 prostate cancer. Clinical presentation, stage and grade distributions for each primary and prognostic variable are reviewed. Over-all, 67 per cent of the patients currently are alive with a 3-year actuarial survival rate of 60 per cent. The presence of incidental stage C or D1 prostate cancer in the surgical specimen implies incomplete surgical excision and it may warrant additional postoperative treatment. However, a significantly increased mortality rate among these patients has not been identified during the limited median followup of 25 months.

Methods in laboratory investigation. Identification and evaluation of histopathology at microelectrode puncture sites.

Tissue puncture techniques using microelectrodes for various measurements have been criticized for producing undetermined degrees of tissue damage. Therefore, a method permitting routine identification of puncture tracks was developed to determine local microelectrode-induced injury. Rabbits were anesthetized and the femoral arteries surgically exposed. A 3-ml mixture of saline-India ink suspension was introduced through an ear vein. Oxygen-sensitive (pO2) microcathodes were advanced into and through the arterial wall at 10- or 20-micron intervals using a stepping microdrive to 150 to 450 micron and then withdrawn. The arteries were fixed in 10% formalin and gelatin embedded, and serial frozen sections (less than or equal to 15 micron) of the microelectrode puncture area were made. We observed within 5 minutes of microcathode withdrawal a dark, punctate, microscopic discoloration within the arterial wall. Histologically, ink distribution within the arterial wall demonstrated an acute permeability change: puncture depths generally less than 300 micron showed ink-lined microelectrode tracks (generally less than 2 micron wide) in the media, and greater puncture depths showed local hemorrhage and focal laminar accumulation of ink which extended from the track. The immediate adjacent area to microelectrode puncture depths less than 300 micron showed an apparent intact internal elastic lamina and media. Therefore, microelectrode damage has been shown to be primarily limited to microelectrode tissue tracks.

Correlation of regional disease and in vivo PO2 in rat mammary adenocarcinoma.

A knowledge of the distribution of oxygen tension (PO2) and vascularization in neoplasia has been fundamental to understanding relationships between tumor growth, hypoxia, and therapy. We have combined recessed oxygen microcathode and freeze-substitution techniques to correlate in situ PO2 profiles and morphologic features in 7,12-dimethylbenz(a)anthracene (DMBA) tumors in rats. Overlying connective tissue of transplanted tumor was exposed by a 1-2 mm incision and a cross-stitch pattern demarcated electrode puncture sites for histologic reference. Three buffered salt solutions (BSS) with different PO2 were each allowed to flow through a well over the tumor where electrodes were placed for calibration. Zero electrode oxygen current was recorded from a buffered yeast-agar mixture of zero torr. PO2 was recorded at 5-mu intervals to approximately 1-2 mm. Atmospheric contamination was eliminated by continuous well flow of BSS, 30 torr. Finally, the tumor and surrounding tissues were quick-frozen in vivo with Freon 22 and liquid nitrogen. The tissue block was freeze-substituted and sectioned. PO2 profiles were superimposed onto correspondingly scaled photomicrographs. A viable periphery with a PO2 range of 50-82 torr and a transition to necrotic areas of PO2, 2-13 torr were observed. This transition was characterized by PO2 gradients within distances of 50-300 mu at variable puncture depths. This technique should be useful in further studies of growth, necrosis, and therapy.

Vasoactive effect of sera from preeclamptic patients.

Investigated was a bioassay method for measurement of vasoactivity in the serum of preeclamptic patients. Intravital microscopy was used to measure the diameter of the principal arteriole and venule in the gastrolienal mesentery of mice before (VD1) and after (VD2) the intravenous injection of sera from preeclamptic primigravid patients and from preeclamptic primigravid patients after treatment with magnesium sulfate (MgSO4). A vasoactive index (VI) was calculated as VD2/VD1. The VIa (vasoactive index for arteriole) of preeclamptic primigravid patients (0.64 +/- 0.39, mean +/- SD) was significantly different (p less than 0.01) from the VIa of normal primigravid patients (0.91 +/- 0.08) and from the VIa of saline controls (0.99 +/- 0.02). Four of the seven preeclamptic primigravid patients had a duration of signs and symptoms dating from the antepartum period (VIa = 0.53 +/-. 0.42), and for three, the diagnosis was made only in the intrapartum period (VIa = 0.77 +/- 0.38). Sera from the MgSO4-treated preeclamptic patients yielded a VIa of 0.91 +/- 0.14, which was not significantly different from that for either the normal primigravid patients or the saline controls. This VIa value was significantly different (p less than 0.01) from the VIa of the untreated preeclamptic patients. These results suggest that here is a vasoactive substance(s) in the sera of preeclamptic patients which may contribute to their arteriolar vasospasm. The magnitude of vasoactivity appears to be related to the duration and severity of preeclampsia but is masked or disappears after treatment of the patient with MgSO4.

Hyperreninemic hypoaldosteronism in the critically ill: a new entity.

To define the changes in adrenal gland function during critical illness, we evaluated 28 severely ill patients with persistent hypotension who were hospitalized in a medical intensive care unit. The patients had increased plasma cortisol (mean +/- SE, 40.1 +/- 10.1 micrograms/dl). PRA was increased in all subjects (21.6 +/- 7.2 ng/ml.h); however, the plasma aldosterone concentration was inappropriately low in 18 of the subjects, with values ranging from 1-9 ng/dl, despite normal serum potassium concentrations (4.3 +/- 0.1 meq/liter) and increased concentrations of the aldosterone percursor, 18-hydroxycorticosterone. These 18 patients had hypotension associated with major infections and a high mortality rate (78%). Infusions of ACTH or angiotensin II were associated with a normal aldosterone response in only 2 of the 14 patients tested, also suggesting that the defect was probably at the level of the zone glomerulosa cell. Although infection was a common underlying illness, no other factors, such as dopamine administration, decreased angiotensin-converting enzyme activity, or increased aldosterone clearance, could be implicated as the cause of the phenomena. Thus, selective hypoaldosteronism in the presence of high renin levels exists in a substantial percentage of hypotensive critically ill patients.

Pathological aspects of the infertile testis.

In this review, the pathological findings from testicular biopsies of men suffering from various types of infertility are presented. The causes of male infertility are divided into three major categories: pretesticular, testicular, and post-testicular causes. The pre-testicular causes of infertility may be defined as extra-gonadal endocrine disorders, such as those originating in the hypothalamus, pituitary, or adrenals, which have an adverse effect on spermatogenesis. The testicular causes of infertility are primary defects of the testes. The post-testicular causes of infertility consist primarily of obstructions of the ducts leading away from the testes. Cases in which the spermatozoa are normal in number but greatly impaired in motility, presumably due to faulty maturation or improper preservation of the spermatozoa during their sojourn in the epididymides, or due to biochemical abnormalities of the seminal plasma, are also included in the postesticular category.

The potential value of immunohistologic techniques in the classification of ovarian and testicular tumors.

The diagnosis of neoplasia continues to rest upon the judicious application of morphologic criteria for the identification of tumor cells. Immunohistologic techniques offer the pathologist an alternative means of cell identification according to the antigenic constitution of the cell or its products. The potential effect of these techniques upon the diagnosis and classification of neoplasia is illustrated by the application of immunoperoxidase methods to the study of alpha-fetoprotein, human chorionic gonadotrophin, and steroid hormone localization in tumors of the ovary and testis.

Triiodothyronine-secreting (toxic) adenoma of the thyroid gland: light and electron microscopic characteristics.

A patient with thyrotoxicosis due to a triiodothyronine (T3)-secreting autonomous adenoma is described. The histmorphology of the neoplasms was similar to other neoplasms previously reported. Ultrastructural features of the adenoma are compatible with a very actively secreting follicular cell and are best compared with the ultrastructure of a diffuse toxic goiter. Distinctive features that separate toxic adenomas from various thyroid carcinomas and normal thyroid parenchyma are discussed.

Breast cancer: lack of prognostic value of adrenal pathology at adrenalectomy.

The adrenal glands of 58 patients undergoing adrenalectomy for advanced breast cancer were reviewed and correlated with subsequent course of the patients' disease. Three patients had thecomatous metaplasia in the adrenal cortex, six patients had myelolipomatous changes, and 13 patients had metastatic breast cancer in their adrenal glands at the time of adrenalectomy. Neither the presence of metastases nor myelolipomatous changes were associated with a long disease-free interval, a long period from mastectomy to adrenalectomy, or a prolonged postadrenalectomy survival. The patients with metastatic breast cancer in the adrenal glands had more widespread disease than patients without adrenal metastases. The presence of breast cancer metastases in the adrenal glands at the time adrenalectomy identifies patients further advanced in the course of their disease, but is not related prognostically to the effect of adrenalectomy.