Seokyung Hahn

Evaluation of the Seventh American Joint Committee on Cancer/International Union Against Cancer Classification of gastric adenocarcinoma in comparison with the sixth classification

The seventh TNM staging system for gastric cancer of the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) had a more detailed classification than the sixth TNM staging system for both the tumor (T) and lymph nodes (N). The authors compared survival rates assessed by the seventh staging system with those by the sixth system.

Adequacy and reporting of allocation concealment: review of recent trials published in four general medical journals

In randomised controlled trials, allocation concealment (separating the process of randomisation from the recruitment of participants) is important for rigorously designed trials.1–4 In 1996 many major medical journals adopted the CONSORT statement (whereby researchers have to include a short checklist of essential items and a flow diagram when reporting trials),5 and this move encouraged the reporting of allocation concealment. We reviewed the prevalence of adequate allocation concealment and its association with the statistical significance of trial results. We searched by hand four general medical journals (the BMJ, JAMA , the Lancet , and the New England Journal of Medicine ) to identify randomised controlled trials published from January 2002 to December 2002. We included articles if the authors reported that participants were randomised and if the trial was published as a full report with the results of the main analyses. We categorised articles according to whether allocation concealment was adequate (the person who executed the allocation sequence was different from the person who recruited …

Reduced osmolarity oral rehydration solution for treating dehydration due to diarrhoea in children: systematic review

Abstract Objectives: To compare reduced osmolarity oral rehydration solution with standard World Health Organization oral rehydration solution in children with acute diarrhoea. Design: Systematic review of randomised controlled trials. Studies: 15 randomised controlled trials including 2397 randomised patients. Outcomes: The primary outcome was unscheduled intravenous infusion; secondary outcomes were stool output, vomiting, and hyponatraemia. Results: In a meta-analysis of nine trials for the primary outcome, reduced osmolarity rehydration solution was associated with fewer unscheduled intravenous infusions compared with standard WHO rehydration solution (odds ratio 0.61, 95% confidence interval 0.47 to 0.81). Three trials reported that no patients required unscheduled intravenous infusion. Trials reporting secondary outcomes suggested that in the reduced osmolarity rehydration solution group, stool output was lower (standardised mean difference in the log scale −0.214 (95% confidence interval −0.305 to −0.123; 13 trials) and vomiting was less frequent (odds ratio 0.71, 0.55 to 0.92; six trials). Six trials sought presence of hyponatraemia, with events in three studies, but no significant difference between the two arms. Conclusion: In children admitted to hospital with dehydration associated with diarrhoea, reduced osmolarity rehydration solution is associated with reduced need for unscheduled intravenous infusions, lower stool volume, and less vomiting compared with standard WHO rehydration solution. What is already known on this topic Oral rehydration solution prevents death from diarrhoea in many developing countries What this study adds Children receiving a reduced osmolarity rehydration solution were less likely to need intravenous infusion than those receiving WHO rehydration solution Reduced osmolarity rehydration solution also reduced stool output and vomiting No difference was found in rates of hyponatraemia

Determinants of Surgical Outcome in Patients With Isolated Tricuspid Regurgitation

Background— We sought to identify preoperative predictors of clinical outcomes after surgery in patients with severe tricuspid regurgitation. Methods and Results— We prospectively enrolled 61 consecutive patients (54 women, aged 57±9 years) with isolated severe tricuspid regurgitation undergoing corrective surgery. Twenty-one patients (34%) were in New York Heart Association functional class II, 35 (57%) in class III, and 5 (9%) in class IV. Fifty-seven patients (93%) had previous history of left-sided valve surgery. Preoperative echocardiography revealed pulmonary artery systolic pressure of 41.5±8.7 mm Hg, right ventricular (RV) end-diastolic area of 35.1±9.0 cm2, and RV fractional area change of 41.3±8.4%. The median follow-up duration after surgery was 32 months (range, 12 to 70). Six of the 61 patients died before discharge; thus, operative mortality was 10%. Three of the 55 patients who survived surgery died during follow-up, and 6 patients required readmission because of cardiovascular problems. Thus, 46 patients (75%) remained event free at the end of follow-up. In the 54 patients who underwent 6-month clinical and echocardiographic follow-up, RV end-diastolic area decreased by 29%, with a corresponding 26% reduction in RV fractional area change. Thirty-three patients (61%) showed improved functional capacity after surgery. On multivariable Cox regression analysis, preoperative hemoglobin level (P<0.001) and RV end-systolic area (P<0.001) emerged as independent determinants of clinical outcomes. On receiver operating characteristic curve analysis, we found that RV end-systolic area <20 cm2 predicted event-free survival with a sensitivity of 73% and a specificity of 67%, and a hemoglobin level >11.3 g/dL predicted event-free survival with a sensitivity of 73% and a specificity of 83%. Conclusions— Timely correction of severe tricuspid regurgitation carries an acceptable risk and improves functional capacity. Surgery should be considered before the development of advanced RV systolic dysfunction and before the development of anemia.

Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial

BACKGROUND Chemotherapy is the standard of care for incurable advanced gastric cancer. Whether the addition of gastrectomy to chemotherapy improves survival for patients with advanced gastric cancer with a single non-curable factor remains controversial. We aimed to investigate the superiority of gastrectomy followed by chemotherapy versus chemotherapy alone with respect to overall survival in these patients. METHODS We did an open-label, randomised, phase 3 trial at 44 centres or hospitals in Japan, South Korea, and Singapore. Patients aged 20-75 years with advanced gastric cancer with a single non-curable factor confined to either the liver (H1), peritoneum (P1), or para-aortic lymph nodes (16a1/b2) were randomly assigned (1:1) in each country to chemotherapy alone or gastrectomy followed by chemotherapy by a minimisation method with biased-coin assignment to balance the groups according to institution, clinical nodal status, and non-curable factor. Patients, treating physicians, and individuals who assessed outcomes and analysed data were not masked to treatment assignment. Chemotherapy consisted of oral S-1 80 mg/m(2) per day on days 1-21 and cisplatin 60 mg/m(2) on day 8 of every 5-week cycle. Gastrectomy was restricted to D1 lymphadenectomy without any resection of metastatic lesions. The primary endpoint was overall survival, analysed by intention to treat. This study is registered with UMIN-CTR, number UMIN000001012. FINDINGS Between Feb 4, 2008, and Sept 17, 2013, 175 patients were randomly assigned to chemotherapy alone (86 patients) or gastrectomy followed by chemotherapy (89 patients). After the first interim analysis on Sept 14, 2013, the predictive probability of overall survival being significantly higher in the gastrectomy plus chemotherapy group than in the chemotherapy alone group at the final analysis was only 13·2%, so the study was closed on the basis of futility. Overall survival at 2 years for all randomly assigned patients was 31·7% (95% CI 21·7-42·2) for patients assigned to chemotherapy alone compared with 25·1% (16·2-34·9) for those assigned to gastrectomy plus chemotherapy. Median overall survival was 16·6 months (95% CI 13·7-19·8) for patients assigned to chemotherapy alone and 14·3 months (11·8-16·3) for those assigned to gastrectomy plus chemotherapy (hazard ratio 1·09, 95% CI 0·78-1·52; one-sided p=0·70). The incidence of the following grade 3 or 4 chemotherapy-associated adverse events was higher in patients assigned to gastrectomy plus chemotherapy than in those assigned to chemotherapy alone: leucopenia (14 patients [18%] vs two [3%]), anorexia (22 [29%] vs nine [12%]), nausea (11 [15%] vs four [5%]), and hyponatraemia (seven [9%] vs four [5%]). One treatment-related death occurred in a patient assigned to chemotherapy alone (sudden cardiopulmonary arrest of unknown cause during the second cycle of chemotherapy) and one occurred in a patient assigned to chemotherapy plus gastrectomy (rapid growth of peritoneal metastasis after discharge 12 days after surgery). INTERPRETATION Since gastrectomy followed by chemotherapy did not show any survival benefit compared with chemotherapy alone in advanced gastric cancer with a single non-curable factor, gastrectomy cannot be justified for treatment of patients with these tumours. FUNDING The Ministry of Health, Labour and Welfare of Japan and the Korean Gastric Cancer Association.

Assessing the potential for bias in meta‐analysis due to selective reporting of subgroup analyses within studies

Subgroup analysis is frequently used to investigate heterogeneity in meta-analysis. Subgroup data are not always available, and researchers should record what data were available for each trial. If data were not available, and it is known that the subgroup data were collected, the potential for selective reporting should be considered. Bias due to selective publishing of reports is widely recognized in meta-analysis. In contrast, selective reporting within studies is little discussed but potentially important. We explored this problem by evaluating the effect of potential bias in subgroup analysis due to within-study selective reporting with an existing meta-analysis. The review addressed malaria chemoprophylaxis in pregnancy. The conclusion in the original review, that benefit is limited to primigravidae, was based on subgroup analysis using the three trials out of five which reported on subgroups. We developed a method of sensitivity analysis that imputes data for the missing subgroups to assess the robustness of the results and the conclusions drawn. In this particular example, our analysis indicates that the estimate of effect reported in the review is most likely to overestimate the true effect and the conclusion that benefit is limited to primigravidae may be false.

Epidermal growth factor receptor tyrosine kinase inhibitors vs conventional chemotherapy in non-small cell lung cancer harboring wild-type epidermal growth factor receptor: a meta- analysis

IMPORTANCE Current guidelines recommend both epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and cytotoxic chemotherapy drugs as standard treatment options for patients with wild-type (WT) EGFR who were previously treated for non-small cell lung cancer (NSCLC). However, it is not clear that EGFR TKIs are as efficacious as chemotherapy in patients with WT EGFR. OBJECTIVE To determine the association between first-generation EGFR TKI vs chemotherapy and survival in advanced NSCLC patients with WT EGFR. DATA SOURCES PubMed, EMBASE, Cochrane database, and meeting abstracts of the American Society of Clinical Oncology and European Society of Medical Oncology through December 2013. STUDY SELECTION Eligible studies were randomized controlled trials comparing EGFR TKI with conventional chemotherapy in patients with advanced NSCLC. Out of 1947 retrieved articles, 11 trials incorporating 1605 patients with WT EGFR were included. DATA EXTRACTION AND SYNTHESIS Two reviewers extracted trial characteristics and outcomes. The risk of bias was evaluated using the Cochrane tool. All measures were pooled using random-effects models and 95% CIs were calculated. MAIN OUTCOMES AND MEASURES The primary outcome was progression-free survival (PFS), measured as hazard ratios (HRs). The secondary outcomes were objective response rate and overall survival, expressed as relative risks and HRs, respectively. RESULTS Among patients with WT EGFR tumors, chemotherapy was associated with improvement of PFS, compared with TKI (HR for TKI, 1.41; 95% CI, 1.10-1.81). No statistically significant subgroup difference was identified in terms of line of treatment (first-line vs second- or later-line), experimental drug, dominant ethnicity, or EGFR mutation analysis method. Trials using more sensitive platforms than direct sequencing were associated with a significant PFS benefit with chemotherapy (HR for TKI, 1.84; 95% CI, 1.35-2.52). The association of chemotherapy with improvement in PFS was also significant in second- or later-line trials (HR, 1.34; 95% CI, 1.09-1.65). The objective response rate was higher with chemotherapy (92/549, 16.8%, vs 39/540, 7.2%, for TKI; relative risk for TKI, 1.11; 95% CI, 1.02-1.21); however, no statistically significant difference was observed with respect to overall survival (HR for TKI, 1.08; 95% CI, 0.96-1.22). CONCLUSIONS AND RELEVANCE Among patients with advanced NSCLC harboring WT EGFR, conventional chemotherapy, compared with first-generation EGFR TKI, was associated with improvement in PFS but not overall survival.

Differences in the HbA1c‐lowering efficacy of glucagon‐like peptide‐1 analogues between Asians and non‐Asians: a systematic review and meta‐analysis

To compare the HbA1c‐lowering efficacy of glucagon‐like peptide‐1 (GLP‐1) analogues between Asians and non‐Asians with type 2 diabetes.

Safety and efficacy of everolimus-versus sirolimus-eluting stents: a systematic review and meta-analysis of 11 randomized trials

BACKGROUND While EES have proven superior to paclitaxel-eluting stents, it remains uncertain whether EES improve clinical outcomes compared to SES, which are the most efficacious among the first-generation drug-eluting stents. We performed a meta-analysis of randomized trials comparing the efficacy and safety of everolimus-eluting stents (EES) versus sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary intervention. METHODS From online and offline search until December 2011, we identified 11 randomized trials (total 12,869 patients). The primary endpoint was major adverse cardiac events. RESULTS The risk of major adverse cardiac events did not differ significantly between the patients treated with EES versus SES [OR, 0.90 (95% CI, 0.77-1.04); P = .162]. However, we found a significant reduction in the risk of repeat revascularization in the EES arm [OR, 0.85 (95% CI, 0.71-1.00); P = .047]. There were no significant differences regarding the risk of cardiac death [OR, 0.97 (95% CI, 0.74-1.27); P = .834], or myocardial infarction [OR, 0.95 (95% CI, 0.75-1.20), P = .656]. The risk of definite or probable stent thrombosis tended to be lower [OR, 0.68 (95% CI, 0.45-1.02); P = .065], while definite ST was significantly lower [OR, 0.44 (95% CI, 0.25-0.80); P = .007] with EES. CONCLUSIONS In a large systematic overview of comparative trials involving percutaneous revascularization with drug-eluting stents, treatment with EES significantly reduced the risk of repeat revascularization and definite ST compared to SES. We found no significant differences in the risk of cardiac death or myocardial infarction.

Irreversible JPEG 2000 compression of abdominal CT for primary interpretation: assessment of visually lossless threshold

To estimate the visually lossless threshold for Joint Photographic Experts Group (JPEG) 2000 compression of contrast-enhanced abdominal computed tomography (CT) images, 100 images were compressed to four different levels: a reversible (as negative control) and irreversible 5:1, 10:1, and 15:1. By alternately displaying the original and the compressed image on the same monitor, six radiologists independently determined if the compressed image was distinguishable from the original image. For each reader, we compared the proportion of the compressed images being rated distinguishable from the original images between the reversible compression and each of the three irreversible compressions using the exact test for paired proportions. For each reader, the proportion was not significantly different between the reversible (0–1%, 0/100 to 1/100) and irreversible 5:1 compression (0–3%). However, the proportion significantly increased with the irreversible 10:1 (95–99%) and 15:1 compressions (100%) versus reversible compression in all readers (P < 0.001); 100 and 95% of the 5:1 compressed images were rated indistinguishable from the original images by at least five of the six readers and all readers, respectively. Irreversibly 5:1 compressed abdominal CT images are visually lossless and, therefore, potentially acceptable for primary interpretation.