Diagnostic utility of a p63/alpha-methyl-CoA-racemase (p504s) cocktail in atypical foci in the prostate.

Prostatic needle biopsy is the preferred method for diagnosing early prostate cancer, providing specific information. In cases of histological cancer mimics, a diagnosis of atypical small acinar proliferation suspected of but not diagnosed as malignancy can be made. In such cases, and in small focus carcinomas, pathologists use 34betaE12, cytokeratin (CK) 5/6 or p63 immunostaining to label basal cells, and alpha-methylacyl-CoA racemase (AMACR/p504s) immunostaining as a positive prostate cancer marker on two distinct slides. However, in cases of small foci, ambiguous lesions might disappear. The purpose of our study was to improve the sensitivity of a cocktail of two antibodies (p63/p504s) with a sample incubation on 260 prostatic specimens, in order to help make a decision in conjunction with standard histology and CK 5/6 immunostaining. We tested 101 small focus prostatic cancers, 104 atypical small acinar proliferation, 19 high-grade prostatic intraepithelial neoplasia, two atypical adenomatous hyperplasia and 34 benign mimics of cancer. After p63/p504s immunostaining, the final diagnoses retained were as follows: 154 prostatic cancers, 14 atypical small acinar proliferation, 30 high-grade prostatic intraepithelial neoplasia, three atypical adenomatous hyperplasia and 62 benign mimics of cancer. To differentiate malignant from benign lesions, we used the criteria of greater sensitivity to p504s/p63 (95%) than to CK 5/6 (57%) or p63 (86%), and higher specificity for p504s/p63 (95%) than for CK 5/6 (88%) or p63 (81%). With the p504s/p63 cocktail, 89% of the ambiguous lesions were classified vs 53% for CK 5/6. Combined use of the two antibodies, one (p504s) as a positive marker and the other (p63) as a negative marker, with a simple immunostaining procedure, may improve diagnostic performance, sensitivity and specificity, leading to a reduction in the risk of false negatives; this technique in cases of atypical small acinar proliferation should reduce the percentage of residual ambiguous lesions and the need for additional biopsies.     

Biomarkers

Epidemiologic, clinical, and basic research has identified several antecedent conditions that predispose individuals to heart failure and its predecessor, asymptomatic left ventricular remodeling and dysfunction (stage B heart failure). Many biochemical markers have been described that characterize the remodeling process and the development of cardiac dysfunction. Although natriuretic peptides and cardiac troponin are currently used in the context of diagnosis, risk stratification, and management of stage C and D heart failure, many other biomarkers provide insights into the underlying pathophysiology of left ventricular dysfunction, suggesting new directions for fundamental research or the development of new therapies.     

A novel mitochondria-targeting method using special staining for the detection of apoptotic hepatocytes

ABSTRACT

Early detection of apoptotic cells on histological slides is of major importance for both diagnostic and research areas. In the current study, the aim was to propose a convenient method to stain the mitochondria and establish whether hepatocytes undergoing apoptosis can be identified in tissue sections using the proposed method. Liver tissue from five adult chinchillas was fixed with 10% neutral buffered formalin for Goldner’s trichrome (GT) and Groat’s iron hematoxylin and eosin (HE) stains and with Kolster’s fixative for the Heidenhain’s iron hematoxylin procedure. The HE and GT-stained sections showed the morphological features consistent with apoptosis i.e., homogenous intensely acidophilic cytoplasm, cell shrinkage with an irregular outline, nuclear shrinkage with cloudy karyoplasm, and karyopyknosis in the late stage. Sections stained with Heidenhain’s iron hematoxylin method was used to pinpoint mitochondria and revealed cells which were undergoing the first stages of the apoptosis process i.e., disappearance of mitochondria from the cell, chromatin condensation and margination, paracentral localization of nucleoli, and vacuolated nuclei. In more advanced stages of apoptosis, cells presented significant nuclear and cytoplasmic changes. It was concluded that this is the first report targeting the mitochondria, by performing inexpensive histological staining techniques, in order to assess dead cells in situ.     

Risk factors associated with fatal influenza,Romania, October 2009 – May 2011

Background

Limited data are available from Central and Eastern Europe on risk factors for severe complications of influenza. Such data are essential to prioritize prevention and treatment resources and to adapt influenza vaccination recommendations.

Objectives

To use sentinel surveillance data to identify risk factors for fatal outcomes among hospitalized patients with severe acute respiratory infections (SARI) and among hospitalized patients with laboratory-confirmed influenza.

Methods

Retrospective analysis of case-based surveillance data collected from sentinel hospitals in Romania during the 2009/2010 and 2010/2011 winter influenza seasons was performed to evaluate risk factors for fatal outcomes using multivariate logistic regression.

Results

During 2009/2010 and 2010/2011, sentinel hospitals reported 661 SARI patients of which 230 (35%) tested positive for influenza. In the multivariate analyses, infection with influenza A(H1N1)pdm09 was the strongest risk factor for death among hospitalized SARI patients (OR: 6·6; 95% CI: 3·3–13·1). Among patients positive for influenza A(H1N1)pdm09 virus infection (n = 148), being pregnant (OR: 7·1; 95% CI: 1·6–31·2), clinically obese (OR: 2·9;95% CI: 1·6–31·2), and having an immunocompromising condition (OR: 3·7;95% CI: 1·1–13·4) were significantly associated with fatal outcomes.

Conclusion

These findings are consistent with several other investigations of risk factors associated with influenza A(H1N1)pdm09 virus infections. They also support the more recent 2012 recommendations by the WHO Strategic Advisory Group of Experts on Immunization (SAGE) that pregnant women are an important risk group for influenza vaccination. Ongoing sentinel surveillance can be useful tool to monitor risk factors for complications of influenza virus infections during each influenza season, and pandemics as well.     

Diagnosis of renal metanephric adenoma: relevance of immunohistochemistry and biopsy

Most renal tumors of the adult are carcinomas. Their treatment is surgical, consisting of limited excision or nephrectomy. In some instances, biopsy of the tumor can be performed in order to adapt treatment. We report the case of a 45 year-old woman presenting with renal tumor. A biopsy of the mass showed a metanephric adenoma. No surgical excision was performed because of the benignity of this tumor. Here we develop the interest of immunohistochemistry for differential diagnosis of metanephric adenoma and other "basophilic small cell tumors" of the kidney. We also put the stress on the growing role of biopsy of renal tumor allowing optimal treatment.     

Surrogate end points in heart failure

Because of the increasing number of pharmacologic strategies available for treatment of heart failure (HF), the time has come to reassess the adequacy of end points used to evaluate therapeutic efficacy. Interest in the use of surrogate end points in clinical studies is increasing. A surrogate end point is defined as a measurement that can substitute for a true end point for the purpose of comparing specific interventions or treatments in a clinical trial. A true end point is one that is of clinical importance to the patient (e.g., mortality or quality of life), whereas a surrogate end point is one biologically closer to the disease process (e.g., ejection fraction or left ventricular volume in HF). The prime motivation for the use of a surrogate end point concerns the possible reduction in sample size or trial duration. Such reductions have important cost implications and in some cases may influence trial feasibility. Another, perhaps more important, aspect of measuring surrogate end points is that they increase our understanding of the mechanism of action of drugs and thus may help physicians to take a more enlightened approach in managing their patients. In this article we have analyzed the possible potentials of the surrogate end points in clinical studies of patients with chronic HF. Other uses of possible surrogates are discussed, and the limitations in finding true surrogates are mentioned. At this time we conclude there is no well established surrogate in HF.     

Thromboprophylaxis does not protect severely injured patients against pulmonary embolism

The existing evidence on the effectiveness of thromboprophylaxis after trauma is conflicting. Although prophylaxis with heparin and/or sequential compression devices is practiced widely, many studies failed to document a clear benefit. A recent meta-analysis suggests that prophylaxis does not reduce posttraumatic deep venous thrombosis rates compared to no prophylaxis. The objective of this prospective study is to examine if the use of thromboprophylaxis prevents posttraumatic pulmonary embolism (PE). Sixty-four critically injured patients with clinical evidence of PE were studied by computed tomographic pulmonary angiography and/or conventional pulmonary angiography. PE was diagnosed in 24 (37.5%) patients. Patients with PE were similar to patients without PE with regard to demographics, injury type and severity, operations, and mortality. Thromboprophylaxis was used with equal frequency between PE and no-PE patients (71% vs 80%, P = 0.4). The type of prophylaxis used was similar between patients with PE (17% heparin, 71% sequential compression devices, 17% combination) and patients without PE (32%, 57%, and 10%, respectively; P = 0.16, 0.28, 0.69, respectively). Current methods of posttraumatic thromboprophylaxis may be inadequate. Practices from nontrauma populations have been erroneously extrapolated to the unique trauma population. To reduce the rate of PE after trauma, new methods of thromboprophylaxis should be considered.     

Sequential compression devices as prophylaxis for venous thromboembolism in high-risk colorectal surgery patients: reconsidering American Society of Colorectal Surgeons parameters

The American Society of Colorectal Surgeons (ASCRS) recently endorsed low-molecular-weight heparin and low-dose heparin as primary prophylaxis for venous thromboembolism (VTE) in highest-risk patients. Our study evaluates the feasibility of sequential compression device (SCD) use for VTE prophylaxis in these patients. Computerized databases of discharge diagnoses from three hospitals were reviewed. All patients with colorectal cancer or inflammatory bowel disease during a 7-year period were identified. Those who underwent major abdominal surgery and received VTE prophylaxis exclusively with SCDs were selected for the study. Patients diagnosed with postoperative VTE were identified through review of the three databases and of patient records for 90 days after surgery. One thousand two hundred eighty-one patients classified as highest-risk under the published ASCRS parameters underwent major abdominal surgery and received SCDs perioperatively. The incidence of clinically detectable postoperative VTE was 0.78 per cent. There were trends toward lower incidence among patients with malignancy (0.53%) compared with inflammatory bowel disease (1.48%, P = 0.09), and those with abdominal compared to pelvic procedures (0.62% vs. 1.04%, P = 0.41). Prophylaxis for perioperative VTE solely with SCD is a viable option for patients classified as highest-risk under ASCRS parameters.