Bruce Latham

Fatty acid oxidation products in human atherosclerotic plaque: an analysis of clinical and histopathological correlates

Markers of lipid peroxidative damage have been shown to be elevated in individuals with risk factors for cardiovascular disease, and human atherosclerotic plaque contains products resulting from lipid peroxidation. In particular, the presence of fatty acid oxidation products such as hydroxyeicosatetraenoic acids (HETEs) has previously been suggested as a marker of plaque instability and symptomatic cerebrovascular disease. The aim of the present study was to quantitate the levels of various oxidation products of linoleic acid (HODEs) and arachidonic acid (HETEs), respectively, in human atherosclerotic plaque tissue and assess their level in relation to plaque histopathology, symptoms of cerebrovascular disease and preexisting atherosclerotic risk factors. We also assessed the correlation between the levels of the hydroxy fatty acid compounds and F(2)-isoprostanes, an established marker of in vivo free radical mediated oxidation. Hydroxy fatty acid oxidation products were identified in all histological subtypes of advanced plaque. However, there were no significant differences in levels between the histopathologically classified sub-groups or between patients symptomatic or asymptomatic for cerebrovascular disease. Arachidonic acid oxidation products were significantly higher in those subjects who also had symptomatic peripheral vascular disease. The level of linoleic acid oxidation products was significantly higher in individuals who consumed alcohol on a regular basis. While F(2)-isoprostanes and fatty acid oxidation products were highly correlated (P<0.01), levels of the hydroxy fatty acid compounds were 20-40-fold higher than F(2)-isoprostanes. Chiral analysis of the plaque extracts indicated that all HODEs and HETEs originated primarily from non-enzymatic lipid peroxidation. While our results do not support previous reports that fatty acid oxidation products such as the HETEs are associated with plaque instability and symptomatic cerebrovascular disease, further work is warranted to determine the potential of these compounds as circulating markers for underlying atherosclerotic disease and lipid peroxidative stress.

Optical coherence micro-elastography: mechanical-contrast imaging of tissue microstructure

We present optical coherence micro-elastography, an improved form of compression optical coherence elastography. We demonstrate the capacity of this technique to produce en face images, closely corresponding with histology, that reveal micro-scale mechanical contrast in human breast and lymph node tissues. We use phase-sensitive, three-dimensional optical coherence tomography (OCT) to probe the nanometer-to-micrometer-scale axial displacements in tissues induced by compressive loading. Optical coherence micro-elastography incorporates common-path interferometry, weighted averaging of the complex OCT signal and weighted least-squares regression. Using three-dimensional phase unwrapping, we have increased the maximum detectable strain eleven-fold over no unwrapping and the minimum detectable strain is 2.6 με. We demonstrate the potential of mechanical over optical contrast for visualizing micro-scale tissue structures in human breast cancer pathology and lymph node morphology.

Quantitative micro-elastography: Imaging of tissue elasticity using compression optical coherence elastography

Probing the mechanical properties of tissue on the microscale could aid in the identification of diseased tissues that are inadequately detected using palpation or current clinical imaging modalities, with potential to guide medical procedures such as the excision of breast tumours. Compression optical coherence elastography (OCE) maps tissue strain with microscale spatial resolution and can delineate microstructural features within breast tissues. However, without a measure of the locally applied stress, strain provides only a qualitative indication of mechanical properties. To overcome this limitation, we present quantitative micro-elastography, which combines compression OCE with a compliant stress sensor to image tissue elasticity. The sensor consists of a layer of translucent silicone with well-characterized stress-strain behaviour. The measured strain in the sensor is used to estimate the two-dimensional stress distribution applied to the sample surface. Elasticity is determined by dividing the stress by the strain in the sample. We show that quantification of elasticity can improve the ability of compression OCE to distinguish between tissues, thereby extending the potential for inter-sample comparison and longitudinal studies of tissue elasticity. We validate the technique using tissue-mimicking phantoms and demonstrate the ability to map elasticity of freshly excised malignant and benign human breast tissues.

Needle optical coherence elastography for the measurement of microscale mechanical contrast deep within human breast tissues

Abstract. Optical coherence elastography (OCE) is an emerging imaging technique that probes microscale mechanical contrast in tissues with the potential to differentiate healthy and malignant tissues. However, conventional OCE techniques are limited to imaging the first 1 to 2 mm of tissue in depth. We demonstrate, for the first time, OCE measurements deep within human tissues using needle OCE, extending the potential of OCE as a surgical guidance tool. We use needle OCE to detect tissue interfaces based on mechanical contrast in both normal and malignant breast tissues in freshly excised human mastectomy samples, as validated against histopathology. Further, we demonstrate the feasibility of in situ measurements >4  cm from the tissue surface using ultrasound guidance of the OCE needle probe. With further refinement, our method may potentially aid in accurate detection of the boundary of the tumor to help ensure full removal of all malignant tissues, which is critical to the success of breast-conserving surgery.

Collecting duct carcinoma of the kidney: a report of three cases and review of the literature

Summary Collecting duct carcinoma (CDC) of the kidney is a rare neoplasm arising from the medullary collecting ducts. The clinicopathological features of three cases are here presented to add to the 42 cases reported so far in the English language literature. Hematuria is the most common presenting symptom, although 10% of patients present with metastatic disease, often in neck lymph nodes. The tumor mass is typically centred on the medulla of the kidney and extends into the cortex. Radiological diagnosis may be difficult because the radiological features of CDC are poorly described. The histological appearances have been described as tubulo‐papillary, tubular, solid and sarcomatoid. Intracytoplasmic mucin may be present. The typical immunohistochemical profile is positive staining with antibodies for low and high molecular weight keratin and epithelial membrane antigen (EMA) and positive staining with the lectin Ulex europaeus agglutinin. Literature reports of cytogenetic characterisation show loss of chromosomes resulting in monosomies. Prognosis is poor as more than half of the reported cases have developed metastases or died within two years of presentation.Abbreviations: CDC, collecting duct carcinoma; EMA, epithelial membrane antigen; FNA, fine needle aspiration; RCC, renal cell carcinoma.

Investigation of Optical Coherence Microelastography as a Method to Visualize Cancers in Human Breast Tissue

An accurate intraoperative identification of malignant tissue is a challenge in the surgical management of breast cancer. Imaging techniques that help address this challenge could contribute to more complete and accurate tumor excision, and thereby help reduce the current high reexcision rates without resorting to the removal of excess healthy tissue. Optical coherence microelastography (OCME) is a three-dimensional, high-resolution imaging technique that is sensitive to microscale variations of the mechanical properties of tissue. As the tumor modifies the mechanical properties of breast tissue, OCME has the potential to identify, on the microscale, involved regions of fresh, unstained tissue. OCME is based on the use of optical coherence tomography (OCT) to measure tissue deformation in response to applied mechanical compression. In this feasibility study on 58 ex vivo samples from patients undergoing mastectomy or wide local excision, we demonstrate the performance of OCME as a means to visualize tissue microarchitecture in benign and malignant human breast tissues. Through a comparison with corresponding histology and OCT images, OCME is shown to enable ready visualization of features such as ducts, lobules, microcysts, blood vessels, and arterioles and to identify invasive tumor through distinctive patterns in OCME images, often with enhanced contrast compared with OCT. These results lay the foundation for future intraoperative studies. Cancer Res; 75(16); 3236-45. ©2015 AACR.

Pulmonary capillaritis associated with the antiphospholipid antibody syndrome and rapid response to plasmapheresis.

Pulmonary capillaritis is an uncommon complication of antiphospholipid antibody syndrome but has important therapeutic implications.

Wide-field optical coherence micro-elastography for intraoperative assessment of human breast cancer margins

Incomplete excision of malignant tissue is a major issue in breast-conserving surgery, with typically 20 - 30% of cases requiring a second surgical procedure arising from postoperative detection of an involved margin. We report advances in the development of a new intraoperative tool, optical coherence micro-elastography, for the assessment of tumor margins on the micro-scale. We demonstrate an important step by conducting whole specimen imaging in intraoperative time frames with a wide-field scanning system acquiring mosaicked elastograms with overall dimensions of ~50 × 50 mm, large enough to image an entire face of most lumpectomy specimens. This capability is enabled by a wide-aperture annular actuator with an internal diameter of 65 mm. We demonstrate feasibility by presenting elastograms recorded from freshly excised human breast tissue, including from a mastectomy, lumpectomies and a cavity shaving.

Predictors of re‐excision in wire‐guided wide local excision for early breast cancer: a Western Australian multi‐centre experience

A significant proportion of breast cancers present as impalpable lesions requiring radiological guidance prior to surgical excision, commonly by hook‐wire placement. Complete lesion excision is an essential part of treatment, and re‐excision may be needed to ensure this and minimize local recurrence. We explore a 1‐year audit of re‐excision of hook‐wire‐guided excisions in two large public breast units in Western Australia and define factors associated with the requirement for re‐excision.

Nephrotic syndrome in a patient with IgA deficiency-associated mesangioproliferative glomerulonephritis

Summary A case of mesangioproliferative glomerulonephritis in a 55-year-old woman with selective IgA deficiency and serum antinuclear antibodies who presented with nephrotic syndrome is described. The patient did not have clinical or laboratory features of systemic lupus erythematosus (SLE) other than antinuclear antibodies. Histology of the patients renal biopsy revealed a mesangioproliferative glomerulonephritis and direct immunofluorescence showed that paramesangial deposits contained predominant IgM with lesser IgG, C3 and C1q. These findings are identical to those previously described in a form of glomerulonephritis associated with IgA deficiency and would be atypical for lupus nephritis. Glomerulonephritis is not a well recognized complication of IgA deficiency, though it has been rarely reported in the literature. This case provides further evidence that IgA deficiency is associated with a unique immune complex-mediated glomerulopathy with characteristic immunopathological and ultrastructural features. It is the first reported case to present with nephrotic syndrome.