Novel Pathologic Factors for Risk Stratification of Gastric "Indefinite for Dysplasia" Lesions.

METHODS: In total, 123 IND cases with final diagnoses of cancer (29.3%), high-grade dysplasia (6.5%), low-grade dysplasia (11.4%), and nonneoplasm (52.8%) were randomly divided into test set (n = 27) and validation set (n = 96). By the image analysis, size, pleomorphism, hyperchromasia, irregularity of nuclei, and ratios of structural atypia area (SAA) to total IND area were measured in the test set. Using the validation set, consensus meetings were held for the evaluation of pathologic factors that predict the final diagnosis. RESULTS: By image analysis, the only ratio of SAA to total IND area was associated with the final diagnosis (p < 0.001). In the consensus meeting for validation, the nuclear factors, except loss of nuclear polarity (p = 0.004-0.026), could not predict the final diagnosis. Conversely, most structural factors could predict the final diagnosis. In particular, SAA > 25% was the most powerful predictive factor. We proposed criteria of risk stratification by using SAA > 25%, loss of surface maturation (LOSM), and loss of nuclear polarity (LONP) (Malignancy rate; Category 0: SAA ≤ 25% without LOSM and LONP; 0%, Category 1: SAA ≤ 25% with any of LOSM or LONP; 15.2%-16.7%, Category 2: SAA > 25% without LOSM and LONP; 44.4%-50.0%, Category 3: SAA > 25% with any of LOSM or LONP 54.5%-55.6%). CONCLUSIONS: Structural atypia was more helpful than nuclear atypia and SAA > 25% was the most powerful predictor for the diagnosis of INDs of the stomach. We propose shortening the follow-up period to six months for Category 1, endoscopic resection for Category 2 and 3, postresection follow-up periods of one year for Category 2, and six months for Category 3.

Gastric Mucosal Atrophy Impedes Housekeeping Gene Methylation in Gastric Cancer Patients.

PURPOSE: Helicobacter pylori infection induces phenotype-stabilizing methylation and promotes gastric mucosal atrophy that can inhibit CpG-island methylation. Relationship between the progression of gastric mucosal atrophy and the initiation of CpG-island methylation was analyzed to delineate epigenetic period for neoplastic transformation. MATERIALS AND METHODS: Normal-appearing gastric mucosa was biopsied from 110 H. pylori-positive controls, 95 H. pylori-negative controls, 99 gastric cancer patients, and 118 gastric dysplasia patients. Gastric atrophy was assessed using endoscopic-atrophic-border score. Methylation-variable sites of eight CpG-island genes adjacent to Alu (CDH1, ARRDC4, PPARG, and TRAPPC2L) or LTR (MMP2, CDKN2A, RUNX2, and RUNX3) retroelements and stomach-specific TFF3 gene were analyzed using radioisotope-labeled methylation-specific polymerase chain reaction. RESULTS: Mean ages of H. pylori-positive controls with mild, moderate, and severe atrophy were 51, 54, and 65 years and those of H. pylori-associated TFF3 overmethylation at the three atrophic levels (51, 58, and 63 years) tended to be periodic. Alu-adjacent overmethylation (50 years) was earlier than TFF3 overmethylation (58 years) in H. pylori-positive controls with moderate atrophy. Cancer patients with moderate atrophy showed late Alu-adjacent (58 years) overmethylation and frequent LTR-adjacent overmethylation. LTR-adjacent overmethylation was frequent in cancer (66 years) and dysplasia (68 years) patients with severe atrophy. CONCLUSION: Atrophic progression is associated with gastric cancer at moderate level by impeding the initiation of Alu-adjacent methylation. LTR-adjacent methylation is increased in cancer patients and subsequently in dysplasia patients.

Prognostic role of beclin-1 in locally advanced non-small cell lung cancer in patients receiving docetaxel-platinum induction chemotherapy.

BACKGROUND/AIMS: The outcome of local treatment for advanced non-small cell lung cancer (NSCLC) remains poor, with therapies such as induction chemotherapy (IC) yielding conflicting results. This study aimed to assess the clinicopathologic and prognostic significance of the excision repair cross-complementation group 1 (ERCC1), beclin-1, and glucose-regulated protein of molecular mass 78 (GRP78) in patients with locally advanced NSCLC receiving docetaxel-platinum IC, along with efficacy and safety. METHODS: This is a retrospective observational cohort study. We reviewed medical records of 31 NSCLC patients receiving docetaxel-platinum IC, and conducted immunohistochemical staining of ERCC1, beclin-1, and GRP78. RESULTS: Response rate was 67.8% with 10.7 months of median relapse-free survival (RFS) and 23.1 months of median overall survival (OS), and no treatment-related death was reported. High expression of ERCC1, beclin-1, and GRP78 was identified in 67.7%, 87.1%, and 67.7%, respectively. Expression of ERCC1 and GRP78 did not reveal statistical significance in survival, whereas high beclin-1 expression revealed longer OS (7.6 months vs. 23.2 months; log-rank p = 0.024). In multivariate analysis, histologic differentiation (hazard ratio [HR], 3.48; p < 0.001), stage (HR, 8.5; p = 0.024), and adjuvant treatment (HR, 16.1; p = 0.001) were related to RFS, and in OS, stage (HR, 5.4; p = 0.037), adjuvant treatment (HR, 8.6; p = 0.004), and beclin-1 expression (HR, 8.2; p = 0.011) were identified as significant prognostic factors. CONCLUSION: Our findings suggest that high beclin-1 expression predicts longer survival in locally advanced NSCLC and docetaxel-platinum IC is a treatment option that deserves consideration.

Electronically Mismatched Cycloaddition Reactions via First-Row Transition Metal, Iron(III)-Polypyridyl Complex.

The iron(III)-polypyridyl complex and its derivatives showed sufficient oxidizing potential to act as a one-electron oxidant, producing radical cations from olefins and promoting the efficient radical cation [2 + 2] and [2 + 4] cycloaddition reactions. Subsequent chain propagation afforded trisubstituted cyclobutane or cyclohexene derivatives, and this facile route enables the replacement of rare metals with sustainable, green, and inexpensive iron in radical cation cycloadditions.

Single-Electron-Transfer Strategy for Reductive Radical Cyclization: Fe(CO)5 and Phenanthroline System.

An electron-transfer strategy using low-valent iron pentacarbonyl [Fe(CO)5] to generate radical species from alkyl iodides was achieved. A range of pyrrolidines, tetrahydrofurans, and carbocycles were synthesized via 5-exo cyclization reactions of alkyl radical intermediates generated by electron transfer from a system involving Fe(CO)5, 1,10-phenanthroline, and diisopropylamine. Moreover, tandem addition reactions with Michael acceptors were also explored. Photophysical and electrochemical studies support a mechanism that involves electron transfer from the low-valent Fe reductant to alkyl iodide.

Knowledge about dementia in South Korean nursing students: a cross-sectional survey.

BACKGROUND: The number of individuals with dementia is increasing substantially due to South Korea's rapidly aging society. Undergraduate nursing students need to have adequate knowledge about dementia to deliver appropriate nursing services. The purpose of this study was to assess the knowledge about dementia among undergraduate nursing students. METHODS: A total of 148 students ranging from freshmen to seniors at a nursing university participated in this study. Data were collected through self-reports using 12-item questionnaires with true/false responses. Knowledge levels about the general characteristics including demographic categories and dementia- related education and training were determined. Factors affecting the score of dementia knowledge were also investigated. RESULTS: The average score and standard deviation for knowledge about dementia were 10.26 and 1.24 out of 12 points. They had relatively low knowledge about the "prevention and treatment" and "causes" of dementia, with overall correct rate of 78.6 % and 85.4 %, respectively. Higher level of knowledge about dementia was associated with increase in grade level (p < 0.001), experience in education on dementia (p = 0.01), previous experience in caring for people with dementia during clinical practice (p < 0.001), and acquiring information on dementia (p = 0.02). Factors that influenced knowledge about dementia included grade level and experience in caring for dementia patients during clinical practice. CONCLUSIONS: This study showed that the level of knowledge about dementia among nursing students was reasonably good. Integrating dementia education and clinical experience into the curricula of undergraduates could improve knowledge about the causes, prevention, and treatment methods for dementia.

Correlation between the prognostic value and the expression of the stem cell marker CD133 and isocitrate dehydrogenase1 in glioblastomas.

Cancer stem cells are thought to be responsible for tumor recurrence and resistance in glioblastomas. An isocitrate dehydrogenase1 (IDH1) mutation, affecting codon132 of the isocitrate dehydrogenase1 gene, has prognostic significance in glioblastomas. We investigated whether stem cell marker expression [CD133, CD34, and vascular endothelial growth factor (VEGF)] and IDH1 mutation correlate with clinical factors and prognosis in glioblastoma. CD133, CD34, and VEGF expression was evaluated by immunohistochemistry in 67 cases of glioblastoma identified between 2005 and 2012. IDH1 mutation was assessed by immunohistochemistry, peptide-nucleic-acid mediated PCR clamping, and direct gene sequencing. Diffuse CD133 expression was detected in 12 (17.9 %) cases and was associated with poor overall survival (OS) (P = 0.010) and progression-free survival (P = 0.017). CD34 and VEGF expression were not associated with prognosis in these samples. IDH1 mutation was detected in ten (14.9 %) cases. Eight were clinically secondary tumors and two were primary tumors (P < 0.001); the mean age of the secondary tumor patients was significantly younger (P = 0.001, 41.20 vs. 59.14). IDH1-positive patients had longer OS than IDH1-negative patients (25.78 vs. 22.95 months), but this difference was not significant. In addition, IDH1 and CD34 expression showed a negative correlation (P = 0.024). Multivariate analysis showed that age, extent of surgery, and diffuse CD133 expression correlated with OS. CD133 may be a survival marker for glioblastoma. Further characterization of CD133, IDH1, and vascular markers in glioblastoma may help identify new therapeutic targets.

CK7, CK20, CDX2 and MUC2 Immunohistochemical staining used to distinguish metastatic colorectal carcinoma involving ovary from primary ovarian mucinous adenocarcinoma.

OBJECTIVE: Colorectal adenocarcinoma, the most common tumor that metastasizes to the ovary, is often difficult to distinguish from primary ovarian mucinous adenocarcinoma (POMA). Obtaining the correct diagnosis is difficult but crucial to treatment and prognosis. METHODS: We evaluated the immunohistochemical (IHC) expression of cytokeratin 7 (CK7), cytokeratin 20 (CK20), CDX2, CEA, MUC2, MUC5AC and alpha-methylacyl-CoA racemase (AMACR) in 22 POMAs and 41 metastatic colorectal adenocarcinomas (MCAOs) involving ovaries. RESULTS: MCAOs, in contrast with POMAs, were almost always negative for MUC5 (97.6%), often negative for CK7 (82.9%), focal or diffuse positive for CDX2 (73.2%), diffuse positive for CK20 (65.9%), focal or diffuse positive for MUC2 (51.2%), diffuse positive for CEA (41.5%) and negative for AMACR (41.5%). We therefore considered CK7 (-), CK20 (diffuse +), CDX2 (+) and MUC2 (+) to be colonic markers and regarded cases with expression of more than two colonic markers as MCAO, those with no expression of colonic markers as POMA and those with expression of one colonic marker as indeterminate. Using CK7/CK20/CDX2/MUC2, 82.5% of the cases were correctly classified, 6.3% were misclassified and 6.3% were indeterminate. CONCLUSION: CK7, CK20, CDX2 and MUC2 IHC staining is a useful adjunctive diagnostic tool to differentiate MCAOs from POMAs, in addition to clinical history and gross and microscopic findings.