Andrew Saxe

Role of sample adequacy in fine needle aspiration biopsy of palpable breast lesions

BACKGROUND The role of fine needle aspiration biopsy (FNAB) in breast lesions remains uncertain because its accuracy has been questioned. We hypothesized that this is related to failure to define standards for adequacy of sample preparation. METHODS We reviewed cytology and pathology reports from 351 patients undergoing FNAB at a 350-bed community, university-affiliated teaching hospital over a 2-year period. Patients were included if they had an open biopsy within 2 years of an FNAB of the same lesion. Cytology reports were reviewed by a cytopathologist unaware of the clinical setting or subsequent histology; surgeons unaware of the cytology reports reviewed histology reports. Cytological diagnoses were benign, likely benign, probable cancer, and definite cancer. Samples were characterized as satisfactory, less than optimal (few mammary epithelial clusters), or inadequate (no mammary epithelial clusters.) We assessed the proportion of inadequate samples, the accuracy of FNAB, and the influence of sample adequacy upon FNAB sensitivity. RESULTS Ninety-nine (28%) FNABs were inadequate, 77 (22%) less than optimal, and 175 (50%) satisfactory. Ninety-five patients (27%) had a final diagnosis of malignancy. FNABs classified as satisfactory or less than optimal and characterized as benign (n = 102) had a negative predictive value (NPV) of 0.91; those termed definite cancer (n = 43) had a positive predictive value (PPV) of 0.98. Only 10% of all cancers were identified in the 28% of FNABs that were classified as inadequate (P <0.01). CONCLUSIONS We concluded that too few FNABs are performed in a fashion that permits definitive cytological interpretation. Inadequate FNABs are less likely to detect malignancy. After excluding inadequate preparations, FNABs interpreted as definite cancer and as benign are highly accurate in identifying patients with and without cancer.

Parathyroid hormone decreases in vivo insulin effect on glucose utilization

Hyperparathyroidism is associated with impaired glucose tolerance, and parathyroidectomy may improve carbohydrate homeostasis. It has been suggested that parathyroid hormone (PTH) suppresses insulin secretion but it is unclear whether it also interferes with the peripheral action of insulin. To evaluate in vivo effects of PTH on insulinmediated glucose utilization, 15 male Sprague Dawley rats were continuously infused with rat PTH (1–34) using an Alzet miniosmotic pump at a rate of 0.03 nm/hour. Controls were infused with the vehicle alone. Following 5 days of PTH infusion, plasma calcium (Ca) levels were higher in the PTH-infused rats (12.3±0.2 versus 9.9±0.1 mg/dl, P<0.01). On the 5th day, glucose (700 mg/kg) and insulin (0.175 U/kg) were given as a bolus infusion through the left femoral vein, blood samples were obtained from the right femoral vein, and plasma glucose and insulin were measured at basal (0 minutes) and at 2, 5, 10, and 20 minutes postinfusion. Basal, nonfasting glucose levels were higher (166±4 versus 155±4 mg/dL, P<0.04) in the PTH-infused rats but their insulin levels were similar to those of controls (6.5±0.6 versus 5.6 ±0.5 ng/ml). Postinfusions and maximal (2 minutes) glucose and insulin levels were similar in both groups. However, although insulin levels were similar in both groups at all measured time points, glucose levels at 20 minutes were higher in the PTH-treated rats (205±13 versus 173±9; P<0.03). Also, calculated glucose disappearance rates (Kg) were decreased in the PTH-infused rats (4.05±0.3 versus 4.63±0.8; P=0.054), suggesting an impaired peripheral effect of insulin on glucose utilization. To gain insight into the potential contribution of the hypercalcemia or the PTH to these abnormalities, correlation evaluations were performed. Only in PTH-infused rats did plasma Ca correlate with plasma glucose at 0 and 20 minutes (r=0.6, P=0.02; r=0.7, P=0.01) and with the area under the glucose curve (r=0.6, P=0.03) during the glucose-insulin infusion. Also only in PTH-infused rats did PTH correlate with 0 (P=0.07) and 20-minute (P=0.02) plasma glucose levels. There was no correlation between either Ca or PTH and basal insulin levels or the area under the insulin curve in either group. Consequently, we suggest that in the rat, PTH infusion associated with hypercalcemia impairs insulin effect on glucose utilization in vivo and this defect may be induced by the Ca, PTH, or both.

Measurement of estrogen and progesterone receptors in abnormal human parathyroid tissue

SummaryEstrogen and/or progestin administration to postmenopausal women with primary hyperparathyroidism lowers serum calcium. We measured cytosolic estrogen receptors (ER) and progesterone receptors (PR) by classical hormone-receptor binding techniques in parathyroid tissue removed from 10 men and 20 women, and ER by immunocytochemistry in tissue from an additional one man and seven women in order to ascertain whether these agents might exert a direct effect upon tissue responsible for hyperparathyroidism. ER were negative (<3.1 fmol bound estradiol/10 mg tissue) in all 8 adenomas and 4 of 5 secondary hyperplasias removed from men, and from women in 19 of 22 adenomas, 2 of 3 secondary hyperplasias, and 3 of 4 primary hyperplasias. PR were negative (<10.1 fmol bound progesterone/10 mg tissue) in 7 of 8 adenomas and all 5 secondary hyperplasias removed from men, and from women in 20 of 22 adenomas, all 3 secondary hyperplasias, and all 4 primary hyperplasias. For immunocytochemical studies, quickfrozen specimens were analyzed with a monoclonal antibody (Abbott Laboratory) directed at nuclear ER. All eight samples—five adenoma and three primary hyperplasia—were negative. We conclude that abnormal human parathyroid tissues have nondetectable levels of ER and PR. It is unlikely that estrogen and progesterone exert a direct, ER, or PR-mediated effect upon parathyroid tissue.

Effects of long-term lithium infusion on normal parathyroid tissue

BACKGROUND Approximately 10% of patients taking lithium for manic-depressive disorders become hypercalcemic. It remains unclear whether lithium initiates disease or promotes underlying hyperparathyroidism. We have previously demonstrated that at therapeutic concentrations lithium stimulates in vitro incorporation of both tritiated thymidine and bromodeoxyuridine into abnormal human parathyroid tissue, reflecting growth-promoting properties. Whether lithium has similar growth-promoting properties in normal parathyroid tissue remains unresolved. METHODS We infused lithium (0 mmol/L, 3 mmol/L, or 10 mmol/L) through implantable subcutaneous pumps into normal rats for 3 months and measured levels of serum lithium, serum calcium, and serum parathyroid hormone (PTH) (with a radioimmunoassay specific for rat PTH 1-34.) On completion of the infusion, bromodeoxyuridine (30 mg/kg) was administered intraperitoneally. The parathyroid glands were removed and measured in two dimensions to calculate gland volume [V = (pi/6) x (d1) x (d2)2.] Parathyroid incorporation of bromodeoxyuridine was assessed by using immunocytochemistry. RESULTS Serum lithium level was significantly (p < 0.05) different between groups and constant within groups. Levels of serum calcium and PTH were inversely related to each other; however, no significant differences were noted between groups with respect to level of serum calcium or serum PTH at any measurement. Similarly, no significant differences were noted between groups with respect to gland size or number of bromodeoxyuridine-positive cells. CONCLUSIONS Long-term lithium infusion in rats for a period representing approximately 15% of their life span failed to evoke changes in parathyroid gland size or function. These data are consistent with (1) lithium as a promoter of hyperparathyroidism and (2) resection of abnormal parathyroid tissue and resumption of lithium for patients requiring long-term therapy.

Leiomyoma of the hand: A case report and review of the literature

An 18-year-old, right-handed black woman presented with a 1-year history of a mass at the base of her right fourth finger. Physical examination revealed a painless 1 • 1 cm soft, mobile mass at the palmar aspect of the fourth metacarpophalangeal joint (Fig. 1) unassociated with sensory or motor compromise. An x-ray film of the right hand showed a soft tissue mass with two microcalcifications, most compatible with a hemangioma. Excision of the tumor was performed under general anesthesia. At surgery, the tumor dissected easily from surrounding structures and was not adherent to tendons, vessels or deep tissue layers (Fig. 2). Microscopic examination revealed a nodule composed of interlacing bundles of smooth nonstriated muscle (Fig. 3). Throughout the lesion were scattered thin-walled vessels that were on occasion associated with small areas of calcification. The nuclei were bland and rounded to slightly fusiform (Fig. 4). Myofibrils were identified by electron microscopy. The surgical wound was closed with a split-thickness skin graft (Fig. 5). At the patients most recent postoperative visit the incision had healed, motor and sensory function were intact, and there was full range of motion.

Effect of Chronic Vitamin D Infusion Upon In Vivo Glucose Disposal

Abstract. We have previously demonstrated that parathyroid hormone (PTH) infusion decreases glucose disappearance rate (Kg) in vivo. Because in the rodent model used it was not possible to determine whether the PTH itself, the induced hypercalcemia, or both contributed to the glucose intolerance, we examined the effect of vitamin D infusion on insulin-mediated glucose disposal. In this model also hypercalcemia is induced but PTH levels are suppressed. Thirty male Sprague Dawley rats were continuously infused with vit D for 5 days using an Alzet miniosmotic pump, at a rate of 9.7 pmol/hour. Thirty controls were infused with the vehicle alone. On the 5th day, glucose 700 mg/kg and insulin 0.35 U/kg were given as a bolus through the left femoral vein and blood samples were obtained from the right femoral vein just prior to and at 2, 5, 10, and 20 minutes post-glucose/insulin infusion. At the end of 5 days, plasma calcium levels were higher in the vit D-infused rats than in the control rats (12.8 ± 0.1 versus 10.0 ± 0.1 mg/dL, P < 0.01) and rat PTH levels were suppressed (2.1 ± 0.1 versus 62 ± 12 pg/ml, P < 0.01). Glucose levels were higher in the vit D animals only at 5 minutes following glucose/insulin bolus (375 ± 7 versus 350 ± 6 mg/dL, P < 0.01) but at no other time. There were no differences between serum insulin levels at any time. Unlike previous findings in PTH-infused rats, Kg (measured from 2 to 20 minutes following glucose/insulin bolus) was not different between groups (4.5 ± 0.3 versus 4.7 ± 0.2, P= 0.92.) A positive correlation between serum calcium and serum glucose was found only at 5 minutes (r = 0.55, P < 0.01) and only in the vit D animals. The areas under the glucose curves approached statistically significant differences (vit D-infused 5258 ± 142 mg/dL/18 minutes versus control 4947 ± 127, P= 0.06.) Analysis of serum glucose data by two-factor analysis of variance (ANOVA) suggests that the two groups differ slightly in glucose values (P= 0.03) but have parallel Kg. In order to define whether different effects of PTH (1–34) and vit D on intracellular calcium [Ca2+]i levels could partly explain the different effects of PTH and vit D infusion on glucose disposal, we investigated the effect of PTH and vit D infusions on basal and concanavalin A (con A)-stimulated changes in mononuclear [Ca+2]i levels. Following 5 days of PTH, vit D, or control infusion, peripheral mononuclear cells were incubated with 50 μg/ml con A. Changes in [Ca+2]i over 5 minutes were calculated by flow cytometric measurement of the calcium sensitive fluo-3 AM dye. Despite achieving significant and comparable degrees of hypercalcemia in the PTH and vit D infused animals, there were no differences in basal or con A-stimulated [Ca+2]i levels from control. Consequently, we conclude that vit D-induced hypercalcemia associated with suppressed PTH levels has mild affects on glucose homeostasis but does not affect glucose disappearance rate in vivo (Kg) as does hypercalcemia induced by PTH infusion, and that neither chronic PTH infusion nor chronic vit D infusion are associated with long-standing changes in [Ca2+]i levels.

Laparoendoscopic Approaches to Occult Gastrointestinal Bleeding

Identification of sites of small bowel hemorrhage remains a difficult problem. Endoscopy performed in association with surgery often proves successful when other attempts have failed. In attempts to minimize morbidity and even increase accuracy, surgeons have explored combining laparoscopic techniques with endoscopy. Although published experiences remain few, expectations remain high. Copyright