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Objectives: To review the evidence demonstrating that early detection of breast cancer substantially decreases death from the disease, and to demonstrate that the significant change in the outcome of breast cancer patients results from a combination of early detection and surgical removal of breast cancer, as treatment of the late stage disease provides little impact on ultimate outcome. Method: Review results of the randomized controlled trials of mammographic screening and the published results of service screening. Results: Both randomized controlled trials and service screening, when performed properly, provide unequivocal evidence demonstrating that arresting the disease in its preclinically detectable phase has significant impact on outcome. Primary emphasis should be upon preventing breast cancer from developing to metastatic disease. Conclusions: Numerous scientific trials have repeatedly and convincingly confirmed that breast cancer is progressive rather than a systemic disease from its inception. Progression of breast cancer can be arrested through detection and treatment at an early phase. The time at which disease progression is arrested has significant impact on clinical outcome, making mammographic screening a key factor in the control of breast cancer.

Although the wider scientifi c community has long embraced the benefi ts of population-based breast screening, there seems to be an active anti-screening campaign orchestrated in part by members of the Nordic Cochrane Centre. These contrary views are based on erroneous interpretation of data from cancer registries and peerreviewed articles. Their specifi c aim seems to be to support a pre-existing opposition to all forms of screening. These individuals, making claims of poor methods, selectively discount overwhelming scientifi c evidence from numerous randomised trials in diff erent countries that organised screening reduces breast cancer mortality. They claim that the signifi cant decrease in breast cancer mortality achieved by screening is due to improvements in treatment alone, discounting the benefi ts of early detection. If true, this would imply that breast cancer is an exception among adenocarcinomas in that early detection does not improve prog nosis—a claim contrary to the evidence. For women with breast cancer, early detection also results in improved quality of life from less extensive surgical treatment. Women with screen-detected breast cancer in the UK have half the mastectomy rate of women with symptomatic cancers— ie, 27% versus 53%. Organised, high-quality breast screening is an important public health initiative by numerous governments worldwide. These policies are based on robust and extensive analysis of individualised patient data from scientifi c trials, with particular attention paid to the balance of potential benefi ts and harms. To imply that such an international action is mass misrepresentation, or that screening is done for the benefi t of self-interested professionals, is as perverse as it is unjustifi ed. Comprehensive guidelines deal with the entire screening process. Organisations responsible for screening programmes regularly review published evidence on the eff ects of mammographic screening, and also contradictory interpretations. We consider the interpretation by Jorgensen, Keen, and Gotzsche, of the balance of benefi ts and harms to be scientifi cally unsound. Women would be better served by focusing eff orts on how best, and not whether, to provide breast screening. The signatories below, charged with provision and implementation of breast screening in many diff erent countries, remain convinced that the scientifi c foundation for populationbased, quality-assured, organised breast screening is one of the major accomplishments of the translation of clinical cancer research into public health practice. Early detection, in combination with appropriate treatment, signifi cantly lowers breast cancer mortality and improves the life quality of patients with the disease.

Women with small mammographically detected breast cancers generally have good long-term outcomes, but a few with T1a (1-5 mm) and T1b (6-10 mm) tumours will eventually die from breast cancer. We investigated whether women at high risk of breast-cancer death could be identified with mammographic criteria and differentiated from women with small cancers of the breast and good outcomes.We prospectively applied mammographic classifications of tumour type to a consecutive series of 343 mammograms of invasive breast cancers of size 1-14 mm. Classifications were: stellate (spiculated) mass with no calcifications; circular or oval lesions with no calcifications; spiculated or circular lesions with non-casting-type calcifications; and casting-type calcifications.20-year survival for women with 1-14 mm invasive tumours with casting-type calcifications was 55%. 14% of 138 women with 1-9 mm tumours had casting-type calcifications on mammography, which accounted for 73% of all breast-cancer deaths (p0.001). T1a, T1b, and 10-14 mm tumours with casting-type calcifications behaved as if they were larger lesions, since the rate of death was similar to that for women with advanced high-grade tumours. Most women who died were node-negative. The long-term survival of women who had tumours of 1-9 mm with no casting-type calcifications was about 95%.Mammographic classification seemed to reliably predict good and bad long-term outcomes for survival in tumours of 14 mm or smaller, and especially for those smaller than 10 mm. The implications for therapy are substantial.

Several image-degrading factors limit the diagnosis of breast calcification from preoperative mammograms. We use specimen radiographs and algorithmically 3D-simulated calcification to produce high-quality data for testing a computerized differential diagnosis system. The preliminary results show that a computer can indeed differentiate explicitly between several mammographically characteristic calcification types. For a radiologist, such a detailed diagnosis could be more useful than simply characterizing the malignancy of the calcification. The results show new possibilities for the future diagnosis systems based on direct digital preoperative imaging.

Since fewer than 20 % of mammographically detected breast calcifications are produced by malignant diseases, detailed analysis of the mammographic appearance of the calcifications should help prevent many unnecessary surgical biopsies. To carry out an automatic computer-based analysis, the calcifications must first be segmented precisely and consistently using well-defined parameters of the mammographic image. Small segmentation errors could easily impair the accuracy of the analysis. We present an algorithm for improving the initial segmentation of individual calcifications for reliable computerized diagnosis.

We introduce a mammographic feature generator which can be used to evaluate image analysis algorithms for digital mammography. Several types of calcifications and focal lesions may be generated, synthetic noise may be added, and the features may be embedded in to a digital mammogram. As an application we demonstrate the use of the generator in comparing the performance of two feature extraction algorithms.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

A 44-year-old man presented with a fistula of the left anterior descending (LAD) coronary artery to a left ventricular pseudoaneurysm 6 months after a stab injury in the left anterior chest. The color Doppler echocardiography suggested, and angiography confirmed, the diagnosis and the lesion was treated successfully. Traumatic coronary artery fistulas are rare complications, and color Doppler echocardiography proved useful for the diagnosis.

In their Comment “What is publication?” (Nov 25, p 1854), Peter Gotzsche and colleagues claim that the Editor of the European Journal of Cancer (EJC) published a paper of theirs and then withdrew it. This is incorrect. Their manuscript was not published and cannot be found on the pages or website of the EJC. Gotzsche and colleagues blame the EJC for allegedly improper conduct but fail to perceive the fatal fl aws in their own article which undoubtedly caused its withdrawal—fl aws that had apparently initially escaped the reviewers. When attempting to estimate the number of cancers which should have been diagnosed in the Swedish Two-County mammography screening trial, Gotzsche and colleagues misquoted the end date of the 11-year trial by nearly 4 years, although the correct dates appear in one of their cited references. An error of this magnitude would render their calculations worthless. More seriously, they failed to account for the precise, stepwise, district-by-district nature of the randomisation process published for the trial. Gotzsche and colleagues refer to this as “new information” received after their manuscript’s withdrawal, but it is described in a publication which they cite and in another previously cited by Gotzsche. Finally, they claim that their own calculations, based on a series of multiple, erroneous assumptions and approximations, should be accepted as accurate in place of the data published in The Lancet for the trial. Pointing an accusing fi nger at peer reviewed published medical research gains attention, but this particularly clumsy attempt was uncovered at a late stage of prepublication. It is to the credit of the EJC that the manuscript was withdrawn.

A soft tissue immersion radiography technique was used to study changes in 4,648 finger joints of 166 patients free from signs of inflammatory joint disease. An age-specific correlation was found for joint swelling, joint space narrowing, joint margin spurs, and intraarticular loose bodies. The distal interphalangeal joints were more commonly swollen in women, and the proximal interphalangeal and metacarpophalangeal joints more commonly swollen in manual laborers. Both correlations are highly significant (P less than 0.001). The second and third digits showed a definite predilection for joint swelling. Swelling of finger joints is closely correlated with age and degenerative disease, and its occurrence in older patients is associated with degenerative changes. In manual laborers it should not be interpreted as evidence for inflammatory joint disease.

Contrast medium concentration in the pancreas as a function of time after intravenous bolus injection was measured in 12 rats with oil-induced acute pancreatitis, 20 rats with Streptozotocin-induced diabetes and 20 rats with subcutaneous granuloma, induced by sponge, whose pancreatic tissue was used as a control. No significant effect of diabetes was observed. Calculated distribution volume and contrast enhancement in the pancreas were increased in pancreatitis relative to diabetes and controls. The increased enhancement was due to a relatively higher accumulation into the extravascular fluid, considered to represent pancreatic oedema. An even more marked and delayed enhancement was observed with the granuloma tissue and exudate, apparently on a similar basis. There appears to be a possibility of differential diagnosis of some pancreatic lesions using contrast enhanced CT.

We report on 3 brothers with a myopathy that also affected their maternal grandfather and great-uncle. Characteristic features are onset in early childhood, very slow progression, normal life expectancy, weakness of proximal limb muscles, especially in the legs, elevation of serum creatine kinase, and no cardiac or intellectual involvement. In biopsy material muscle fibers are almost never necrotic but show excessive autophagic activity and exocytosis of the phagocytosed material. We suggest that this family has an undescribed type of congenital myopathy, for which we propose the name X-linked myopathy with excessive autophagy.

Both normal and experimentally hydronephrotic rabbits were imaged at 0.02 T using partial saturation (PS 160/30) and inversion recovery (IR 1000/200/40) sequences. The signal intensity of normal renal medulla and cortex markedly increased after the injection of 0.1 mmol/kg of Gd-DOTA. In the unilateral total hydronephrosis the dilated renal pelvis did not contrast enhance after 15 and 35 min of Gd-DOTA injection. The enhancement pattern was similar in 1- and 3-week-old hydronephrosis. The effect of Gd-DOTA on renal T1 times at 0.02 T was studied using rats. Fifteen minutes after the Gd-DOTA injection (0.1 mmol/kg) the T1 times of excised rat kidneys decreased from 311 to 90 ms. The authors conclude that the enhancement of the MR signal of the kidney by Gd-DOTA at an ultralow magnetic field (0.02 T) is similar to its enhancement at higher fields (greater than 0.15 T).

The contrast enhancement of six contrast media (CM) was compared in 13 tissues of the rat after rapid intravenous bolus injection. The rats were sacrificed at 0 and 40 seconds and 2, 5, and 15 minutes after contrast injection. 125I labeled diatrizoate, metrizamide, ioxaglate, iohexol, iopamidol, and a nonionic dimer, iodecol, were each injected at a dose of 612 mg iodine per kg body weight, and iodine concentration (IC) and contrast enhancement were calculated from radioactivity measurements. Higher blood IC values were obtained with the nonionic CM; similar enhancement patterns were seen in the spleen, heart, lungs, and brain. Renal IC was directly related to the number of iodine atoms per ion or molecule of CM. In consequence, renal IC was inversely related to the CM osmolality, but no such correlation was seen with the blood IC. Metrizamide produced the greatest IC in the organs of the gastrointestinal tract. There was no apparent correlation of IC with molecular structure of physicochemical parameters of the CM in any of the other tissues studied.

The distribution volume of 125l-diatrizoate in rat tissues was studied 5 seconds to 5 minutes after intravenous injection and 5 seconds to 2 minutes after intra-arterial injection. Immediately after injection, diatrizoate was distributed into a larger volume than plasma. Marked temporal changes in the distribution volume of individual tissues occurred during the first 2 minutes. At 5 minutes, the diatrizoate space approached the total extracellular fluid volume, with more than 80% of the contrast agent remaining outside the blood vessels. Thus the relative magnitude of contrast enhancement of a tissue appears to be related to the volume of the rapidly equilibrating extracellular space. Intra-arterial administration can significantly overload muscle with contrast material for about 2 minutes. This and other temporal changes in contrast distribution may prove useful in contrast-enhanced computed tomography using short scanning times.

In order to assess their potential usefulness in conjunction with dynamic CT scans of the liver, functional images of several variables related to blood flow were created from dynamic CT scans of 15 patients with a variety of liver diseases. Seven of the patients received intra-arterial and intravenous boluses of contrast; the other eight received intravenous boluses alone. Intra-arterial contrast injections yielded superior functional images, but useful functional images could also be created from studies with intravenous boluses. Although respiratory motion artifacts caused some problems, images that can be interpreted in terms of effective distribution volume, transit time, and blood flow were successfully created. Functional imaging of the liver can provide a useful display of regional physiologic differences.

Infusion of dilute contrast agent through an upper extremity vein results in marked opacification of the superior vena cava and the ipsilateral subclavian and brachiocephalic veins in computed tomography of the upper mediastinum. Also, the cranial arteries are well opacified. Images obtained by this method display anatomical relationships to better advantage and permit more accurate interpretation of anatomical relationships of the upper mediastinal masses. Improved anatomical details are obtained as compared to noncontrast scans or scans after bolus injection. In cases of suspected venous occlusion, functional diagnostic information is also achieved.

The aim of contrast enhancement is to increase the difference in attenuation coefficients between pathological lesions and the surrounding normal tissues. Unlike cranial CT, in body CT the contrast-enhanced scans should be taken when the blood and normal tissue levels of contrast enhancement are at their maximum possible levels. This has not been feasible in most currently available scanners, and most reports in the literature on contrast enhancement in CT have used suboptimal enhancement. In most cases, maximal enhancement will occur immediately at the end of a rapid intravenous injection using a high dose of contrast media. Repeat scans of certain slice levels at fixed time intervals may further improve diagnostic accuracy. Computers are only beginning to be used to analyze the reconstructed CT image, and recent increases in scanning rapidity make optimum contrast enhancement much more feasible. Renal toxicity from high doses of contrast media places a rather indefinite upper limit to contrast enhancement, which can be partially overcome with intra-arterial contrast media injection at CT. Nonenhanced scans should always precede contrast enhancement in body CT. In this article the experimental and theoretical background to CT contrast enhancement is reviewed and suggestions for optimum application are made in the light of present limitations of the technique. Improvement in both detection and differentiation of pathological lesions should result from minimizing the overlap of CT attenuation measurements of normal and pathological tissue by increasing the difference between their means and decreasing the range of variability of individual attenuation measurements.