Patterns of nodal staging during breast conservation surgery in the medicare patient: will the ACOSOG Z0011 trial change the pattern of care?

ACOSOG Z0011 spares axillary dissection (AD) in breast conservation surgery (BCS) patients with T1/T2 tumors and 1-2 positive nodes. Current patterns of care and the impact of Z0011 on AD versus additional surgery rates for Medicare patients undergoing BCS are unknown. SEER data linked to Medicare claims for 1999-2005 were reviewed for women with invasive nonmetastatic breast cancer who underwent nodal staging on the same day as BCS. There were 3,280 women with T1/T2 tumors and positive nodes who underwent same-day nodal staging; 2,532 (77.2 %) of these women had 1-2 positive nodes. Assuming 25.7 % have extracapsular extension, 651 women would require AD. However, 1,881 women, or 57.4 % of those with T1/T2 tumors and positive nodes, would be spared AD. Meanwhile, among the 748 women having ≥ 3 positive nodes, 579 underwent same-day AD, but under Z0011, would now wait for permanent section. A total of 160 of these women underwent re-excision or completion mastectomy at a later date anyway, when delayed AD could be performed. The remaining 419 women with ≥ 3 positive nodes would require an additional surgery date for the sole purpose of completion AD. The Z0011 paradigm would consequently necessitate an additional surgery date for 1,070 (651 + 419) women, or 32.6 % of those with T1/T2 tumors and positive nodes. The Z0011 paradigm appears to increase the number of Medicare patients undergoing BCS who require an additional surgery date but decrease the number requiring AD to a greater extent. Future changes in the use of AD or axillary irradiation may yet modify that impact substantially.

Guilty by association: Assessment of environmental loadings on arsenic distribution in two Pacific Island rivers.

This work evaluates the immediate risk of arsenic toxicity in two major river systems located in Western Viti Levu, Fiji and Guadalcanal, the Solomon Islands. Using principal component analysis, the associations between the major inorganic arsenic species, As (V) and As(III) and those of the controlling parameters, pH, dissolved oxygen and temperature were investigated in these aquatic systems. As(III) was found to be the dominant form of total inorganic As concentrations in five of the thirteen sites studied. There remains a high risk of As(III) exposure from these sites in the rivers. The study also examined the potential role of mine adits in influencing the distinct water chemistry at the sites. Over 50% of As was found to exist as the more toxic As(III) species at some sites (with higher levels near the gold mines) in both river systems. This finding implies that there may be health risk to populations relying on the river waters for agriculture. As(V) at most sites across both rivers exceeded 13 µg/L, defined as a trigger value for aquatic ecosystems by Australia and New Zealand standards. The PCA indicated that spatial variations play a significant role in water chemistries between sites further from the mine adit location in the Metapona River. In the Sabeto River system, there was also considerable intra-variability in the water chemistries between sites. Further detailed studies are necessary to determine a complete profile of As species and associated biogeochemical processes in these rivers which could lead on to identify appropriate containment or mitigation measures.

Age-related development of a refractive index plateau in the human lens: evidence for a distinct nucleus.

The human lens comprises two distinct regions in which the refractive index changes at different rates. The periphery contains a rapidly increasing refractive index gradient, which becomes steeper with age. The inner region contains a shallow gradient, which flattens with age, due to formation of a central plateau, of RI = 1.418, which reaches a maximum size of 7.0 x 3.05 mm around age 60 years. Formation of the plateau can be attributed to compression of fibre cells generated in prenatal life. Present in prenatal but not in postnatal fibre cells, gamma-crystallin may play a role in limiting nuclear cell compression.

Experimental and computational analyses of the effects of slice distortion from a metallic sphere in an MRI phantom.

Susceptibility artifacts due to metallic prostheses are a major problem in clinical magnetic resonance imaging. We theoretically and experimentally analyze slice distortion arising from susceptibility differences in a phantom consisting of a stainless steel ball bearing embedded in agarose gel. To relate the observed image artifacts to slice distortion, we simulate images produced by 2D and 3D spin-echo (SE) and a view angle tilting (VAT) sequence. Two-dimensional SE sequences suffer from extreme slice distortion when a metal prosthesis is present, unlike 3D SE sequences for which--since slices are phase-encoded--distortion of the slice profile is minimized, provided the selected slab is larger than the region of interest. In a VAT sequence, artifacts are reduced by the application of a gradient along the slice direction during readout. However, VAT does not correct for the excitation slice profile, which results in the excitation of spins outside the desired slice location and can lead to incorrect anatomical information in MR images. We propose that the best sequences for imaging in the presence of a metal prosthesis utilize 3D acquisition, with phase encoding replacing slice selection to minimize slice distortion, combined with excitation and readout gradient strengths at their maximum values.

Shape of the retinal surface in emmetropia and myopia.

PURPOSE: To determine and compare the shapes of the retinas of emmetropic and myopic eyes. METHODS: Nonrotationally symmetrical ellipsoids were mathematically fitted to the retinal surfaces of 21 emmetropic and 66 myopic eyes (up to -12 D) of participants aged 18 to 36 years (mean, 25.5) using transverse axial and sagittal images derived from magnetic resonance imaging. RESULTS: The shapes of the ellipsoids varied considerably between subjects with similar refractive errors. The shapes were oblate (steepening toward the equator) in most of the emmetropic eyes (i.e., the axial dimensions of the ellipsoids were smaller than both the vertical and horizontal dimensions). As myopia increased, all ellipsoid dimensions increased with the axial dimension increasing more than the vertical dimension, which in turn increased more than the horizontal dimension (increases in approximate ratios 3:2:1). The relative difference in the increase of these dimensions meant that as the degree of myopia increased the retinal shape decreased in oblateness. However, few myopic eyes were prolate (flattening toward the equator). Independent of myopia, the ellipsoids were tilted about the vertical axis by 11 degrees +/- 13 degrees , and ellipsoid centers were decentered horizontally by 0.5 +/- 0.4 mm nasally and 0.2 +/- 0.5 mm inferiorly, relative to the fovea. CONCLUSIONS: In general both emmetropic and myopic retinas are oblate in shape, although myopic eyes less so. This finding may be relevant to theories implicating the peripheral retina in the development of myopia.

Eye shape in emmetropia and myopia.

PURPOSES: To determine axial, vertical, and horizontal eye dimensions in myopic and emmetropic eyes by using magnetic resonance imaging (MRI) and to relate these to different ocular expansion models of myopia development. METHODS: The internal length (cornea to retina), height and width (both retina to retina) were measured in emmetropic and myopic eyes (up to -12 D) of 88 participants aged 18 to 36 years. Participants were positioned supine in a clinical MRI scanner. The fixation target was imaged straight ahead of the subject by an overhead 45 degrees inclined mirror. Eye images were acquired with a 7.5-cm receive-only radio frequency surface coil. Axial (horizontal through middle of eye) and sagittal (vertical through visual axis) sections were taken with a T(1)-weighted fast spin-echo sequence. RESULTS: With an increase in myopic refractive correction, myopic eyes became much larger in all three dimensions, but more so in length (0.35 mm/D, 95% confidence interval [CI] 0.28-0.40) than in height (0.19 mm/D, 95% CI 0.09-0.29) and more so in height than in width (0.10 mm/D, 95% CI 0.01-0.20). Based on height and length dimensions, 25% and 29% of myopic eyes exclusively fitted global expansion and axial elongation models, respectively. Based on width and length dimensions, 17% and 39% of myopic eyes exclusively fitted the global expansion and axial elongation models, respectively. CONCLUSIONS: Although there are considerable individual variations, in general myopic eyes are elongated relative to emmetropic eyes, more in length than in height and even less in width. Approximately a quarter of the myopic participants fitted each of the global expansion or axial elongation model exclusively. The small proportions are due primarily to the large variability in the dimensions of emmetropic eyes.

A new model of arteriovenous fistula to study hemodialysis access complications.

PURPOSE: This report presents a new animal model of arteriovenous fistula (AVF) with attention given to surgical techniques as well as hemodynamic and pathologic measurements. Of note, this model was created with a tunneled central catheter with the purpose of studying therapeutic interventions, including hemodialysis. METHODS: Side-common carotid artery to end-external jugular vein AVFs were created in eight minipigs. A tunneled central catheter was also placed in the internal jugular vein. After 28 days, hemodynamic measurements of AVF flow and stenosis were performed. The minipigs were then euthanized and the AVFs were harvested for pathologic measurements of neointimal hyperplasia and thrombus volumes. In order to account for variable size of the AVFs, percentage luminal stenosis and degree of intima-media thickening were calculated. RESULTS: After 28 days, all eight AVFs remained patent. On average, 19% of arterial blood flow that approached the AVF traveled through the anastomosis. The average luminal stenosis by angiogram was 61.1%. The average neointimal hyperplasia and thrombus volumes were 1.4×10(8) and 3.8×10(8) µm3, respectively. The average luminal stenosis and intima-media thickening were 65.2% and 430.4 µm, respectively. CONCLUSIONS: This AVF model is ideal because of the relative ease of surgery and husbandry, lack of complications, as well as consistent and rapid development of the neointimal lesion which underlies AVF failure.

HPLC analysis of asymmetric dimethylarginine, symmetric dimethylarginine, homoarginine and arginine in small plasma volumes using a Gemini-NX column at high pH.

There is increasing recognition of the clinical importance of endogenous nitric oxide synthase inhibitors in critical illness. This has highlighted the need for an accurate high performance liquid chromatography (HPLC) method for detection of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in small volumes of blood. Here, the validation of an accurate, precise HPLC method for the determination of ADMA, SDMA, homoarginine and arginine concentrations in plasma is described. Solid phase extraction is followed by derivatisation with AccQ-Fluor and reversed phase separation on a Gemini-NX column at pH 9. Simultaneous detection by both UV-vis and fluorescence detectors affords extra validation. This solid phase extraction method gives absolute recoveries of more than 85% for ADMA and SDMA and relative recoveries of 102% for ADMA and 101% for SDMA. The intra-assay relative standard deviations are 2.1% and 2.3% for ADMA and SDMA, respectively, with inter-assay relative standard deviations of 2.7% and 3.1%, respectively. Advantages of this method include improved recovery of all analytes using isopropanol in the solid phase extraction; sharp, well-resolved chromatographic peaks using a high pH mobile phase; a non-endogenous internal standard, n-propyl L-arginine; and accurate and precise determination of methylated arginine concentrations from only 100microL of plasma.

Squamous cell carcinoma of the nipple following radiation therapy for ductal carcinoma in situ: a case report.

INTRODUCTION: Radiation-induced nonmelanoma skin cancer was first reported seven years after the discovery of X-rays, but has received relatively little consideration in the literature. Specifically, nonmelanoma skin cancer after conservative surgery and radiation for early stage breast cancer has not been well studied. We report the case of a woman who developed squamous cell carcinoma of the nipple nine years after conservative surgery and radiation for ductal carcinoma in situ of the ipsilateral breast. We also review the relevant literature available to date. CASE PRESENTATION: A 66-year-old African-American woman presented to the hospital with a non-healing ulcer of the right nipple. Her past medical history was significant for right breast ductal carcinoma in situ for which she had undergone lumpectomy and whole breast radiation therapy nine years previously. Mammography and magnetic resonance imaging studies were negative for recurrent breast cancer. However, the latter demonstrated abnormal enhancement in the nipple-areolar region. An incisional biopsy of the lesion demonstrated invasive squamous cell carcinoma. Subsequently, the patient underwent wide excision of the nipple-areolar complex. Sentinel lymph-node biopsy was offered but our patient declined. She was considered to have local disease and hence no further treatment was recommended. CONCLUSION: This case represents the first reported occurrence of squamous cell carcinoma of the nipple to follow conservative surgery and radiation for ductal carcinoma in situ of the ipsilateral breast. It is likely that radiation overexposure resulted in a radiation burn and subsequent radiodermatitis, placing it at risk for squamous cell carcinoma. A diagnosis of squamous cell carcinoma should be considered in a patient with a nipple lesion following radiation therapy for breast cancer.

Retrospective 3D registration of trabecular bone MR images for longitudinal studies.

PURPOSE: To evaluate an automatic 3D registration algorithm for serial high-resolution images of trabecular bone (TB) in studies designed to evaluate the response of the trabecular architecture to intervention or disease progression. MATERIALS AND METHODS: An efficient algorithm for registering high-resolution 3D images of TB is presented. The procedure identifies the six parameters of rigid displacement between two scans performed at different timepoints. By assuming a relatively small through-plane rotation, considerable time is saved by combining the results of a collection of regional 2D registrations throughout the TB region of interest (ROI). The algorithm was applied to 26 pairs of MR images acquired 6 months apart. Reproducibility of local TB structural parameters (plate, rod, and junction density) computed in manually selected regions were compared between baseline and registered follow-up images. RESULTS: All 26 registrations were completed successfully in less than 30 seconds per image pair. The resampled follow-up images agreed with baseline to around one pixel throughout the volume at 137 x 137 x 410 microm(3) image resolution. Structural parameters in each region correlated well from baseline to follow-up with intraclass correlation coefficients ranging between 85%-97% for TB plate density. Interregional variations in the parameters were large as compared with intraregion reproducibility. CONCLUSION: The proposed algorithm was successful in automatically registering baseline and follow-up TB images in a translational study, and may be useful in regional analyses in longitudinal MR studies of TB architecture.

Mathematical models for describing the shape of the in vitro unstretched human crystalline lens.

We developed orthogonal least-squares techniques for fitting crystalline lens shapes, and used the bootstrap method to determine uncertainties associated with the estimated vertex radii of curvature and asphericities of five different models. Three existing models were investigated including one that uses two separate conics for the anterior and posterior surfaces, and two whole lens models based on a modulated hyperbolic cosine function and on a generalized conic function. Two new models were proposed including one that uses two interdependent conics and a polynomial based whole lens model. The models were used to describe the in vitro shape for a data set of twenty human lenses with ages 7-82years. The two-conic-surface model (7mm zone diameter) and the interdependent surfaces model had significantly lower merit functions than the other three models for the data set, indicating that most likely they can describe human lens shape over a wide age range better than the other models (although with the two-conic-surfaces model being unable to describe the lens equatorial region). Considerable differences were found between some models regarding estimates of radii of curvature and surface asphericities. The hyperbolic cosine model and the new polynomial based whole lens model had the best precision in determining the radii of curvature and surface asphericities across the five considered models. Most models found significant increase in anterior, but not posterior, radius of curvature with age. Most models found a wide scatter of asphericities, but with the asphericities usually being positive and not significantly related to age. As the interdependent surfaces model had lower merit function than three whole lens models, there is further scope to develop an accurate model of the complete shape of human lenses of all ages. The results highlight the continued difficulty in selecting an appropriate model for the crystalline lens shape.

Changes in lens dimensions and refractive index with age and accommodation.

PURPOSE: To measure changes in human eye lens dimensions and refractive index with age and state of accommodation. METHODS: MRI methods were used to measure refractive index maps and lens geometry (diameter and thickness) of an axial slice through the lens in 44 volunteers aged 18 to 59 years, with an accommodation stimulus of 0.17 D (unaccommodated state). In a subpopulation of 26 young volunteers aged 18 to 33 years, lens dimensions were also measured in an accommodated (6.67 D stimulus) state. For a subpopulation of six of the young volunteers (22 to 33 years), refractive index maps were also acquired with an accommodation stimulus of 6.67 D. RESULTS: Unaccommodated lens thickness increased significantly with age (T = 3.31 +/- 0.10 mm + 0.0180 +/- 0.0036 mm x Age; p < 0.0001). Lens diameter (D = 9.33 +/- 0.0033 mm) and central refractive index (nc = 1.4198 +/- 0.0067) showed no significant age dependence. Lens thickness increased (DeltaT = 0.050 +/- 0.024 mm/D) and diameter decreased (DeltaD = -0.067 +/- 0.030 mm/D) on accommodation. A slight decrease in central refractive index with accommodation was not statistically significant. CONCLUSIONS: The results are consistent with the Helmholtz theory of accommodation.