Geoffrey Watson

Tumor mitotic rate is a more powerful prognostic indicator than ulceration in patients with primary cutaneous melanoma: an analysis of 3661 patients from a single center.

The current study was performed to determine whether tumor mitotic rate (TMR) is a useful, independent prognostic factor in patients with localized cutaneous melanoma.

Diagnosis of metastatic melanoma by fine-needle biopsy : Analysis of 2,204 cases

Fine-needle biopsy (FNB) has been reported as a rapid, minimally invasive technique for the diagnosis of metastatic melanoma. The diagnostic accuracy of FNB was assessed in a consecutive series of 2,204 FNBs of clinically suspicious lesions from patients with previous primary melanomas treated at the Sydney Melanoma Unit, Sydney, Australia, between January 1992 and December 2002. The sensitivity and specificity of FNB were 96.3% and 98.9%, respectively. There were 5 false-positive cases (0.6%), which were verified as metastatic adenocarcinoma (3 cases) or reactive processes (organizing hematoma and chronic osteomyelitis, 1 each). False-negative diagnoses (6.7% of cases) were associated with a variety of clinicopathologic factors, including difficult-to-access anatomic sites (eg, high axilla or deep inguinal), small lesions, and lesional characteristics such asfibrosis, necrosis, or cystic change. FNB is a highly accurate, rapid, and cost-effective procedure for the diagnosis of metastatic melanoma and should be considered as the initial diagnostic procedure of choice in patients with melanoma with clinically suspected metastases.

Information Theoretic Ranking of Four Models of Diffusion Attenuation in Fresh and Fixed Prostate Tissue Ex Vivo

To compare the theoretical information content of four popular models of diffusion‐weighted signal attenuation.

Microscopic diffusion anisotropy in formalin fixed prostate tissue: preliminary findings.

Diffusion tensor microimaging at 16.4 T with 40 μm isotropic voxels was used to investigate anisotropic water diffusion in prostate tissue at spatial resolution approaching the cellular scale. Nine normal glandular tissue samples were collected from the peripheral zone of six formalin fixed radical prostatectomy specimens. Fibromuscular stromal tissue exhibited microscopic diffusion anisotropy (mean fractional anisotropy range 0.47–0.66) significantly higher (P < 0.01, Students t‐test) than in epithelium‐containing voxels (mean fractional anisotropy range 0.31–0.54) in six of the seven normal tissue samples in which both compartments could be measured. Fiber tracking demonstrated principle stromal fiber directions consistent with myocyte orientation seen on light microscopy of the same sample. Diffusion tensor microimaging may be valuable for investigation of variable results from attempts to measure diffusion anisotropy in the prostate in vivo. Magn Reson Med, 2012.

Biexponential diffusion decay in formalin‐fixed prostate tissue: Preliminary findings

Magnetic resonance microimaging was used to measure diffusion decay over an extended b‐factor range in a formalin‐fixed normal prostate sample and a Gleason pattern 3+4 cancer tissue sample. The coefficients of biexponential fits to diffusion decay data from 1600 voxels of dimension 160 × 160 × 160 μm3 in each sample were correlated with underlying epithelial and stromal compartment partial volumes estimated from high‐resolution apparent diffusion coefficient (ADC) data (40 × 40 × 40 μm3 voxels) from the same tissue. In the normal tissue sample, the signal fractions of the low and high ADC components of the biexponential fits correlated linearly with partial volumes of epithelial tissue (R2 = 0.6) and stromal tissue (R2 = 0.5), respectively. Similar but weaker correlations were observed in the cancer sample. Epithelium‐containing high spatial resolution voxels appeared to be composed of ∼60% low ADC and ∼40% high ADC component. Stromal voxels appeared to be composed of ∼20% low ADC and ∼80% high ADC component. This preliminary report suggests that distinctly different diffusion properties in microscopically adjacent cell types contribute to the multiexponential diffusion decay phenomenon in prostate tissue. Magn Reson Med, 2012.

Diagnostic Accuracy of Fine Needle Biopsy for Metastatic Melanoma and Its Implications for Patient Management

BackgroundThe use of fine needle biopsy (FNB) for the diagnosis of metastatic melanoma can lead to the early removal and treatment of metastases, reduce the frequency of unnecessary surgery, and facilitate the staging of patients enrolled in clinical trials of adjuvant therapies. In this study, the accuracy of FNB for the diagnosis of metastatic melanoma was investigated.MethodsA retrospective cohort study was performed with 2204 consecutive FNBs performed on 1416 patients known or suspected to have metastatic melanoma. Almost three-quarters (1582) of these FNBs were verified by either histopathologic diagnosis following surgical resection or clinical follow-up.ResultsFNB for metastatic melanoma was found to have an overall sensitivity of 92.1% and a specificity of 99.2%, with 69 false-negative and 5 false-positive findings identified. The sensitivity of the procedure was found to be influenced by six factors. The use of immunostains, reporting of the specimen by a cytopathologist who had reported >500 cases, lesions located in the skin and subcutis, and patients with ulcerated primary melanomas were factors associated with a significant improvement in the sensitivity of the test. However, FNBs performed in masses located in lymph nodes of the axilla and FNBs that required more than one needle pass to obtain a sample were far more likely to result in false-negative results.ConclusionsFNB is a rapid, accurate, and clinically useful technique for the assessment of disease status in patients with suspected metastatic melanoma.

Assessment of non-Gaussian diffusion with singly and doubly stretched biexponential models of diffusion-weighted MRI (DWI) signal attenuation in prostate tissue.

Non‐Gaussian diffusion dynamics was investigated in the two distinct water populations identified by a biexponential model of diffusion in prostate tissue. Diffusion‐weighted MRI (DWI) signal attenuation was measured ex vivo in two formalin‐fixed prostates at 9.4 T with diffusion times Δ = 10, 20 and 40 ms, and b values in the range 0.017–8.2 ms/µm2. A conventional biexponential model was compared with models in which either the lower diffusivity component or both of the components of the biexponential were stretched. Models were compared using Akaikes Information Criterion (AIC) and a leave‐one‐out (LOO) test of model prediction accuracy. The doubly stretched (SS) model had the highest LOO prediction accuracy and lowest AIC (highest information content) in the majority of voxels at Δ = 10 and 20 ms. The lower diffusivity stretching factor (α2) of the SS model was consistently lower (range ~0.3–0.9) than the higher diffusivity stretching factor (α1, range ~0.7–1.1), indicating a high degree of diffusion heterogeneity in the lower diffusivity environment, and nearly Gaussian diffusion in the higher diffusivity environment. Stretched biexponential models demonstrate that, in prostate tissue, the two distinct water populations identified by the simple biexponential model individually exhibit non‐Gaussian diffusion dynamics. Copyright

Effect of formalin fixation on biexponential modeling of diffusion decay in prostate tissue.

To evaluate the effect of formalin fixation on biexponential modeling of diffusion decay in prostate tissue.

Microscopic diffusivity compartmentation in formalin-fixed prostate tissue.

MR microimaging at 16.4 T with 40‐μm isotropic voxels was used to investigate compartmentation of water diffusion in formalin‐fixed prostate tissue. Ten tissue samples (∼ 28 mm3 each) from five organs were imaged. The mean diffusivity of epithelial, stromal, and ductal/acinar compartments was estimated by two methods: ( 1 ) manual region of interest selection and ( 2 ) Gaussian fitting of voxel diffusivity histograms. For the region of interest‐method, the means of the tissue sample compartment diffusivities were significantly different (P < 0.001): 0.54 ± 0.05 μm2/ms for epithelium‐containing voxels, 0.91 ± 0.17 μm2/ms for stroma, and 2.20 ± 0.04 μm2/ms for saline‐filled ducts. The means from the histogram method were also significantly different (P < 0.001): 0.45 ± 0.08 μm2/ms for epithelium‐containing voxels, 0.83 ± 0.16 μm2/ms for stroma, 2.21 ± 0.02 μm2/ms for duct. Estimated partial volumes of epithelial, stromal, and ductal/acinar compartments in a “tissue only” subvolume of each sample were significantly different (P < 0.02) between cancer and normal tissue for all three compartments. It is concluded that the negative correlation between apparent diffusion coefficient and cancer Gleason grade observed in vivo results from an increase of partial volume of epithelial tissue and concomitant decrease of stromal tissue and ductal space. Magn Reson Med, 2012.

Intraobserver and interobserver variability for the histologic diagnosis of chorioamnionitis

OBJECTIVES The interobserver and intraobserver variability for the histopathologic diagnosis of chorioamnionitis was examined. STUDY DESIGN Two examiners independently reviewed archived slides from 250 placentas. They were blinded to the original diagnosis and details of the pregnancy. Definitions for two important diagnoses were made and a protocol for recording information used in trial before the study. Slides were examined under conditions reflecting normal working practice. RESULTS A high level of agreement for the diagnosis of chorioamnionitis and umbilical vessel vasculitis (kappa range 0.78-0.81) between the examiners was found. Comparison of the agreement between each examiner and their original diagnosis was also excellent (kappa range 0.90-0.91). CONCLUSION This study has audited the reliability of the diagnosis of chorioamnionitis, a common and important placental finding. The reproducible and reliable degree of agreement demonstrated permits further research to be undertaken relating this diagnosis to adverse postnatal outcomes.