PURPOSE: Clinical implications of single patient classifier (SPC) and microsatellite instability (MSI) in stage II/III gastric cancer have been reported. We investigated SPC and the status of MSI and Epstein-Barr virus (EBV) as combinatory biomarkers to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer. MATERIALS AND METHODS: Tumor specimens and clinical information were collected from patients enrolled in CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy. The results of nine-gene based SPC assay were classified as prognostication (SPC-prognosis) and prediction of chemotherapy benefit (SPC-prediction). Five quasimonomorphic mononucleotide markers were used to assess tumor MSI status. EBV-encoded small RNA in situ hybridization was performed to define EBV status. RESULTS: There were positive associations among SPC, MSI, and EBV statuses among 586 patients. In multivariate analysis of disease-free survival, SPC-prognosis [hazard ratio (HR): 1.879 (1.101–3.205), 2.399 (1.415–4.067), p=0.003] and MSI status (HR: 0.363, 95% confidence interval: 0.161–0.820, p=0.015) were independent prognostic factors along with age, Lauren classification, TNM stage, and chemotherapy. Patient survival of SPC-prognosis was well stratified regardless of EBV status and in microsatellite stable (MSS) group, but not in MSI-high group. Significant survival benefit from adjuvant chemotherapy was observed by SPC-Prediction in MSS and EBV-negative gastric cancer. CONCLUSION: SPC, MSI, and EBV statuses could be used in combination to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.
Biomarkers ; Capecitabine ; Chemotherapy, Adjuvant ; Classification ; Disease-Free Survival ; Drug Therapy ; Herpesvirus 4, Human ; Humans ; In Situ Hybridization ; Microsatellite Instability ; Microsatellite Repeats ; Multivariate Analysis ; Prognosis ; RNA ; Stomach Neoplasms

PURPOSE: The modification of the cancer classification system aimed to improve the classical anatomy-based tumor, node, metastasis (TNM) staging by considering tumor biology, which is associated with patient prognosis, because such information provides additional precision and flexibility. MATERIALS AND METHODS: We previously developed an mRNA expression-based single patient classifier (SPC) algorithm that could predict the prognosis of patients with stage II/III gastric cancer. We also validated its utilization in clinical settings. The prognostic single patient classifier (pSPC) differentiates based on 3 prognostic groups (low-, intermediate-, and high-risk), and these groups were considered as independent prognostic factors along with TNM stages. We evaluated whether the modified TNM staging system based on the pSPC has a better prognostic performance than the TNM 8th edition staging system. The data of 652 patients who underwent gastrectomy with curative intent for gastric cancer between 2000 and 2004 were evaluated. Furthermore, 2 other cohorts (n=307 and 625) from a previous study were assessed. Thus, 1,584 patients were included in the analysis. To modify the TNM staging system, one-grade down-staging was applied to low-risk patients according to the pSPC in the TNM 8th edition staging system; for intermediate- and high-risk groups, the modified TNM and TNM 8th edition staging systems were identical. RESULTS: Among the 1,584 patients, 187 (11.8%), 664 (41.9%), and 733 (46.3%) were classified into the low-, intermediate-, and high-risk groups, respectively, according to the pSPC. pSPC prognoses and survival curves of the overall population were well stratified, and the TNM stage-adjusted hazard ratios of the intermediate- and high-risk groups were 1.96 (95% confidence interval [CI], 1.41–2.72; P < 0.001) and 2.54 (95% CI, 1.84–3.50; P < 0.001), respectively. Using Harrell's C-index, the prognostic performance of the modified TNM system was evaluated, and the results showed that its prognostic performance was better than that of the TNM 8th edition staging system in terms of overall survival (0.635 vs. 0.620, P < 0.001). CONCLUSIONS: The pSPC-modified TNM staging is an alternative staging system for stage II/III gastric cancer.
Biology ; Classification ; Cohort Studies ; Gastrectomy ; Humans ; Neoplasm Metastasis ; Neoplasm Staging* ; Pliability ; Prognosis ; RNA, Messenger ; Stomach Neoplasms*

OBJECTIVE: To prospectively evaluate the performance of diffusion-weighted imaging (DWI) to monitor bowel inflammation after medical therapy for Crohn's disease (CD). MATERIALS AND METHODS: Before and following 1–2 years of medical therapy, between October 2012 and May 2015, 18 randomly selected adult CD patients (male:female, 13:5; mean age ± SD, 25.8 ± 7.9 years at the time of enrollment) prospectively underwent MR enterography (MRE) including DWI (b = 900 s/mm²) and ileocolonoscopy. Thirty-seven prospectively defined index lesions (one contiguous endoscopy-confirmed inflamed area chosen from each inflamed anatomical bowel segment; 1–4 index lesions per patient; median, 2 lesions) were assessed on pre- and post-treatment MRE and endoscopy. Visual assessment of treatment responses on DWI in 4 categories including complete remission and reduced, unchanged or increased inflammation, and measurements of changes in apparent diffusion coefficient (ΔADC), i.e., pre-treatment–post-treatment, were performed by 2 independent readers. Endoscopic findings and CD MRI activity index (CDMI) obtained using conventional MRE served as reference standards. RESULTS: ΔADC significantly differed between improved (i.e., complete remission and reduced inflammation) and unimproved (i.e., unchanged or increased inflammation) lesions: mean ± SD (× 10⁻³ mm²/s) of -0.65 ± 0.58 vs. 0.06 ± 0.15 for reader 1 (p = 0.022) and -0.68 ± 0.56 vs. 0.10 ± 0.26 for reader 2 (p = 0.025). DWI accuracy for diagnosing complete remission or improved inflammation ranged from 76% (28/37) to 84% (31/37). A significant negative correlation was noted between ΔADC and ΔCDMI for both readers with correlation coefficients of -0.438 and -0.461, respectively (p < 0.05). CONCLUSION: DWI is potentially a feasible tool to monitor quantitatively and qualitatively bowel inflammation of CD after medical treatment.
Adult ; Crohn Disease* ; Diffusion ; Endoscopy ; Follow-Up Studies ; Humans ; Inflammation* ; Longitudinal Studies* ; Magnetic Resonance Imaging ; Prospective Studies*

Chronic obstructive pulmonary disease (COPD) is a substantially under-diagnosed disorder, and the diagnosis is usually delayed until the disease is advanced. However, the benefit of early diagnosis is not yet clear, and there are no guidelines in Korea for doing early diagnosis. This review highlights several issues regarding early diagnosis of COPD. On the basis of several lines of evidence, early diagnosis seems quite necessary and beneficial to patients. Early diagnosis can be approached by several methods, but it should be confirmed by quality-controlled spirometry. Compared with its potential benefit, the adverse effects of spirometry or pharmacotherapy appear relatively small. Although it is difficult to evaluate the benefit of early diagnosis by well-designed trials, several lines of evidence suggest that we should try to diagnose and manage patients with COPD at early stages of the disease.
Early Diagnosis ; Humans ; Korea ; Pulmonary Disease, Chronic Obstructive ; Spirometry

Social welfare services for respiratory-disabled persons in Korea are offered based on the respiratory impairment grade, which is determined by 3 clinical parameters; dyspnea, forced expiratory volume in 1 second (FEV1), and arterial oxygen tension. This grading system has several limitations in the objective assessment of respiratory impairment. We reviewed several guidelines for the evaluation of respiratory impairment and relevant articles. Then, we discussed a new grading system with respiratory physicians. Both researchers and respiratory physicians agreed that pulmonary function tests are essential in assessing the severity of respiratory impairment, forced vital capacity (FVC), FEV1 and single breath diffusing capacity (DLco) are the primarily recommended tests. In addition, we agreed that arterial blood gas analysis should be reserved for selected patients. In conclusion, we propose a new respiratory impairment grading system utilizing a combination FVC, FEV1 and DLco scores, with more social discussion included.
Blood Gas Analysis ; Disability Evaluation ; Dyspnea ; Forced Expiratory Volume ; Humans ; Korea ; Oxygen ; Pulmonary Diffusing Capacity ; Respiratory Function Tests ; Respiratory System ; Social Welfare ; Spirometry ; Vital Capacity

PURPOSE: To evaluate the efficacy of photodynamic therapy (PDT) with verteporfin for polypoidal choroidal vasculopathy (PCV) in Korean patients. METHODS: Clinical data of patients who were treated with PDT for PCV and followed up for more than 6 months were collected from 14 hospitals around the country. The changes in the best corrected visual acuity, angiographic outcome, retinal thickness measured by optical coherence tomography (OCT), and adverse effects of treatment were evaluated. RESULTS: Eighty six patients (86 eyes) were recruited (male: 75.6%, age: 65.9+/-8.3 years, mean follow-up: 14.8+/-10.2 months). The mean logMAR visual acuity at baseline was 0.55+/-0.32 and did not show any statistically significant difference from the final mean logMAR visual acuity (0.53+/-0.54) (p=0.639). The mean treatment session number of PDT was 2+/-1.2. Visual acuity stabilized or improved in 70.9% of patients. Visual acuity improved by more than 2 lines in 33 eyes (38.4%) and worsened by more than 2 lines in 21 eyes (24.4%) of patients. Vascular leakage decreased in 62.5% of patients in fluorescein angiography and polypoidal lesions disappeared or were reduced in 57.3% of patients in indocyanine green angiography. There was no systemic adverse effect of PDT, but increased subretinal hemorrhage after PDT occurred in 10 eyes (11.6%). CONCLUSIONS: In polypoidal choroidal vasculopathy, photodynamic therapy with verteporfin is safe and effective for preserving visual acuity and reducing vascular leakage and retinal thickness.
Angiography ; Choroid ; Eye ; Fluorescein Angiography ; Hemorrhage ; Humans ; Indocyanine Green ; Photochemotherapy ; Porphyrins ; Retinaldehyde ; Retrospective Studies ; Tomography, Optical Coherence ; Triazenes ; Visual Acuity

BACKGROUND: A diagnosis of malignant pleural effusion is clinically important, as the prognosis of lung cancer patients with malignant pleural effusion is poor. The diagnosis will be difficult if a cytological test is negative. This study was performed to investigate whether the detection of hypermethylation of the p16 (CDKN2A) and retinoic acid receptor b2 (RARB2) genes in pleural fluid is useful for a diagnosis of malignant pleural effusion. METHODS: Pleural effusion was collected from 43 patients and was investigated for the aberrant promoter methylation of the RARB2 and CDKN2A genes by use of methylation-specific PCR. Results were compared with findings from a pleural biopsy and from pleural fluid cytology. RESULTS: Of 43 cases, 17 cases of pleural effusion were due to benign diseases, and 26 cases were from lung cancer patients with malignant pleural effusion. Hypermethylation of the RARB2 and CDKN2A genes was not detected in the case of benign diseases, independent of whether or not the patients had ever smoked. In 26 cases of malignant pleural effusion, hypermethylation of RARB2, CDKN2A or either of these genes was detected in 14, 5 and 15 cases, respectively. The sensitivities of a pleural biopsy, pleural fluid cytology, hypermethylation of RARB2, hypermethylation of CDKN2A, or hypermethylation of either of the genes were 73.1%, 53.8%, 53.8%, 19.2%, and 57.7%, respectively; negative predictive values were 70.8%, 58.6%, 58.6%, 44.7%, and 60.7%, respectively. If both genes are considered together, the sensitivity and negative predictive value was lower than that for a pleural biopsy, but higher than that for pleural fluid cytology. The sensitivity of hypermethylation of the RARB2 gene for malignant pleural effusion was lower in small cell lung cancers than in non-small cell lung cancers. CONCLUSION: These results demonstrate that detection of hypermethylation of the RARB2 and CDKN2A genes showed a high specificity, and sensitivity was higher than for pleural fluid cytology. With a better understanding of the pathogenesis of lung cancer according to histological types at the molecular level, and if appropriate genes are selected for hypermethylation testing, more precise results may be obtained.
Biopsy ; Genes, p16 ; Humans ; Lung Neoplasms ; Methylation ; Pleural Effusion ; Pleural Effusion, Malignant ; Polymerase Chain Reaction ; Prognosis ; Receptors, Retinoic Acid ; Smoke

PURPOSE: To investigate the effects of repeated photodynamic therapy (PDT) for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) in Korean patients. METHODS: Clinical data of patients who were treated with repeated (3 times or more) PDT for subfoveal choroidal neovascularization secondary to AMD and followed up for more than 6 months were collected from 17 hospitals around the country. Visual outcomes at 12 and 24 months, follow-up were compared between subtypes of choroidal neovascularization. The factors related to final visual prognosis and PDT-related adverse effects were evaluated. RESULTS: 244 patients (244 eyes) were recruited (male: 60%, age: 67.7+/-9.1 years). The portion of patients with predominantly classic, minimally classic, and occult without classic choroidal neovascularization was 57%, 13%, and 24%, respectively and that of patients with visual improvements or less than moderate visual loss at 24 months follow-up were 28%, 38%, 30% and 47%, 56%, and 65%, respectively. Baseline visual acuity and age were significantly related to the final visual prognosis (p<0.05). PDT-related adverse events developed in 15 (6.1%) patients, but most were mild and transient. CONCLUSIONS: Repeated PDT for subfoveal choroidal neovascularization secondary to AMD has effects comparable to those of previous prospective, controlled trials without any significant safety concerns in Korea.
Choroid* ; Choroidal Neovascularization* ; Follow-Up Studies ; Humans ; Korea ; Macular Degeneration* ; Photochemotherapy* ; Prognosis ; Visual Acuity

PURPOSE: This study was undertaken to evaluate the clinical results of pars plana vitrectomy on posterior segment complications in posterior uveitis. METHODS: We reviewed the records of 20 eyes of 19 uveitis patients who were followed up for 6 months or more after vitrectomy. RESULTS: The mean follow-up period was 20 months. Final visual acuity improved in 10 eyes (50%), was maintained in 6 (30%), and decreased in 4 (20%). The mean improvement of vision was 1.6 lines (p=0.019). Detached retina was reattached in 8 (80%) among the 10 eyes with primary surgery. Postoperative complications were cataract (7 eyes), macular degeneration (2 eyes), retinal detachment (2 eyes), and recurrence (1 eye). CONCLUSIONS: These results suggest that pars plana vitrectomy may be a safe and effective treatment for posterior segment complications in posterior uveitis, but that early and complete vitrectomy should be considered for a better visual prognosis.
Cataract ; Follow-Up Studies ; Humans ; Macular Degeneration ; Postoperative Complications ; Prognosis ; Recurrence ; Retina ; Retinal Detachment ; Uveitis ; Uveitis, Posterior* ; Visual Acuity ; Vitrectomy*

Cultures of primary human alveolar bone-derived cells were established from alveolar bone chips obtained from normal individuals undergoing tooth extraction. These cells were expanded in vitro until passage 3 and used for the in vivo assays. Cells were loaded into transplantation vehicles, and transplanted subcutaneously into immunodeficient mice to study the capacities of human alveolar bone-derived cells to form bone in vivo. Transplants were harvested 12 weeks after transplantation and evaluated histologically. Of 10 human alveolar bone-derived cell transplants, two formed a bone-like tissue that featured osteocytes and mineral. Eight of the ten formed no osseous tissue. These results show that cells from normal human alveolar bone are capable of forming bone-like tissue when transplanted into immunodeficient mice.
Animals ; Cell Culture Techniques ; Humans* ; Mice ; Osteocytes ; Osteogenesis* ; Tissue Engineering ; Tooth Extraction ; Transplants