Gastric cancer is a disease with the second cancer-related mortality in the world. Helicobacter pylori infection that is one of major causes of gastric carcinogenesis induces a chronic inflammation in stomach. The epithelial-mesenchymal transition and/or the accumulation of genetic mutation occur during regenerating the injured gastric epithelial cells due to chronic inflammation by the infection of H. pylori. Normal gastric cells can be transformed into cancer stem cells by the epithelial-mesenchymal transition and/or the accumulation of genetic mutation that initiate the development of gastric cancer. Gastric epithelial cells, bone marrow-derived cells and gastric stem cells in gastric tissue might be the source of gastric cancer stem cells as the target cells that might be susceptible for epithelial-mesenchymal transition and/or the accumulation of genetic mutation. Normal stem cells in gastric tissue regenerating the injured gastric tissue also have the potential to be cancer stem cells known as the origin of cancer development when their ability for regulating differentiation and/or proliferation of normal stem cells is damaged by epithelial-mesenchymal transition and/or the accumulation of genetic mutation. Therefore if the mechanism regulating the transformation of normal stem cells to cancer stem cells is discovered, it might suggest the fundamental therapeutic strategy for preventing the development of gastric cancer by the chronic infection of H. pylori.
Carcinogenesis* ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Helicobacter pylori* ; Helicobacter* ; Inflammation ; Mortality ; Neoplastic Stem Cells ; Stem Cells* ; Stomach ; Stomach Neoplasms

Intracranial germ cell tumors (ICGCT) occur in 2-11% of children with brain tumors between 0-19 years of age. For treatment of germinoma, relatively low radiation doses with or without chemotherapy show excellent 10 year survival rate of 80-100%. Past studies showed that neoadjuvant chemotherapy combined with focal radiotherapy resulted in unacceptably high rates of periventricular tumor recurrence. The use of generous radiation volume which covers the whole ventricular space with later boost treatment to primary site is considered as standard treatment of intracranial germinomas. For non-germinomatous germ cell tumors (NGGCT), 10-year overall survival rate is still much inferior than that of intracranial germinoma despite intensive chemotherapy and high-dose radiotherapy. Craniospinal radiotherapy combined with cisplatin-based chemotherapy provides the best treatment outcome for NGGCT; 60-70% of overall survival rate. There is a debate on the surgical role whether surgery can contribute to improved treatment outcome of NGGCT when added to combined chemoradiotherapy. Because higher dose of radiotherapy is required for treatment of NGGCT than for germinoma, it is tested whether whole ventricular irradiation can replace craniospinal irradiation in intermediate risk group of NGGCT to minimize radiation-related late toxicity in the recent studies. To minimize the treatment-related neural deficit and late sequelae while maintaining long-term survival rate of ICGCT patients, optimized administration of chemotherapy and radiotherapy should be selected. Use of technically upgraded radiotherapy modalities such as intensity-modulated radiotherapy or proton beam therapy is expected to bring an improved neurocognitive outcome with longitudinal assessment of the patients.
Biology ; Brain Neoplasms ; Chemoradiotherapy ; Child ; Craniospinal Irradiation ; Drug Therapy ; Germinoma ; Humans ; Neoplasms, Germ Cell and Embryonal* ; Proton Therapy ; Radiotherapy* ; Radiotherapy, Intensity-Modulated ; Recurrence ; Survival Rate ; Treatment Outcome

Background: and Purpose: To identify biomarkers for prediction of the progression to dementia in mild cognitive impairment (MCI) patients, evaluation of brain structure changes has been validated by a comprehensive visual grading scale (CVRS) through magnetic resonance imaging (MRI). In this study, we specifically elucidated for the cognitive change of MCI patients classified based on AT(N) pathological status classification during the follow-up period of 3 years through the CVRS. Methods: The 301 patients with initial MCI visited at least once for follow-up period. The data used in this study were obtained from the Alzheimer's disease (AD) Neuroimaging Initiative study. Brain atrophy was assessed by CVRS using MRI. AT(N) profiles were classified by cerebrospinal fluid abnormality. Based on the AT(N) assessment, all individuals in this study were divided into 3 groups (normal state biomarker, suspected non-Alzheimer's pathology [SNAP], or Alzheimer's continuum). The cox regression was used to analyze the hazard ratios of CVRS for progression to dementia. Results: Sixty-three progressed and 238 remained stable to dementia and the CVRS (mean±standard deviation) had significant difference between progressive MCI and stable MCI (p<0.001). Univariate and multivariate cox regression results (p<0.001) showed the independence of initial CVRS as a predictor for the progression to dementia. Moreover, comparing the classified AT(N) pathology group, SNAP and AD, effectiveness of CVRS as a predictor was verified only in Alzheimer's continuum. Conclusions The initial CVRS score as a predictor of dementia progression was independently validated at the stage of Alzheimer's progression among AT(N) pathologically differentiated MCI.

PURPOSE: To evaluate the efficacy of catheter-directed thrombolysis in treating symptomatic deep venous thrombosis (DVT) in lower limbs. METHODS: Between Jan. 1999 and Dec. 2002, 29 consecutive patients with DVT had received thrombolytic therapy. The male: female ratio was 6: 23 and the mean age was 50.3+/-13.5 years. The mean duration of symptom was 9.9+/-22.1 days. Catheter-directed infusions of urokinase were administrated via ipsilateral popliteal veins and the angioplasty and stent placement performed after the thrombolytic procedure. The mean dosage of urokinase and duration of thrombolysis were 2, 435, 000+/-887, 000 units and mean duration of thrombolysis was 36.8+/-17.9 hours. Oral medication of warfarin continued at least six months or more. To evaluate the venous patency, duplex ultrasonography or CT venography were performed. RESULTS: Lysis was complete in 17 patients (58.6%, all acute DVT), partial in 11 (37.9%), with only one patient failing. Iliac vein stenosis had shown in 16 patient after thrombdysis. Which were treated with balloon angioplasty and stent insertion. As a postprocedural complication, vaginal bleeding occurred in two patients; one was treated with transfusion but the other stopped without treatment. CONCLUSION: Catheter-directed thrombolysis with urokinase is effective for the treatment of DVT in lower limbs. However further study will be reguired to evaluate the relationship between the incidence of postthrombotic syndrome and thrombolytic therapy alone.
Angioplasty ; Angioplasty, Balloon ; Constriction, Pathologic ; Female ; Humans ; Iliac Vein ; Incidence ; Lower Extremity ; Male ; Phlebography ; Popliteal Vein ; Postthrombotic Syndrome ; Stents ; Thrombolytic Therapy ; Ultrasonography ; Urokinase-Type Plasminogen Activator* ; Uterine Hemorrhage ; Venous Thrombosis* ; Warfarin

PURPOSE: Popliteal artery entrapment syndrome (PAES) is rare but major cause of non-atheromatous popliteal arterial insufficiency in young. Because of its rareness, it is often neglected or misdiagnosed as thrombosis or embolism. Consequently surgeons would lose the appropriate time of treatment. METHOD: We reviewed 11 cases of PAES from 1994 to 2002 regarding to clinical characteristics, image findings, management and their results. RESULT: Two of 11 patients had bilateral involvement. All patients were male and aged 12 to 45 year old (mean; 32.1). Intermittent claudication was presented as initial symptom in all. One had toe gangrene. Conventional arteriography (11 cases) was used as initial diagnostic method. CT (7 cases) and MR (4 cases) angiography were also used to make diagnosis. Type II PAES were most common in 7 limbs. 11 limbs of 10 patients underwent operation. One was managed conservatively because of advanced liver cirrhosis. Resection of medial head of gastrocnemius and popliteal arterial bypass were performed in 7 limbs. One myectomy with femoroposterotibial bypass, one femoropopliteal bypass without myectomy, and myectomy with patch angioplasty were performed. Postoperative complication occurred in two limbs. One had occlusion of graft, another had occluded segment of endarterectomised popliteal artery. Primary graft patency at 6 mo, 1 yr and 3 yr were 81% 81%, 81% respectively. CONCLUSION: In young patients with claudication who have localized lesion at popliteal artery, clinicians should pay attention to rule out PAES. Accurate diagnosis can be achieved by CT or MR angiography. Early surgical correction is recommended to minimize surgical procedure and reduce complication of the disease.
Angiography ; Angioplasty ; Diagnosis ; Embolism ; Extremities ; Gangrene ; Head ; Humans ; Intermittent Claudication ; Liver Cirrhosis ; Male ; Middle Aged ; Popliteal Artery* ; Postoperative Complications ; Thrombosis ; Toes ; Transplants

Purpose: The starting time for probiotic supplementation in preterm infants after birth varies widely. This study aimed to investigate the optimal time for initiating probiotics to reduce adverse outcomes in preterm or very low birth weight (VLBW) infants. Methods: Medical records of preterm infants born at a gestational age (GA) of <32 weeks or VLBW infants in 2011–2020 were reviewed respectively. The infants who received Saccharomyces boulardii probiotics within 7 days of birth were grouped into an early introduction (EI) group, and those who received supplemented probiotics after 7 days of birth were part of the late introduction (LI) group. Clinical characteristics were compared between the two groups and analyzed statistically. Results: A total of 370 infants were included. The mean GA (29.1 weeks vs. 31.2 weeks, p<0.001) and birth weight (1,235.9 g vs. 1491.4 g, p<0.001) were lower in the LI group (n=223) than in the EI group. The multivariate analysis indicated that factors affecting the LI of probiotics were GA at birth (odds ratio [OR], 1.52; p<0.001) and the enteral nutrition start day (OR, 1.47; p<0.001). The late probiotic introduction was associated with a risk of late-onset sepsis (OR, 2.85; p=0.020), delayed full enteral nutrition (OR, 5.44; p<0.001), and extrauterine growth restriction (OR, 1.67; p=0.033) on multivariate analyses after adjusting for GA. Conclusion Early supplementation of probiotics within a week after birth may reduce adverse outcomes among preterm or VLBW infants.

Suicide is a tragedy that has massive impact on society. In order to prevent suicide, active government intervention is necessary. The suicide rate in Seoul is rapidly increasing and is more than five times higher than that in the state of Massachusetts (MA) during the last decade, especially in the elderly. The suicide prevention program of MA is one of the most effective suicide prevention programs in the United States. The program views suicide as a preventable public health problem, and emphasizes treatment of depression and de-stigmatization of mental health illnesses to prevent suicide. Also, through active collaboration with mental health professionals, they try to identify at-risk populations and help them to get medical interventions. The program also actively collaborates with the regional coalition program and the Samaritans in taking care of the elderly, and supports the elderly in feeling worthwhile after retirement by helping them to work for communities as volunteers. For its part, the Seoul suicide prevention program puts more emphasis on "life respect culture" and "emotional support to high risk individuals by regular visiting". The annual budget of the Seoul suicide prevention program is one-quarter and that for mental health is about one-twentieth that of MA. Considering the high suicide rate and lower mental health service usage in Seoul, it is crucial to raise awareness of depression and decrease the stigma on mental illnesses. Furthermore, educational efforts with long-term investment in research on suicide are necessary.
Aged ; Budgets ; Cooperative Behavior ; Depression ; Humans ; Investments ; Massachusetts* ; Mental Health ; Mental Health Services ; Public Health ; Retirement ; Seoul ; Suicide* ; United States* ; Volunteers

Background: Microvascular ultrasonography (MVUS) is a third-generation Doppler technique that was developed to increase sensitivity compared to conventional Doppler. The purpose of this study was to compare MVUS with conventional color Doppler (CD) and power Doppler (PD) imaging to distinguish Graves’ disease (GD) from destructive thyroiditis (DT). Methods: This prospective study included 101 subjects (46 GDs, 47 DTs, and eight normal controls) from October 2020 to November 2021. All ultrasonography examinations were performed using microvascular flow technology (MV-Flow). The CD, PD, and MVUS images were semi-quantitatively graded according to blood flow patterns. On the MVUS images, vascularity indices (VIs), which were the ratio (%) of color pixels in the total grayscale pixels in a defined region of interest, were obtained automatically. Receiver operating characteristic curve analysis was performed to verify the diagnostic performance of MVUS. The interclass correlation coefficient and Cohen’s kappa analysis were used to analyze the reliability of MVUS (ClinicalTrials.gov:NCT04879173). Results: The area under the curve (AUC) for CD, PD, MVUS, and MVUS-VI was 0.822, 0.844, 0.808, and 0.852 respectively. The optimal cutoff value of the MVUS-VI was 24.95% for distinguishing GD and DT with 87% sensitivity and 80.9% specificity. We found a significant positive correlation of MVUS-VI with thyrotropin receptor antibody (r=0.554) and with thyroid stimulating immunoglobulin bioassay (r=0.841). MVUS showed high intra- and inter-observer reliability from various statistical method. Conclusion In a real time and quantitative manner, MVUS-VI could be helpful to differentiate GD from thyroiditis in thyrotoxic patients, with less inter-observer variability.

Background: The prevalence of young-onset diabetes (YOD) has been increasing worldwide. As the incidence of YOD increases, it is necessary to determine the characteristics of YOD and the factors that influence its development and associated complications. Methods: In this retrospective study, we recruited patients who were diagnosed with type 2 diabetes mellitus between June 2001 and December 2021 at a tertiary hospital. The study population was categorized according to age: YOD (age <40 years), middle-age-onset diabetes (MOD, 40≤ age <65 years), and late-onset diabetes (LOD, age ≥65 years). We examined trends in glycemic control by analyzing fasting glucose levels during the first year in each age group. A Cox proportional-hazards model was used to determine the relative risk of developing complications according to glycemic control trends. Results: The fasting glucose level at the time of diagnosis was highest in the YOD group (YOD 149±65 mg/dL; MOD 143±54 mg/dL; and LOD 140±55 mg/dL; p=0.009). In the YOD group, glucose levels decreased at 3 months, but increased by 12 months. YOD patients and those with poor glycemic control in the first year were at a higher risk of developing complications, whereas the risk in patients with LOD was not statistically significant. Conclusion YOD patients had higher glucose levels at diagnosis, and their glycemic control was poorly maintained. As poor glycemic control can influence the development of complications, especially in young patients, intensive treatment is necessary for patients with YOD.

Economic evaluations in the healthcare are used to assess economic efficiency of pharmaceuticals and medical interventions such as diagnoses and medical procedures. This study introduces the main concepts of economic evaluation across its key steps: planning, outcome and cost calculation, modeling, cost-effectiveness results, uncertainty analysis, and decision-making. When planning an economic evaluation, we determine the study population, intervention, comparators, perspectives, time horizon, discount rates, and type of economic evaluation. In healthcare economic evaluations, outcomes include changes in mortality, the survival rate, life years, and quality-adjusted life years, while costs include medical, non-medical, and productivity costs. Model-based economic evaluations, including decision tree and Markov models, are mainly used to calculate the total costs and total effects. In cost-effectiveness or costutility analyses, cost-effectiveness is evaluated using the incremental cost-effectiveness ratio, which is the additional cost per one additional unit of effectiveness gained by an intervention compared with a comparator. All outcomes have uncertainties owing to limited evidence, diverse methodologies, and unexplained variation. Thus, researchers should review these uncertainties and confirm their robustness. We hope to contribute to the establishment and dissemination of economic evaluation methodologies that reflect Korean clinical and research environment and ultimately improve the rationality of healthcare policies.