• Radiation Oncology Journal
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• v.27 no.1
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• pp.29-34
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• 2009

Purpose: This study was designed to evaluate long-term results in terms of failure, survival and voice preservation after radiation therapy for early glottic cancer. Materials and Methods: From February 1988 to December 2003, 70 patients with early glottic cancer were treated with radiation therapy at Keimyung University Dongsan Medical Center. Patient age distribution was from 39 to 79 years, with a median age of 62 years. All patients had squamous cell carcinoma. According to the TNM stage, 58 patients had stage I disease, 12 patients had stage II disease; 67 patients were male. The laryngeal area was irradiated with the use of bilateral opposing fields with/without a wedge filter with 6 MV photons at a total dose of $54{\sim}70.2$ Gy in $1.8{\sim}2.2$ Gy fractions over $6{\sim}8$ weeks. We delivered a median radiation dose of 60 Gy for stage I patients and a median radiation dose of 66 Gy for stage II patients. Salvage surgery was performed in patients with local recurrence. The voice preservation rate was analyzed after all treatments including salvage surgery. Follow-up periods were from 13 to 180 months, with a median follow-up period of 77.5 months. The survival rate was analyzed by the use of the Kaplan Meier method and log rank test. A comparison of two groups was performed with the use of the chi-squared test. Results: The local control rate was 98.5% (69/70). The five-year-overall survival rate was 93.9%. The five-year disease free survival rate (5YDFS) was 84.1% and the 5YDFS after radiation and salvage surgery was 92.8%. According to stage, the 5YDFS was 93.1% and 91.7% for stage I and stage II respectively. Thirteen patients (18.5%) had local failure with 24 months of median time to local failure and nine patients received salvage surgery; however, four patients were lost to follow-up after a diagnosis of recurrence. Only two patients died due to a distant metastasis at 33 months and 71 months after radiation therapy, respectively. Nine patients died due to other diseases with a median time of 73 months. There were no severe acute or chronic complications after radiation therapy. Voice preservation was ultimately achieved in 88.5% (62/70) of patients. Conclusion: We considered that radiation therapy was effective and we achieved excellent survival and voice preservation in early laryngeal cancer. The use of radiation therapy should be the first choice for the treatment of early glottic cancer.

• Tuberculosis and Respiratory Diseases
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• v.60 no.2
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• pp.160-170
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• 2006

Background : The aberrant promoter hypermethylation of p16INK4a, as a tumor suppressor gene, is contributory factor to non-small cell lung cancer(NSCLC). However, its potential diagnostic impact of lung cancer is unclear. This study measured the level of $p16^{INK4a}$ promoter hypermethylation in the sputum and blood, and compared this with the level measured in the tissue obtained from NSCLC and pulmonary inflammation. Methods : Of the patients who visited the Our Lady of Mercy Hospital in Incheon, Korea for an evaluation of a lung mass and underwent blood, sputum, and tissue tests, 23patients (18 NSCLC, 5 pulmonary inflammation) were enrolled in this study. DNA was extracted from each sample and the level of p16INK4amethylation was determined using methylation-specific polymerase chain reaction. Results : $p16^{INK4a}$ methylation of the blood was observed in 88.9% (16 of 18) and 20.0% (1 of 5) of NSCLC and from pulmonary inflammation samples, respectively (P=0.008). Methylation of the sputum was observed in 83.3% (10 of 12) 80.0% (4 of 5) of NSCLC and pulmonary inflammation samples, respectively (P=1.00). Among the 8 NSCLC tissue samples, methylation changes were detected in 75.0% of samples (6 cases). Four out of seven tissue samples (57.1%) showed concordance, being methylated in both the blood and sputum. Conclusions : There was a higher level of $p16^{INK4a}$ methylation of the blood from NSCLC patients than from pulmonary inflammation. The tissue showed a high concordance with the blood in the NSCLC samples. These findings suggest that $p16^{INK4a}$ promoter hypermethylation of the blood can used to discriminate between NSCLC and pulmonary inflammation.

• Tuberculosis and Respiratory Diseases
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• v.64 no.4
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• pp.278-284
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• 2008

Background: TRAIL is a promising anticancer agent which induces selective tumor cell death due to a unique receptor system that includes death receptors and decoy receptors. DR5 TRAIL receptor is an originally identified p53-regulated death receptor gene that was induced, by doxorubicine, only in cells with a wild-type p53 status. We investigated that focused on the correlation between the DR5 and p53 expressions in non-small cell lung cancer (NSCLC). Methods: Immunohistochemical analysis, with using avidin-biotinylated horseradish peroxidase complex, was carried out in 89 surgically resected NSCLC formalin-fixed paraffin-embedded tissue sections. As primary antibodies, we used anti-DR5 polyclonal antibody and anti-p53 monoclonal antibody. A negative control was processed with each slide. The positive tumor cells were quantified twice and these values were expressed as percentage of the total number of tumor cells, and the intensity of immunostaining was expressed. The analysis of the DR5 expression was done separately in tumor area and in a nearby region of normal tissue. Results: The DR5 expression was high in the bronchial epithelium (89% of cases) but this was almost absent in type I & II pneumocytes, lymphocytes and smooth muscle cells. High DR5 expression rate in tumor was seen in 28% (15/53) of squamous cell carcinomas, in 47% (15/32) of adenocarcinomas and, in 50% (2/4) of large cell carcinomas. The DR5 expression did not show any statistical significance relationship with the T stage, N stage, or survival. However, the DR5 expression showed significant inverse correlation with the p53 expression. (p< 0.01). Conclusion: We demonstrated that the DR5 expression in NSCLC via immunohistochemical analysis is relatively tumor-specific except for that in the normal bronchial epithelium and it is significantly dependent on the p53 status. This might be in vivo evidence for the significance of the DR5 gene as a p53 downstream gene.

• Journal of Yeungnam Medical Science
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• v.11 no.1
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• pp.72-81
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• 1994

Total 55 patients with nonsmall cell lung cancer treated with radiation therapy at Department of Therapeutic Radiology, Yeungnam University Hospital, between May-1 1986 and April-30 1993 were retrospectively analyzed by clinical characteristics, failure patterns, follow up duration and survival ratio according to prognostic factors. Obtained results were as follows : 1. Male to female ratio was 17.3 2. Sixth and seventh decades were predominant age group. 3. The patients were 8 in stage I-II, 34 in stage IIIA, 13 in stage IIIb, respectively. 4. Forty five patients out of 55 were squamous cell carcinoma. 5. Primary tumor were originated from upper lobe bronchi predominantly. 6. The size of the primary tumor, lymph node involvement and the degree of differentiation were important in evaluation of prognosis. 7. In conclusion, for patients with poor prognostic factors systemic chemotherapy and multidisciplinary approach were recommended for better treatment outcome and improvement of survival.

• Radiation Oncology Journal
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• v.21 no.2
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• pp.112-117
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• 2003

Purpose: The effects of hypefractionation radiation therapy, such as the failure pattern and survival, on the treatment results in advanced stage head and neck cancer were studied. Materials and Methods: Between September 1990 and October 1998, 24 patients with advanced stage (III, IV) head and neck cancers, were treated using hyperfractionation radiation therapy in the Department of Radiation Oncology at the Keimyung University Dongsan Medical Center. The male to female ratio was 7 : 1, and the age range from 38 to 71 years with the median of 56 years. With regard to the TNM stage, 11 patients were stage III and 13 were stage IV. The sites of primary cancer were the nasopharynx in six, the hypopharynx in 6, the larynx in five, the oropharynx in three, the maxillary sinus in three, and the oral cavity in one patient. The radiotherapy was delivered by 6 MV X-ray, with a fraction size of 1.2 Gy at two fractions a day, with at least 6 hours inter-fractional interval. The mean total radiation doses was 72 Gy, (ranging from 64.4 to 75.8 Gy). Follow-up periods ranged between 3 and 136 months, with the median of 52 months. Results: The overall survival rates at 3 and 5 years in all patients were 66.7$\%$, and 52.4$\%$. The disease-free survival rates at 3 and S years (3YDFS, 5YDFS) in all patients were 66.7$\%$ and 47.6$\%$. The 3YDFS and 5YDFS in stage III patients were 81.8$\%$ and 63.6$\%$, and those in stage IV patients were 53.8$\%$ and 32.3$\%$. Ten patients were alive with no local nor distant failures at the time of analyses. Six patients (25$\%$) died due to distant metastasis and 12.5$\%$ died due to local failure. Distant metastasis was the major cause of failure, but 2 patients died due to unknown failures and 3 of other diseases. The distant metastasis sites were the lung (3 patients), the bone (1 patient), and the liver (2 patients). One patient died of second esophageal cancer. There were no severe late complications, with the exception of 1 osteo-radionecrosis of the mandible 58 months after treatment. Conclusion: Although this study was peformed on small patients group, we considered hypefractionated radiation therapy for the treatment of advanced stage head and neck cancer might improve the disease free survival and decrease the local failure with no increase in late complications despite of the slight Increase in acute complications.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.251-256
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• 2000

Purpose : To evaluate efficacy and complication of stereotactic radiosurgery using stereotactic body frame. Methods and Materials :From December 1997 to June 1999, 11 patients with primary and metastatic tumors were treated with stereotactic radiosurgery using stereotactic body frame(Precision TherapyTu). Three patients were treated with primary hepatoma and seven with metastatic tumor from liver, lung, breast, trachea and one with arteriovenous malformation on neck. We used vacuum pillow for immobilization and made skin marker on sternum and tibia area with chest marker and leg marker. Diaphragm control was used for reducing movement by respiration. CT-simulation and treatment planning were peformed. Set-up error was checked by CT-Simulator before each treatment. Dose were calculated on the 80$\~$90$\%$ isodose of isocenter dose and given consecutive 3 fractions for total dose of 30 Gy (10 Gy/fraction). Results :Median follow-up was 12 months. One patient (9$\%$) showed complete response and four Patients (36$\%$) showed partial response and others showed stable disease. Planning target volumes (PTV) ranged from 3 to 111 cc (mean 18.4 n). Set-up error was within 5 mm in all directions (X, Y, Z axis). There was no complication in all patients. Conclusion :In Primary and metastatic tumors, stereotactic body frame is very safe, accurate and effective treatment modality.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.68-76
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• 1998

Background: Patients with centrally recurred bronchogenic carcinoma make a complaint of many symptoms like hemoptysis, cough & dyspnea. At these conditions, the goal of treatment is only to relieve their symptoms. High dose rate brachytherapy(HDR-BT) is the palliative treatment modality of centrally located endobronchial tumor regardless of previous external irradiation(XRT) on the same site in symptomatic patients. Methods: We studied the effects of HDR-BT in 26 patients with symptomatic recurrent lung cancer. Patients(male: 24, mean age: 54yrs)were treated with HDR-BT underwent bronchoscopic placement of $^{192}Ir$ HDR after loading unit(Gammamed$^{(T)}$, Germany) to deliver 500cGY intraluminal irradiation at a depth of 1cm every lwk on 3 occasions. Evaluation at base line and 4wks after HDR brachytherapy included chest X-ray, bronchscopy, symptoms (Standadized Scale for dyspnea,cough,hemoptysis), and Karnofsky performance scale. Results: Endobronchial obstruction was improved in 11/26 patients(37%). Atelectasis in chest X-ray was improved in 5/15 patients(33%). Hemoptysis, dyspnea & cough were improved in 5/10 patients (50%), 5/8 patients (62%) & 10/18 patients (56%) respectively. Karnofsky performance status was changed from 76.4 scores in pretreatment to 77.6 scores after treatment. During HDR-BT, massive hemoptysis (2 patients) and pneumothorax(1 patient) were occurred as complications. Conclusion: We concluded that HDR-BT gave additional benefits for the control of symptoms and general performance and endobronchial obstruction & atelectasis. And HDR-BT will be an additional treatment for the recurrent and endobronchial obstructive lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.591-598
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• 2001

Background : Primary adenoid cystic carcinoma arising in the bronchus is an uncommon disease that is histologically and ultrastructurally identical to the salivary gland tumor of the same name and regarded as a slow growing low-grade malignancy. We examined its clinical characteristics. Method : We collected 13 Korean cases of primary adenoid cystic carcinoma arising in the bronchus including 5 cases of our own and 8 cases from the literature. Result : The patients ages ranged from 20 to 74. Men numbered 9 and women 4. The presenting symptoms were cough, dyspnea, and hemoptysis. The fiberoptic bronchoscopic findings were primarily hypervascular polypoid mass with a smooth surface that obstructed airway totally or near totally. There were three inoperable cases including two cases with distant metastasis to bone or cervical lymph node and one case with mediastinal invasion. The remaining 10 patients underwent surgical resection. Among them, two patients received postoperative radiotherapy. The median survival was 21 months in the 8 surgical and evaluable cases. One patient lived 13 years without recurrence. The prognosis was relatively favorable in operable cases. Conclusion : It was not common for primary adenoid cystic carcinoma arising in the bronchus to have distant metastasis or invasion to the mediastinum on presentation. The prognosis was relatively favorable in operable cases. It would be important to perform flexible bronchoscopy for early diagnosis and to do surgical treatment if possible.

• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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• pp.168-184
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• 2001

Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.5-19
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• 1998

Introduction: Direct histologic and bacteriologic examination of a representative specimen of lung tissue is the only certain method of providing an accurate diagnosis in various pulmonary diseases including diffuse pulmonary diseases. The purpose of national survey was to define the indication, incidence, effectiveness, safety and complication of open and thoracoscopic lung biopsy in korea. Methods: A multicenter registry of 37 university or general hospitals equipped more than 400 patient's bed were retrospectively collected and analyzed for 3 years from the January 1994 to December 1996 using the same registry protocol. Results: 1) There were 511 cases from the 37 hospitals during 3 years. The mean age was 50.2 years(${\pm}15.1$ years) and men was more prevalent than women(54.9% vs 45.9%). 2) The open lung biopsy was performed in 313 cases(62%) and thoracoscopic lung biopsy was performed in 192 cases(38%). The incidence of lung biopsy was more higher in diffuse lung disease(305 cases, 59.7%) than in localized lung disease(206 cases, 40.3%) 3) The duration after abnormalities was found in chest X-ray until lung biopsy was 82.4 days(open lung biopsy: 72.8 days, thoracoscopic lung biopsy: 99.4 days). The bronchoscopy was performed in 272 cases(53.2%), bronchoalveolar lavage was performed in 123 cases(24.1%) and percutaneous lung biopsy was performed in 72 cases(14.1%) before open or thoracoscopic lung biopsy. 4) There were 230 cases(45.0%) of interstitial lung disease, 133 cases(26.0%) of thoracic malignancies, 118 cases(23.1%) of infectious lung disease including tuberculosis and 30 cases (5.9 %) of other lung diseases including congenital anomalies. No significant differences were noted in diagnostic rate and disease characteristics between open lung biopsy and thoracoscopic lung biopsy. 5) The final diagnosis through an open or thoracoscopic lung biopsy was as same as the presumptive diagnosis before the biopsy in 302 cases(59.2%). The identical diagnostic rate was 66.5% in interstitial lung diseases, 58.7% in thoracic malignancies, 32.7% in lung infections, 55.1 % in pulmonary tuberculosis, 62.5% in other lung diseases including congenital anomalies. 6) One days after lung biopsy, $PaCO_2$ was increased from the prebiopsy level of $38.9{\pm}5.8mmHg$ to the $40.2{\pm}7.1mmHg$(P<0.05) and $PaO_2/FiO_2$ was decreased from the prebiopsy level of $380.3{\pm}109.3mmHg$ to the $339.2{\pm}138.2mmHg$(P=0.01). 7) There was a 10.1 % of complication after lung biopsy. The complication rate in open lung biopsy was much higher than in thoracoscopic lung biopsy(12.4% vs 5.8%, P<0.05). The incidence of complication was pneumothorax(23 cases, 4.6%), hemothorax(7 cases, 1.4%), death(6 cases, 1.2%) and others(15 cases, 2.9%). 8) The 5 cases of death due to lung biopsy were associated with open lung biopsy and one fatal case did not describe the method of lung biopsy. The underlying disease was 3 cases of thoracic malignancies(2 cases of bronchoalveolar cell cancer and one malignant mesothelioma), 2 cases of metastatic lung cancer, and one interstitial lung disease. The duration between open lung biopsy and death was $15.5{\pm}9.9$ days. 9) Despite the lung biopsy, 19 cases (3.7%) could not diagnosed. These findings were caused by biopsy was taken other than target lesion(5 cases), too small size to interpretate(3 cases), pathologic inability(11 cases). 10) The contribution of open or thoracoscopic lung biopsy to the final diagnosis was defininitely helpful(334 cases, 66.5%), moderately helpful(140 cases, 27.9%), not helpful or impossible to judge(28 cases, 5.6%). Overall, open or thoracoscopic lung biopsy were helpful to diagnose the lung lesion in 94.4 % of total cases. Conclusions: The open or thoracoscopic lung biopsy were relatively safe and reliable diagnostic method of lung lesion which could not diagnosed by other diagnostic approaches such as bronchoscopy. We recommend the thoracoscopic lung biopsy when the patients were in critical condition because the thoracoscopic biopsy was more safe and have equal diagnostic results compared with the open lung biopsy.