Peter B. Dean

A novel method for prediction of long-term outcome of women with T1a, T1b, and 10–14 mm invasive breast cancers: a prospective study

BACKGROUND 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. METHODS 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. FINDINGS 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 (p<0.001). 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%. INTERPRETATION 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.

Extravascular Contrast Material: The Major Component of Contrast Enhancement

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.

Hepatic CT contrast enhancement: effect of dose, duration of infusion, and time elapsed following infusion.

Contrast enhancement of the liver of anesthetized, paralyzed, and artificially ventilated rabbits was measured during suspended respiration prior to, during, and after the intravenous infusion of meglumine diatrizoate at doses of 208, 416, and 624 mg I/kg. Infusion time was 30 seconds, and, at the highest dose, infusion times of 1, 2, and 4 minutes were also used. Highest contrast enhancement values were obtained at the conclusion of each infusion, with contrast enhancement increasing proportionately with increase in dose. Highest enhancement was obtained at all times studied from the most rapid infusion. Unlike cranial CT, optimum hepatic contrast enhancement in body CT requires rapid contrast medium injection with immediate CT scanning with a very fast scanner.

Practical breast pathology

Contents 1. Normal breast tissue or fibrocystic change? 2. General morphology of breast lesions 3. Hyperplastic changes with and without atypia 4. Ductal carcinoma in situ (DCIS) 5. The most usual types of invasive breast carcinoma 6. The most common benign lesions and their borderline and malignant counterparts 7. Fine - needle aspiration or core biopsy: a preoperative diagnostic algorithm 8. The postoperative work-up 9. Assessment of the most important prognostic factors 10. Case demonstrations

The pressing need for better histologic-mammographic correlation of the many variations in normal breast anatomy.

Abstract Mammography screening calls for a reevaluation of the working relationship between physicians dealing with the diagnosis and treatment of breast diseases. In this new era, histologic-mammographic correlation needs to be extended to correctly describe the deceptive mammographic findings that correspond to variations in normal breast tissue. Progress in histologic-mammographic correlation can only be made by overcoming the limitations inherent to the traditional histologic technique by examining a histologic specimen of greater length, width, and depth. There are several distinct advantages to using the large-section histology technique in the diagnosis of breast diseases. The subgross (three-dimensional) histology technique serves to bridge the gap that separates the pathologist and radiologist, bringing them to a common ground for a better understanding of breast morphology. These improvements in communication between the members of the diagnostic team will serve to optimize the sensitivity and specificity of breast cancer diagnosis.

The diagnostic potential of contrast enhancement pharmacokinetics.

Diastizoate concentrations in the blood and twelve tissues and organs of 20 rats were measured at 40 seconds, and 2, 5, 15 and 60 minutes after bolus intravenous administration of 125 I-labeled diatrizoate and 131 I-labeled albumin. Contrast enhancement (HU) and distribution volumes(%) were calculated from this data, and the results are presented graphically. The tissues can be separated into two groups according to the rapidity of extravascular contrast medium uptake. The liver appeared to concentrate the contrast medium. Curves of local contrast enhancement with time could be constructed by a CT scanner from the data of several consecutive scans and are of potential importance in the differential diagnosis of lesions detected on CT. Repeat postcontrast CT scans could be used to detect and characterize lesions which raise a diagnostic problem. The potential diagnostic advantages of calculating percent distribution volumes from CT scans are demonstrated and discussed.

Effect of population-based screening on breast cancer mortality

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.

Comparative pharmacokinetics of gadolinium DTPA and gadolinium chloride.

Dean PB, Niemi P, Kivisaari L, Kormano M. Comparative pharmacokinetics of gadolinium DTPA and gadolinium chloride. Invest Radiol 1988;23(Suppl 1):S258‐S260. An intravenous injection of 153Gd‐labeled gadolinium‐DTPA or gadolinium chloride was given to 60 rats, which were killed either 15, 40, 120, 300, 900, or 3600 seconds later. Tissue concentrations of gadolinium in the blood, liver, spleen, stomach, pancreas, renal cortex, renal medulla, lungs, heart, adrenals, gluteal muscle, fat, skin, thymus, brain, thyroid, and parathyroids were measured. Five animals were killed at each time interval with gadolinium‐DTPA, and at each of the latter four time intervals (15 and 40 seconds excluded) with gadolinium chloride. The pharmacokinetics of gadolinium‐DTPA and chloride differ markedly in terms of tissue concentration, distribution volumes, and the time course of these parameters. Gadolinium, when injected as a chloride, evidently forms insoluble carbonate and phosphate precipitates in the blood, which are taken up by the reticuloendothelial system. The distribution of gadolinium‐DTPA on dynamic MRI should closely parallel the distribution of iodinated contrast media on dynamic computed tomography.

Contrast Enhancement Pharmacokinetics of Six Ionic and Nonionic Contrast Media

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.

Novel biparametric MRI and targeted biopsy improves risk stratification in men with a clinical suspicion of prostate cancer (IMPROD Trial)

To evaluate the role of a 3T biparametric magnetic resonance imaging (bpMRI), T2‐weighted imaging, and three separate diffusion‐weighted imaging acquisitions combined with targeted biopsy (TB) for improving risk stratification of men with elevated prostate‐specific antigen (PSA).