• Journal of Chest Surgery
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• v.34 no.6
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• pp.447-453
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• 2001

Background: Although pulmonary resection is the standard approach for the management of pulmonary metastases from soft tissue sarcoma, most of them are unresectable and chemotherapy remains the only option. The effectiveness of the cytotoxic drugs may be limited by the toxicities that occur before the therapeutic dose is reached. The regional administration of doxorubicin using pulmonary arterial perfusion in a rodent model can produce 10 to 25 times higher concentrations in the lung than systemic administration with minimal systemic toxicities. However, it is unclear whether a high concentration of doxorubicin has beneficial effects for killing cancer cells. Material and Method: We studied this to evaluate the dose-dependent cytotoxic and apoptotic effects of doxorubicin on methylcholanthrene-induced rat fibrosarcoma(MCA) cells. This study examined the cytotoxicity and apoptosis-related gene expressions(Fas, FasL, Bax, caspase 1, caspase 2, caspase 8, Bcl-2, Bcl-xL, Bcl-xS) in MCA cells after 24 hours exposure to various concentrations of doxorubicin such as 1, 5, 10, 50, and 100 $\mu$M. Result: Dose-dependent cytotoxicity was observed after 24 hours exposure to doxorubicin. However, peak apoptosis after 24 hours exposure was observed at 5 $\mu$M of doxorubicin. Above 5 $\mu$M, apoptotic activity was decreased with dose-increment. All mRNA levels of apoptosis-related genes after 24 hours exposure were up-regulated above the control level at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment except caspase 8, which showed higher levels than the control level at 5 $\mu$M. Apoptosis-related protein levels were highest at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment. However, Bax and Bcl-xL proteins steadily showed higher levels than the control throughout the different concentrations of doxorubicin. Conclusion: These results suggest that apoptosis is the main cytotoxic mechanism in low concentrations of doxorubicin in MCA cells and apoptosis-related genes, such as Bax, caspase 8, and Bcl-xL, are involved. At high concentrations, doxorubicin still can kill MCA cells, even when apoptosis is inhibited, and have its propriety for achieving much cytotoxicity against MCA cells.

• Journal of Chest Surgery
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• v.42 no.6
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• pp.732-737
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• 2009

Background: Many video-assisted thoracic surgery (VATS) lobectomies are performed as a potential alternative to thoracotomy despite the controversy about the safety and the associated morbidity/mortality rates. Material and Method: Between November 2006 and August 2008, we performed 87 lobectomies (VATS 36, Thoracotomy 51) and we retrospectively reviewed the surgical treatment results. A VATS lobectomy was performed by a 4~5 cm thoracotomy without rib spreading and this included anatomic hilar dissection, individual vessel and bronchus stapling and lymph node dissection. Result: We studied 52 male and 35 female patients whose age ranged from 6 to 79 (average age: $59.8{\pm}15.0$ years). The cases were diagnosed with lung cancer (66) (SQC 24, ADC 38, others 4), pulmonary metastasis (2), carcinoid (2) and benign diseases (17). There was no intraoperative death. Postoperative complications were seen in 5 (15.6%) VATS and 33 (64.7%) thoracotomies, and perioperative death caused by adult respiratory distress syndrome occurred in 1 (2.8%) VATS and 3 (5.9%) thoracotomies. Three patients Underwent conversion to thoracotomy (8.3%). The mean time to chest tube removal was 6 days for VATS and 9.4 days for thoracotomy (p<0.001), and the mean length of the hospital stay was 8 days for VATS and 12.8 days for thoracotomy (p<0.001). Conclusion: VATS lobectomy can be performed safely with low morbidity/mortality rates. Furthermore, all the patients benefited from earlier postoperative rehabilitation and less pain and they were candidates for an earlier return to normal activities.

• Radiation Oncology Journal
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• v.7 no.2
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• pp.247-257
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• 1989

Thirty patients with nonresectable hepatocellular carcinoma (HCC) due to either locally advanced lesion or association with liver cirrhosis, treated with combined radiotherapy and hyperthermia between April 1988 and July 1988, at Dept. of Radiation Oncology, Yonsei university College of medicine, were analysed. External radiotherapy of a total dose of 3060cGy/3.5 wks was given. Hyperthermia was given twice a week with a total of 6 treatment sessions using 8MHz radiofrequency capacitive type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases hyperthermia was given within 30 minutes after radiotherapy for 30~60min. Temperature was measured by inserting thermocouple into the tumor mass under the ultrasonographic guidance only for those who had not bleeding tendency. As a result, partial response (PR) was achieved in 12 patients (40%), and symptomatic improvement was observed in 22 patients (78.6%) among 28 patients who had suffered from abdominal pain. The most significant factor affecting the tumor response rate was the type of tumor (single massive: 10/14, 71.4%; diffuse infiltrative: 2/10, 20%; multinodular:0/6, 0%; p<0.005). There were not any significant side effects relating to combined treatment. The overall 1 year survival rate was 34%, with 50% in the PR group and 22% in the no response group (NR), respectively. Median survival was 6.5 months and longer for those of PR than of NR (11 mos. vs 5, p<0.05). In conclusion, combined radiotherapy and hyperthermia appeared to be effective in local control and symptomatic palliation of HCC. Further study including a larger number of the patients to confirm its effect in survival and detrimental side effect should be urged.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.271-276
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• 1991

A series of 510 patients with carcinoma of the uterine cervix given the curative radiation therapy from March 1979 through December 1986 was evaluated to determine the value of intravenous pyelography (IVP), cystoscopy, sigmoidoscopy, and abdomino-pelvic CT as staging work-up prior to treatment. On IVP and cystoscopy, $10.7\%$(49/456) and $5.3\%$(24/452) showed abnormality, respectively, but only $0.7\%$(3/413) did on sigmoidoscopy. As a result of these work-ups prerequisite to FIGO staging, twenty six ($5.1\%$) out of 510 patients were upstaged from the stage determined by the findings of physical examination alone. The proportions of upstaging in each stage were as follows; none in stage IB (35), IIA (89) and IIIA (8), $7.9\%$(20/252) in stage IIB (14 patients to FIGO stage IIIB, 6 patients to FIGO stage IVA), and $4.8\%$(6/126) in stage IIIB (all to FIGO stage IVA). Positive findings of staging work-ups were found only in patients with advanced stages of stage IIB or over determined by physical examination alone but not in those with earlier stages. CT was performed in 337 patients. CT detected pelvic lymph node (LN) enlargement in $25.2\%$ (85/337) and paraaortic LN enlargement in $7.4\%$(25/337). Pelvic LN positivity was well correlated with increasing stage but paraaortic LN positivity was not. In the evaluation of parametrial involvement, CT findings were in accordance with those of physical examination only in $65.6\%$ (442/674). When compared with endoscopic studeies, CT had much lower positive predictive value than negative predicitive value in the evaluation of adjacent organ invasion. The staging work-ups should be individualized by the disease extent of each patient, and then the efficiency of work-uus may be increased without compromising the appropriate FIGO staging and treatment.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.277-284
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• 1991

Survival data, prognostic factors, and patterns of failure were retrospectively analyzed for a total of 76 patients with adenocarcinoma of the uterine cervix treated between January 1981 and December 1987, which represents $4.1\%$ of all primary cervical carcinomas treated, at Department of Radiation Oncology, Yensei Cancer Center, Yonsei University College of Medicine. The mean age of the patients was 49 years (range, $27\~79$ years) and the peak incidence was in the group 50 to 59 years of age. More half of the patients were postmenopausal (46/76= $60.5\%$). Most patients ($76\%$) had abnormal vaginal bleeding either alone or in combination with other symptoms. The proportion of stage IIb was $43.4\%$. There were 4 major histologic subtypes: pure adenocarcinoma (48/76=$63.2\%$), adenosquamous carcinoma (20/76=$26.3\%$), papillary (5/76=$6.6\%$) and clear cell carcinoma (3/76=$3.9\%$). Of the many clinicopathologic variables evaluated for prognosis, the most significant prognostic factors were stage of disease and the size of tumor. The overall 5-year survival rate was $68\%$, and the 5-year survival rates for stage Ib, II and III were $90\%,\;66\%\;and\;54\%$, respectively. Control of pelvic tumors was achieved in $93.8\%,\;90.2\%\;and\;50.0\%$ of cases of stage Ib, II and III disease, respectively. In present study, treatment modalities (radiation therapy alone/combined operative and radiation therapy) did not affect the local control of tumor and the survival.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.67-76
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• 2006

Purpose: Oral mucositis is a common toxicity of radiation or chemotherapy, which is used a treatment for head and neck cancer. We investigated effects of recombinant human epidermal growth factor (rhEGF) on radiation-induced oral mucositis in rat model. Materials and Methods: Spraque-Dawley rats (7 per group) exposed to a single dose of 25 Gy (day 0) on their head, except for one group, were randomly divided into un-treated, vehicle-treated, and two rhEGF-treated groups. Rats were topically applied with rhEGF (15 or $30{\mu}g/oral$ cavity/day) or vehicle to their oral mucosa. Survival rate of rats, weight changes, and food intakes were examined from day 0 to 18 after radiation. Histology study was performed from oral mucosa of rats at day 7 and 18 after radiation. Results: rhEGF-treated groups (15 or $30{\mu}g/oral$) showed all survival rate 33%, whereas un-treated and vehicle-treated groups showed all survival rate 0% at the end of experiment. rhEGF-treated groups statistically had less weight loss compared to vehicle-treated group from day 2 to 7 after radiation. Food intake of rats with rhEGF treatment turned to increase at day 14 after radiation. At 7 day after radiation, un-treated and vehicle-treated groups showed severe pseudomembraneous or ulcerative oral mucositis. On the other hand, rhEGF-treated groups had no more than cellular swelling and degeneration of epidermal cells in oral mucosa of rats. Conclusion: These results suggest that rhEGF has significantly positive effects on radiation-induced oral mucositis in rats. rhEGF display a therapeutic potential on a clinical level.

• Radiation Oncology Journal
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• v.23 no.2
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• pp.123-130
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• 2005

Purpose: We wanted to improve the setup reproducibility of breast cancer patients when utilizing a commercially available breast board for radiation therapy. The breast board was modified by using a new head rest and 2 types of board fixation devices. Materials and Methods: A conventional head/neck rest was modified to be positioned in various slots of the breast board, and it was fabricated 1 cm thinner to provide more comfort to a patient when the patient's neck was rotated. This rest improves the uncertainty of the daily setup. Also, the sagging problems at the left and right sides became negligible with the two types of board fixation devices: (1) the stair type, and (2) the arm type. The first device consists of an upper/lower holder with 4 stair-types of grooves and 4 rectangular Inserts. In order to cover the whole range of vertical setup of the breast board, 4 rectangular inserts were needed, and each covered 10 steps. The arm-type fixation device was also fabricated and attached to the breast board, It had two aluminum bars that were fixed by utilizing a lock-type of screw. These devises were evaluated with two volunteers in order to prove the effectiveness of the improved setup accuracy. Results; The developed cranio-caudal fixation device demonstrated that it could reduce the cranio-caudal error by nearly $55\%$ compared to the old device. As for left-and-right inclination, the stair-type and arm-type fixation devices can reduce the relative inclination by nearly $80\%$ and $90\%$, respectively, compared to the breast board without the fixation device. Conclusion: It was verified that the developed devices were effective for positioning the patients and for avoiding inclination of the breast board.

• Radiation Oncology Journal
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• v.23 no.2
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• pp.71-77
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• 2005

Purpose: This retrospective study was conduced to analyze the treatment results and to evaluate the prognostic factors affecting the survival of nasopharyngeal carcinoma patients. Materials and Methods: From 1987 to 2002, we analyzed 43 patients who had nasopharyngeal carcinomas that were histologically confirmed and who had also completed the planned radiation therapy course at Keimyung University Dongsan Medical Center According to the 6th edition of American Joint Committee on Cancer staging system, 12 patients ($27.9\%$) were at Stage 11, 13 ($30.2\%$) were at Stage III and 18 ($41.9\%$) were at Stage IV Histopathologically, there were 15 ($34.9\%$) squamous cell carcinomas, 8 ($18.5\%$) nonkeratinizing carcinomas, 17 ($39.5\%$) undifferentiated carcinomas, and 3 ($7.0\%$) lymphoepitheliomas. Among the total 43 patients, 31 patients ($72.1\%$) were treated with only radiation therapy. Neoadjuvant chemotherapy was peformed on 7 patients ($16.3\%$) and concurrent chemoradiotherapy was performed on S patients ($11.6\%$). Cisplatin and 5-Fluorouracil were administered to 11 patients for 4 cycles, and Cisplatin and Taxotere were administered to 1 patient for 6 cycles. The range of the total radiation dose delivered to the primary tumor was from 61.2 to 84 Gy (median 70.4 Gy), The follow-up period ranged from 2 to 197 months with median follow-up of 84 months. Results: The local control rate at 6 months after radiation therapy was $90.7\%$. The five year overall survival and disease free survival rates were $50.7\%$ and $48.9\%$, respectively. On the multivariate analysis, the age, T-stage ($T_{1-3}\;vs\;T_4$), N-stage and AJCC stage were the statistically significant prognostic factors affecting survival (p<0.05). The patterns of failure were as follows: local failure only in 3 patients ($7.0\%$), local and systemic failure in 1 patient ($2.3\%$), and distant metastasis only in 11 patients ($25.6\%$). Conclusion: The prognostic factors affecting the outcome of nasopharyngeal carcinoma were age, T-stage (7$T_{1-3}\;vs\;T_4$), N-stage and stage. Because systemic metastasis was the main failure pattern noted for nasopharyngeal carcinoma, systemic chemotherapy is needed to decrease the rate of distant metastasis for nasopharyngeal carcinoma. In audition, research for more effective chemotherapeutical regimens and schedules is also needed.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.316-324
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• 2004

Purpose : In radiotherapy of tumors in liver, enough planning target volume (PTV) margins are necessary to compensate breathing-related movement of tumor volumes. To overcome the problems, this study aims to obtain patients' body movements by using a moving phantom and an ultrasonic sensor, and to develop respiration sating techniques that can adjust patients' beds by using reversed values of the data obtained. Materials and Methods : The phantom made to measure patients' body movements is composed of a microprocessor (BS II, 20 MHz, 8K Byte), a sensor (Ultra-Sonic, range $3\~3$ m), host computer (RS232C) and stepping motor (torque 2.3 Kg) etc., and the program to control and operate it was developed. The program allows the phantom to move within the maximum range of 2 cm, its movements and corrections to take place In order, and x, y and z to move successively. After the moving phantom was adjusted by entering random movement data (three dimensional data form with distance of 2 cm), and the phantom movements were acquired using the ultra sonic sensor, the two data were compared and analyzed. And then, after the movements by respiration were acquired by using guinea pigs, the real-time respiration gating techniques were drawn by operating the phantom with the reversed values of the data. Results : The result of analyzing the acquisition-correction delay time the three types of data values and about each value separately shows that the data values coincided with one another within $1\%$ and that the acquisition-correction delay time was obtained real-time $(2.34{\times}10^{-4}sec)$. Conclusion : This study successfully confirms the clinic application possibility of respiration gating techniques by using a moving phantom and an ultrasonic sensor. With ongoing development of additional analysis system, which can be used in real-time set-up reproducibility analysis, it may be beneficially used in radiotherapy of moving tumors.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.57-63
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• 2010

Purpose: We performed an immunohistochemical study with pre-treatment biopsy specimens to evaluate the prognostic significance of four biomolecular markers which can be used as a predictive assay for radiotherapy (RT) treatment of nasopharyngeal carcinoma (NPC). Materials and Methods: From January 1998 through December 2006, 68 patients were histologically diagnosed as non-metastatic NPC and treated by RT. Only 38 patients had the paraffin block for the immunohistochemical study. Thirty-one patients had undifferentiated carcinoma and 7 patients had squamous cell carcinoma. Thirtytwo patients (84%) had advanced stage NPC (2002 AJCC Stage III~IV). Immunohistochemical staining was performed for Met, COX-2, nm23-H1, and epidermal growth factor receptor (EGFR) expression using routine methods. Results: The median follow-up time was 30 months (range, 11 to 83 months) for all patients, and 39 months (range, 19 to 83 months) for surviving patients. The 5-year overall survival (OS) rate of the patients with high Met extent (${\geq}50%$) was significantly lower than that of the patients with low Met extent (48% vs. 84%, p=0.02). In addition, Met extent was also a significant prognostic factor in multivariate analysis (p=0.01). No correlation was observed between Met extent and T stage, N stage, stage group, gender, age, and the response to chemotherapy or RT. Met extent showed moderate correlation with COX-2 expression (Pearson coefficient 0.496, p<0.01), but COX-2 expression did not affect OS. Neither nm23-H1 or EGFR expression was a prognostic factor for OS in this study. Conclusion: High Met extent (${\geq}50%$) might be an independent prognostic factor that predicts poor OS in NPC treated with RT.