Diffusion- and perfusion-weighted MRI response to thrombolysis in stroke

Diffusion- and perfusion-weighted magnetic resonance imaging provides important pathophysiological information in acute bra-in ischemia. We performed a prospective study in 19 sub-6-hour stroke patients using serial diffusion- and perfusion-weighted imaging before intravenous thrombolysis, with repeat studies, both subacutely and at outcome. For comparison of ischemic lesion evolution and clinical outcome, we used a historical control group of 21 sub-6-hour ischemic stroke patients studied serially with diffusion- and perfusion-weighted imaging. The two groups were well matched for the baseline National Institutes of Health Stroke Scale and magnetic resonance parameters. Perfusion-weighted imaging-diffusion-weighted imaging mismatch was present in 16 of 19 patients treated with tissue plasminogen activator, and 16 of 21 controls. Perfusion-weighted imaging-diffusion-weighted imaging mismatch patients treated with tissue plaminogen activator had higher recanalization rates and enhanced reperfusion at day 3 (81% vs 47% in controls), and a greater proportion of severely hypoperfused acute mismatch tissue not progressing to infarction (82% vs -25% in controls). Despite similar baseline diffusion-weighted imaging lesions, infarct expansion was less in the recombinant tissue plaminogen activator group (14cm(3) vs 56cm(3) in controls). The positive effect of thrombolysis on lesion growth in mismatch patients translated into a greater improvement in baseline to outcome National Institutes of Health Stroke Scale in the group treated with recombinant tissue plaminogen activator, and a significantly larger proportion of patients treated with recombinant tissue plaminogen activator having a clinically meaningful improvement in National Institutes of Health Stroke Scale of;2:7 points. The natural evolution of acute perfusion-weighted imaging-diffusion-weighted imaging mismatch tissue may be altered by thrombolysis, with improved stroke outcome. This has implications for the use of diffusion- and perfusion-weighted imaging in selecting and monitoring patients for thrombolytic therapy.

Is there a role for axillary dissection for patients with operable breast cancer in this era of conservatism?

Background: The trend in breast cancer surgery is toward more conservative operative procedures. The new staging technique of sentinel node biopsy facilitates the identification of pathological node-negative patients in whom axillary dissection may be avoided. However, patients with a positive sentinel node biopsy would require a thorough examination of their nodal status. An axillary dissection provides good local control, and accurate staging and prognostic information to inform decisions about adjuvant therapy. In addition, the survival benefit of axillary treatment is still debated. The objectives of the present study were to examine the pattern of lymph node metastases in the axilla, and evaluate the merits of a level III axillary dissection. Methods : Between June 1997 and May 2000, 308 patients underwent a total of 320 level III dissections as part of their treatment for operable invasive breast cancer. The three axillary levels were marked intraoperatively, and the contents in each level were submitted and examined separately. The patterns of axillary lymph node (ALN) metastases were examined, and factors associated with 4 positive nodes, and level III ALN metastases were evaluated by univariate and multivariate analyses. Results: An average of 25 lymph nodes were examined per case (range: 8-54), and using strict anatomical criteria, the mean numbers of ALN found in levels I, II and III were 18 (range: 2-43), 4 (range: 0 19), and 3 ( range: 0-11), respectively. Axillary lymph node involvement was found in 45% of the cases (143/320). Of the 143 cases, 78% (n = 111) had involvement of level I nodes only, and 21% (n = 30) had positive ALN in levels II and, or, III, in addition to level I. Involvement of lymph nodes in level II or III without a level I metastasis was found in two cases only (0.6%). By including level II, in addition to level I, in the dissection, four cases (1%) were converted from one to three positive nodes to 4 positive nodes (P = 0.64). By the inclusion of level III to a level I and II dissection, three cases (1%) were converted from one to three positive nodes to 4 positive nodes (P = 0.74). Involvement of lymph nodes in level III was found in 22 cases (7%), and 51 cases (16%) had 4 positive nodes. Palpability of ALN, pathological tumour size, and lymphovascular invasion (LVI), were significantly associated with level III involvement and 4 positive nodes by univariate and multivariate analyses. The frequencies of level III involvement and 4 positive nodes in patients with palpable ALN were 22% and 42%, respectively. The corresponding frequencies in patients with a clinically negative axilla, and a primary tumour which was >20 mm and LVI positive, were over 14% and 31%, respectively. Conclusion: Level III axillary dissection is appropriate for patients with palpable ALN, and in those with a tumour which is >20 mm and LVI positive, principally to reduce the risk of axillary recurrence. Staging accuracy is achieved with a level II dissection, or even a level I dissection alone based on strict anatomical criteria. Sentinel node biopsy is a promising technique in identifying pathological node-positive patients in whom an axillary clearance provides optimal local control and staging information.

Long-term survival of women with breast cancer in New South Wales

Several long-term studies of breast cancer survival have shown continued excess mortality from breast cancer up to 20-40 years following treatment. The purpose of this report was to investigate temporal trends in long-term survival from breast cancer in all New South Wales (NSW) women. Breast cancer cases incident in 1972-1996 (54,228) were derived from the NSW Central Cancer Registry a population-based registry which began in 1972. All cases of breast cancer not known to be dead were matched against death records. The expected survival for NSW women was derived from published annual life tables. Relative survival analysis compared the survival of cancer cases with the age, sex and period matched mortality of the total population. Cases were considered alive at the end of 1996, except when known to be dead. Proportional hazards regression was employed to model survival on age, period and degree of spread at diagnosis. Survival at 5, 10, 15, 20 and 25 years of follow-up was 76 per cent, 65 per cent, 60 per cent, 57 per cent and 56 per cent. The annual hazard rate for excess mortality was 4.3 per cent in year 1, maximal at 6.5 per cent in year 3, declining to 4.7 per cent in year 5, 2.7 per cent in year 10, 1.4 per cent in year 15, 1.0 per cent for years 16-20, and 0.4 per cent for years 20-25 of follow-up. Relative survival was highest in 40-49 year-olds. Cases diagnosed most recently (1992-1996) had the highest survival, compared with cases diagnosed in previous periods. Five-year survival improved over time, especially from the late 1980s for women in the screening age group (50-69 years). Survival was highest for those with localised cancer at diagnosis: 88.4 per cent, 79.1 per cent, 74.6 per cent, 72.7 per cent and 72.8 per cent at 5, 10, 15, 20 and 25 years follow-up (excluding those aged greater than or equal to 70 years). There was no significant difference between the survival of the breast cancer cases and the general population at 20-25 years follow-up. Degree of spread was less predictive of survival 5-20 years after diagnosis, compared with 0-5 years after diagnosis, and was not significant at 20-25 years of follow-up. Relative survival from breast cancer in NSW women continues to decrease to 25 years after diagnosis, but there is little excess mortality after 15 years follow-up, especially for those with localised cancer at diagnosis, and the minimal excess mortality at 20-25 years of follow-up is not statistically significant. (C) 2002 Elsevier Science Ltd. All rights reserved.

Breast cancer in Western Australia: clinical practice and clinical guidelines

Objectives: To review changes in patterns of care for women with early invasive breast cancer in Western Australia from 1989 to 1999, and compare management with recommendations in the 1995 National Health and Medical Research Council guidelines. Design and setting: Population-based surveys of all cases listed in the Western Australian Cancer Registry and Western Australian Hospital Morbidity Data System. Main outcome measures: Congruence of care with guidelines. Results: Data were available for 1649 women with early invasive breast cancer (categories pT1 or pT2; pN0 or pN1; and M0). In 1999, 96% had a preoperative diagnosis by fine-needle aspiration or core biopsy (compared with 66% in 1989), with a synoptic pathology report on 95%. Breast-conserving surgery was used for 66% of women with mammographically detected tumours (v 35% in 1989) and 46% of those with clinically detected tumours (v 28% in 1989), with radiotherapy to the conserved breast in 90% of these cases (83% in 1989). Adjuvant chemotherapy was given to 92% of premenopausal women with node-positive disease and 63% with poor-prognosis node-negative tumours (v 78% and 14%, respectively, in 1989). Among postmenopausal women with receptor-positive tumours, tamoxifen was prescribed for 91% of those with positive nodes (85% in 1989) and 79% of those with negative nodes (30% in 1989). Among postmenopausal women with receptor-negative tumours, chemotherapy was prescribed for 70% with positive nodes (v 33%) and 58% with negative nodes (v none). Conclusions: Patterns of management of women with early invasive breast cancer in Western Australia during the 1990s changed significantly in all respects toward those recommended in the 1995 guidelines.

Surgical caseload and outcomes for women with invasive breast cancer treated in Western Australia

We have assessed the outcomes for all women diagnosed with invasive breast cancer in Western Australia during 1989, 1994 and 1999, and compared the results for surgeons who treat 20 or more cases per year with those of surgeons who treat less. Women treated by high caseload surgeons were more likely to retain their breast (53.3% vs. 36.7%, p < 0.001), have adjuvant radiotherapy (50.0% vs. 30.6%, p < 0.001), and be alive after 4 years (1989, 86% vs. 82%; 1994, 89% vs. 84%; 1999, 90% vs. 79%, HR 0.71, p = 0.03). Adjusting for age and year of diagnosis, women were not more likely to be treated with adjuvant chemotherapy (29.2% vs. 20.9%, p = 0.28). In 1989 35% of women were treated by high caseload surgeons. By 1999 this had risen to 82%. The results confirm that women treated by high caseload surgeons have better outcomes. (C) 2004 Elsevier Ltd. All rights reserved.

Refining the perfusion-diffusion mismatch hypothesis

Background and Purpose-The Echoplanar Imaging Thrombolysis Evaluation Trial ( EPITHET) tests the hypothesis that perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch predicts the response to thrombolysis. There is no accepted standardized definition of PWI-DWI mismatch. We compared common mismatch definitions in the initial 40 EPITHET patients. Methods-Raw perfusion images were used to generate maps of time to peak (TTP), mean transit time (MTT), time to peak of the impulse response (Tmax) and first moment transit time (FMT). DWI, apparent diffusion coefficient ( ADC), and PWI volumes were measured with planimetric and thresholding techniques. Correlations between mismatch volume (PWIvol-DWIvol) and DWI expansion (T2(Day) (90-vol)-DWIAcute-vol) were also assessed. Results-Mean age was 68 +/- 11, time to MRI 4.5 +/- 0.7 hours, and median National Institutes of Health Stroke Scale (NIHSS) score 11 (range 4 to 23). Tmax and MTT hypoperfusion volumes were significantly lower than those calculated with TTP and FMT maps (P < 0.001). Mismatch >= 20% was observed in 89% (Tmax) to 92% (TTP/FMT/MTT) of patients. Application of a +4s ( relative to the contralateral hemisphere) PWI threshold reduced the frequency of positive mismatch volumes (TTP 73%/FMT 68%/Tmax 54%/MTT 43%). Mismatch was not significantly different when assessed with ADC maps. Mismatch volume, calculated with all parameters and thresholds, was not significantly correlated with DWI expansion. In contrast, reperfusion was correlated inversely with infarct growth (R= -0.51; P = 0.009). Conclusions-Deconvolution and application of PWI thresholds provide more conservative estimates of tissue at risk and decrease the frequency of mismatch accordingly. The precise definition may not be critical; however, because reperfusion alters tissue fate irrespective of mismatch.

Preliminary study of human breast tissue using synchrotron radiation combining WAXS and SAXS techniques

Using synchrotron radiation, we combined simultaneously wide angle X-ray scattering (WAXS) and small angle X-ray scattering (SAXS) techniques to obtain the scattering profiles of normal and neoplastic breast tissu-es samples at the momentum transfer range 6.28 nm(-1) <= Q(=4 pi.sin(theta/2)lambda) <= 50.26 nm(-1) and 0.15 nm(-1) <= Q <= 1.90 nm(-1), respectively. The results obtained show considerable differences between the scattering profiles of these tissues. We verified that the combination of some parameters (ratio between glandular and adipose peak intensity and third-order axial peak intensity) extracted from scattering profiles can be used for identifying breast cancer. (c) 2009 Elsevier Ltd. All rights reserved.