Expression profiling identifies genes involved in neoplastic transformation of serous ovarian cancer

Background: The malignant potential of serous ovarian tumors, the most common ovarian tumor subtype, varies from benign to low malignant potential (LMP) tumors to frankly invasive cancers. Given the uncertainty about the relationship between these different forms, we compared their patterns of gene expression. Methods: Expression profiling was carried out on samples of 7 benign, 7 LMP and 28 invasive (moderate and poorly differentiated) serous tumors and four whole normal ovaries using oligonucleotide microarrays representing over 21,000 genes. Results: We identified 311 transcripts that distinguished invasive from benign tumors, and 20 transcripts that were significantly differentially expressed between invasive and LMP tumors at p < 0.01 (with multiple testing correction). Five genes that were differentially expressed between invasive and either benign or normal tissues were validated by real time PCR in an independent panel of 46 serous tumors (4 benign, 7 LMP, 35 invasive). Overexpression of SLPI and WNT7A and down-regulation of C6orf31, PDGFRA and GLTSCR2 were measured in invasive and LMP compared with benign and normal tissues. Over-expression of WNT7A in an ovarian cancer cell line led to increased migration and invasive capacity. Conclusion: These results highlight several genes that may play an important role across the spectrum of serous ovarian tumorigenesis

Gata3 immunohistochemical staining is a useful marker for metastatic breast carcinoma in fine needle aspiration specimens

Aims: The utility of GATA3 immunohistochemistry (IHC) as an aid to the cytological diagnosis of metastatic breast carcinoma in fine needle aspiration (FNA) specimens was investigated. Materials and Methods: Cell block sections from 111 FNA cases of metastatic malignancy were stained for GATA3, including metastases from 43 breast and 44 nonmammary adenocarcinomas, 19 melanomas, 4 urothelial carcinomas, and 1 thyroid medullary carcinoma. Sites sampled included lymph nodes (87), bone (8), liver (5), lung (6), superficial masses (4), and pelvic mass (1). Results: Ninety-one percent (39/43) of metastatic breast carcinoma cases were positive for GATA3. All estrogen receptor (ER)-positive were also GATA3 positive cases. The majority (9/14; 64%) of ER-negative and 37% (3/8) of triple-negative cases were positive for GATA3. All nonmammary adenocarcinoma cases were negative with the exception of one case of metastatic pancreatic adenocarcinoma. Metastatic melanoma cases were all negative but 75% (3/4) urothelial carcinomas expressed GATA3. Conclusions: GATA3 IHC staining is a useful addition to IHC panels for FNA samples in specific settings such as distinguishing metastatic breast from lung carcinoma or melanoma

Claudin-4 immunohistochemistry is a useful pan-carcinoma marker for serous effusion specimens

Objective: To evaluate the utility of claudin-4 as a pan-carcinoma marker in cell-blocks of effusion specimens and compare results with Ber-Ep4 staining. Methods: Effusion cell-blocks (n = 284) were stained for claudin-4 and results compared with Ber-Ep4. Cases included 172 metastatic malignancies (137 adenocarcinomas, 20 small cell lung tumours, eight metastatic melanoma, four squamous cell carcinoma, three urothelial cell carcinoma), 49 benign reactive cases and 63 mesotheliomas. Results: All 49 benign effusions were negative. Only 1/63 (1.6%) mesotheliomas was positive for claudin-4. Claudin-4 staining was positive in 131/137 (95.6%) adenocarcinoma cases. Cases negative for claudin-4 included single cases of metastases from breast, colon, stomach, prostate, kidney and ovary. Claudin-4 outperformed Ber-Ep4. Sensitivity (95.6% vs 85.4%), specificity (99.1% vs 86.6%), negative predictive value (94.9% vs 82.9%) and positive predictive value (99.2% vs 88.6%) were all higher for claudin-4 compared with Ber-Ep4, respectively. Only two cases were claudin-4−/Ber-Ep4+. Significantly (P Conclusions: Claudin-4 staining is a useful addition to IHC panels for effusions specimens with superior performance to Ber-Ep4.</p

Investigation of lymphoid lesions of the head and neck using combined fine needle aspiration cytology and flow cytometry:Accuracy and pitfalls

Objective: We reviewed the diagnostic utility of combined fine needle aspiration cytology (FNAC) and flow cytometry (FC) in the diagnosis of lymphoid lesions of the head and neck. Method: In total, 1402 patients with combined FNAC-FC reports were correlated with follow-up information. Rapid on-site evaluation (ROSE) of cytological specimens was performed in 52% of cases. Results: In total, 211 lymphoid malignancies were identified, including 198 non-Hodgkin lymphoma (NHL) and 13 Hodgkin lymphoma (HL). Accuracy measures for NHL were: sensitivity 95.5%; specificity 99.9%; PPV 99.5%; NPV 99.2%; accuracy 99.3%. Only seven of 13 cases of HL were detected by FNAC-FC. False negative cases included HL (six cases), diffuse large B-cell lymphoma (four), T-cell lymphoma (two), follicular lymphoma (one), marginal zone cell lymphoma (one) and B-cell NHL, not otherwise specified (one). Two false positive results were identified: one immunoblastic hyperplasia reported as suspicious for HL and one case reported as suggestive of NHL that was found to be reactive hyperplasia. Cases collected with ROSE had a significantly lower rate (P Conclusions: FNAC-FC is a highly sensitive and specific test for NHL. Diagnostic errors mostly involved HL, large cell lymphomas and T-cell lymphomas. ROSE results in a significantly higher adequacy rate for FC and higher sensitivity for NHL.</p

Fibroadenoma and intraduct papilloma--a common pathogenesis?

This report describes two cases, each showing fibroepithelial proliferation, admixed with intraduct papillomas. Case 1 was from a 13-year-old female who presented with a breast mass, while case 2 was from a 60-year-old female who also had a breast lump. Case 1 showed proliferative breast disease with multiple small papillomas, some with leaf-like contours. Broad-based parenchymal proliferations protruding into ducts were also seen, and there were overlap features between the two ends of this spectrum. Case 2, similarly, demonstrated a mixed intraductal proliferation, with papillomas on narrow stalks together with low-grade phyllode areas extending into ducts from a wider base. That fibroadenoma and intraduct papilloma may have a common pathogenesis is discussed

Comorbidity polypharmacy score and its clinical utility: A pragmatic practitioner′s perspective

Modern medical management of comorbid conditions has resulted in escalating use of multiple medications and the emergence of the twin phenomena of multimorbidity and polypharmacy. Current understanding of how the polypharmacy in conjunction with multimorbidity influences trauma outcomes is limited, although it is known that trauma patients are at increased risk for medication-related adverse events. The comorbidity-polypharmacy score (CPS) is a simple clinical tool that quantifies the overall severity of comorbidities using the polypharmacy as a surrogate for the "intensity" of treatment necessary to adequately control chronic medical conditions. Easy to calculate, CPS is derived by counting all known pre-injury comorbid conditions and medications. CPS has been independently associated with mortality, increased risk for complications, lower functional outcomes, readmissions, and longer hospital stays. In addition, CPS may help identify older trauma patients at risk of post-emergency department undertriage. The goal of this article was to review and refine the rationale for CPS and to provide an evidence-based outline of its potential clinical applications

Evaluation of a model for glycemic prediction in critically ill surgical patients.

We evaluated a neural network model for prediction of glucose in critically ill trauma and post-operative cardiothoracic surgical patients. A prospective, feasibility trial evaluating a continuous glucose-monitoring device was performed. After institutional review board approval, clinical data from all consenting surgical intensive care unit patients were converted to an electronic format using novel software. This data was utilized to develop and train a neural network model for real-time prediction of serum glucose concentration implementing a prediction horizon of 75 minutes. Glycemic data from 19 patients were used to "train" the neural network model. Subsequent real-time simulated testing was performed in 5 patients to whom the neural network model was naive. Performance of the model was evaluated by calculating the mean absolute difference percent (MAD%), Clarke Error Grid Analysis, and calculation of the percent of hypoglycemic (≤70 mg/dL), normoglycemic (>70 and <150 mg/dL), and hyperglycemic (≥150 mg/dL) values accurately predicted by the model; 9,405 data points were analyzed. The models successfully predicted trends in glucose in the 5 test patients. Clark Error Grid Analysis indicated that 100.0% of predictions were clinically acceptable with 87.3% and 12.7% of predicted values falling within regions A and B of the error grid respectively. Overall model error (MAD%) was 9.0% with respect to actual continuous glucose modeling data. Our model successfully predicted 96.7% and 53.6% of the normo- and hyperglycemic values respectively. No hypoglycemic events occurred in these patients. Use of neural network models for real-time prediction of glucose in the surgical intensive care unit setting offers healthcare providers potentially useful information which could facilitate optimization of glycemic control, patient safety, and improved care. Similar models can be implemented across a wider scale of biomedical variables to offer real-time optimization, training, and adaptation that increase predictive accuracy and performance of therapies

Pre-injury beta blocker use does not affect the hyperdynamic response in older trauma patients

Purpose: Trauma dogma dictates that the physiologic response to injury is blunted by beta-blockers and other cardiac medications. We sought to determine how the pre-injury cardiac medication profile influences admission physiology and post-injury outcomes. Materials and Methods: Trauma patients older than 45 evaluated at our center were retrospectively studied. Pre-injury medication profiles were evaluated for angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACE-I/ARB), beta-blockers, calcium channel blockers, amiodarone, or a combination of the above mentioned agents. Multivariable logistic regression or linear regression analyses were used to identify relationships between pre-injury medications, vital signs on presentation, post-injury complications, length of hospital stay, and mortality. Results: Records of 645 patients were reviewed (mean age 62.9 years, Injury Severity Score >10, 23%). Our analysis demonstrated no effect on systolic and diastolic blood pressures from beta-blocker, ACE-I/ARB, calcium channel blocker, and amiodarone use. The triple therapy (combined beta-blocker, calcium channel blocker, and ACE-I/ARB) patient group had significantly lower heart rate than the no cardiac medication group. No other groups were statistically different for heart rate, systolic, and diastolic blood pressure. Conclusions: Pre-injury use of cardiac medication lowered heart rate in the triple-agent group (beta-blocker, calcium channel blocker, and ACEi/ARB) when compared the no cardiac medication group. While most combinations of cardiac medications do not blunt the hyperdynamic response in trauma cases, patients on combined beta-blocker, calcium channel blocker, and ACE-I/ARB therapy had higher mortality and more in-hospital complications despite only mild attenuation of the hyperdynamic response

Comorbidity-Polypharmacy Scoring Facilitates Outcome Prediction in Older Trauma Patients

Objectives To determine the association between comorbidity–polypharmacy score (CPS) and clinical outcomes in a large sample of older trauma patients, focusing on outcome prognostication. Design The CPS combines number of preinjury medications and comorbidities to more objectively quantify the severity of comorbid conditions. Setting An urban tertiary care level 1 trauma center in the Midwest. Participants Trauma patients aged 45 and older. Methods Participants were stratified into four groups according to CPS ranges. Survival analyses were performed using Kaplan–Meier/Mantel-Cox testing. Factors influencing mortality, complications, and survivor discharge destination were evaluated using analysis of covariance and multivariate logistic regression. Results Records for 469 individuals (mean age 62.1, mean injury severity score 9.3) were reviewed. Higher CPS is associated with greater mortality, complications, longer hospital and intensive care unit stay, and need for discharge to a facility. Higher CPS is associated with lower 90-day survival (Mantel-Cox, P \u3c .001). Mortality was independently associated with older age (odds ratio (OR) = 1.06 per year), higher injury severity score (OR = 1.19 per point), and higher CPS (OR = 1.11 per point) in multivariate analysis (all P \u3c .01). Complications and need for discharge to a facility were independently associated with older age and higher injury severity score and CPS. Conclusion CPS can be readily determined in the era of medication reconciliation. Trauma patients with CPS of 15 or greater are at greater risk of poor clinical outcomes. CPS constitutes a useful adjunct to currently available injury severity scoring tools as a predictor of morbidity, mortality, hospital resource utilization, and postdischarge disposition in older trauma patients