The risk factors for lymph node metastasis in early gastric cancer patients who underwent endoscopic resection: is the minimal lymph node dissection applicable?

Purpose

The purpose of this study was to identify risk factors associated with lymph node (LN) metastasis in early gastric cancer patients who underwent endoscopic resection (ER) and to evaluate the feasibility of minimal LN dissection in these patients.

Methods

From January 2001 to March 2011, patients who underwent gastrectomy with lymphadenectomy due to the potential risk of LN metastasis after ER were enrolled at National Cancer Center, Korea. The incidence, risk factors, and distribution of LN metastasis were evaluated.

Results

Of the 147 enrolled patients, the LN metastasis was identified in 12 patients (8.2 %). The incidence of LN metastasis was not significantly increased in patients with submucosal invasion, lymphovascular invasion, and mixed undifferentiated histology [odds ratio (OR), 5.55, 1.349, and 0.387; 95 % confidence interval (CI), 0.688–43.943, 0.405–4.494, and 0.081–1.84, respectively]. Tumor size more than 2 cm was significantly associated with LN metastasis (OR, 14.056; 95 % CI, 1.76–112.267). The incidence of LN metastasis gradually increased from 3.2 to 20 %, as number of risk factors increased (P = 0.019). LN metastasis was present primarily along the perigastric area in all except two patients (1.4 %) with skip metastasis to extragastric area.

Conclusions

Standard surgery with at least D1 + LN dissection must be recommended for patients who proved to have risk factors for LN metastasis after ER, because the potential of skip metastasis is not negligible. Nevertheless, the minimal LN dissection, such as sentinel basin dissection, might be applied cautiously in patients with small-sized tumors after ER.     

Effect of Dupilumab in Korean Patients With Uncontrolled Moderate-to-Severe Asthma: A LIBERTY ASTHMA QUEST Sub-analysis

PurposeTo assess the effect of dupilumab on the annualized severe exacerbation rates, change in forced expiratory volume at first second (FEV1), overall asthma control and health-related quality of life in Korean patients from the LIBERTY ASTHMA QUEST study.MethodsOf the 1,902 patients enrolled in the LIBERTY ASTHMA QUEST study, a phase-3, randomized, double-blind, placebo-controlled, parallel-group study on dupilumab, 74 (4%) were Korean. The patients were randomly assigned to 4 treatment groups (2:2:1:1). The sub-analysis reported herewith was performed with the pooled groups of dupilumab and placebo from the 4 original treatment groups in the LIBERTY ASTHMA QUEST study. The efficacy endpoints were annualized rate of severe exacerbation events during the 52-week study period and changes from baseline in pre-bronchodilator FEV1 in week 12. Asthma control, asthma quality of life and the effect of treatment on the levels of type 2 inflammatory biomarkers were assessed. The safety profile was also evaluated.ResultsIn Korean patients, annualized severe exacerbation rates were reduced with dupilumab (n = 49) compared to placebo (n = 25) (0.259 vs 1.942) during the 52-week treatment period. The relative risk reduction with dupilumab was 87% (P < 0.001). Improvements in pre-bronchodilator FEV1 (mean difference of 0.24 L, P = 0.021) were observed in week 12 in dupilumab-treated patients. Additionally, improvements in asthma control and asthma-related quality of life were observed; the FeNO and serum immunoglobulin E levels were reduced. The incidence of adverse events and serious adverse events was comparable between the dupilumab and placebo group. A total of 11 patients from the dupilumab group reported 63 injection site reactions.ConclusionsDupilumab, as an add-on therapy in severe asthma, is efficacious and has an acceptable safety profile in Korean patients.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02414854","term_id":"NCT02414854"}}NCT02414854     

The First Korean Family with Hemoglobin-M Milwaukee-2 Leading to Hereditary Methemoglobinemia

Hemoglobin M (HbM) is a group of abnormal hemoglobin variants that form methemoglobin, which leads to cyanosis and hemolytic anemia. HbM-Milwaukee-2 is a rare variant caused by the point mutation CAC>TAC on codon 93 of the hemoglobin subunit beta (HBB) gene, resulting in the replacement of histidine by tyrosine. We here report the first Korean family with HbM-Milwaukee-2, whose diagnosis was confirmed by gene sequencing. A high index of suspicion for this rare Hb variant is necessary in a patient presenting with cyanosis since childhood, along with methemoglobinemia and a family history of cyanosis.     

Suppressive effect of inducible nitric oxide synthase (iNOS) expression by the methanol extract of Actinodaphne lancifolia

Nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) has played a crucial role in various pathophysiological processes including inflammation and carcinogenesis. Therefore, the inhibitors of NO synthesis or iNOS gene expression have been considered as potential anti-inflammatory and cancer chemopreventive agents. In our continuous search for iNOS inhibitors from natural products we have evaluated indigenous Korean plant extracts using an assay for inhibition of nitric oxide formation on lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. As a result, the methanolic stem extract of Actinodaphne lancifolia showed an inhibitory activity of NO production in a dose-dependent manner (IC50 = 2.5 microg/ml). Additional study demonstrated that the extract of Actinodaphne lancifolia significantly suppressed the iNOS protein and gene expression in a dose-dependent manner. These results suggest that Actinodaphne lancifolia could be a potential candidate for developing an iNOS inhibitor from natural products. Further elucidation of active principles for development of new cancer chemopreventive and/or anti-inflammatory agents could be warranted.     

Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells

The inhibitors of prostaglandin biosynthesis and nitric oxide production have been considered as potential anti-inflammatory and cancer chemopreventive agents. In this study, we evaluated approximately 170 methanol extracts of natural products including Korean herbal medicines for the inhibition of prostaglandin E(2) production (for COX-2 inhibitors) and nitric oxide formation (for iNOS inhibitors) in lipopolysaccharide (LPS)-induced mouse macrophages RAW264.7 cells. As a result, several extracts such as Aristolochia debilis, Cinnamomum cassia, Cinnamomum loureirii, Curcuma zedoaria, Eugenia caryophyllata, Pterocarpus santalius, Rehmania glutinosa and Tribulus terrestris showed potent inhibition of COX-2 activity (>80% inhibition at the test concentration of 10 micro g/ml). In addition, the extracts of A. debilis, Caesalpinia sappan, Curcuma longa, C. zedoaria, Daphne genkwa and Morus alba were also considered as potential inhibitors of iNOS activity (>70% inhibition at the test concentration of 10 micro g/ml). These active extracts mediating COX-2 and iNOS inhibitory activities are warranted for further elucidation of active principles for development of new cancer chemopreventive and/or anti-inflammatory agents.     

Long-term outcome in patients with obscure gastrointestinal bleeding after negative capsule endoscopy

AIM:To investigate long-term outcome in obscure gastrointestinal bleeding(OGIB) after negative capsule endoscopy(CE) and identify risk factors for rebleeding.METHODS:A total of 113 consecutive patients underwent CE for OGIB from May 2003 to June 2010 at Seoul National University Hospital.Ninety-five patients(84.1%) with a subsequent follow-up after CE of at least 6 mo were enrolled in this study.Follow-up data were obtained from the patients’ medical records.The CE images were reviewed by two board-certified gastroenterologists and consensus diagnosis was used in all cases.The primary outcome measure was the detection of rebleeding after CE,and factors associated with rebleeding were evaluated using multivariate analysis.RESULTS:Of the 95 enrolled patients(median age 61 years,range 17-85 years),62 patients(65.3%) were male.The median duration of follow-up was 23.7 mo(range 6.0-89.4 mo).Seventy-three patients(76.8%) underwent CE for obscure-overt bleeding.Complete examination of the small bowel was achieved in 77 cases(81.1%).Significant lesions were found in 38 patients(40.0%).The overall rebleeding rate was 28.4%.The rebleeding rate was higher in patients with positive CE(36.8%) than in those with negative CE(22.8%).However,there was no significant difference in cumulative rebleeding rates between the two groups(log rank test;P = 0.205).Anticoagulation after CE examination was an independent risk factor for rebleeding(hazard ratio,5.019;95%CI,1.560-16.145;P = 0.007),regardless of CE results.CONCLUSION:Patients with OGIB and negative CE have a potential risk of rebleeding.Therefore,close observation is required and alternative modalities should be considered in suspicious cases.