Whole slide imaging for human epidermal growth factor receptor 2 immunohistochemistry interpretation: Accuracy, Precision, and reproducibility studies for digital manual and paired glass slide manual interpretation

Background: The use of digital whole slide imaging for human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) could create improvements in workflow and performance, allowing for central archiving of specimens, distributed and remote interpretation, and the potential for additional computerized automation. Procedures: The accuracy, precision, and reproducibility of manual digital interpretation for HER2 IHC were determined by comparison to manual glass slide interpretation. Inter- and intra-pathologist reproducibility and precision between the glass slide and digital interpretations of HER2 IHC were determined in 5 studies using DAKO HercepTest-stained breast cancer slides with the Philips Digital Pathology System. In 2 inter-method studies, 3 pathologists interpreted glass and digital slides in sequence or in random order with a minimum of 7 days as a washout period. These studies also measured inter-observer reproducibility and precision. Another two studies measured intra-pathologist reproducibility on cases read 10 times by glass and digital methods. One additional study evaluated the effects of adding IHC control slides with each run, using 1 pathologist interpreting glass and digital slides randomized from the sets above along with appropriate controls for each slide in the set. Results: The overall results show that there is no statistical difference between the variance of performance when comparing glass and digital HER2 interpretations; and there were no effects noted when control tissues were evaluated in conjunction with the test slides. Conclusions: The results show that there is an equivalence of result when interpreting HER2 IHC slides in breast cancer by either glass slides or digital images. Digital interpretation can therefore be safely and effectively used for this purpose

The metabolic syndrome and severity of diabetic retinopathy

BACKGROUND: While metabolic syndrome has been strongly implicated as a risk factor for macrovascular diseases, such as stroke and cardiovascular disease, its relationship with microvascular diseases, including diabetic retinopathy, has been less defined. The purpose of this pilot study was to investigate the association between metabolic syndrome and the presence and severity of diabetic retinopathy. METHODS: A retrospective case–control chart review at the University of Iowa ophthalmology and primary care clinics included 100 patients with proliferative diabetic retinopathy (PDR), 100 patients with nonproliferative diabetic retinopathy (NPDR), 100 diabetic patients without diabetic retinopathy, and 100 nondiabetic patients who were randomly selected. Using the International Diabetes Foundation definition, the prevalence of metabolic syndrome and the number of components of metabolic syndrome were compared among these groups. RESULTS: The prevalence of metabolic syndrome in patients with diabetes was 69.3%, which was significantly higher than that in patients without diabetes (27%; P<0.0001) (odds ratio [OR] =6.28; 95% confidence interval [CI]: 3.76–10.49; P=0.0004). However, there was no significant difference in the prevalence of metabolic syndrome between diabetics with and without diabetic retinopathy, with rates of 67.5% and 73%, respectively (P=0.36) (OR =0.77; 95% CI: 0.45–1.32; P=0.34). In addition, there was no significant difference between the PDR and NPDR groups, with rates of 63% and 72%, respectively (P=0.23) (OR =0.70; 95% CI: 0.38–1.30; P=0.26). CONCLUSION: The metabolic syndrome was highly prevalent in patients with diabetes, but it was not associated with the presence or severity of retinopathy

The metabolic syndrome and severity of diabetic retinopathy.

BackgroundWhile metabolic syndrome has been strongly implicated as a risk factor for macrovascular diseases, such as stroke and cardiovascular disease, its relationship with microvascular diseases, including diabetic retinopathy, has been less defined. The purpose of this pilot study was to investigate the association between metabolic syndrome and the presence and severity of diabetic retinopathy.MethodsA retrospective case-control chart review at the University of Iowa ophthalmology and primary care clinics included 100 patients with proliferative diabetic retinopathy (PDR), 100 patients with nonproliferative diabetic retinopathy (NPDR), 100 diabetic patients without diabetic retinopathy, and 100 nondiabetic patients who were randomly selected. Using the International Diabetes Foundation definition, the prevalence of metabolic syndrome and the number of components of metabolic syndrome were compared among these groups.ResultsThe prevalence of metabolic syndrome in patients with diabetes was 69.3%, which was significantly higher than that in patients without diabetes (27%; P&lt;0.0001) (odds ratio [OR] =6.28; 95% confidence interval [CI]: 3.76-10.49; P=0.0004). However, there was no significant difference in the prevalence of metabolic syndrome between diabetics with and without diabetic retinopathy, with rates of 67.5% and 73%, respectively (P=0.36) (OR =0.77; 95% CI: 0.45-1.32; P=0.34). In addition, there was no significant difference between the PDR and NPDR groups, with rates of 63% and 72%, respectively (P=0.23) (OR =0.70; 95% CI: 0.38-1.30; P=0.26).ConclusionThe metabolic syndrome was highly prevalent in patients with diabetes, but it was not associated with the presence or severity of retinopathy

T-cell infiltration in autosomal dominant neovascular inflammatory vitreoretinopathy

PurposeAutosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a familial blinding disease of unknown pathophysiology. The eyes and sera from patients with ADNIV were studied to understand the immune response in this condition.MethodsThe clinical case of an ADNIV patient was reviewed. Eye specimens from two donors with ADNIV were examined with a panel of standard histopathological stains and immunohistochemical markers. These findings were compared to specimens of noninflammatory eye disease. Sera from twelve patients were also tested against retinal protein western blots for the presence of autoretinal antibodies.ResultsEach of the ADNIV and control eyes showed degenerative features of phthisis bulbi. Immunohistological stains revealed a supraciliary T-cell infiltrate in ADNIV eyes composed of cluster of differentiation-4 (CD4) positive and cluster of differentiation-8 (CD8)-positive cells. No immunoglobulin or B cells were detected in these eyes. Inflammatory cells were absent from the control eyes. No specific autoretinal antibodies were detected in ADNIV sera.ConclusionsAberrant T-cell-mediated processes may underlie ADNIV, and therapeutics directed at T cells may better manage inflammation in these patients. Genes related to T-cell function are high priority screening candidates

Emerging Concepts for the Endoscopic Management of Superficial Esophageal Adenocarcinoma

Endoscopic therapy has revolutionized the treatment of Barrett's esophagus with high-grade dysplasia (HGD) or intramucosal adenocarcinoma by allowing preservation of the esophagus in many patients who would previously have had an esophagectomy. This paradigm shift initially occurred at high-volume centers in North America and Europe but now is becoming mainstream therapy. There is a lack of uniform guidelines and algorithms for the management of these patients. Our aim was to review important concepts and pitfalls in the endoscopic management of superficial esophageal adenocarcinoma. A small group colloquium consisting of gastroenterologists, surgeons, and pathologists reviewed published data and discussed personal and institutional experiences with endotherapy for HGD and superficial esophageal adenocarcinoma. The group reviewed data and provided recommendations and management algorithms for seven areas pertaining to endoscopic therapy for Barrett's HGD and superficial adenocarcinoma: (1) patient selection and evaluation; (2) imaging and biopsy techniques; (3) devices; (4) indications for resection versus ablation; (5) ER specimen handling, processing, and pathologic evaluation; (6) patient care and follow-up after endoscopic therapy; and (7) complications of endoscopic therapy and treatment options. Endoscopic therapy is preferred over esophagectomy for most patients with HGD or intramucosal adenocarcinoma, and may be applicable to select patients with submucosal tumors. Clear guidelines and management algorithms will aid physicians and centers embarking on endoscopic therapy and enable a standardized approach to the management of these patients that is applicable internationally