Angiosarcoma of the breast: a 30 year perspective with an optimistic outlook.

The aim of this study was to investigate the incidence and clinicopathological features of angiosarcoma of the breast by focusing on those cases passing through a busy general teaching hospital over a 30 year period. A search was carried out of all cases in the files of the Department of Pathology of the Royal London Hospital from 1970 to 2000. Four cases were identified as primary angiosarcomas involving the breast. The medical and surgical histories, macroscopic and microscopic features and clinical outcome with long-term follow-up are described in each case. Similarities were identified, such as initial presentation with a 'bruise' and a latent period before the diagnosis was established. Half of our cases followed irradiation for breast cancer. In all cases the prognosis after surgery was excellent. The rarity of primary mammary angiosarcoma was confirmed. In younger patients the lesion was not associated with previous radiotherapy, but the older patients presented after radiotherapy for adenocarcinoma of the breast. Although very uncommon, these tumours must be considered in the differential diagnosis, especially with the increasing use of fine-needle-aspiration and core biopsy for preoperative diagnosis. The prognosis after complete surgical excision may be better than generally believed.

Secondary neoplasms of the breast: a survey of the 20th Century.

BACKGROUND: A 90-year archive of surgical and postmortem material was reviewed to establish the incidence, presentation, and pathology of tumors secondary to the breast. METHODS: A search was performed on all cases contained within the files of the Pathology Department of the Royal London Hospital from 1907 to 1999. RESULTS: Sixty patients were identified with unequivocal, secondary, nonmammary neoplasms involving the breast. Hematologic tumors predominated, particularly among the more recent cases, with carcinoma less frequent overall but more numerous in the earlier part of the 20th century. There were several surprising and sometimes unique findings, with occasional metastases from primary tumors of the esophagus, retina, pancreas, thyroid, and skin. Other primary tumor sites included the stomach, lungs, and kidney. In line with expectations, the majority of tumors occurred in women. CONCLUSIONS: Secondary tumors to the breast are rare. In the current series, these tumors comprised 3% of the breast tumors in the files under review. The majority of these were metastases from the contralateral breast. However, the existence of metastatic nonmammary tumors to the breast should be appreciated so that secondary tumors from unusual sites are not overlooked, particularly with the widespread use of fine-needle aspiration cytology and needle core biopsies for preoperative diagnosis. In fact, 0.43% of the breast malignancies in the current report originated from sites outside the breast. Of these one-third represented spread from an occult primary. Furthermore, the current data suggest a move from carcinomatous metastases to hematologic malignancies over the last century, possibly reflecting earlier diagnosis of the former and an increase in the prevalence of the latter.

Variable venous anatomy of the popliteal fossa demonstrated by duplex scanning.

BACKGROUND: Location of the sapheno-popliteal junction (SPJ) is highly variable and therefore often difficult to identify correctly at operation. The anatomy is often complicated by associated pathology in the popliteal fossa, which makes clinical examination unreliable. OBJECTIVE: The purpose of our study was to quantify this variability and record other concomitant pathology in patients with sapheno-popliteal junction incompetence. METHODS: We retrospectively reviewed duplex scans of 544 patients with 638 legs showing SPJ incompetence, from a total of approximately 4000 patients attending our laboratory between August 1993 and August 1995. RESULTS: We found that 51% of sapheno-popliteal junctions were located within 2 cm above the popliteal skin crease and a further 36% within 4 cm, with the remaining situated anywhere between 4 and 10 cm above the popliteal skin crease. Additionally 18% of patients had either Giacomini or gastrocnemius vein incompetence in addition to SPJ incompetence, further complicating the clinical picture. CONCLUSION: When SPJ incompetence is suspected, duplex scanning identifies the exact location of the junction and other associated pathology in the popliteal fossa, and allows the position of the junction to be marked on the leg preoperatively.

Endothelial activation in patients with chronic venous disease.

OBJECTIVES: Leukocyte trapping due to leukocyte-endothelial activation has been implicated as the cause of lipodermatosclerosis and ulceration in patients with chronic venous disease. We investigated endothelial activity in normal controls and patients subjected to short-term venous hypertension. METHODS: Twenty-five normal volunteers and 30 patients with chronic venous disease divided into two groups: varicose veins with skin changes (LDS, n = 15); and varicose veins without skin changes (VVs, n = 15) were studied. Blood samples were taken from a foot vein before and after experimental venous hypertension. Plasma levels of ELAM-1 (endothelial leukocyte adhesion molecule-1), ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), and von Willebrand factor (vWf) was measured by an ELISA. RESULTS: There was a significant rise in the plasma concentration of ELAM-1, ICAM-1 and VCAM-1 in patients and normal controls in response to venous hypertension. Basal levels of plasma VCAM-1 and vWf were higher in patients with LDS compared to patients with VVs. The magnitude of rise of VCAM-1 was greater in patients with LDS compared to patients with VVs (p = 0.01, Mann-Whitney U-test). There was no difference in the basal levels or in the magnitude of change in plasma ICAM-1 and ELAM-1 between the two patient groups. CONCLUSION: Venous hypertension results in endothelial activation which may aid endothelial-leukocyte adhesion. Patients with LDS exhibit increased VCAM-1, which is a counterligand for receptors expressed by monocytes and lymphocytes signifying that these cells may be more important in the development of skin changes.

Short-term restorative nutrition in malnourished patients: pro's and con's of intravenous and enteral alimentation using compositionally matched nutrients.

In a prospective controlled clinical study 30 patients with moderate degree of malnutrition, normal liver and kidneys, and a functioning gastrointestinal tract were randomized to receive a free amino acid and small peptide enteral diet (15 patients) or an isonitrogenous isocaloric parenteral support for at least 10 days (total energy: 2900 kcal, nitrogen: 14.5 g, carbohydrates: 380 g, fat: 112 g, N/non protein calories: 1/175). The parenteral and enteral diets had the same protein/lipid/carbohydrate composition. The data indicated that both routes led to positive nitrogen balance. Nitrogen equilibrium was achieved by day 3 in the TPN group and by day 5 in the enteral group. There were no significant changes in serum albumin within either group. Serum level of transferrin reached a significant increase in both groups (p = 0.003). Thyroxine-binding prealbumin rose significantly in both groups as well (p = 0.019 and 0.004 respectively). Statistically significant rises in lymphocyte counts (p = 0.003 and 0.001 respectively), in levels of C3 (p = 0.009 and 0.001 respectively), IgA (p = 0.002), IgG (p = 0.004 and 0.003 respectively) and IgM (p = 0.004) occurred in either treatment group. There was a high incidence of negative skin tests at the start of the study in the enteral group (73.3%) and the TPN group (60%). By the end of the study the incidence of negative results for this test was 40.0% and 26.6% respectively. Despite maintenance of similar glucose levels in both groups, TPN led to significantly (p = 0.000) higher serum insulin levels. The serum insulin increased almost linearly over the study period, and eventually prevented fat mobilization and lipolysis, so that free fatty acid levels had fallen significantly (p = 0.000). A significant elevation of the liver enzymes over the study period occurred in the TPN group, but not in the enterally fed patients. The present findings provide no evidence that semi-elemental diets are in any way inferior to isonitrogenous isocaloric regimes parenterally given for a short period of time.

The use of thallium-201 and technetium-99m subtraction scintigraphy for the localisation of parathyroid adenomas.

Parathyroid adenomas account for approximately 85% of cases of primary hyperparathyroidism. Several preoperative localisation techniques exist to aid the surgeon during neck exploration, with varying degrees of success. We report on the results of a modification of the established technique of thallium and technetium subtraction scintigraphy. The operative findings of 60 patients undergoing neck exploration for parathyroid adenoma were correlated with preoperative thallium and technetium subtraction scintigraphy scans. The radio-isotopes were administered in the reverse order to conventional administration, resulting in enhanced imaging. The adenomatous glands were correctly localised in all cases. The 100% sensitivity of this modified scanning technique supports a strategy of unilateral scan-directed neck exploration.

Cardiac output in asymptomatic primary hyperparathyroidism: a stigma of early cardiovascular dysfunction?

The resting cardiac output pre- and postoperatively in 10 patients with asymptomatic primary hyperparathyroidism has been studied. All patients had normal renal function and arterial blood pressure without a previous history of cardiovascular disease. Ten normotensive patients with a non-toxic goitre awaiting thyroidectomy were studied as controls. The mean cardiac output of the hyperparathyroid patients was 7.2 l/minute (range 5.3-8.9) and of the control group 5.8 l/minute (range 5.2-6.3). Following a successful parathyroidectomy with return of the serum calcium to normal, the mean cardiac output was 6.3 l/minute (range 4.9-7.8) (p < 0.04). In 8 of the 10 patients there was a fall in the cardiac output following surgery; in 2 there was an increase. These results suggest that hyperparathyroid patients often have an elevated cardiac output which may fall following a successful parathyroidectomy.

Correlation between albuminuria and positively charged amino acids in gastrointestinal cancer.

This study was designed to examine a possible relationship between plasma free positively charged amino acid concentrations and the degree of microalbuminuria in patients with gastrointestinal cancer. In 42 consecutive patients (22 men and 20 women), comprised of 25 with histologically proven colorectal or gastric cancer, 9 controls and 8 weight-losing patients with benign gastrointestinal disease urinary albumin and plasma amino acid analysis was performed. Microalbuminuria was more prevalent in weight-losing cancer patients (65%) compared with their weight-stable counterparts, benign gastrointestinal patients and controls. This difference reached statistical significance at the 5% level. Additionally, a significant positive correlation (rs = 0.8, p < 0.05) was observed between ornithine and urinary albumin loss in this group of patients. This study suggests that plasma free amino acid alterations in weight-losing gastrointestinal cancer patients may have an effect on renal tubular protein reabsorption.

Lipid fuel metabolism after abdominal surgery.

The work investigated fuel interrelationships in surgical patients infused with saline (Group I) or glucose (Group II) (13 patients in each group) on the day of surgery and subsequently maintained solely on saline until the fifth postoperative day. Blood concentrations of non-esterified fatty acids (NEFA) and ketone bodies were markedly increased in response to surgical stress on the day of surgery only in patients who were not administered carbohydrate. Increased concentrations of lactate and glucose were observed on the day of surgery in patients infused with either saline or glucose. As both fatty acid and ketone body concentrations were decreased by glucose infusion, impaired glucose utilization immediately after surgery is not a simple consequence of increased oxidation of lipid fuels. Glucose and lactate concentrations declined after the day of surgery. Despite a progressive fall in plasma non-esterified fatty acid concentrations from the first to fifth post-operative days, blood ketone body concentrations were strikingly elevated in both groups of patients. The findings emphasize the role of the liver in post-operative fatty acid turnover.

Micronutrients in gastrointestinal cancer.

The monitoring of micronutrients and the relationship between dietary intake and micronutrient status prior to and after surgery in patients with histologically proven gastrointestinal adenocarcinoma, both weight-stable and weight-losing (> 7.5% of their pre-illness weight) has been studied and the results compared to controls. Plasma vitamin C and red blood cell thiamine levels were significantly lower in weight-losing cancer patients when compared to their weight-stable counterparts (P < 0.05 and P < 0.02 respectively). Weight-losing patients had a lower vitamin C (P < 0.05) and thiamine (P < 0.002) intake, and a higher elevation in plasma C-reactive protein and a lower prealbumin level (P < 0.02), when compared to both weight-stable cancer patients and controls. Plasma vitamin C, prealbumin and C-reactive protein levels remained unchanged after curative resections of the tumours compared to a preoperative value, and there was a highly significant correlation between plasma vitamin C and dietary intake of vitamin C. This study suggests that the lower vitamin C and thiamine status in weight-losing gastrointestinal cancer patients prior to surgery is due to a lower micronutrient intake and an acute phase response to their illness. Dietary intake of vitamin C appears to be the major factor in determining plasma vitamin C concentration following curative surgical resection.

The effects of infusion of amino acids alone or in combination with glucose and fat on thyroid hormone and other metabolite interactions in surgery.

The effects of infusion of amino acids alone or in combination with carbohydrate and lipid on triiodothyronine (T3) and reverse triiodothyronine (rT3) status, substrate availability and metabolism in surgically-stressed and clinically euthyroid patients were examined. The characteristic post-operative decline in T3 concentration was observed in all patient groups (p < 0.001) (8 patients in each group). However, infusion with amino acids alone retarded the decline in T3; the decrease was lower than those found in the controls and the mixed nutrition group and restoration of T3 values was incomplete, even by the sixth post-operative day. The pattern of increase in rT3 was similar in all 3 patient groups. However, the T3/rT3 ratio dropped to its lowest level on day 1 in the control group and the mixed infusion group (p < 0.001), with a complete restoration by the sixth post-operative day, whereas in the amino acids infused group the ratio was lowest on day 2 (p < 0.001) and was still significantly low by day 6 compared with the pre-operative value (p < 0.001). The findings, in the group infused with amino acids of a less prominent hyperglycaemia, with the significant slowing of T3 response and the significant correlation of rT3 with the plasma glucose, indicate a link between hyperglycaemia and the thyroid hormone response to surgical trauma. No correlations were found between thyroid hormone or urea concentrations, and the blood concentrations of free fatty acids, 3-hydroxybutyrate, or urea; or between thyroid hormone and the percentage of total urea nitrogen excretion. Results show that the changes in fat metabolism after operation are unlikely to be responsible for the changes in T3 and rT3. In conclusion, whereas the post-operative response of T3 concentration can be partially modified by the nutrition regimen employed, that of rT3 is largely related to surgical stress.