• Journal of Chest Surgery
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• v.37 no.8
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• pp.691-701
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• 2004

Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.894-902
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• 1996

Background : Tumor angiogenesis is the growth of new vessels toward and within tumor. It has been demonstrated that the growth of tumor beyond a certain size requires angiogenesis and it is closely involved in tumor progression and metastasis. The finding that intensity of neovascularization correlates independently with metastasis may lead to identification of patients in whom radical surgery should be supplemented by systemic treatment. Method : We have collected paraffin blocks of bronchoscopic biopsy of patients with non-small cell lung cancer. We highlighted the vessel by staining endothelial cell with JC70 monoclonal antibody(to CD31) immunohistochemically and counted microvessels under 200 X field using light microscopy. Results : 1) The mean microvessel count was $32.7{\pm}20.8$ (9-96) in total 29 cases. 2) There were no correlations between microvessel counts and pathologic cell type, T staging, node melastasis(N) and hematogenous metastasis(M) (p>0.05). 3) The median follow-up duration was 15 months(2-46) and there was no correlation between the microvessel counts and survival rate of lung cancer patients (p>0.05). Conclusion : Tumor angiogenesis seems to be an important prognostic factor suggesting the probability of metastasis. But the microvessel count in the bronchoscopic biopsy specimen was inadequate and very limited. There has been no data about angiogenesis of lung cancer in korea yet So the study of tumor angiogenesis using resected lung tumor specimen would be demanded.

• Journal of Chest Surgery
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• v.41 no.3
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• pp.354-359
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• 2008

Background: Warfarin is used as an anticoagulant and it is mainly excreted by the liver metabolism (the R-form is mainly metabolized by cytochrome p450 3A4, and the S form by cytochrome p450 2C9). Rifampin is usually used for tuberculosis or endocarditis, and it is a representative drug that induces the CYP families, including 3A4 and 2C9. The anticoagulation effect of warfarin decreases through the increased metabolism that's due to the induction of enzymes, and this iscaused by rifampin when patients take these two medicines together. No one has suggested appropriate guidelines regarding this drug interaction even though an appropriate adjustment of warfarin's dosage is needed. We examined the drug interaction in patients who received warfarin-rifampin combination therapy according to the time interval, and the factors affecting drug interaction were analyzed. Based on the data, we tried to determine the clinically available warfarin dosage guidelines before and after taking this drug combination. Material and Method: We reviewed the OO University Hospital anticoagulation service team's follow up sheets that were filled out from Jan '1998 to Sep 2006 for the patient who took warfarin - rifampin combination therapy (n=15). Result: The average INR of all the patient before rifampin administration was $2.25{\pm}0.52$ $(mean{\pm}SD)$, and that value for the first 100 days after rifampin administration was $1.98{\pm}0.28$. The p value for these two sets of data showed no correlation (paired t-test, p>0.05). The average INR of all the patient before rifampin cessation was $2.19{\pm}0.34$, and the value after rifampin cessation was $2.49{\pm}0.43$. The p value of these two showed correlation (paired t-test, p<0.05) but the average INR falls between the therapeutic INR range. Conclusion: The warfarin dose adjustment equation of before and after warfarin-rifampin combination therapy was derived based on this study's results because the warfarin dosage adjustment of the anticoagulation service team was considered appropriate.

• Journal of Chest Surgery
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• v.35 no.12
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• pp.882-889
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• 2002

Acute Complications of Remodelling Plasty of Costochondral Rib Cage For Pectus excavatum Recently, Remodelling Plasty of Costochondral Rib Cage has been introduced as an minimally invasive procedure and expanded its application for pectus excavatum. Outcomes and acute complications were reviewed Material and Method: A retrospective survey of 55 patients who underwent Remodelling Plasty of Costochondral Rib Cage from September, 1999 to February, 2002 was conducted to review complications, postoperative treatments, and outcomes. Result: Age ranged from 1 to 27 years(mean 11.4 $\pm$ 7.1). 35(64%) were less than 15-year old and 20(36%) were more than 15-year old. There were 44(80%) Male patients and 11(20%) female patients. Length of hospital stay was 7.8 $\pm$ 2.1 days for less than 15-Y-old group, 10.6 $\pm$ 6.2 days for more than 15-Y-old group(p ＝ 0.042) One substernal bar was inserted in 52 patients and two substernal bars were inserted in 3 patients. As for stabilizer, one lateral side was fastened in 15 patients and both lateral sides were fastened in 6 patients. In the less than 15-Y-old group, 4 patients needed stabilizer, whereas in the more than 15-Y-old group, 18 patients needed stebilizer(s)(p ＝ 0.000). Including all kinds of complications, 28(51 %)patients had postoperative complications. Of them, only 7 patients were treated for complications(C-tube insertion was done in 7 patients and reoperation for bar refixation or removal was done in 3 patients of them). Conclusion: Most complications after Remodelling Plasty of Costochondral Rib Cage For Pectus Excavatum were trivial without treatment although C-tube drainage was needed in some patients. However bar displacement such as rotation and lateral sliding should be corrected as soon as detected in order not to remove the bar(the worst situation).

• Applied Microscopy
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• v.34 no.1
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• pp.31-42
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• 2004

Acute respiratory distress syndrome (ARDS) is a kind of acute lung injury characterized by inflammatory disruption of alveolar-capillary barrier and notorious for its high mortality. Neutrophils cause cell damage through the production of free radicals, inflammatory mediators, and proteases in ARDS. $PLA_2$ might serve a primary regulatory role in the activation of neutrophils. This present study was performed to elucidate the effect of rutin known as $PLA_2$ inhibitor on ARDS induced by endotoxin. Endotoxin had increased lung myeloperoxidase (MPO) activity, BAL (bronchoalveolar lavage) protein content, numbers of neutrophils in BALF (bronchoalveolar lavage fluid) compared with those of control rat (p<0.001). In addition, histological evidence of lung injury was correlated with neutrophil influx into alveolar space and cerrous perhydroxide granules were found in lining of endothelial cell, alveolar type I, II cells. In contrast, pretreated group of rutin had significantly decreased all of the parameters (p<0.001). These data suggest that inhibition of $PLA_2$ is one step approach that block the process of ARDS. Accordingly, we conclude that rutin can be used as the prophylactic agent for ARDS on the bases of these experimental results.

• Journal of Chest Surgery
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• v.31 no.8
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• pp.739-748
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• 1998

Background: It has been well documented that transient occlusion of the coronary artery causes myocardial ischemia and finally cell death when ischemia is sustained for more than 20 minutes. Extensive studies have revealed that ischemic myocardium cannot recover without reperfusion by adequate restoration of blood flow, however, reperfusion can cause long-lasting cardiac dysfunction and aggravation of structural damage. The author therefore attempted to examine the effect of postischemic reperfusion on myocardial ultrastructure and to determine the rationales for recanalization therapy to salvage ischemic myocardium. Materials and methods: Young Holstein-Friesian cows(130∼140 Kg body weight; n=40) of both sexes, maintained with nutritionally balanced diet and under constant conditions, were used. The left anterior descending coronary artery(LAD) was occluded by ligation with 4-0 silk snare for 20 minutes and recanalized by release of the ligation under continuous intravenous drip anesthesia with sodium pentobarbital(0.15 mg/Kg/min). Drill biopsies of the risk area (antero-lateral wall) were performed at just on reperfusion(5 minutes), 1-, 2-, 3-, 6-, 12-hours after recanalization, and at 1-hour assist(only with mechanical respiration and fluid replacement) after 12-hour recanalization. The materials were subdivided into subepicardial and subendocardial tissues. Tissue samples were examined with a transmission electron microscope (Philips EM 300) at the accelerating voltage of 60 KeV. Results: After a 20-minute ligation of the LAD, myocytes showed slight to moderate degree of ultrastructural changes including subsarcolemmal bleb formation, loss of nuclear matrix, clumping of chromatin and margination, mitochondrial destruction, and contracture of sarcomeres. However, microvascular structures were relatively well preserved. After 1-hour reperfusion, nuclear and mitochondrial matrices reappeared and intravascular plugging by polymorphonuclear leukocytes or platelets was observed. However, nucleoli and intramitochondrial granules reappeared within 3 hours of reperfusion and a large number of myocytes were recovered progressively within 6 hours of reperfusion. Recovery was apparent in the subepicardial myocytes and there were no distinct changes in the ultrastructure except narrowed lumen of the microvessels in the later period of reperfusion. Conclusions: It is likely that the ischemic myocardium could not be salvaged without adequate restoration of coronary flow and that the microvasculature is more resistant to reversible period of ischemia than subendocardium and subepicardium. Therefore, thrombolysis and/or angioplasty may be a rational method of therapy for coronarogenic myocardial ischemia. However, it may take a relatively longer period of time to recover from ischemic insult and reperfusion injury should be considered.

• Journal of Chest Surgery
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• v.34 no.12
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• pp.895-900
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• 2001

Background : This study aimed to evaluate the usefulness of preoperative placement of intraaortic balloon pump(IABP) in reducing operative risk and facilitating posterior vessel OPCAB in high risk patients with left main disease( 75％ stenosis), intractable resting angina, postinfarction angina, or left ventricular dysfunction(ejection fraction 35％). Material and Method : One hundred eighty- nine consecutive patients who underwent multi-vessel OPCAB including posterior vessel revascularization were studied. The patients were divided into group I(n=74) that received preoperative or intraoperative IABP and group II(n=115) that did not receive IABP. In group I, there were 39 patients with left main disease, 40 patients with intractable resting angina, 14 patients with left ventricular dysfunction and 7 patients with postinfarction angina. Ten patients received intraoperative IABP support due to hemodynamic instability during OPCAB. Result : There was one operative mortality in group I and two mortalities in group II. The average number of distal anastomoses was not different between group I and group II(3.5$\pm$0.9 vs 3.4$\pm$0.9, p=ns). There were no significant differences in the number of posterior vessel anastomosis per patient between the two groups. There were no differences in ventilator support time, length of hospital stay, and morbidity between the two groups. There was one case of IABP-related complication in group I. Conclusion : IABP facilitates posterior vessel OPCAB in high risk patients, with comparable surgical results to low risk patients

• Journal of Chest Surgery
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• v.42 no.3
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• pp.331-336
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• 2009

Background: Open surgical repair of abdominal aortic aneurysms was initiated by Dubost in 1952. Despite the rapid expansion of percutaneous endovascular repair, open surgical repair is still recognized for curative intent. We retrospectively analyzed surgical outcome, complications, and mortality-related factors for patients with abdominal aortic aneurysms over a 6 year period. Material and Method: We analyzed 18 patients who underwent surgery for abdominal aortic aneurysms between March 2002 and March 2008. The indications for surgery were rupture, a maximal aortic diameter >60 mm, medically intractable hypertension, or pain. Result: The mean age was $66.6{\pm}9.3$ years (range, $49\sim81$ years). Twelve patients (66.7%) were males a 6 patients were females. Extension of the aneurysm superior to the renal artery existed in 6 patients (33.3%), and extension to the iliac artery existed in 13 patients (72.2%). Five patients (27.8%) had ruptured aortic aneurysms. The mean maximal diameter of the aorta was $72.2{\pm}12.9$ mm (range, $58\sim109$ mm). Surgery was performed by a midline laparotomy, and 6 patients underwent emergency surgery. The mean total ischemic time from aorta clamping to revascularization was $82{\pm}42$ minutes (range, $35\sim180$ minutes). The mortality rate was 16.7%; the mortality rate for patients with ruptured aneurysms was 60%, and the mortality rate for patients with unruptured aneurysms was 0%. The postoperative complications included one each of renal failure, femoral artery and vein occlusion, and wound infection. The patients who were discharged had a long-term survival of $34{\pm}26$ months (range, $4\sim90$ months). Rupture and emergency surgery had a statistically significant mortality-related factor (p < 0.05). Conclusion: Emergency surgery for ruptured aortic aneurysms continues to have a high mortality, but unruptured cases are repaired with relative safety. Successfully operated patients had long-term survival. Even though endovascular aortic repair is the trend for abdominal aortic aneurysms, aggressive application should be determined with care. Experience and systemic support of each center is important in the treatment plan.

• Journal of Chest Surgery
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• v.42 no.2
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• pp.193-200
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• 2009

Background: The long-term administration of oral anticoagulant to the patients with a mechanical heart valve prosthesis is mandatory. However, the appropriate intensity of oral anticoagulant therapy to prevent thromboembolic or hemorrhagic complications is still controversial. We tried to apply low intensity anticoagulant therapy for which the International Normalized Ratios ranged between 1.5 and 2.5, and we analyzed the anticoagulation-related long term outcomes. Material and Method: From January 1992 to December 2002, 144 patients who underwent a single cardiac valve replacement were included in the study, and their ages ranged from 15 to 72 years (mean age: $47.4{\pm}15.1$): there were 49 aortic valve replacements (AVR) and 95 mitral valve replacements (AVR). The patients were followed up monthly or bi-monthly at the outpatient clinic with clinical examinations and measuring the prothrombin time to adjust the International Normalized Ratios (INRs) within the low-intensity target range between 1.5 and 2.5. Result: The follow-up period was 835.3 patient-years (mean: $5.9{\pm}3.5$) and the INRs of 7,706 measurements were available for evaluation. The mean INRs of the aortic and the mitral valve replacement groups were significantly different (p<0.01). All the patients' INRs were within the target range in 61.9% of the measurements. The mean INRs $(2.16{\pm}0.23)$ of the patients with atrial fibrillation, which was found in 30.3% of the patients, were definitely higher than those $(2.03{\pm}0.27)$ measured in the patients with regular rhythm (p<0.01). Thromboembolic episodes occurred in 9 patients with an incidence of 1.08%/patient-year. Major bleeding occurred in 2 patients (MVR) with an incidence of 0.24%/patient-year. The patients who displayed better compliance showed a lower incidence of complications (p=0.000). Conclusion: The anticoagulation therapy with a low-intensity target range after MVR or AVR seems to be effective and feasible, and increasing the patients’ compliance should be done for achieving more effective anticoagulation therapy.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.65-71
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• 2006

Background : Hemoptysis, when massive and untreated, has a mortality rate of over 50 percents, is considered as one of most dreaded of all respiratory emergencies and can have a variety of underlying causes. Bronchial artery embolization (BAE) has become an established procedure in the management of massive and recurrent hemoptysis, and its efficacy is widely documented thereafter by number of articles. However, the long-term success rate of BAE is known to be unfavorable. Risk factors influencing that control failure are inevitably needed. Materials and methods : Seventy-five patients underwent bronchial artery embolization due to massive hemoptysis in Severance Hospital from Jan. 2000 to Jan. 2005. Nine patients' data were not available and could not be contacted with. Finally 66 patients' (48 males, 18 females) medical records were analyzed retrospectively during a mean follow up period of 20.4 months (ranging from 1 month to 54 months). Results : Among 66 patients whose data were available, 23(34.9%) patients had recurrent major hemoptysis. Patients' age, sex, underlying disease, previous intervention history, and number of feeding vessels had no statistical validity as risk factors of recurred major hemoptysis. But bilaterality of lesion, amount of hemoptysis, and pleural thickening were revealed as meaningful factors for predicting relapse (p = 0.008, 0.018, and 0.001, respectively). Conclusion : According to our series, patients presenting with larger amount of hemoptysis, pleural thickening of chest radiography and bilateral lesion are associated with increased risk of major hemoptysis in patients treated with BAE.