• 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.

• Journal of Chest Surgery
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• v.40 no.2 s.271
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• pp.114-121
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• 2007

Background: Apoptosis plays a crucial role in carcinogenesis, as well as in development and tissue homeostasis. Terminal deoxyribonucleotidyl transferase mediated neck end labelling (TUNEL) and in situ nick end labelling (ISEL) have been used to investigate the apoptosis in tissues. Since the introduction of the M30 monoclonal antibody to overcome drawbacks of TUNEL and ISEL, the apoptosis in various tumors, with the exception of pulmonary carcinomas, has been studied. In this study, attempts were made to examine the correlation of apoptosis in non-small cell carcinomas, using both M30 and the expression of p53 protein, with the clinicopathological factors. Material and Method: Forty five patients with surgically resected non-small cell carcinomas were included. Immunohistochemical staining with M30 and p53 monoclonal antibody were peformed, and their expressions compared with the clinicopathological features. The overall survival time and recurrence-free survival time were calculated, and the factors influencing the survival time analyzed using a univariate analysis. The effects of the expression stati of M30 and p53 on the risks of cancer related to both death and recurrence were evaluated using a multivariate analysis. Result: The p53 positive group had many more M30 positive cells than the p53 negative group (p53 positive group; $61.7{\pm}26.8$ cells vs. p53 negative group; $45.6{\pm}29.6$ cells, p=0.005) and significantly more p53 positive patients showing at least 10 positive cells (apoptotic index, $Al{\ge}1$) on M30 staining (p53 positive group; 52.4% (11/21) vs. p53 negative group 16,7% (4/24), p=0.025). In the univariate analysis, the survival times in relation to smoking (pack-year), performance status (PS) and Al showed significant differences. The multivariate analysis demonstrated the relative risk (R.R) of cancer death increased almost 7.5-fold (R.R 7.482; 95% Cl $1.886{\sim}29.678$; p=0.004) and the risk of recurrence almost 3,8-fold (R.R 3.795; 95% Cl: $1.184{\sim}12.158$; p=0.025) in the high Al (${\ge}1$) compared to the low Al (<1) group. There was no prognostic effect of p53 expression on the survival time or risk of cancer death and recurrence. Conclusion: In non-small cell lung carcinomas, M30 immunohistochemistry was an excellent method for analyzing apoptosis; the high apoptotic index could be an adverse prognostic predictive factor.

• Journal of Chest Surgery
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• v.25 no.9
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• pp.948-954
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• 1992

In spite of recent progress in anticancer chemotherapy, the survival of patients with metastases to the lung treated nonsurgically has been extremely poor. So we adopted more aggressive surgical approaches for the treatment of patients with pulmonary metastases since 1985. We experienced 22 operations of metastatic lung cancer in 19 patients in the department of Thoracic & Cardiovascular Surgery in Kosin Medical College since 1985, so we reviewed the results of treatment retrospectively. The results were as follows: 1. The primary organs of metastatic lung cancer were 4 cases in each of the breast, uterus, and extremities, 3 cases in the rectum, 2 cases in the kidney, 1 case in each of the pelvis and liver, and the pathological findings were 13 cases in carcinoma and 6 cases in sarcoma. 2. The treatments for primary lesions were 15 cases of the operations with anticancer chemotherapy or radiation therapy, 2 cases of choriocarcinoma with anticancer chemotherapy only, 1 cases of uterine cervical carcinoma with chemo-radiation therapy, and 1 case of pelvic synovia sarcoma with intra-arterial anticancer chemotherapy. 3. Disease free intrerval were as follows: 7 cases were in 2 years to 4 years, 4 cases were in 1 year to 2 years, and 5 cases were beyond one year, of them one case was discovered primary lesion and metastatic lung tumor concomittently. 3 cases were above 4 years, of them one case of breast cancer were above 13 years especially. 4. The sites of metastatic lung cancer was 15 lesions in the right lung, and 9 lesions in the left lung, And the lobar sites were 10 lesions in the upper lobe, 2 lesions in the middle lobe, and 12 lesions in the lower lobe. 5. The operative methods of metastatic lung cancer were 7 case of partial resection of lung, 12 cases of pulmonary lobectomy, 1 case of pneumonectomy and 1 case of dissection of mediastinal lymph node. 6. The postoperative complications were 1 case of mild respiratory insufficency, 1 cases of pyothorax, and 1 case of urethral stricture. 7. Postoperative adjuvant therapy were as follows: No adjuvant therapy were 4 cases, anti-cancer chemotherapy were 8 cases, radiation therapy was 1 case, and combined with chemo k radiation therapy were 8 cases. 8. The results of long term follow-up were as follows: The 5 patients were died at 2 months, 22 months, 24 months, 32 months, and 49 months postoperatively, so mean survival period was 32 months postoperatively excluding one patient who was died at 2 months postoperatively. And 14 patients are aliving, of them 3 patients are living in recurred state, and the other 11 patients are living without any evidence of recurrence.

• Journal of Chest Surgery
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• v.29 no.7
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• pp.753-758
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• 1996

From January 1987 to December 1994, twenty five patients with cancer of the esophagus were t eated surgically at the department of Thoracic and Cardiovascular Surgery, Tae Jeon Eul ll General Hospital. Among them, male was 24 cases, female was 1 case, with age ranged from 40 to 74 years, mean age was 60.4 years. The most common symptoms were dysphagia 92.0%, general weakness 28.0%, subsiernal pain 16.0%, weight loss 16.0 oyo , The tumor locations were the upper third in 2, middle third in 17, lower third in 6. Surgical treatment was done with transthoracic esophagectomy and esophagogastrostomy 1~4 cases, transthoracic esophagectomy and esophagocologastrostomy 5 cases, Transthoracic esophagectomy and jeT junal interposition 2 cases, palliative feeding gastrostomy 4 cases. The postoperative complications included anstomotic leakage in 3 cases, empyema in 3 cases, wound in- fection in 2 cases, atelectasis in 2 cases, pleural effusion in 1 case, hoarseness in 1 case, pneumothorax in 1 case, necrosis of jejunal loop in 1 case, aspiration pneumonia in 1 case. The operative mortal ty were 3 cases (12.0 %) and causes of death were aspiration pneumonia 1 case. sepsis and respiratory failure in each 1 . The mean survival period was 9.75 months. Recurrence of cancer revealed in 3 cases.

• Journal of Korean Neurosurgical Society
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• v.42 no.4
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• pp.311-316
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• 2007

Objective : The objective of this study is to investigate the safety, surgical efficacy, and advantages of a polyaxial screw-rod system for posterior occipitocervicothoracic arthrodesis. Methods : Charts and radiographs of 32 patients who underwent posterior cervical fixation between October 2004 and February 2006 were retrospectively reviewed. Posterior cervical polyaxial screw-rod fixation was applied on the cervical spine and/or upper thoracic spine. The surgical indication was fracture or dislocation in 18, C1-2 ligamentous injury with trauma in 5, atlantoaxial instability by rheumatoid arthritis (RA) or diffuse idiopathic skeletal hyperostosis (DISH) in 4, cervical spondylosis with myelopathy in 4, and spinal metastatic tumor in 1. The patients were followed up and evaluated based on their clinical status and radiographs at 1, 3, 6 months and 1 year after surgery. Results : A total of 189 screws were implanted in 32 patients. Fixation was carried out over an average of 3.3 spinal segment (range, 2 to 7). The mean follow-up interval was 20.2 months. This system allowed for screw placement in the occiput, C1 lateral mass, C2 pars, C3-7 lateral masses, as well as the lower cervical and upper thoracic pedicles. Satisfactory bony fusion and reduction were achieved and confirmed in postoperative flexion-extension lateral radiographs and computed tomography (CT) scans in all cases. Revision surgery was required in two cases due to deep wound infection. One case needed a skin graft due to necrotic change. There was one case of kyphotic change due to adjacent segmental degeneration. There were no other complications, such as cord or vertebral artery injury, cerebrospinal fluid leak, screw malposition or back-out, or implant failure, and there were no cases of postoperative radiculopathy due to foraminal stenosis. Conclusion : Posterior cervical stabilization with a polyaxial screw-rod system is a safe and reliable technique that appears to offer several advantages over existing methods. Further biomechanical testings and clinical experiences are needed in order to determine the true benefits of this procedure.

• Radiation Oncology Journal
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• v.29 no.3
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• pp.181-190
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• 2011

Purpose: Thoracic radiotherapy is a major treatment modality of stage III non-small cell lung cancer. The normal lung tissue is sensitive to radiation and radiation pneumonitis is the most important dose-limiting complication of thoracic radiation therapy. This study was performed to identify the clinical and dosimetric parameters related to the risk of radiation pneumonitis after definitive radiotherapy in stage III non-small cell cancer patients. Materials and Methods: The medical records were reviewed for 49 patients who completed definitive radiation therapy for locally advanced non-small cell lung cancer from August 2000 to February 2010. Radiation therapy was delivered with the daily dose of 1.8 Gy to 2.0 Gy and the total radiation dose ranged from 50.0 Gy to 70.2 Gy (median, 61.2 Gy). Elective nodal irradiation was delivered at a dose of 45.0 Gy to 50.0 Gy. Seven patients (14.3%) were treated with radiation therapy alone and forty two patients (85.7%) were treated with chemotherapy either sequentially or concurrently. Results: Twenty-five cases (51.0%) out of 49 cases experienced radiation pneumonitis. According to the radiation pneumonitis grade, 10 (20.4%) were grade 1, 9 (18.4%) were grade 2, 4 (8.2%) were grade 3, and 2 (4.1%) were grade 4. In the univariate analyses, no clinical factors including age, sex, performance status, smoking history, underlying lung disease, tumor location, total radiation dose and chemotherapy were associated with grade ${\geq}2$ radiation pneumonitis. In the subgroup analysis of the chemotherapy group, concurrent rather than sequential chemotherapy was significantly related to grade ${\geq}2$ radiation pneumonitis comparing sequential chemotherapy. In the univariate analysis with dosimetric factors, mean lung dose (MLD), $V_{20}$, $V_{30}$, $V_{40}$, MLDipsi, $V_{20}$ipsi, $V_{30}$ipsi, and $V_{40}$ipsi were associated with grade ${\geq}2$ radiation pneumonitis. In addition, multivariate analysis showed that MLD and V30 were independent predicting factors for grade ${\geq}2$ radiation pneumonitis. Conclusion: Concurrent chemotherapy, MLD and $V_{30}$ were statistically significant predictors of grade ${\geq}2$ radiation pneumonitis in patients with stage III non-small cell lung cancer undergoing definitive radiotherapy. The cutoff values for MLD and $V_{30}$ were 16 Gy and 18%, respectively.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6311-6318
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• 2012

Background: HER2/neu overexpression due to gene amplification is an important factor in breast cancer, modifying the sensitivity to anti-HER2 monoclonal antibody therapy. The clinical significance of HER2 expression in non small cell lung carcinoma (NSCLC) is currently under evaluation. The tumor suppressor gene PTEN negatively regulates the HER2/PI3K/Akt signalling pathway. The purpose of this study was to evaluate the role of simultaneous alteration in HER2 and PTEN protein expression in relation to biological behaviour of NSCLCs. Materials and Methods: Protein expression was determined by immunohistochemistry in sixty-one (n=61) NSCLC cases along with CISH for HER2 gene analysis and detection of chromosome 17 aneuploidy. Patients were followed-up for a period of 34 to 41 months after surgery. Results: HER2 overexpression (2+/3+score) was detected in 17 (27.9%) patients while loss of PTEN expression was observed in 24 (39.3%) cases, low expression in 29 (47.6%) and overexpression in 8 (13.1%). Simultaneous HER2 overexpression and PTEN low/loss of expression were correlated with metastasis (71.4% vs 36.2% p=0.03). Analysis in the subgroup of 22 patients of pTNM stage III with lymph node status N1 or N2 revealed that there was a relationship between the number of positive regional lymph node groups and simultaneous deregulation of the two genes (p=0.04). Multivariate analysis determined that HER2 overexpression was associated with an increasing risk of developing metastases (OR: 4.3; 95%CI: 1.2-15.9; p: 0.03) while PTEN overexpression was associated with lower risk (OR: 0.1; 95%CI: 0.1, 1.0; p: 0.05). Conclusions: Simultaneous HER2/PTEN deregulation is a significant genetic event that leads to a more aggressive phenotype of NSCLC.

• The Korean Journal of Cytopathology
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• v.1 no.2
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• pp.152-157
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• 1990

A 70-year-old female who was diagnosed as myxoid chondrosarcoma by fine needle aspiration of a pleural mass is described. She presented with left chest discomfort of 4 months' duration and aggravating dyspnea and chest pain for 2 months. Chest X-ray and CT scan revealed a large lobulated low density mass invading chest wall at the left pleural cavity and massive pleural fluid. Fine needle aspiration was done under the impression of mesothelioma or metastatic cancer. The aspirates from the mass were very cellular and composed of isolated or clustered forms of large plump cells. Abundant cytoplasm was blulsh opaque and the margin was rounded in the isolated cells, whereas clustered cells show ill-defined ceil borders and aggregating tendency. The nuclei were eccentric, round to ovoid, and had fine chromatin pattern and multiple small nucleoli. Cellular pleomorphism or mitotic figure was not definite. These findings were consistent with cytologic features of chondrosarcoma. Final diagnosis was confirmed as myxoid chondrosarcoma by mediastinoscopic biopsy and the tumor showed strong positivity for S-100 protein.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3057-3063
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• 2014

Background: Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) has been intensively studied. The gold standard for ALK detection is FISH, but this is not routinely conducted in clinical practice, so that the IHC method has a role. The aim of this study was to identify the incidence of ALK rearrangement and risk or prognostic factors for ALK positivity using both of IHC and FISH methods. Materials and Methods: From January 2008 to December 2012, 267 completely resected NSCLC patients in Chiang Mai University Hospital were enrolled in this study. Clinical and pathological variables and outcomes of treatment were retrospectively reviewed. IHC and FISH were used to evaluate ALK rearrangement. Sensitivity and specificity of IHC were analyzed. Multivariable analysis was used to identify clinico-pathological correlations with positive results of IHC and clinical outcomes. Results: Twenty-two (8.2%) of 267 specimens were IHC-positive for ALK with intense cytoplasmic staining, whereas only 10 (3.8%) were FISH-positive. Sensitivity, specificity and the positive likelihood ratio with IHC were 80.0%, 94.9%, and 15.8 respectively. Age less than 55 years (RR 4.4, 95%CI 1.78-10.73, p value=0.001) and presence of visceral pleural invasion (VPI) (RR 2.9, 95%CI 1.21-6.78, p value =0.017) were identified as risk factors for ALK rearrangement with FISH. There were no statistically significant differences in other clinical and pathological variables. ALK rearrangement was not a prognostic factor for tumor recurrence or overall survival. Conclusions: The incidences of ALK positivity in completely resected NSCLCs in northern Thailand were 8.2% by IHC and 3.8% by FISH. IHC with mouse monoclonal, Ventana D5F3 antibody can be used as a screening tool before FISH method because of high specificity and high positive likelihood ratio. Age less than 55 years and VPI are risk factors for ALK positivity.

• Journal of Chest Surgery
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• v.16 no.2
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• pp.231-242
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• 1983

A clinical study was performed on 75 cases of the esophageal cancer and benign esophageal diseases experienced at Department of thoracic & cardiovascular surgery, School of Medicine, Keimyung University during 3 year period from 1978 to 1982. Of 75 cases of the surgical esophageal diseases, there were 35 patients of the esophageal cancer. 17 patients of benign esophageal stenosis, 10 patients of esophageal perforation, 4 patients of diverticulum. 3 patients of achalasia, 2 patients of congenital T-E fistula, one of upper esophageal web, one of esophageal foreign body, one of leiomyoma and patient of hemangioma. First, esophageal carcinoma was more frequent in men than in women by a ratio of five to one, and the peak incidence occurred in the 5th to 6th decade. Dysphagia was the most common symptom in 88.6 percent of our cases. The tumor was located mostly in the middle & the lower one third [91.4%]. The histological diagnosis was made in 35 cases. The squamous cell carcinoma was the most common [82.9%] and the rest was the adenocarcinoma in the lower one third [17.1%]. Thirty-five cases were operated and resection was feasible in the twenty-five patients [71.4%] with 2 cases of hospital mortality [5.7%]. All but two of the esophageal stenosis were caused by corrosive esophagitis and ages ranged from 7 to 70 years with average age of 32 years. Corrective operations were performed on 17 patients of esophageal stenosis of whom 12 patients had esophagocologastrostomy, 3 patients esophagogastrostomy and in non-corrosive esophageal stenosis one case and esophagoplasty and another case had release of external compression. There was one complication of stenosis of the esophageal perforation were traumatic in five cases, empyema in three cases, caustics in one case and postemetic in one case. 10 patients of the esophageal perforation underwent operation: primary closure in 5 cases, two staged colon interposition in 2, esophagogastrostomy in 1 and closed thoracotomy in 2 cases There were 2 complications of leakage of anastomosis sites in postoperative period. 4 patients of traction type of diverticulum underwent diverticulectomy & 3 patients of achalasia underwent modified Heller`s operation. 2 patients of congenital esophageal atresia had distal tracheoesophageal fistula & underwent one staged operation with the results of one death caused by pneumonia. Upper esophageal web had divulsion through the esophagoscope and foreign body in upper esophagus was removed through cervical esophagotomy. One case of leiomyoma in esophagus had esophagectomy and reconstruction with right colon. And one case of hemangioma in esophagus had esophagectomy & esophagogastrostomy.