Clinical outcomes of the Otago-Southland Breast Cancer Screening Programme 1991-1996.

AIM: To document the clinical outcome of the Otago-Southland Breast Cancer Screening Programme through its first two rounds of screening, from 1991-1996. METHODS: Review and analysis of clinical and pathological records. RESULTS: In the first round of screening, 13,876 women were screened, giving 75% uptake; 12.2% were referred for assessment and 126 cancers detected, 9.1 per thousand women screened. For the 9946 incidence screens in the second round, 3.9% of women screened were referred to assessment and 50 cancers detected, 5.0 per thousand women screened. The uptake and cancer detection rates exceed the targets and exceed other published results; the size distribution of the cancers detected was comparable to the Swedish two-counties study, showing that the results should produce an ultimate mortality reduction. The referral rate to assessment was higher than expected in the first round of screening, but within the targeted range in the second round. The benign to malignant ratio for all biopsies was 1.4:1 for the prevalence screen of the first round and 1.2:1 for the incidence screens in the second round, both exceeding the targets set. CONCLUSIONS: The results show that the uptake and clinical results of the programme exceed expectations and that a large number of small invasive tumours have been successfully detected. These results are comparable to the best of overseas studies, and give confidence that mortality reductions will ultimately occur.

Venous endothelial changes in therapeutic arteriovenous fistulae.

Specimens of veins of therapeutic arteriovenous fistulae from five patients were examined by an en face immunohistochemical technique to investigate endothelial morphology and the presence of the vasoactive peptide endothelin-1 (ET-1). These were compared with control segments of long saphenous veins from six patients. Venous endothelium from the arteriovenous shunts was mostly intact even overlying phlebosclerotic plaques. Occasional small areas of denudation, with associated platelets, were present in the depressions of 'jet' lesion however. The endothelial cells were generally elongated and interspersed with foci of polyhedral cells. The control saphenous veins contained elongated endothelial cells without detectable denudation. Image analysis of histological sections of veins from the shunts indicated significantly less intact elastic tissue than control veins but greater mononucleated endothelial cell density in en face preparations. ET-1 staining was considerably stronger in endothelium from the fistulae than in the control saphenous veins and was most intense over the raised crescentic ridges of jet lesions, stenoses and phlebosclerotic plaques. Endothelial mitoses and cells with hyperchromatic nuclei stained more strongly for ET-1 than surrounding cells. These results indicate that the endothelial cells lining veins associated with arteriovenous fistulae are dynamically altered by the increased haemodynamic stresses associated with these shunts. Furthermore ET-1 may act as a localising factor associated with intimal thickening at sites of 'jet' lesions, stenosis and phlebosclerosis.

Preservation of skin vasoconstrictor responses in chronic atherosclerotic peripheral vascular disease.

Peripheral neuropathy is often found in ischemic limbs with nondiabetic atherosclerotic peripheral vascular disease (PVD). Sensory symptoms such as burning pain are common in severely ischemic limbs, and sympathectomy has been undertaken for ischemic rest pain. The authors assessed noninvasive quantitative skin vasomotor reflexes in toes and standard systemic cardiovascular autonomic tests in 44 PVD subjects with varying severity of limb ischemia, 30 age-matched control subjects, and nine PVD subjects associated with diabetes. Skin vasoconstrictor reflexes to inspiratory gasp, Valsalva maneuver, and postural change, and the postischemic reactive hyperemic response, were evaluated by the measurement of skin blood flow on toe pads by use of a laser Doppler flowmeter. Vasoconstrictor responses were not significantly different between PVD toes, even in severely ischemic limb, and age-matched controls. Reactive hyperemia was significantly less in PVD than in controls. Cardiovagal and systemic vasoconstrictor reflexes were also evaluated. All PVD subjects showed normal systemic cardiovascular reflexes. In contrast, these reflexes were severely impaired in diabetic PVD. The authors demonstrated that skin vasoconstrictive sympathetic reflex is preserved in chronically ischemic limbs with PVD, suggesting that sympathetic nerve fibers are relatively resistant to chronic ischemia.

Pathology of acute and chronic ischaemic neuropathy in atherosclerotic peripheral vascular disease.

The peripheral nerve pathology in ischaemic limbs with atherosclerotic peripheral vascular diseases (PVD) is difficult to ascertain because of the limited number of reports. In addition, it has been debated whether chronic ischaemia per se could cause morphological abnormalities in peripheral nerves. In this prospective study, we examined pathological findings in the sural, saphenous, deep peroneal, superficial peroneal and tibial nerves, taken from seven acutely and nine chronically ischaemic amputated legs in which ischaemia was due to non-diabetic severe PVD. For morphological comparison, nerves were also taken from amputated legs without ischaemic disease and those in which PVD was associated with diabetes. In acutely ischaemic nerves, pathological changes were dependent upon the duration of ischaemia. Axonal degeneration of both myelinated and unmyelinated nerve fibres (MFs and UMFs) with occluded vessels was prominent, if acute ischaemia was present for > 24 h. Focal lesions, a hallmark of acute ischaemic neuropathy, were seen in both acute and chronic PVD nerves. Chronic PVD nerves also revealed considerable variations in the density of MFs between the fascicles of individual nerves and between the nerves of individual subjects: demyelination and remyelination, endoneurial oedema particularly at the subperineurial region, swollen endothelial cells, various but infrequent axonal changes, and relative preservation of UMFs were also seen. All pathological changes found in acute and chronic PVD nerves, except for a high rate demyelinated and remyelinated nerve fibres, have been described in experimental models of acute ischaemic/reperfusion injury. Demyelination could be induced by chronic ischaemia. Thus, pathological alterations in chronic ischaemic neuropathy may be due to the combined effects of acute ischaemia/reperfusion and chronic hypoxia.

Endothelin-1 is increased overlying atherosclerotic plaques in human arteries.

The distribution of Endothelin-1 (ET-1), a potent vasoactive peptide, within endothelium of human atherosclerotic arteries was examined using a novel en face immunohistochemical technique. The vast majority of endothelial cells were immunoreactive for ET-1. Staining intensity was increased in areas overlying atherosclerotic plaques, calcified media, fatty streaks and about flow dividers, compared with adjacent regions. Multinucleated 'giant' endothelial cells were more common in regions containing strong ET-1 staining than elsewhere. Clusters of leucocytes (probably monocytes) were frequently observed adhering to the endothelial monolayer but not neighbouring regions of denudation. Occasionally underlying macrophage/foam cells and smooth muscle cells were exposed to the surface and included in the en face (Häutchen) preparation. Smooth muscle cells did not stain for ET-1 while macrophages and the larger foam cells were positive for ET-1. These results support the hypothesis that expression of ET-1, at sites containing atheromatous disease, may be involved in the development of atherosclerosis.

Chelation therapy for intermittent claudication. A double-blind, randomized, controlled trial.

BACKGROUND: The use of repeated intravenous infusions of EDTA, which has become known as "chelation therapy," has been promoted for treating intermittent claudication as well as a wide range of other disorders. Multiple reports of excellent results in large numbers of patients have encouraged the use of this regimen. The lack of well-controlled studies substantiating the benefits of this treatment has limited its use mainly to private clinics. The aim of the study was to assess the benefits of chelation therapy in patients with intermittent claudication. METHODS AND RESULTS: A double-blind, randomized, controlled trial included 32 patients with intermittent claudication who were randomized to a treatment group (15) and a control group (17). Main outcome measures were subjective and measured walking distances and ankle/brachial pulse indices. Other outcome measures included lifestyle and subjective parameters of improvement, cardiac function, ECG, renal function, hematology, blood glucose, and lipid biochemistry. No clinically significant differences in main outcome measures between chelation therapy and placebo groups were detected up to 3 months after treatment. Measures of mood state, activities of daily living, and quality of life factors were not consistently affected by chelation therapy. An equal proportion (13%) of each group thought that they had received the active agent. The proportion of patients showing an improvement in walking distance was not significantly different between the chelation group (60%) and the control group (59%). CONCLUSIONS: Chelation therapy has no significant beneficial effects over placebo in patients with intermittent claudication.

Amputations in the surgical budget.

AIM: To describe the extent and distribution of in patient costs of nontraumatic lower limb amputations and to identify areas of high cost as a basis for cost saving strategic planning. METHODS: Retrospective review of 134 consecutive admissions resulting in lower limb amputations for reasons other than trauma over a 33 month period. General surgical and orthopaedic costs were compared. More detailed cost distribution analysis was then conducted for a group of general surgical amputees corroborating data from the resource utilisation system, Otago surgical audit and patient records. RESULTS: The mean cost of admission for nontraumatic lower limb amputations performed by general surgeons was $11,342 (median $21,439 range $144-$43,022) and was significantly more expensive than orthopaedic amputations, mean $2318 (median $6277 range $307-$13,907) p < 0.001. Of general surgical patients, 38.7% had diabetes and these accounted for 36.1% of total costs. Most amputations (73.9%) in diabetics were of the minor type compared with 29.0% in the nondiabetic group (p < 0.001). Ward costs accounted for the largest proportion of total cost 55.6% (95% CI 45.1, 66.0). For major amputees 40% (95% CI 31.4, 48.1) of in-hospital time was used for rehabilitation. CONCLUSION: Nontraumatic amputations are costly. Diabetics, having mainly minor amputations, account for a disproportionate amount of the cost. Length of hospital stay is the most important determinant of cost, much of which is spent on rehabilitation. A case is made for early definitive surgery and a greater use of community based services and low cost centres in rehabilitation.

The role of computerized tomography in aorto-iliac vascular disease.

Computerized tomography (CT) now has a definite place in the assessment of aortic vascular disease. In a study of 96 patients with abdominal or thoracic aorto-iliac problems, CT proved most useful in the management of haemodynamically stable patients with abdominal aortic aneurysms that were suspected of leaking. The complex anatomy associated with thoracic and abdominal aneurysms and aortic dissection was clearly defined. The interpretation of scans on postoperative aortic graft patients was difficult and less often helpful. The incidental finding of aortic disease during abdominal scans for a variety of other indications was infrequent and seldom contributed to patient management. The indications for CT have become far more selective.

Percutaneous transluminal angioplasty for the ischaemic lower limb: the early Dunedin experience.

A consecutive series of 60 percutaneous transluminal angioplasties has been performed in 53 patients with severe peripheral ischaemia over a 4 year period. There were 78 lesions dilated with an initial technical success rate of 78%. Forty-eight lesions were dilated for severe claudication and 30 for rest pain or necrosis. There was a mean followup of 24 months (range 9-56) for the immediately successful angioplasties. When these were analysed according to symptomatic relief, 59% of claudicants with iliac lesions were still improved at 2 years, compared with 86% of those with femoropopliteal lesions. Amongst patients treated for rest pain or necrosis there was a 100% success rate at 2 years for iliac lesions, compared with 49% for femoropopliteal lesions. The overall success of this procedure in this high risk group is reflected by the fact that at 2 years 85% of claudicants and 72% of those with rest pain and necrosis have avoided any further procedure. This encouraging early experience confirms the place of interventional radiology in the management of peripheral vascular disease.

An evaluation of pelvic lymphoscintigraphy in the staging of colorectal carcinoma.

Lymphoscintigraphy was used to delineate the lymphatic drainage of the rectum and distal colon in 18 patients with carcinoma of the rectum or sigmoid colon, in four with inflammatory disease of the large bowel and in 20 controls without colorectal pathology. Abdominal imaging was performed after submucosal injection of either 4 mCi 99mTc-antimony sulphide colloid or 0.5 mCi 99mTc-dextran into the rectum through a proctoscope. In nine patients with colorectal carcinoma, abdominal imaging was performed immediately pre-operatively and the excised specimen of large bowel was also imaged in vitro immediately postoperatively. The presence or absence of nodal uptake of radionuclide on abdominal scanning did not discriminate between normal and diseased large bowel, and the extent of nodal uptake demonstrated either by abdominal scans or by in vitro scans of excised specimens bore no relationship to the presence or absence of nodal metastases demonstrated histologically in the cancer patients. Pelvic lymphoscintigraphy as performed in this study has no demonstrable value in the diagnosis or staging of colorectal cancer.