Fifty cases of Paget's disease of the breast treated surgically at The Johns Hopkins Hospital during the past 30 years were studied. Nineteen patients had Paget's disease confined to the nipple and 31 had an associated palpable tumor. An underlying intraductal or infiltrating duct carcinoma of the breast was present in each case. In six cases, the underlying tumor was 2 cm or more from the nipple with no apparent anatomic connection to the Paget lesion, and one case was encountered in whom intradermal Paget's disease develop in the area of a congenitally absent nipple. These findings support the theory of an intradermal origin for the Paget cell. Survival rates of patients with Paget's disease and a palpable breast mass were similar to those of patients with infiltrating duct carcinoma, the presence of axillary node metastases being the most important prognostic factor. Actuarial five- and ten-year survival rates were 22% and 9.9% for patients with positive nodes. The modified radical mastectomy is recommended as primary therapy for this group of patients. In contrast, none of the patients with Paget's disease of the nipple and no evidence of a palpable breast mass developed recurrent carcinoma. A total mastectomy without an axillary node dissection is the treatment of choice in this type of patient.

Late hypocalcemia appears associated with thyroidectomy for Graves' disease more frequently than with thyroidectomy for other conditions. Of 62 total thyroidectomies done by a single surgeon, 28 were done for carcinoma, 18 for benign disease (primarily nontoxic nodules with a history of radiation therapy to the head and neck (RT)) and 16 for Graves' disease. Mean calcium concentrations measured two months or more after surgery were 9.38 +/- 0.07 (SEM)mg/% for patients with cancer, 8.79 +/- 0.31 mg/dl for patients with Graves' disease and 9.38 +/- 0.08 mg/dl for patients with other benign diseases. No patient without Graves' disease developed late hypocalcemia. In contrast, six of 16 patients with Graves' developed significant late hypocalcemia requiring calcium therapy. The incidence of hypocalcemia after total thyroidectomy for Graves' disease was significantly greater than that seen in other conditions (p < 0.01). Since no parathyroids were removed in the patients with Graves' disease, and since branches of the inferior thyroid artery were invariably ligated distal to the parathyroids, we hypothesized that the late hypocalcemia might be associated with a peculiarity in scar formation in the presence of this autoimmune disease. Accordingly, parathyroid autotransplantation was performed synchronously as a prophylactic measure in nine subsequent patients undergoing total thyroidectomy for Graves' disease; no instance of late hypocalcemia has occurred in this group. The decreased incidence of late hypocalcemia is highly significant (p < 0.01). Although the precise etiology of late hypocalcemia after thyroidectomy for Graves' disease remains undetermined, this experience indicates that synchronous parathyroid autotransplantation is beneficial in preventing this complication.

UDP-galactose:N-acetylglucosamine galactosyltransferase (GT) is a membrane-bound enzyme active in the biosynthesis of the carbohydrate moiety of glycoproteins and glycolipids. A soluble form of GT, present in human serum, has recently been found to be elevated in the presence of various neoplasms. In this study, GT levels were measured in randomized serum samples obtained from normal controls (group I, n = 49), patients with benign breast disease (group II, n = 46), disease controls (group III, n = 50), patients with primary breast carcinoma (group IV, n = 53), and untreated metastatic breast cancer (group V, n = 23). Although substantial serum GT elevations were observed in individual control patients with active inflammatory or metabolic diseases, the mean GT levels were significantly higher in the groups with breast carcinoma (P < 0.001, 0.001, 0.02; P < 0.001, 0.001, 0.001 for groups IV and V vs groups, 1, II, and III, respectively). Furthermore, when serum GT levels were correlated with the properative clinical stage of breast cancer, significant elevations were found in 14.3% (3/21) of stage I, 66.7% (8/12) of stage II, 78.6% (11/14) of stage III, and 96.5% (28/29) of stage IV patients. These data indicate that serum GT levels are elevated in the presence of breast carcinoma and that the enzyme elevations correlate positively with the clinical stage of disease. Serum GT may be potentially useful in the detection of recurrent breast carcinoma and as a marker of tumor response to therapy for advanced disease.

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increased with stage of disease, and the differences between mean levels were found to be significant in stages 1 and 2 versus 3 and 4 (p<0-001). This suggests a positive correlation between the preoperative CEA level and tumour burden defined by pathological staging. When the results were compared with the histological type of lung carcinoma, CEA elevations occurred most frequently with adenocarcinoma, followed by undifferentiated and squamous cell carcinoma, reflecting perhaps the origin of this oncofetal antigen from the endodermally derived bronchial mucosa. These data indicate that preoperative serum CEA levels quantitatively reflect the extent of tumour assessed pathologically at operation and confirm the potential usefulness of this antigen as a biological tumour marker in the management of bronchial neoplasms.

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As a primary feasibility study for the selection of biomarkers for more extended clinical evaluation, 17 potential biomarker candidates were measured in the body fluids of patients with ovarian carcinoma. For comparative purposes, patients were staged and separated into three groups: those considered completely free of disease, those with residual but minimal tumor, and those with advanced disease. Individual markers included plasma carcinoembryonic antigen, serum human chorionic gonadotrophin, urinary beta-aminoisobutyric acid, serum UDP-galactosyltransferase, and urinary hydroxyproline. Structurally related groups of biomarkers included six modified nucleosides and three polyamines analyzed in urine, and three serum protein-bound neutral carbohydrates. The respective chromatographic methods developed for these latter biochemical materials enabled all the individual compounds in each group to be quantitated simultaneously in one analytical run. The general frequency and degree of elevation for the total number of biomarkers was directly proportional to increasing tumor burden with specific exceptions, human chorionic gonadotropin and beta-aminoisobutyric acid. Galactosyltransferase was the most frequently elevated in the limited disease categories. Several of the biomarkers were elevated in the majority of patients with advanced disease and appeared potentially superior to carcinoembryonic antigen or human chorionic gonadotrophin.