RABL6A Promotes Oxaliplatin Resistance in Tumor Cells and Is a New Marker of Survival for Resected Pancreatic Ductal Adenocarcinoma Patients.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by early recurrence following pancreatectomy, rapid progression, and chemoresistance. Novel prognostic and predictive biomarkers are urgently needed to both stratify patients for clinical trials and select patients for adjuvant therapy regimens. This study sought to determine the biological significance of RABL6A (RAB, member RAS oncogene family-like protein 6 isoform A), a novel pancreatic protein, in PDAC.

A process model for direct correlation between computed tomography and histopathology application in lung cancer.

Rationale And Objectives: Multimodal imaging techniques for capturing normal and diseased human anatomy and physiology are being developed to benefit patient clinical care, research, and education. In the past, the incorporation of histopathology into these multimodal datasets has been complicated by the large differences in image quality, content, and spatial association.

Materials And Methods: We have developed a novel system, the large-scale image microtome array (LIMA), to bridge the gap between nonstructurally destructive and destructive imaging such that reliable registration between radiological data and histopathology can be achieved.

Subacute exposure to N-ethyl perfluorooctanesulfonamidoethanol results in the formation of perfluorooctanesulfonate and alters superoxide dismutase activity in female rats.

Perfluorooctanesulfonamides, such as N-ethyl perfluorooctanesulfonamidoethanol (N-EtFOSE), are large scale industrial chemicals but their disposition and toxicity are poorly understood despite significant human exposure. The hypothesis that subacute exposure to N-EtFOSE, a weak peroxisome proliferator, causes a redox imbalance in vivo was tested using the known peroxisome proliferator, ciprofibrate, as a positive control. Female Sprague-Dawley rats were treated orally with N-EtFOSE, ciprofibrate or corn oil (vehicle) for 21 days, and levels of N-EtFOSE and its metabolites as well as markers of peroxisome proliferation and oxidative stress were assessed in serum, liver and/or uterus.

Recommendations for the reporting of surgically resected thymic epithelial tumors.

Thymic epithelial tumors include thymoma and thymic carcinoma. Histologic findings and extent of disease are key determinants of prognosis and help guide postoperative management in patients with thymic epithelial tumors. Given the relative rarity of these tumors, the use of tumor guidelines and checklists can facilitate accurate and comprehensive pathologic reporting in this setting.

Mandatory second opinion in cytopathology.

Background: Mandatory review of outside pathologic material is intended to detect interpretive errors that may have a clinically significant impact on patient care. Prior to definitive treatment of referred patients, the University of Iowa Carver College of Medicine requires a review of pertinent pathologic material previously obtained at outside institutions. The aims of this study were to determine if this local standard of practice has a measurable impact on patient care.

Altered expression of iron regulatory genes in cirrhotic human livers: clues to the cause of hemosiderosis?

Hepatic iron deposition unrelated to hereditary hemochromatosis occurs commonly in cirrhosis but the pathogenesis of this condition is unknown. The aim of this study was to compare the expression of genes involved in the regulation of iron metabolism in cirrhotic (n=22) and control human livers (n=5). Transcripts were quantitated by real-time RT-PCR and protein levels were assessed by western blot.

Generation and characterization of monoclonal antibodies to NIAM: a nuclear interactor of ARF and Mdm2.

Nuclear interactor of ARF and Mdm2 (NIAM) is a newly discovered growth inhibitor that helps maintain chromosomal stability. It is functionally linked to the ARF-Mdm2-p53 tumor suppressor pathway and is predicted to be a tumor suppressor, but the lack of antibodies capable of detecting the endogenous human protein has delayed efforts to define its role in human tumorigenesis. This study reports the development, screening, and characterization of several monoclonal antibodies (MAbs) that specifically recognize endogenous human NIAM protein by Western blotting, immunoprecipitation, immunofluorescence, and immunohistochemistry.

Regulation of 14-3-3sigma expression in human thyroid carcinoma is epigenetically regulated by aberrant cytosine methylation.

Increased 14-3-3sigma expression has been observed by immunohistochemistry in papillary and anaplastic tumors, but not follicular thyroid cancers. 14-3-3sigma mRNA expression and methylation status was examined in tumor cell lines and primary thyroid tissues using real-time RT-PCR, bisulfite sequencing and methylation-specific PCR. Most of the 27 CpG's in the gene's CpG island were methylated in normal thyroid, TPC-1, NPA, FTC-238 and 2-7, which did not express 14-3-3sigma.

Mandatory second opinion in surgical pathology referral material: clinical consequences of major disagreements.

Second opinion in pathology is intended to expose clinically significant errors that have a direct impact on patient care. Before definitive treatment of referred patients, our institution requires a second opinion of outside surgical pathology slides. We sought to determine if this local standard of practice has a measurable impact on patient care via clinical and pathologic follow-up.

Differential expression of stress-inducible proteins in chronic hepatic iron overload.

Introduction: Oxidative stress can trigger a cellular stress response characterized by induction of antioxidants, acute phase reactants (APRs) and heat shock proteins (HSPs), which are presumed to play a role in limiting tissue damage. In rodents, hepatic iron overload causes oxidative stress that results in upregulation of antioxidant defenses with minimal progressive liver injury. The aim of this study was to determine whether iron overload modulates expression of other stress-responsive proteins such as APRs and HSPs that may confer protection against iron-induced damage in rodent liver.

Comparison of fungal culture versus surgical pathology examination in the detection of Histoplasma in surgically excised pulmonary granulomas.

Context: Granulomatous pulmonary nodules are common in areas endemic for Histoplasma infection, and may require surgical excision to exclude neoplasia. Surgeons may elect to routinely send material directly to the clinical microbiology laboratory for fungal and mycobacterial cultures.

Objective: To determine if tissue from surgically excised pulmonary granulomatous nodules removed from patients in a geographic area endemic for Histoplasma infection should be routinely submitted for fungal culture.

Small peripheral pulmonary adenocarcinoma: morphologic and molecular update.

The dichotomous histopathologic separation of lung carcinoma into "small cell" and "nonsmall cell" categories is validated by marked clinical and biologic differences between these groups of tumors. However, nonsmall cell carcinoma represents a heterogenous group of tumors, and the subclassification of nonsmall cell lung carcinoma at the molecular, morphologic, and epidemiologic levels has led to the promise of precise treatment and better prognostication. Histomorphologic aspects of small peripheral adenocarcinomas that represent good prognosis include pure bronchioloalveolar carcinoma, minimal invasion within a mixed invasive and lepidic growth pattern tumor, and minimal scar within a lepidic growth pattern tumor.

Immunohistochemical expression of osteopontin in epithelioid mesotheliomas and reactive mesothelial proliferations.

The morphologic distinction of epithelioid mesothelioma from a reactive mesothelial proliferation can be difficult. Recent studies have demonstrated that serum osteopontin levels are increased in patients with mesotheliomas. We sought to determine if osteopontin expression is diagnostically helpful in distinguishing epithelioid mesothelioma from reactive mesothelial proliferations.

Subinvolution of the placental site as an anatomic cause of postpartum uterine bleeding: a review.

Context: Subinvolution of the placental site is an anatomic cause of delayed postpartum uterine bleeding that may be underrecognized by general surgical pathologists.

Objective: To review the physiology of uteroplacental arterial development and normal postpartum involution, and to present the characteristic clinical and histopathologic features of subinvolution.

Data Sources: Literature review (MEDLINE via PubMed and Ovid) regarding the pathology and pathophysiology of placental site subinvolution.

Chronic iron overload stimulates hepatocyte proliferation and cyclin D1 expression in rodent liver.

Hepatomegaly is commonly observed in hepatic iron overload due to human hemochromatosis and in animal models of iron loading, but the mechanisms underlying liver enlargement in these conditions have received scant attention. In this study, male rats were treated with iron dextran or dextran alone for 6 months. Chronic iron loading resulted in a > 50-fold increase in hepatic iron concentration.

A simple, focused, computerized query to detect overutilization of laboratory tests.

Context: Although there is nearly universal agreement that laboratory tests are overutilized, the degree of overutilization in a given institution is difficult to quantify and monitor across time.

Objective: To detect and clearly document repetitive daily ordering of a commonly ordered laboratory test (serum sodium) by employing a simple, focused, computerized query of a test result database followed by chart review and validation.

Design: A retrospective computerized query of our clinical data repository was performed to find inpatients who displayed normal serum sodium test results on 4 or more consecutive days, without any abnormal values during the same admission.

A preliminary diagnosis service provides prospective blinded dual-review of all general surgical pathology cases in an academic practice.

Quality assurance of diagnostic accuracy in surgical pathology is an important part of a pathologist's total quality management program. At our academic institution, the quality of diagnostic accuracy is monitored via dual-review of every general surgical pathology case, which accounts for nearly 20,000 cases per year. This comprehensive dual-review is achieved by operating a preliminary diagnosis service, staffed by a senior or board eligible resident.

Telomerase reverse transcriptase subunit expression is associated with chondrosarcoma malignancy.

Expression of the telomerase reverse transcriptase subunit telomerase reverse transcriptase gene is associated with most human malignancies. Because telomerase reverse transcriptase is rarely expressed in normal tissue, its presence in pathologic specimens is considered a marker of transformed cells. Moreover, high levels of expression have been correlated with poor prognosis in many cancers.

Low-level endotoxin induces potent inflammatory activation of human blood vessels: inhibition by statins.

Background: Low-level endotoxemia (ie, >or=50 pg/mL) in apparently healthy subjects was recently identified as a powerful, independent risk factor for atherosclerosis.

Methods And Results: We treated human saphenous veins (HSVs) with low levels of endotoxin. Release of the proinflammatory chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) was measured by ELISA.