Axillary node metastases in relation to size and location of breast cancers: analysis of 147 patients.

This prospective study of 147 patients undergoing axillary lymphadenectomy for treatment of breast cancer over a 3 1/2-year period relates frequency and number of involved lymph nodes to the size and location of the tumor within the breast. A total of 35.3 per cent of patients in the entire series had axillary metastases. Of 29 patients with cancers 0-10 mm, five had axillary metastases (17.2%). All five cancers were located at the upper outer quadrant (UOQ) of the breast. Thirteen of 58 patients with cancers 11-20 mm had positive nodes. Eight of the 13 cancers were at the UOQ. Only one of 13 patients with cancer at the lower inner quadrant had nodal metastases. A total of 25.8 per cent of cancers 0-20 mm located at the upper half of the breast were associated with positive nodes, in contrast with 11.1 per cent of those located in the center and 7.1 per cent of those located in the lower half of the breast; likewise, 28 per cent of cancers 0-20 mm located at the lateral aspect of the breast had axillary nodes involved, and 11.5 per cent when cancer was located in the median half. Using such an analysis, 25 per cent of all lymphadenectomies could have been omitted, as could 37.9 per cent of those performed for T1 cancers (0-20 mm) without compromising systemic adjuvant therapy.

Physical, psychological, and economic advantages of accelerated discharge after surgical treatment for breast cancer.

The economic benefits of outpatient surgery and of short hospital stay have been amply emphasized over the past 5 years. The economic, physical, and psychological benefits of such an approach for treating patients with early breast cancer are detailed in this report. Of 208 patients treated by the author over a 3-year period (1991-1993), 63 (30.3%) were treated on an outpatient basis. Of 132 patients undergoing axillary node dissection, 29 (21.9%) were sent home the day of operation, and 95 (72%) stayed in the hospital overnight. The median number of lymph nodes removed was 17 and the median length of stay for all patients was one day; 31.8 per cent of these patients developed seromas, and 2 were readmitted for infected seromas. The per diem cost for our hospital in 1993 was $684. The program incorporates a strong institutional support component, with unlimited access to physicians and nurses, and has led to significant cost savings. It has also led to better physical and psychological recovery, emphasizing patient comfort, control and independence, and strong family interactions. Because 75 per cent of our 300 patients treated for breast cancer in our setting each year undergo axillary node dissection, $153,900 is expended for each day patients stay in our hospital, and presumably $92 million is expended country-wide. Adopting such a program can lead to significant savings without compromising the quality of care. The physical and psychological benefits of such an approach outweigh any minor inconveniences on patients and families.

Fish oil and oat bran in combination effectively lower plasma cholesterol in the rat.

Male rats were fed a semi-purified diet containing oat bran or wheat bran with or without a marine fish oil to investigate the effects of such combinations on lipid metabolism. Oat bran alone and wheat bran plus fish oil gave lower plasma cholesterol concentrations than wheat bran alone while oat bran plus fish oil gave the lowest. Oat bran increased plasma triacylglycerols compared with wheat bran but oat bran plus fish oil gave concentrations similar to those seen with wheat bran plus fish oil. Oat bran gave higher hepatic cholesterol synthesis rates and a higher activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase compared to wheat bran. The addition of fish oil to either bran diet decreased cholesterol synthesis but HMG CoA reductase activity was not reduced. Oat bran increased hepatic acyl coenzyme A:cholesterol acyl transferase (ACAT) activity and increased the ratio of esterified to unesterified cholesterol in hepatic microsomal membranes compared with wheat bran. Fish oil decreased hepatic LDL receptor activity and increased HDL binding activity when added to the wheat bran diet but these effects were not seen with oat bran. Oat bran also had no effect on hepatic lipoprotein receptor activity compared with wheat bran. These results show that fish oil and oat bran have complementary cholesterol lowering effects in the rat.

Retroendocytosis of high density lipoproteins by the human hepatoma cell line, HepG2.

When human HepG2 hepatoma cells were pulsed with 125I-labeled high density lipoproteins (HDL) and chased in fresh medium, up to 65% of the radioactivity released was precipitable with trichloroacetic acid. Cell-internalized 125I-HDL contributed to the release of acid-precipitable material; when cells were treated with trypsin before the chase to remove 125I-HDL bound to the outer cell membrane, 50% of the released material was still acid-precipitable. Characterization of the radioactive material resecreted by trypsinized cells revealed the presence of particles that were similar in size and density to mature HDL and contained intact apolipoproteins (apo) A-I and A-II. The release of internalized label occurred at 37 degrees C but not at 4 degrees C. Monensin, which inhibits endosomal recycling of receptors, decreased the binding of 125I-HDL to cells by 75%, inhibited the release of internalized radioactivity as acid-precipitable material by 80%, and increased the release of acid-soluble material by 90%. In contrast, the lysosomal inhibitor chloroquine increased the association of 125I-HDL to cells by 25%, inhibited the release of precipitable material by 10%, and inhibited the release of acid-soluble radioactivity by 80%. Pre-incubation with cholesterol caused a 50% increase in the specific binding, internalization, and resecretion of HDL label. Cholesterol affected the release of acid-precipitable label much more (+90%) than that of acid-soluble material (+20%). Taken together, these findings suggest that HepG2 cells can bind, internalize, and resecrete HDL by a retroendocytotic process. Furthermore, the results with cholesterol and monensin indicate that a regulated, recycling, receptor-like molecule is involved in the binding and intracellular routing of HDL.

Modulation of the hypolipidemic effect of fish oils by dietary fiber in rats: studies with rice and wheat bran.

Adult male rats were fed a purified diet containing rice bran or wheat bran with or without a marine fish oil to investigate the possible effects of such dietary combinations on lipid metabolism. Plasma and hepatic triacylglycerols and hepatic lipogenesis were lowered significantly by feeding fish oil with rice bran but not with wheat bran. Plasma cholesterol and hepatic cholesterol synthesis were significantly lower in animals fed fish oil with either bran. Liver microsomal free cholesterol was significantly lower in rats fed rice bran alone than in all other groups. Hepatic low density lipoprotein (LDL) receptor activity was significantly higher in the two groups fed rice bran than in the two groups fed wheat bran. Fish oil significantly decreased hepatic LDL receptor activity and increased hepatic high density lipoprotein (HDL) binding activity with wheat bran but had no significant effects on these parameters when added to the rice bran diet. However, when the data for all groups were pooled, there was a significant negative correlation between hepatic HDL binding activity and LDL receptor activity. Cecal volatile fatty acids were significantly higher in rats fed rice bran, were unaffected by adding fish oil to either bran diet and did not appear to mediate any of the effects of the brans and fish oil on plasma lipids and hepatic lipid metabolism. The combination of rice bran plus fish oil therefore appears to have more beneficial effects on lipid metabolism than wheat bran plus fish oil.

Multiparametric deoxyribonucleic acid and cell cycle analysis of breast carcinomas by flow cytometry. Clinicopathologic correlations.

Using intact ethanol-fixed cytokeratin monoclonal (CAM 5.2) and propidium iodide dual-stained cells, we have performed two-color multiparametric flow cytometric (FCM) DNA analysis and S-phase fraction (SPF) determination on 165 mechanically dissociated breast carcinomas. Sixty-seven patients were axillary node positive, 33 patients node negative; 59 had biopsy only and in 8, FCM was performed on tissue from metastatic lesions. Overall, 62% of the tumors contained aneuploid cell populations. Abnormal cellular DNA content (aneuploidy) was significantly correlated with high nuclear grade (p less than 0.001), lack of estrogen receptors (p less than 0.001), presence of vascular invasion (p less than 0.04), high histologic grade (p less than 0.04), and tumor size (p less than 0.03) but not with patient age (p greater than 0.07) or axillary node status (p greater than 0.50). SPF values derived from ungated histograms had a positively skewed frequency distribution (range 2 to 30%, N = 152) with an overall median of 11% (diploid, 8.9%; aneuploid, 15.7%). Higher SPF values were significantly correlated with aneuploidy (p less than 0.001), presence of necrosis (p less than 0.001), lack of estrogen receptor (p less than 0.0001), high nuclear grade (p less than 0.001), vascular invasion (p less than 0.003), tumor size (p less than 0.006), and high histologic grade (p less than .004) but not the presence of lymph node metastases (p greater than 0.56). Mean SPF values were significantly higher when calculated from cytokeratin gated DNA histograms (14.1% versus 11.5%, p less than 0.001), probably due to exclusion of contaminating stromal/inflammatory cells; and significantly lower when calculated from debris subtracted histograms (7.8% versus 11.4%). Cytokeratin gated and debris subtracted SPF values both had a greater degree of correlation than ungated values with clinicopathologic factors of known prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Full thickness abdominal wall resection for recurrent and metastatic neoplasms. A report of three cases.

Full thickness infiltration of the abdominal wall by intraabdominal cancer, especially after effective prior therapy, is frequently considered a sign of inoperability. Such patients are treated with irradiation, chemotherapy, or locally destructive means (laser, cryosurgery) with limited success. Full thickness resection of portions of the abdominal wall has not been widely used in such settings because of concerns regarding abdominal wall reconstruction and also because of the perceived noncurative nature of such "radical" procedures. While long-term prognosis in patients with abdominal wall infiltration by cancer depends upon various factors, technical considerations regarding reconstruction need not prevent effective local palliative therapy. Bridging large defects can be successfully accomplished by using available synthetic material of a durable, inert nature. Polyprophylene (Marlex) mesh, a readily available and inexpensive inert fabric, meets all desirable features for such use. This paper details the successful treatment of three patients in whom recurrent carcinoma infiltrated the full thickness of the abdominal wall and caused intractable pain. In all three, full thickness portions of the abdominal wall were resected, segments of intestine and of urinary bladder were also excised, and the defects were closed using a double layer of polypropylene mesh. Complete relief of pain was accomplished and the cosmetic and functional results were excellent. Illustration A depicts procedure in patients one and two. Illustration B depicts procedure in patient three.

Demonstration of a high density lipoprotein (HDL)-binding protein in Hep G2 cells using colloidal gold-HDL conjugates.

Solubilized membrane proteins of Hep G2 cells were electrophoretically separated on polyacrylamide gels and electrotransferred onto nitrocellulose paper. Overlaying the nitrocellulose with human high density lipoproteins conjugated to colloidal gold revealed the presence of a single protein band with an apparent molecular mass of 80 kDa. Binding of the conjugates to this protein was specific for high density lipoproteins in as much as it was effectively displaced by an excess of unlabelled high density lipoproteins but not by a similar excess of unlabelled low density lipoproteins. Binding was not dependent on Ca2+ as 10 mM EDTA had no effect. The binding activity of the solubilized membranes was increased by incubating the cells with non-lipoprotein cholesterol. This was detected on electroblots and quantified with a new dot blot assay using the colloidal gold-high density lipoprotein conjugates.

The effects of dietary fish oil on hepatic high density and low density lipoprotein receptor activities in the rat.

Rats were fed either a standard ration diet or that diet supplemented with 8% by wt of a marine fish oil or safflower oil. After 10 days, plasma triacylglycerols, total cholesterol, high density lipoprotein (HDL) cholesterol, hepatic cholesterol and fatty acid synthesis and hepatic low density lipoprotein (LDL) receptor activity were significantly depressed while HDL receptor activity was significantly increased in rats fed fish oil. Fish oil-induced effects on cholesterol metabolism in the rat therefore include reciprocal changes in the activities of hepatic LDL and HDL receptors.

Major abdominal operations on Jehovah's Witnesses.

Thirteen major operations have been successfully performed on 11 Jehovah's Witnesses, without complications. After detailed preadmission assessment, all patients received pretreatment assurances that their religious beliefs would be respected, regardless of the circumstances in the operating room. There were no untoward effects of this policy. Whereas the religious and legal aspects of the issue may be confusing and unacceptable to some surgeons, those undertaking to treat such patients must use ancillary means, technical variations, and alternatives to standard procedures in order to minimize risks and achieve acceptable results. Preoperative agreement should be viewed as binding by the surgeon and should be adhered to regardless of events developing during and after operation. Such an approach constitutes the best preoperative preparation, orients the patients positively toward their surgical treatment, and diverts the surgeon's attention from the legal and philosophical considerations to the surgical and technical ones, thus, allowing him to perform optimally and serve his patient's best interests. The recovery phase in this small series of electively performed operations occurred at anticipated rates and no postoperative complications developed.

Carcinomas of the colon and rectum. A comparison of staging classifications.

Five staging methods for colorectal cancer were compared to the Dukes method in order to assess which methods were most sensitive and specific. Three hundred fifty-two patients with resected carcinomas of the colon and rectum were followed from 6 to 11 years or until death. All patients were staged by intraoperative and pathological criteria. Survival curves were constructed for each stage. The pTNM system was most sensitive at predicting death. The Gastrointestinal Tumor Study Group (GITSG) system was the most specific at predicting survival. However, the Dukes system did no worse than either of these staging systems and predicted relatively few false-positive and false-negative cases. The sensitivity and correctness of the Dukes system was improved by adding information regarding percent of lymph node metastases, ulceration of the primary tumor, and adjacent organ invasion.

Localization of residual medullary thyroid cancer by thallium/technetium scintigraphy.

Whole-body thallium/technetium subtraction scintiscans, with thallium 201 chloride and technetium 99m pertechnetate, were obtained on 10 patients with medullary thyroid cancer with postoperative elevations of serum calcitonin values. Seven patients had the hereditary variant of medullary thyroid cancer (the multiple endocrine neoplasia, type II syndrome) while three patients had the sporadic form. Negative scans were obtained on five patients with basal calcitonin levels less than 3 ng/ml (normal less than 0.35 ng/ml). Five other patients with elevated calcitonin levels (range 3.6 to 69.2 ng/ml; mean 28.3 ng/ml) had positive scans that have guided further surgical approaches. Serum calcitonin appears to remain the most sensitive indicator of residual medullary thyroid cancer while localization of this residual tumor tissue frequently can be obtained through thallium/technetium subtraction imaging in both the hereditary and sporadic forms of the disease.

Breast lesions examined by digital angiography. Work in progress.

Differentiation of benign from malignant lesions in screening for breast cancer is usually arrived at via surgical biopsy, an invasive and costly procedure. Digital subtraction angiography (DSA) of the breast is a less invasive procedure. DSA imaging patterns from 22 patients with malignant and benign lesions were compared with surgical biopsy findings. DSA examinations were performed with the breast in an immobilization device and contrast medium was injected into the superior vena cava. Images were produced with a low kilovoltage (50 kVp) to enhance contrast, and a technique yielding an average dose to the breast of less than 2 rad (0.02 Gy) was used. Preliminary clinical results demonstrate the potential of DSA for differentiation of benign and malignant lesions and justify further investigations of its use as an alternative to surgical biopsy.

The clinical course after definitive operation for medullary thyroid carcinoma.

Thorough family studies that used the radioimmunoassay procedure for calcitonin (CT) during the past 12 years have provided data on 70 patients from 12 kindreds with hereditary medullary thyroid cancer (hereditary group) and 28 patients with sporadic or nonhereditary medullary thyroid cancer (sporadic group). Serum CT elevations after total thyroidectomy as evidence of residual tumor have been encountered in 21 of 25 patients in the hereditary group with palpable tumors preoperatively (84%) and in 13 of 24 in the sporadic group (54%). However, none of 26 patients with hereditary nonpalpable lesions found by family screening studies have been found to have postoperative CT elevations. Both cervical lymphadenectomy in patients with lymph node involvement at initial operation and reexploration in those with CT elevations after total thyroidectomy have been unsuccessful in the eradication of metastatic disease. These data emphasize the value of thorough family studies that use stimulated CT measurements in the detection of early and curable neoplasms. Involvement of the parathyroid glands or the adrenal medulla that occurred in the hereditary multiple endocrine neoplasia syndromes varied from family to family; it influenced the clinical course and required regular surveillance with calcium and catecholamine studies. Separation of hereditary from sporadic cases has practical value in the identification of family members at risk and also in the provision of prognostic data.

The role of fine needle aspiration cytology in the management of solid breast tumors.

The value of fine needle aspiration cytology in patients with breast masses has found limited acceptance in the United States. When employed consistently, however, it has been reliable and has facilitated patient management. A positive cytological diagnosis of cancer has always been confirmed by histology, while "atypical," "suspicious," and "abnormal" categories represent cancer in varying degrees of frequency and open biopsy is usually necessary. The method is quick, easy, and causes no morbidity. The critical aspects for its success are those of interested surgeons and cytopathologists, and appropriate sampling and processing technique. In our experience with fine needle aspiration cytology in 38 patients with breast tumors, all 23 patients with cytological diagnosis of cancer, three of four with suspicious, and one of three with atypical smears proved to have cancer. Two of four patients with unsatisfactory smears had carcinoma on biopsy, both of the infiltrating lobular variety. Based on this limited experience, as well as on information in the available literature, fine needle aspiration cytology is strongly recommended in the evaluation and management of patients with breast tumors.

Work in progress: radioisotopic evaluation of gastroplasty patients.

Radioisotopic gastric emptying studies, using technetium-99m-sulfur-colloid-labeled egg, were performed in 14 patients who had undergone gastroplasty. The radioisotopic method was found to be a good quantitative indicator of the amount of solids that empty from the stomach and a useful tool in the longterm follow-up of gastroplasty patients. It was particularly helpful in evaluating the efficacy of surgery in patients with poor postsurgical weight reduction.