Inter-observer Reproducibility in the Pathologic Diagnosis of Gastric Intraepithelial Neoplasia and Early Carcinoma in Endoscopic Submucosal Dissection Specimens: A Multi-center Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. MATERIALS AND METHODS: We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. RESULTS: The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. CONCLUSION: The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.

Proper Cut-off Levels of Serum Specific IgE to Cefaclor for Patients with Cefaclor Allergy

PURPOSE: Cefaclor, a second-generation oral cephalosporin, is known to cause IgE-mediated hypersensitivity. Assays of serum-specific IgE (sIgE) to cefaclor are commercially available via the ImmunoCAP system (Thermo Fisher Scientific). While serum levels of sIgE >0.35 kU/L are considered indicative of an allergy, some patients with cefaclor allergy show low serum IgE levels. This study aimed to evaluate the proper cut-off levels of sIgE in the diagnosis of immediate hypersensitivity to cefaclor. MATERIALS AND METHODS: A total of 269 patients with drug allergy history, who underwent assays of sIgE to cefaclor at Ajou University hospital and Dong-A University Hospital, were reviewed retrospectively. Among them, 193 patients exhibited cefaclor-induced immediate hypersensitivity with certain or probable causality of an adverse drug reaction according to the WHO-UMC (the World Health Organization-the Uppsala Monitoring Centre) algorithm, and 76 controls showed delayed hypersensitivity reactions to non-antibiotics. RESULTS: In total, 126 of the 193 patients (65.3%) experienced anaphylaxis; they had higher serum sIgE levels than patients with immediate hypersensitivity who did not experience anaphylaxis (6.36±12.39 kU/L vs. 4.28±13.61 kU/L, p < 0.001). The best cut-off value for cefaclor-induced immediate hypersensitivity was 0.11 kU/L, with sensitivity of 80.2% and specificity of 81.6%. A cut-off value of 0.44 kU/L showed the best sensitivity (75.4%) and specificity (65.7%) for differentiating anaphylaxis from immediate hypersensitivity reactions. CONCLUSION: Patients with cefaclor anaphylaxis exhibit high serum IgE levels. A cut-off value of 0.11 kU/L of sIgE to cefaclor is proper for identifying patients with cefaclor allergy, and 0.44 kU/L may be useful to detect anaphylaxis.

Long-Term Clinical Outcomes of Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer: A Prospective Multicenter Cohort Study

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been regarded as a curative treatment for early gastric cancer (EGC) in indicated cases. The aim of this study was to evaluate the nationwide long-term clinical outcomes of ESD for EGC in Korea. METHODS: A prospective multicenter cohort study was performed to evaluate the long-term efficacy of ESD for EGC within pre-defined indications at 12 institutes in Korea. The cases that met the expanded criteria upon pathological review after ESD were followed for 5 years. The primary outcome was 5-year disease specific free survival. RESULTS: Six hundred ninety-seven patients with 722 EGCs treated with ESD were prospectively enrolled and followed for 5 years. Complete resection was achieved in 81.3% of the cases, and curative resection was achieved in 86.1%. During the 5-year follow-up, the overall survival rate was 96.6%, and the disease specific free survival rate was 90.6%. Local recurrence developed in 0.9%, and metachronous tumor development occurred in 7.8%; both conditions were treated by endoscopic or surgical treatment. Distant metastasis developed in 0.5% during follow-up. CONCLUSIONS: ESD showed excellent long-term clinical outcomes and can be accepted as a curative treatment for patients with EGC who meet the expanded criteria in final pathology studies.

Quality of Life after Endoscopic Submucosal Dissection for Early Gastric Cancer: A Prospective Multicenter Cohort Study

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been an established treatment for indicated early gastric cancer (EGC) without deterioration of quality of life (QOL) compared with surgical resection. The aim of this study was to evaluate long-term QOL in patients undergoing ESD for EGC. METHODS: Patients scheduled to undergo curative ESD for EGC were prospectively enrolled from 12 institutions between May 2010 and December 2011. Assessments of QOL with Korean versions of the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire-core (QLQ-C30) and a gastric cancer-specific questionnaire (STO22) were performed at baseline and at 7 days, 3 months, and 6 months after ESD. RESULTS: A total of 666 subjects were assessed for QLQ-C30 and QLQ-STO22. The mean QLQ-C30 score was 69.5 at baseline, 68.8 at 7 days, 73.1 at 3 months, and 73.2 at 6 months. The global health status on the EORTC QLQ-C30 was significantly improved after 3 and 6 months (p=0.0003 and p<0.0001, respectively). The QLQ-C30 and STO22 scores were not significantly different, or they only slightly deteriorated between before and immediately after ESD, but they were significantly improved after 3 and 6 months (p<0.05). CONCLUSIONS: QOL did not deteriorate immediately after ESD, and it improved more significantly at up to 6 months in patients who underwent curative ESD for EGC without significant complications.

The Role of Autophagy in the Pathogenesis of Atherosclerosis

Autophagy is a life-sustaining process by which cytoplasmic constituents are segregated in double-lipid bilayer membrane vesicles and undergo degradation into lysosomes. In recent studies, the basal autophagy is an indispensable process mediating proper vascular function in the body. Moreover, autophagy activated by many stress-related stimuli in the arterial wall protects endothelial cells and smooth muscle cells against cell death and the progression of vascular disease including atherosclerosis. Autophagy is protective to atherosclerosis during early stage but becomes dysfunctional in advanced atherosclerotic lesions. Following this finding, the need is emphasized which pharmacological development with compounds that activate the protective effects of autophagy in the vascular disease. Autophagy stimulated by oral or vascular delivery of rapamycin or derivatives effectively suppressed the atherosclerotic plaque growth and plaque destabilization. In this review, the recent finding is summarized on the role of autophagy in atherosclerosis and find out whether the activation or rescue of autophagy could provide a breakthrough in the treatment of atherosclerosis.

Short-Term Outcomes of Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer: A Prospective Multicenter Cohort Study

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC) that has demonstrated a minimal risk of lymph node metastasis in retrospective studies. We sought to prospectively evaluate the short-term outcomes of ESD treatment in EGCs. METHODS: A prospective multicenter cohort study of neoplasms 3 cm or less in diameter at endoscopic size evaluation was performed in 12 Korean ESD study group-related university hospitals and the National Cancer Center. Resected specimens were evaluated by the central pathologic review board. RESULTS: A patient cohort (n=712) with a total of 737 EGCs was analyzed. The margin-freeen bloc resection rate was 97.3%, and curative resection of 640 lesions (86.8%) was achieved. Lower curative resection rates were associated with lesions 2 to 3 cm in size prior to ESD compared with lesions 2 cm or less in size (78.6% vs 88.1%, respectively, p=0.009). Significant factors associated with noncurative resection were moderately or poorly differentiated histological type, posterior wall tumor location, tumor size larger than 3 cm, ulceration, and submucosal invasion. Delayed bleeding occurred in 49 patients (6.9%), and 12 patients (1.7%) exhibited perforations. CONCLUSIONS: ESD is an effective treatment with a high curative resection rate for EGCs that meets relatively conservative pre-ESD indications. Long-term survival outcomes should be evaluated in follow-up studies.

Biodistribution of 99mTc Labeled Integrin Antagonist

The selective targeting of an integrin alphavbeta3 receptor using radioligands may enable the assessment of angiogenesis and integrin alphavbeta3 receptor status in tumors. The aim of this research was to label a peptidomimetic integrin alphavbeta3 antagonist (PIA) with 99mTc(CO)3 and to test its receptor targeting properties in nude mice bearing receptor-positive tumors. PIA was reacted with tris-succinimidyl aminotriacetate (TSAT) (20 mM) as a PIA per TSAT. The product, PIA-aminodiacetic acid (ADA), was radiolabeled with [99mTc(CO)3(H2O)3](+1), and purified sequentially on a Sep-Pak C-18 cartridge followed by a Sep-Pak QMA anion exchange cartridge. Using gradient C-18 reverse-phase HPLC, the radiochemical purity of 99mTc(CO)3-ADA-PIA (retention time, 10.5 min) was confirmed to be > 95%. Biodistribution analysis was performed in nude mice (n = 5 per time point) bearing receptor-positive M21 human melanoma xenografts. The mice were administered 99mTc(CO)3-ADA-PIA intravenously. The animals were euthanized at 0.33, 1, and 2 hr after injection for the biodistribution study. A separate group of mice were also co-injected with 200 microg of PIA and euthanized at 1 hr to quantify tumor uptake. 99mTc(CO)3-ADA-PIA was stable in phosphate buffer for 21 hr, but at 3 and 6 hr, 7.9 and 11.5% of the radioactivity was lost as histidine, respectively. In tumor bearing mice, 99mTc(CO)3-ADA-PIA accumulated rapidly in a receptor-positive tumor with a peak uptake at 20 min, and rapid clearance from blood occurring primarily through the hepatobiliary system. At 20 min, the tumor-to-blood ratio was 1.8. At 1 hr, the tumor uptake was 0.47% injected dose (ID)/g, but decreased to 0.12% ID/g when co-injected with an excess amount of PIA, indicating that accumulation was receptor mediated. These results demonstrate successful 99mTc labeling of a peptidomimetic integrin antagonist that accumulated in a tumor via receptor-specific binding. However, tumor uptake was very low because of low blood concentrations that likely resulted from rapid uptake of the agent into the hepatobiliary system. This study suggests that for 99mTc(CO)3-ADA-PIA to be useful as a tumor detection agent, it will be necessary to improve receptor binding affinity and increase the hydrophilicity of the product to minimize rapid hepatobiliary uptake.

Dietary intake, dietary habits, and depression in Korean women with polycystic ovary syndrome

The purpose of this study was to investigate and examine the relationship between dietary habits, food intake patterns, and depression in Korean women with polycystic ovary syndrome (PCOS). The Center for Epidemiologic Studies Depression Scale Korean Version was used to determine whether a participant was depressed or not. The dietary habits were assessed by the Min-Dietary Assessment (MDA) method, and food intake data were collected by the 24-hour recall method on two non-consecutive days, at least 7 days apart, and the average of the two days was used to estimate the usual dietary intake. The total MDA scores of the Depression Group was significantly lower than that of the No-Depression Group (31.5 +/- 6.4 vs 33.4 +/- 6.0, p = 0.027). The intake of cereals/potatoes/sugar products, milk and milk products, plant protein, and calcium for the Depression Group were significantly lower compared to the No-Depression Group. The Depression Group had a significantly higher percentage of energy intakes from protein as well as the consumption of fish and shellfish compared to the No-Depression Group. There was a significant inverse relationship between milk and milk products consumption and the prevalence of depression [OR (95% CI) for the highest tertile compared to the lowest: 0.390 (0.177-0.857); p for trend = 0.016]. There were also significant positive relationships between the prevalence of depression and the consumption of the following: fish and shellfish [OR (95% CI) for the highest tertile compared to the lowest: 2.319 (1.128-4.770); p for trend = 0.009], animal protein (p for trend = 0.049), and the percentage of energy intakes from protein [OR (95% CI) for the highest tertile compared with the lowest: 2.546(1.156-5.609); p for trend = 0.025]. Further studies are needed in order to investigate whether the intake of protein and of animal protein is indeed associated with depression in PCOS patients in Korea and the possible mechanisms thereof. The results of our study can be applicable for the development of effective nutrition counseling and education programs regarding PCOS patients with depression as part of their successful treatment regimen.

Comparison of Isoflurane and Propofol Anesthesia on Postoperative Nausea, Vomiting and Recovery after Tonsillectomy in Children / 대한마취과학회지

BACKGROUND: The purpose of this study was to compare prospectively two different anesthetic techniques with isoflurane or propofol for postoperative nausea, vomiting and recovery after tonsillectomy in children. METHODS: Sixty children, ASA physical status I, were assigned randomly to one of two groups. In group I, anesthesia was induced with thiopental 5 mg/kg and maintained with isoflurane 1~1.5 vol%. In group P, anesthesia was induced with fentanyl 1 mcg/kg, propofol 2 mg/kg and maintained with propofol infusion 5~10 mg/kg/hr. Both group received vecuronium 0.1 mg/kg for tracheal intubation and were ventilated with 33% O2 in N2O. The time to extubation, time to eye opening, PACU time, incidence and numbers of postoperative nausea and vomiting, and degree of sedation were recorded as well as perioperative complications. RESULTS: There were no significant difference in the duration of anesthesia and PACU time between two groups. The time to extubation and eye opening of group P were significantly shorter than group I (p<0.05). The degree of sedation and incidence of postoperative nausea and vomiting of group P were significantly lower than group I (p<0.05). But the frequency of intraoperative bradycardia was significantly higher in group P than group I (p<0.05). CONCLUSIONS: Propofol-fentanyl anesthesia results in less nausea and vomiting during postoperative period and more rapid recovery compared to isoflurane anesthesia and may be recommended in children undergoing tonsillectomy and adenoidectomy.

Postoperative Severe Hemorrhage Due to Disseminated Intravascular Coagulation: A case report / 대한마취과학회지

Disseminated intravascular coagulation (DIC) is a pathological syndrome in which activation of coagulation cascade leads to fibrin clot formation, consumption of platelets and coagulation factors, and secondary fibrinolysis. We report a case of severe postoperative hemorrhagic diathesis due to DIC. A 59-year-old man was scheduled for reduction of tibia fracture and anatrophic nephrolithotomy of staghorn calculi. On the fifth postoperative day, second operation was performed for nephrectomy due to perirenal hematoma. Two days later, third operation was performed for hemostasis because of the continuous bleeding. Coagulation tests showed positive DIC profiles of thrombocytopenia, hypofibrinogenemia, increased fibrin degradation products, and prolonged prothrombin time and thrombin time. The patient recovered uneventfully and discharged on the 59th postoperative day.

A Case of Symmetrical Peripheral Gangrene in Disseminated Intravascular Coagulation

The symmetrical peripheral gangrene syndrome consists of sudden onset of symmetrical gangrene of the fingers, toes and more raely, the nose, upper lip, ear lobes, or genitalia. There is no evidence of occulusion of large vessels or vasculitis. We experienced a case of symmetrical peripheral gangrene developed in fingers and toes with disseminated intravascular coagulation in 20 day-old permature infant with sepsis by Enterobacter aerogenes. Thereafter, we presented a case with a brief review of the related literatures.

A case of hypodipsic hypernatremia

Hypodipsic hypernatremia is characterized by chronic or recurrent episodes of severe hypernatermia associated with dehydration and a lack of thirst. This constellation of deficits suggests that the syndrome is due to hypodipsia of destruction of the hypothalamic osmoreceptors that regulate thirst and ADH secretion. We report a child with abnormalities of the central nervous system who had hypernatremia and a lack of thirst without detectable abnormalities in the osmoregulation of ADH secretion. The patient was a 11 month old female and her chief complaints were poor oral intake and weight gain. There were recurrent hypernatremia with hyperosmosis and normal level of plasma ADH. With intravenous rehydratin, oral intake was improved and plasma sodium level decreased.

A clinical study of bronchial asthma in children

This report is a clinical analysis and comparative study with previous report of bronchial asthma at National Medical Center on bronchial asthma in children who were admitted to the MP dept. of national Medical Center from January 1987 to December 1990. The results of the study were as follows: 1) The out-break ratio of bronchial asthma is 3.7% of hospitalized children which is no change that about 4% since 1980. 2) The children under 6 years of ge was 62.7% which among under 3 years was 33.1%. The rate of under 3 year children is increased as previous study. 3) The out-break of bronchial asthma was most common in September and October and so peak incidence was noted in fall and duration of hospitalization was most 2 week. 4) Familial allergic history was positive in 54.6% and bronchial asthma was most common. The presence of allergic past history was 52.2%) and atopic dermatitis was most common 5) Eosinophilia was found in 80.8% and elevated IgE was also in 61.6% of bronchial asthma. 6) We could get positive results of IgE RAST and skin test: D. pteronyssinus, D. farinae, Houst dust. 7) The most frequent findigs of the chest radiograph were within normal limits. 8) The clinical improvement rate of bronchial asthma is 52.5%.

Cow mild allergy in infant who neonatal onset

Cow milk allergy can be defined as an adverse immunologic reactions to cow milk protein. The term is often mistakenly applied to other causes of milk intolerence, such as lactase deficiency and galactosemia, which must be differenciated and excluded. We have experienced 10 children of cow milk allergy at neonatal onset who had suffered from G-I symtoms, such as diarrhea, irritability, weight loss, vomiting and abdominal distension. One half of this patients had family history of allergic diseas. All patients have positive specific IgE RAST to cow's milk protein, milk elimination test and milk challenge test. Brest milk feeding and soy bean formula feeding and soy bean formula feeding have started after diagnosis and then gastrointestinal symtoms and signs of all patients are improved but other allergic diseases are combined in 5 children.