Helicobacter pylori (H pylori) infection induces a chronic inflammatory response, which promotes gastric carcinogenesis. 15-hydroxyprostaglandin dehydrogenase (15–PGDH) plays a key role as a tumor suppressor in gastrointestinal cancers. The aim of this study was to elucidate the role of 15-PGDH in gastric carcinogenesis associated with H pylori. 15-PGDH expression in gastric biopsies from H pylori-infected (n=25) and non-infected (n=15) subjects was analyzed by quantitative real-time PCR, western blot analysis, and immunohistochemisty. 15-PGDH DNA methylation was evaluated by methylation specific PCR and pyrosequencing. The expression of 15-PGDH, Snail, ERK1/2, TLR4 and MyD88 in response to H pylori infection was assessed by immunoblot analysis. Compared to negative specimens, H pylori positive specimens had 2-fold lower 15-PGDH mRNA levels and significantly less 15-PGDH protein. In four H pylori infected subjects with longitudinal follow-up, the suppression of 15-PGDH expression was reversed by H pylori eradication therapy. In parallel with suppressing 15-PGDH expression, H pylori infection activated expression of TLR4 and MyD88 expression, increased levels of phospho-ERK1/2, and increased expression of epidermal growth factor receptor (EGFR)-Snail. Inhibition of Snail and MyD88 reversed suppression of 15-PGDH expression and small interfering Myd88 reduced phosphorylated ERK1/2. Similarly, treatment with an ERK1/2 and EGFR inhibitor also restored 15-PGDH expression. Heliocobacter pylori appeared to promote gastric carcinogenesis by suppressing15-PGDH. This process is mediated by the TLR4/MyD88 pathway via ERK1/2 or EGFR - Snail transcriptional regulation. 15-PGDH may be a useful marker and a potential therapeutic target in H pylori-induced gastric carcinogenesis.
Gastric cancer; Helicobacter pylori; 15-prostaglandin dehydrogenase
Endobronchial metastasis is defined as documented extrathoracic malignancies metastatic to the endobronchus within a bronchoscopically visible range. Although the clinical and radiologic findings of endobronchial metastasis are similar to primary lung cancer, treatment and prognosis may be different. We hereby investigated the clinical, radiologic and bronchoscopic aspects of endobronchial metastases (EBM) in Korean patients.
Materials and Methods
A total of 43 patients with EBM who underwent bronchoscopic biopsies from June 1991 to December 2009 at Severance Hospital, Yonsei University College of Medicine in Seoul, Korea, were analyzed retrospectively. We evaluated clinical, radiologic and bronchoscopic characteristics of EBM.
The patients consisted of 27 males and 16 females and their ages ranged from 18 to 77 years. The common primary cancers related to EBM were rectal (16.3%), colon (11.6%), breast (9.3%) and uterine (9.3%) cancers. The mean interval from diagnosis of primary cancer to EBM was 36 months, and the mean survival duration from diagnosis of EBM was 16.1 months in 33 deceased patients.
EBM develop in various types of malignancies at various times with unremarkable manifestations. Therefore, physicians should consider the possibility of EBM, especially if a patient has a history of any malignancy, regardless of respiratory symptoms. Respiratory symptoms related with EBM can be treated by various safe procedures.
Endobronchial; metastasis; bronchoscopy
Isolated pulmonary valve stenosis (PS) makes up 6-9% of all congenital heart defects among children. The initial gold standard for diagnosis, follow-up of PS is by echocardiography. However, the most accurate diagnosis still remains to be measurement of the pressure gradient through transcatheterization. The purpose of this study is to compare the difference between the echocardiographic data to the cardiac catheterization data on the diagnosis, treatment, and follow-up in patients diagnosed as PS, and to see what parameters should be closely monitored.
A total of 112 patients (Male : Female = 46 : 66) who underwent balloon pulmonary valvuloplasty (BPV) at Severance Cardiovascular Hospital, between December, 2002 to August, 2012 were retrospectively analyzed. The patients were all under 16 years of age and critical PS patients who underwent BPV were excluded from this study.
The pre-BPV right ventricle (RV)-pulmonary artery (PA) systolic pressure gradient and post-BPV systolic pressure gradient showed statistically significant decrease. The pre-BPV RV-PA systolic pressure gradient and 3 month post-BPV systolic pressure gradient showed statistically significant decrease. The consistency between the echocardiographic data and cardiac catheterization data shows statistically significant consistency. The mean pressure gradient and systolic pressure gradient on the echocardiography shows high consistency when comparing with the cardiac catheterization data.
Our study shows that BPV in PS is a safe and effective procedure in children and adolescent. The standard echocardiographic evaluation of PS, during diagnosis and follow-up, should include mean transpulmonic pressure gradient, as well as the peak systolic pressure gradient. The success of the procedure should be held off until at least 3 months, only if the patients do not show any symptoms.
Pulmonary valve stenosis; Percutaneous balloon pulmonary valvuloplasty; Echocardiography; Systolic pressure gradient; Mean transpulmonic pressure gradient
Patent foramen ovale (PFO) has been known to be the cause of transient ischemic attacks or stroke, and transcatheter device closure has been the treatment of choice for these defects. Combined defect of abnormal drainage of left superior vena cava (LSVC) to left superior pulmonary vein (LSPV) in PFO patients is an uncommon combination, and both can act as a pathway for paradoxical embolism. We report a successful closure of PFO, using Amplatzer® PFO occluder (St. Jude Medical, St. Paul, MN, USA) and persistent LSVC connected to LSPV using an Amplatzer® Vascular Plug II (St. Jude Medical, St. Paul, MN, USA). Because this combined anomaly of PFO and persistent LSVC can be treated by a single transcatheter intervention, if clinically suspected, a complete evaluation for this anomaly should be considered.
Patent foramen ovale; Persistent left superior vena cava; Transcatheter; Occluder; Vascular plug; Amplatzer®
A 66-year-old female presented with a 1-month history of dyspepsia. An initial upper gastrointestinal endoscopy with biopsy revealed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma. A rapid urease test was positive for Helicobacter pylori. Endoscopic ultrasound (EUS) and computed tomography (CT) revealed a 30×15-mm lymph node (LN) in the subcarinal area. Histopathologic and phenotypic analyses of the biopsy specimens obtained by EUS-guided fine-needle aspiration revealed a MALT lymphoma, and the patient was diagnosed with a stage 4E gastric MALT lymphoma. One year after H. pylori eradication, the lesion had disappeared, as demonstrated by endoscopy with biopsy, CT, fusion whole-body positron emission tomography, and EUS. Here, we describe a patient with gastric MALT lymphoma that metastasized to the mediastinal LN and regressed following H. pylori eradication.
Marginal zone B-cell lymphoma; Stomach
ALADIN gene has been known to cause achalasia, alacrima, adrenal abnormalities and a progressive neurological syndrome. A considerable proportion of achalasia patients has been known to show alacrima (decreased secretion of tear). However, the genetic mechanism between achalasia and alacrima has not been defined yet. We postulated that ALADIN gene may be involved in the occurrence of early-onset achalasia; thus, we investigated the correlation of ALADIN gene in early-onset achalasia patients.
From 1989 to 2007, patients who were diagnosed as primary achalasia before age 35 were enrolled. All of the enrolled patients were asked for (1) blood sampling for DNA, (2) Shirmer test and (3) dysphagia questionnaires.
The ALADIN gene in exon 1, 2, 10, 11 and 12 from 19 patients was investigated (M:F = 12:7). The mean age of patients at diagnosis was 27 ± 5 (15-35) years old. Eight out of 19 (42%) showed alacrima by the positive Shirmer test. In spite of thorough exam in the genetic study, there was no definite abnormal genetic finding in this study.
A considerable number of achalasia patients showed alacrima. Due to the limitation of this study, it is difficult to conclude that early-onset achalasia may have significant correlations with the ALADIN gene.
AAAS protein; Esophageal achalasia; Human; Shirmer test
Early tumor detection is crucial for the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging using a target-activatable probe may permit earlier disease detection. Matrix metalloproteinases (MMPs) participate in tumorigenesis and tumor growth. The aim of this study was to determine whether NIRF imaging using an MMP-activatable probe can detect colon tumors at early stages.
We utilized two murine colon cancer models: a sporadic colon cancer model induced by azoxymethane (AOM), and a colitis-associated cancer model induced by a combination of AOM and dextran sodium sulfate (DSS). Colonic lesions were analyzed by histologic examination, Western blotting, immunohistochemical staining, and NIRF imaging using an MMP-activatable probe.
Multiple variable-sized tumors developed in both models and progressed from adenomas to adenocarcinomas over time. At the early stage of the AOM/DSS model, diffuse inflammation was observed within the tumors. MMP expression increased progressively through normal, inflammation, adenoma, and adenocarcionoma stages. NIRF signal intensities were strongly correlated with each tumor stage from adenoma to adenocarcinoma. NIRF imaging also distinguished tumors from inflamed mucosa.
NIRF imaging using a protease-activatable probe may be a useful tool for early tumor detection. This approach could translate to improve the endoscopic detection of colon tumors, especially in patients with inflammatory bowel disease.
Colon cancer; Inflammatory bowel disease; Near-infrared fluorescence; Matrix metalloproteinases
Benign bronchoesophageal fistula (BEF) is a rare condition that is usually treated surgically; however, less invasive endoscopy procedures have been attempted to overcome the disadvantages of surgery. The aim of this study was thus to determine the results of endoscopic management as a primary treatment in patients with BEF.
We retrospectively analyzed data from 368 patients with BEF who were treated at a tertiary care, academic medical center between January 2000 and August 2009.
Benign causes were found for only 18 of the 368 patients. Of these, seven were treated endoscopically and the others by surgery or other methods. The first endoscopy procedures failed in all seven patients, with second trials of endoscopy performed in four patients at a median of 8 days (range, 3 to 11 days) after the first procedure. The second endoscopic procedure was successful in two out of four patients; one patient showed no recurrence of the fistula, whereas the second patient experienced a recurrence after 24 months. All patients underwent successful surgical procedures after the failure of endoscopic treatment, with no further recurrences.
Although we observed a low rate of success for primary endoscopic treatment of benign BEF, the invasive nature of surgery suggests the need for a prospective study with a large number of patients to evaluate the efficacy of less invasive procedures such as endoscopic treatment.
Esophageal fistula; Endoscopy; Fibrin glue
To determine if the maintenance effectiveness and tolerability of aripiprazole demonstrated in a 12-week study were maintained in an extension phase (up to 26 weeks).
This study was the extension of our switching study from other antipsychotics to aripiprazole in symptomatically stable patients with schizophrenia or schizoaffective disorder. All the patients were randomly assigned to the aripiprazole group or the non-aripiprazole group. The effectiveness analysis consisted of the comparison of the upper bound of the 95% confidence interval (CI) of the mean Clinical Global Impression-Improvement (CGI-I) score to 4 (no change) at the end of the study.
At the baseline, the aripiprazole group (n=135) and the non-aripiprazole group (n=31) were comparable with respect to their mean ages, gender distribution, baseline Positive and Negative Syndrome Scale scores, and Clinical Global Impression-Severity (CGI-S) scores. The study showed that the mean CGI-I score was 2.92 (95% CI: 2.72-3.12) in the aripiprazole group and 2.81 (95% CI: 2.35-3.26) in the non-aripiprazole group at 26 weeks. In the aripiprazole group, the remission rates at 12 and 26 weeks were 74.8% and 72.6%, respectively, and 80.2% of the patients with remission at 12 weeks maintained their remission state until the end of the study. About one-fourth of the patients in the aripiprazole group reported one or more spontaneous treatment-emergent adverse events, such as insomnia, headache, and nausea.
This study suggested that most clinically stable outpatients with schizophrenia maintain their remission states after being switched to aripiprazole, without serious symptom aggravation and adverse events over a course of 26 weeks.
Aripiprazole; Maintenance; Switch; Schizophrenia; Schizoaffective disorder
We examined the association between heart rate variability (HRV) and survival duration to evaluate the usefulness of HRV as a prognostic factor for hospice cancer patients. In terminally ill cancer patients who visited the Hospice clinic, we checked demographic data, Karnofsky performance scale (KPS), HRV, dyspnea, anorexia, as well as fasting blood glucose and total cholesterol. After following up their duration of survival, we examined meaningful prognostic factors for predicting life expectancy through the survival analysis. A total of 68 patients were included in final analysis. As KPS was lower, or when combined with dyspnea or anorexia, the survival duration was much shorter. HRV parameters except heart rate were all impaired in most patients. In particular, the group with mean heart rate of 100 or more beats per minute and the group with standard deviations of normal-to-normal R-R intervals (SDNN) of 21.3 ms (75 percentile) or less showed significantly shorter survival duration. The final multivariate analysis adjusting for age, gender, fasting blood glucose, and total cholesterol showed that KPS, dyspnea, anorexia, and SDNN were significant prognostic factors in survival duration. For the first time, we report that SDNN is a prognostic factor in terminal cancer patients.
Terminal Care; Life Expectancy; Prognosis; Heart Rate Variability
This study aimed to examine the effectiveness of quetiapine and the effects of dosage relates to its effectiveness on schizophrenia and schizoaffective disorder in a naturalistic setting in Korean people.
This study was a 24-week, open-label, non-comparative, naturalistic study of quetiapine in patients diagnosed with schizophrenia and schizoaffective disorder according to DSM-IV. We stratified the patients into mild [(clinical global impression severity (CGI-S) <4 at baseline)] and severe groups (CGI-S ≥4 at baseline). We investigated the response rate, defined as clinical global impression improvement (CGI-I) ≤2, in the severe group and the aggravation rate in the mild group using the last-observation-carried-forward (LOCF) and the Kaplan-Meier method (K-M).
During the 24 weeks, 151 (18.4%) of the participants dropped out of the study. There was a significant decrease in the mean CGI-S score, from 4.5±1.1 at baseline to 2.8±1.1 at 24 weeks. The response rate of severe group was 54.5% (estimated by LOCF) and 73.3% (K-M estimated) at 24 weeks. All patients who completed the study had taken a mean quetiapine dosage of 507.9±245.9 mg daily. The decrease of CGI-S score in high-dose group (the maximum dose was 750 mg/d or above) was statistically significant than that in recommended-dose group (the maximum dose was less than 750 mg/d).
This study demonstrated the long-term effectiveness of quetiapine in the treatment of schizophrenia and schizoaffective disorder in a naturalistic setting in Korean people. This study suggests that higher than recommended quetiapine dosages could be more effective in some patients.
Schizophrenia; Quetiapine; Naturalistic study; High-dose
Surgical resection is the mainstay treatment for gastrointestinal stromal tumors (GISTs). Laparoscopic surgery can be considered for treating these tumors since their biologic behavior lends them to curative resection without requiring large margins or extensive lymphadenectomy. Despite complete resection, GISTs frequently recur specifically in the liver and peritoneum. Although they occur in other upper gastrointestinal malignancies, recurrences of GISTs at the port sites after laparoscopic surgery have rarely been reported. We describe here a patient with abdominal wound metastasis after laparoscopic surgery for GIST.
Gastrointestinal stromal tumors; Abdominal wound metastasis; Laparoscopic surgery
Reflux esophagitis is inversely associated with the presence of atrophic gastritis, and endoscopic grading of atrophic gastritis correlates with histological evaluation. The aim of this study was to investigate the association of the endoscopic grade of atrophic gastritis with gastroesophageal and gastropharyngeal reflux.
A total of 627 patients, who underwent endoscopy and ambulatory 24-hour dual-probe pH monitoring, were included in this study. The grade of atrophic gastritis was endoscopically classified into 2 types with the atrophic pattern system: the closed-type (C-type) and the open-type (O-type). We compared the findings from endoscopy and ambulatory pH monitoring for these 2 types.
The O-type was significantly associated with a lower prevalence of reflux esophagitis (p=0.001). All variables showing gastroesophageal reflux in the distal probe were significantly lower in the O-type than in the C-type (p<0.05). Similarly for the proximal probe, all variables, except the supine time of pH<4, were significantly lower in the O-type than in the C-type (p<0.05). The frequency of gastroesophageal reflux disease and gastropharyngeal reflux disease was in significantly lower in the O-type than in the C-type (p<0.001, p=0.012, respectively).
Endoscopic grading of atrophic gastritis is easy and is inversely associated with gastroesophageal and gastropharyngeal reflux.
Atrophic gastritis; Endoscopy; Gastroesophageal reflux; Gastropharyngeal reflux
Extraskeletal Ewing's sarcoma (EES) is a branch of neuroectodermal tumor (PNET), which is very rare soft tissue sarcoma. We report a case of EES/PNET arising is the lung of a 67-yr-old man. Computed tomography, bone scintigraphy, and positron emission tomography confirmed the mass to have a primary pulmonary origin. The mass showed positive reactivity in the Periodic Acid Schiff (PAS) stain and MIC-2 immunoreactivity in immunohistochemical stain. Fluorescence in situ hybridization (FISH) was performed, which revealed an EWSR1 (Ewing sarcoma breakpoint region 1) 22q12 rearrangement. The diagnosis was confirmed both pathologically and genetically. The mass lesion was resected, and the patient is currently undergoing chemotherapy.
Sarcoma; Ewing's; Neuroectodermal Tumors; Primitive; Peripheral; Lung
The aim of this study was to investigate the effects of antidepressant treatment on serum cytokines and nutritional status in hemodialysis patients. Twenty-eight hemodialysis patients with a depressed mood were given 20 mg of fluoxetine for 8 weeks. The degree of depressive symptoms, the serum levels of interleukin-1β, interleukin-2, interleukin-6, tumor necrosis factor-α, c-reactive protein, and markers of nutritional status were assessed at baseline and after treatment. The outcome was assessed in terms of response to treatment (>50% reduction in the score of the Hamilton depression rating scale). Antidepressant treatment decreased the serum level of interleukin-1β in both response and nonresponse groups, and increased the serum level of interleukin-6 only in the response group. At baseline, the level of interleukin-6 in the response group was lower than in the nonresponse group. Antidepressant treatment also increased fat distribution significantly in the response group which might have slightly improved the nutritional status. This study suggests that antidepressant treatment improve depressive symptoms and may affect immunological functions and nutritional status in chronic hemodialysis patients with depression.
Depression; Antidepressive Agents; Cytokines; Nutritional Status; Renal Dialysis