Neutrophils contain cholesterol crystals in transfusion-related acute lung injury (TRALI).

OBJECTIVES: Intracellular components of transfusion-related acute lung injury (TRALI) were investigated by transmission electron microscopy. METHODS: The lungs from 2 fatal TRALI cases and 2 controls, previously studied by scanning electron microscopy, were studied by transmission electron microscopy. Morphologic data by light and phase microscopy, along with scanning and transmission electron microscopic observations, were collated. RESULTS: The 2 fatal TRALI cases exhibited dense laminated material within capillaries and postcapillary venules, similar to material identified within their neutrophils when viewed by transmission electron microscopy. This material polarized light and is presumed to be cholesterol crystals. CONCLUSIONS: The damage to the pulmonary vascular endothelium in TRALI is related to formation of cholesterol crystals originating within neutrophils.

Molecular pathology of pancreatic neuroendocrine tumors.

Pancreatic endocrine tumors (PETs) are rare neoplasms which account for 1% to 2% of all pancreatic malignancies. The diagnostic, grading and prognostic criteria for PETs have been controversial in surgical pathology and clinical medicine. The newly updated 2010 WHO classification introduced in clinical practice will give more insight into genetic and molecular changes related to PET subtypes. These neoplasms can be graded into 1 of 3 tiers, based on histologic characteristics in likeness to epithelial neuroendocrine tumors in other anatomic sites. Most PETs are sporadic, however, some of them, may occur as part of familial tumors (inherited syndromes) such as multiple endocrine neoplasia type 1 (MEN1 syndrome), von Hippel-Lindau disease (VHL), neurofibromatosis type 1 (NF-1), and tuberous sclerosis (TSC). In sporadic endocrine pancreatic tumors, losses of chromosome 1 and 11q as well as gain on 9q appear to be early events in the development of pancreatic tumors. Multiple genetic defects may accumulate with time and result in pancreatic neuroendocrine tumor progression and malignancy. Although PETs may be similar or identical in histologic appearance to neuroendocrine tumors of the gastrointestinal tract, differences in their underlying biology and likely differences in response to therapeutic agents suggest that they should be treated and investigated as a distinct entity. The correlation of PI3K/Akt/mTOR pathway in the pathogenesis of PETs has been reported, and clinical trials data of mTOR inhibitors is promising.

Genetics and molecular pathology of gastric malignancy: Development of targeted therapies in the era of personalized medicine.

Gastric malignancy constitutes a major cause of cancer deaths worldwide. Despite recent advances in surgical techniques combined with neoadjuvant chemotherapy and radiotherapy approaches, patients with advanced disease still have poor outcomes. An emerging understanding of the molecular pathways that characterize cell growth, cell cycle, apoptosis, angiogenesis, invasion and metastasis has provided novel targets in gastric cancer therapy. In this review, recent advances in the understanding of molecular tumorigenesis for common gastric malignancies are discussed. We also briefly review the current targeted therapies in the treatment of gastric malignancies. Practical insights are highlighted including HER2 testing and target therapy in gastric adenocarcinoma, morphologic features and molecular signatures of imatinib-resistance GISTs, and recent investigations aimed at tumor-specific therapy for neuroendocrine tumors.

One-day quadruple therapy compared with 7-day triple therapy for Helicobacter pylori infection.

BACKGROUND: Eradication of Helicobacter pylori infection has had an impact on the treatment and recurrence rates of peptic ulcer disease and malignancies such as mucosa-associated lymphoid tissue lymphoma. Treatment options are cumbersome, expensive, and associated with side effects. METHODS: Randomized, prospective, open-labeled equivalence trial with a parallel-group design to compare eradication rates of H pylori with a 1-day, 4-drug regimen with a 7-day, 3-drug regimen. A total of 160 patients with dyspepsia and a Glasgow Dyspepsia Severity Score of at least 3 had a urea breath test labeled with carbon 14. Patients who tested positive were randomized to 1 of the 2 study groups. The study was designed to test the therapeutic equivalence of 1-day and 7-day regimens based on the percentage of H pylori eradication in each group at 5 weeks. RESULTS: The 1-day treatment group (n = 80) had a slightly higher eradication percentage (95%) than the 7-day group (90%). The possible inferiority of the 1-day treatment relative to the 7-day treatment, a 15% difference in the number of patients whose infection was not eradicated at 5 weeks, was rejected (P<.001; 90% confidence interval, 2.7%-11%). Both groups demonstrated a mean decrease of 7.5 points in the Glasgow Dyspepsia Severity Score. The 2 groups showed no significant differences in side effects. Patients whose treatment failed (4 in the 1-day treatment group and 7 in the 7-day treatment group) were re-treated for 10 days. One patient from the 7-day treatment group still tested positive after the second treatment. CONCLUSIONS: The 1-day treatment proved to be statistically similar to the 7-day treatment for the eradication of H pylori in patients with dyspepsia and a positive urea breath test. Further evaluation will be necessary to determine whether the 1-day regimen is adequate for patients with peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, or gastric adenocarcinoma.