Relationship between low estrogen receptor values and other prognostic factors in primary breast tumors.

BACKGROUND: The current study compared the immunocytochemical expression of estrogen (ER) and progesterone (PgR) receptors by malignant breast cells to the hormone receptor concentrations reported from radioligand assays. These values were examined in relation to DNA ploidy and the fraction of cells in S phase. METHODS: ER and PgR concentrations, DNA ploidy, and S-phase fractions were measured by standard techniques with 124 samples of invasive ductal carcinoma. Suspensions of tumor cells were examined by immunocytochemical assay (ICA) for the percentages of ER and PgR positive cells. RESULTS: Twenty-six of the 38 tumors from patients 50 years of age or younger were classified as high S-phase fraction, and 28 tumors had aneuploid levels of DNA. The 20 ER positive tumors each contained less than 100 fmol/mg. Thirty-nine of the 86 tumors from patients older than 50 years were classified as high S phase, and 41 were aneuploid. Sixty-five samples were considered ER positive by radioligand assay. ICA showed that tumors in either age group with less than 40 fmol/mg did not contain ER positive cells. The proportion of samples with PgR levels between 10 and 100 fmol/mg was small, and fewer PgR positive tumors were categorized as negative when examined by ICA for receptor containing cells. The reclassification of the hormone receptor status of a tumor based on ICA appeared to be independent of S-phase and ploidy values. CONCLUSIONS: Tumors that are classified as ER or PgR positive based on accepted cutoff values for radioligand assays may actually be receptor negative because the tumors do not appear to contain receptor positive cells.

Management of coexistent carotid and coronary artery disease.

Simultaneous coronary artery bypass grafting (CABG) and carotid endarterectomy (CE) were done on 133 patients over an 8-year period. Twenty-seven patients (20%) had previous transient ischemic attacks (TIAs), 12 (9%) had previous strokes, and the remainder (71%) were asymptomatic. All asymptomatic patients had greater than 85% stenosis of the internal carotid artery demonstrated by noninvasive ultrasonography and four-vessel angiography. CE was performed prior to the sternotomy for coronary artery bypass, under the same anesthesia. Nineteen patients had bilateral carotid artery disease. Postoperatively, three patients (2.3%) suffered strokes, an additional three patients (2.3%) suffered transient upper extremity weakness, and one patient from each of these groups died. There were no postoperative strokes or TIAs in patients with bilateral carotid artery disease. Average length of hospital stay was 10 days. Our experience leads us to conclude that the morbidity and mortality of the simultaneous procedure are not affected by bilateral carotid artery disease. In patients with symptomatic coronary artery disease and symptomatic carotid artery disease or asymptomatic carotid artery disease with a high-grade stenosis, we think that simultaneous repair of both lesions should be done.

Protein turnover in advanced lung cancer patients.

Understanding the extent to which changes in whole-body protein kinetics contribute to the commonly observed weight loss and decrease in lean body mass (LBM) in patients with cancer is currently obscured by conflicting reports in the literature. While several studies have reported significant increases in whole-body protein turnover (WBPT), synthesis (WBPS), and catabolism (WBPC) in patients with cancer, others have failed to confirm these observations. We have measured whole-body protein kinetics using a primed constant infusion of 15N-glycine in a homogenous group of 32 newly diagnosed advanced lung cancer patients with comparable staging and before any antineoplastic treatment, and in 19 normal healthy volunteer controls. Urinary urea and ammonia 15N enrichment was determined in individually collected urine samples obtained during the 24-hour study period and averaged for the determination of protein kinetics. During the last 6 hours of urine collection, samples were obtained hourly for determination of 15N plateau enrichment. Twenty-four-hour urinary nitrogen and creatinine excretion was determined from 24-hour pooled urine samples. Resting metabolic expenditure (RME) was determined by indirect calorimetry and LBM was estimated from deuterium oxide dilution. Age body weight, LBM, RME, and 24-hour urinary nitrogen excretion did not differ between cancer and control subjects. WBPT, WBPC, and WBPS (g/kg/d) were significantly increased in lung cancer patients. However, when the same results were expressed either per kilogram LBM or per gram 24-hour urinary creatinine excretion, WBPT, WBPC, and WBPS rates were not statistically different from those of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose metabolism in advanced lung cancer patients.

Although it is generally accepted that altered nutrient intake and metabolism are responsible for the progressive loss of body weight observed in most advanced cancer patients, there is still considerable controversy regarding the contributory role of changes in both resting energy expenditure (REE) and glucose metabolism. Several studies suggest increases in both REE and glucose appearance in advanced cancer patients compared with healthy control subjects, whereas others revealed no changes in either metabolic parameter. We measured REE with indirect calorimetry and glucose kinetics with a primed constant infusion of D-[U-14C]glucose and D-[6-3H]glucose over the last 4 h of a 24-h fast in 32 advanced lung cancer patients immediately after diagnosis and before any chemotherapy or radiotherapy and in 19 healthy volunteer subjects. REE for the lung cancer group was not significantly different from that in the control group (1535.8 +/- 78.0 vs. 1670.2 +/- 53.9 kcal/day, respectively, p = 0.151). When REE was expressed as a function of body weight, or lean body mass, no differences between the two groups were observed. The rate of glucose appearance was 9.88 +/- 0.36 mumol.kg-1.min-1 in the cancer patients and 10.15 +/- 0.53 mumol.kg-1.min-1 in control subjects (p = 0.667), of which 50.4 versus 58.2%, respectively, was oxidized. The amount of glucose recycled was 13.54 +/- 1.22% in cancer patients and 15.08 +/- 0.99% in control subjects (p = 0.394). The amount of VCO2 from direct oxidation of glucose was 23.39 +/- 0.74% in cancer patients and 27.45 +/- 1.36% in control subjects (p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of deoxyribonucleic acid ploidy status on survival of patients with carcinoma of the endometrium.

This retrospective study was performed to determine the clinical usefulness of deoxyribonucleic acid (DNA) ploidy and the amount of DNA in the nucleus of the tumor cell on the prognosis of patients with carcinoma of the endometrium. Five year follow-up study was obtained for 121 patients. Flow cytometric analysis was used to determine tumor cell ploidy from paraffin-embedded specimens. Patients were grouped according to ploidy, clinical stage and grade and whether or not they received postoperative radiation. The data were subjected to a Cox proportional hazards regression analysis, and only ploidy status and clinical stage were significantly associated with survival time. Of the 121 patients observed, 44.6 per cent were aneuploid and 55.4 per cent, euploid. Preliminary chi-square analysis indicated a strong survival advantage to those patients with euploid endometrial carcinoma. The over-all five year survival rate for patients with aneuploid tumors was 53.7 per cent, as opposed to 80.6 per cent for patients with euploid tumors (p less than 0.01). Eighty-seven patients were Stage I, 39 aneuploid, 48 euploid. The five year survival rate for patients with Stage I aneuploid was 71.8 versus 85.4 per cent for those who were euploid. Twenty-one patients were Stage II; seven aneuploid and 14 euploid. The five year survival rate for aneuploid patients was 14.3 versus 85.7 per cent for euploid patients. The over-all five year survival rate for those with Stage I and II was 85.5 per cent euploid and 63.0 per cent aneuploid, p less than 0.05. Patients with Stage III or IV had poor outcome regardless of ploidy status. These data show that patients with euploid Stage I and II carcinoma of the endometrium have a significant survival advantage over patients with aneuploid tumors. We, therefore, believe that ploidy status may be used to facilitate the determination of prognosis in carcinoma of the endometrium.

Protein C activity, stage of disease, and vascular thrombosis in colon carcinoma.

To determine the etiology of the increased incidence of postoperative deep venous thrombosis (DVT) in patients with carcinoma of the colon, serum levels of protein C were measured preoperatively in 65 patients with colorectal adenocarcinoma. Noninvasive lower-extremity Doppler studies were performed on all patients prior to discharge to assess patency of the deep veins. Six patients (9%) were found to have DVT. The protein C level was considered elevated if it was greater than 125% of control values and reduced if less than 75% of control values. The development of DVT was found to be independent of the serum carcinoembryonic antigen, albumin, total protein, hemoglobin, hematocrit, platelet count, prothrombin time, partial thromboplastin time, and the patient's age and percentage of ideal body weight. There was an inverse relationship between the protein C level (p less than 0.001), Dukes stage of the tumor (p less than 0.001), and the development of DVT. Linear regression analysis revealed that only the tumor stage and the protein C level could be used to predict the development of DVT. The data show that for these patients with colorectal malignancy, the development of DVT may be related to decreased levels of protein C.

Prognostic applications of DNA analysis in solid malignant lesions in humans.

Analysis of the DNA of tumors using flow cytometry is a technologic method that can be used to investigate the biologic nature of tumors. While not conclusive, results suggest that this biologic information may be useful in identifying patients with malignant disease who have a worse prognosis. The differentiation of patients with aneuploid tumors into those with hypoploid tumors and those whose tumors are hyperploid may be a further refinement of the technique. Also, a combination of this biologic criteria may allow a more accurate selection of patients than either method alone. Further investigative work needs to be done to fully evaluate the clinical usefulness of flow cytometric DNA analysis and answer these and other questions.

Whole-body protein kinetics in elective surgical patients receiving peptide or amino acid solutions.

We compared the efficacy of two enteral solutions that were isonitrogenous and of identical amino acid composition but differed in that one solution contained only free amino acids whereas the other contained a mixture of free amino acids and peptides. Protein kinetics and nitrogen balance were evaluated in a group of six elective surgical patients. Primed-constant infusion with 15N-glycine was started 24h after gynecologic surgery and sustained over 3 days. During the first postoperative day, patients received enteral 0.45% saline. During postoperative days two and three, the patients received either the free amino acid solution or the mixture of peptides and free amino acids in a crossover design. There were no differences in protein kinetics or nitrogen balance with the two treatments.

A physiologic basis for the provision of fuel mixtures in normal and stressed patients.

It has been suggested that lipid is a preferred fuel in stressed patients. We evaluated glucose oxidation in 20 patients (sepsis, cancer of the colon, multiple trauma, controls) while they received TPN (5.65 mg glucose/kg/min). Respiratory quotient (RQ) was measured by indirect calorimetry and the percent VCO2 arising from the oxidation of glucose was measured using [U-14C] glucose. Since RQs were 1.0 or greater in all patients, the nonprotein energy utilized by them was calculated to be derived completely from glucose. However, the kinetic data showed that glucose contributed only 55-60% of the VCO2. Protein oxidation contributed less than 20% of the VCO2, as calculated from urinary nitrogen. The difference must have been derived from fatty acid oxidation. The glucose turnover that was not oxidized was presumed to be converted to lipid at an RQ of 8.6. The net oxygen consumption and carbon dioxide production from this overall distribution resulted in an RQ of about 1.0 with only 60% coming from glucose oxidation. Since all patients responded in the same manner, it appears that the proper ratio of glucose and lipid was dictated on a physiologic basis and not on the type of disease.

Glucose metabolism and colorectal carcinoma.

We evaluated nine patients with colorectal cancer and six control patients in a postabsorptive state in an attempt to define the effect of cancer on glucose turnover, oxidation, recycling, and resting metabolic expenditures (RME). The glucose kinetics were determined using a double-labeled [U-14C] glucose and [6-3H] glucose, and energy expenditures were measured by indirect calorimetry. In addition, we also measured the same parameters in the cancer patient group on a total parenteral nutrition (TPN)-glucose system on the fourth day before and on the fifth day after removal of tumor. In the postabsorptive state, glucose turnover and oxidation rates were similar in the cancer and control group; however, the mean glucose pool size of the cancer group was 47% larger than the control group and was statistically significant (P = .05). Glucose recycling was also two times the control group and was statistically significant (P = .05). The recycling of glucose, both preoperatively and postoperatively, continued in the face of infused glucose; however, the rate was suppressed compared with the fasting cancer group. Postabsorptive RME of the cancer group did not differ from those predicted by the Harris-Benedict equation. Following a 4-day infusion of TPN-glucose that supplied a mean of two times the patients' energy needs, the preoperative cancer group showed a mean increase in RME of 25.6% and a 31.58% increase on the fifth postoperative day of TPN-glucose, presumably due to increased lipogenesis and to a much lesser extent from the increased protein synthesis (4 g positive N balance).(ABSTRACT TRUNCATED AT 250 WORDS)

The content of tumor DNA as an indicator of prognosis in patients with T1N0M0 and T2N0M0 carcinoma of the breast.

To determine if the flow cytometric measurement of the content of the tumor DNA could provide prognostic information in T1N0M0 and T2N0M0 carcinoma of the breast, we isolated nuclei from paraffin-embedded tumor specimens from 128 consecutive patients who underwent modified radical mastectomy and were found to have a T1 or T2N0M0 carcinoma of the breast. The content of DNA of the nuclei was determined by flow cytometry. Although the average tumor size was not significantly different, 17 of 56 patients with aneuploid tumors died of cancer compared with 2 of 72 with euploid tumors. The 10-year overall actuarial survival rate of the euploid and aneuploid groups was 72% and 67%, respectively (p less than 0.02). A hazards model of the data shows that the DNA content of the tumor is the most significant indicator of prognosis, with a 2.25-fold increased risk of death for patients with aneuploid tumors. These data show that the tumor DNA content can be used to identify a group of patients with T1 or T2N0M0 carcinoma of the breast with the same prognosis as a group of patients without carcinoma of the breast that would be unlikely to benefit from adjuvant therapy.

Energy requirements for cancer patients and the effect of total parenteral nutrition.

Limited data are available concerning resting metabolic expenditure (RME) in cancer patients and the effect of RME by varying glucose intake. This study describes the measurements on 21 patients with colorectal cancer while fasting and with incremental levels of standard TPN-glucose system by central vein. Following an overnight fast, the measured mean +/- SEM percent difference from the predicted RME for the male group was 4.13 +/- 1.67% and the female group, 2.09 +/- 2.09%. The overall mean percent difference of 2.95 +/- 1.45 suggests that colorectal cancer does not cause an increase in energy expenditure. Hepatic metastases in 11 of the patients did not influence RME. The data from the 21 patients indicate a statistically significant increase in RME with TPN compared to postabsorptive states in females of 37%, in males 21.88%, and combined of 29.88%. Progressively greater increases in RME were seen when calories provided incrementally exceeded the basal RME. Carbohydrate loading in excess of the patient's calorie need, as indicated by the respiratory quotient (RQ) greater than 1.0, results in fat synthesis and other energy-costing processes. The basal RME demonstrates that these cancer patients are not hypercatabolic, but do respond to high-level force-feeding with markedly increased metabolic expenditures.

Truncus arteriosus with interrupted aortic arch: report of a successful surgical repair.

The association of truncus arteriosus with interrupted aortic arch represents a formidable surgical challenge. Two successful repairs have been reported, but none for the past ten years. This report presents a third successful repair using a technique that allows the widely patent ductus arteriosus to maintain continuity between the truncus (with pulmonary arteries detached) and the descending aorta. Right ventricle-pulmonary artery continuity is established in the usual way with a porcine-valved conduit. While long-term potential difficulties with this approach are recognized, it appears to give satisfactory initial palliation and to be an acceptable method of treatment for this combination of defects. The embryology and the anatomy of the lesion are briefly discussed.

Technical evaluation of factors interfering in the carcinoembryonic antigen assay.

Storage of serum or plasma at room temperature (RT) or 4 degrees C for eight days did not alter the level of carcinoembryonic antigen (CEA). However, storage of whole blood at RT for 8 days resulted in false elevated CEA levels compared to controls. Heating of serum or plasma at 56 degrees C for 30 min or freezing and thawing for fifteen times did not change the CEA levels in these specimens. Comparison of CEA levels in the serum and plasma of the same specimens showed significantly higher levels of CEA in plasma than serum specimens. Collection of blood in tubes with different anticoagulants showed significantly false elevated levels of CEA only when blood was collected in heparinized tubes. These data indicate the importance of knowing the factors interfering in the CEA assay when interpreting its results.

The effect of major thermal injury and carbohydrate-free intake on serum triglycerides, insulin, and 3-methylhistidine excretion.

The severely burned patient responds differently to starvation ketosis in the early stage of injury as compared to the normal individual. A similar response has been observed in the patient after skeletal trauma and sepsis. In order to determine the extent of muscle protein contribution and the mechanism(s) involved, 11 burn patients with 35% to 80% BSA burn were resuscitated using carbohydrate-free solutions for 3 days followed by unrestricted intake. Blood was drawn daily and 24-hour urinary nitrogens were determined. Controls consisted of 10 preoperative elective surgical patients and two normal volunteers. The burned patients lost a mean +/- SEM of 17.1 +/- 1.72 g nitrogen per day on the third day. The mean +/- SEM ketone body response on the third day for burned patients was 385 +/- 77 mumol/l compared to 727 +/- 81 mumol/l for control patients. The mean +/- SEM 3-methylhistidine loss for burned patients on the third day was 9.83 +/- 0.82 mumol/kg compared to 3.6 mol/kg for control patients. Insulin levels on the third day of fast were three times the normal group. This insulin increase may be the modulating factor that suppresses excessive fat mobilization. This metabolic response causes a lower plasma ketone level, which may then necessitate the need for continued protein catabolism for glucose production for certain tissues. The protein contribution to the hypercatabolic response as assessed by increased urinary nitrogen losses is in part supported by an increased muscle protein breakdown as indicated by increased 3-methylhistidine excretion.

Rapidly progressive proptosis secondary to Burkitt's lymphoma. Origin in the ethmoidal sinuses.

A case of unilateral proptosis secondary to Burkitt's lymphoma occurred in the ethmoidal sinuses. Involvement of the skull and paranasal sinuses by Burkitt's lymphoma may masquerade initially as an infectious process delaying diagnosis and treatment. The tumor's rapid growth and dramatic response to therapy with the potential for long-term remission and cure emphasize the need for prompt diagnosis and treatment.