• Radiation Oncology Journal
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• v.12 no.1
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• pp.9-16
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• 1994

Hypothesis that hypoxic tumors should be more responsive to the addition of preferential hypoxic cell cytotoxin SR 4233 (tirapazamine) to fractionated irradiation was tested in the mouse SCCVll carcinoma and RIF-1 sarcoma, Model of hypoxic tumor was established using the tumor bed effect: tumors growing in the preirradiated tissue (preirradiated tumors) were more hypoxic than tumors growing in the unirradiated tissue (unirradiated tumors). When the tumors reached a mean volume of 100 $mm^{3}$, both unirradiated and preirradiated tumors were treated with a fractionated course of 6${\times}$2 Gy in 3 days or 8${\times}$2.5 Gy in 4 days with SR 4233 (0.08 mmol/kg/injection) given 30 minutes before each irradiation or without SR 4233. Compared to the unirradiated tumors, hypoxic preirradiated tumors were approximately 5 times more resistant to fractionated irradiation alone but were approximately 5 times more responsive to SR 4233. Addition of SR 4233 Potentiated the effect of fractionated irradiation in both unirradiated and preirradiated tumors. Potentiation in the preirradiated tumors was morequal to or greater than that in the unirradiated tumors and seemed to be higher for more fractionated treatment. We confirm the hypothesis in a transplantable mouse tumor. Present results suggest that radioresistance of some hypoxic tumors can be overcome with hypoxic cytotoxin.

• Tuberculosis and Respiratory Diseases
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• v.51 no.3
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• pp.224-231
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• 2001

Purpose : An anthracofibrosis(AF), dark multiple anthracotic pigmentations combined with narrowing and obstruction of bronchi, was reported to be strongly related with past and active pulmonary tuberculosis. This study was performed to determine whether anti-tuberculous regiemens would be helpful in patients with anthracofibrosis who failed to demonstrate the evidences of pulmonary tuberculosis. Methods : Twenty-two patients with multiple anthracotic pigmentations in bronchial mucosa with luminal narrowing were enrolled in this study. The bacteriological and histological findings for Mycobacterium tuberculosis was reviwed in each patients. They are composed of 8 males and 14 females ranging from 55 to 85 years old in age. Results: The most common symptoms were coughing(73%, 16/22), followed by sputum(41%, 9/22), dyspnea on exertion(32%, 7/22), and hemoptysis(27%, 6/22). The evidence of pulmonary tuberculosis, defined by positive AFB smear or culture of Mycobacterium tuberculosis from sputum or bronchial washing fluid or histological findings of granuloma with caseous necrosis, were found in eleven patients(50%) and the others has showed no evidences. Among 11 patients without pulmonary tuberculosis, only one patient showed the evidences of pulmonary tuberculosis after 16 months, and the 8 patients still showed no evidence of pulmonary tuberculosis during follow-up periods of ranging from 8 months to 60 months. Conclusions : Beause the anthracofibrosis is closely related to tuberculosis, it needs to find out extensively the evidences of tuberculosis in patients with anthracofibrosis. Chemotherapy for tuberculosis should be administrated only with confirmation of tuberculosis on bacteriologic study.

• Radiation Oncology Journal
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• v.14 no.3
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• pp.201-209
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• 1996

Purpose : To assess the efficacy of high dose rate - intracavitary radio-therapy (HDR-ICR) in the radiotherapy of FIGO stage IB squamous cell carcinoma of uterine cervix and to determine the optimum dose combination scheme of external radiotherapy and ICR to achieve acceptable local control without severe complication. Materials and Methods : One hundred and sixty two patients with FIGO stage Ib squamous cell carcinoma of uterine cervix who received definitive radiotherapy between May 1979 and December 1990 were retrospectively analyzed. All the patients received external radiotherapy combined with HDR-ICR. External dose of 40-46 Gy in 4.5-5 weeks was given to whole pelvis(median 45 Gy) and ICR dose of 30-39 Gy in 10-13 times was given to the point A. Midline shielding was done after 20-45 Gy of external radiotherapy(median 40 Gy) Summation of external dose Plus ICR dose to the point A range were 64.20-95.00 Gy. and mean was 83.94 Gy. We analyzed the local control rate, survival rate, and late complication rate. Rusults : Initial complete response rate was $99.4\%$ for all patients. Overall 5-year survival rate was $91.1\%$ and 5-year disease free survival rate was $90.9\%$. Local failure rate was $4.9\%$ and distant failure rate was $4.3\%$. Tumor size was the only significant prognostic factor. When tumor size greater than 3cm, 5-rear survival rate was $92.6\%$ and less than 3cm, that was $79.6\%$. Late complication rate was $23.5\%$ with $18.5\%$ of rectal complication and $4.9\%$ of bladder complication. Mean rectal dose summation of external midline dose plus ICR rectal point dose was lower in the patients without rectal complication(74.88 Gr) than those with rectal complication (78.87 Gy). Complication rate was increased with low rate of improvement of survival rate when summation of external midline dose plus point A or point R dose by ICR was greater than 70-75 Gy. Conclusion : The definitive radiation therapy using high dose rate ICR in FIGO stage IB uterine cervical cancer is effective treatment modality with good local control and survival rate without severe complication.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.244-250
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• 2000

Purpose : To see the relationship between the response to chemotherapy and the final outcome of neoadiuvant chemotherapy and radiotherapy in patients with mocanry advanced hypopharyngeal cancer. Methods and Materials :A retrospective analysis was done for thirty-two patients with locally advanced hypopharyngeal cancer treated in the Seoul National University Hospital with neoadiuvant chemotherapy and radiotherapy from August 1979 to July 1997. The patients were treated with Co-60 teletherapy unit or 4MV or 6MV photon beam produced by linear accelerator. Daily fractionation was 1.75 to 2 Gy, delivered five times a week. Total dose ranged from 60.8 Gy to 73.8 Gy. Twenty-nine patients received continuous infusion of cisplatin and 5-FU. Other patients were treated with cisplatin combined with bleomycin or vinblastin. Twenty-four (75$\%$) patients received all three prescribed cycles of chemotherapy delivered three weeks apart. Six patients received two cycles, and two patients received only one cycle. Results :The overall 2-year and 5-year survival rates are 65.6$\%$ and 43.0$\%$, respectively. 5-year local control rate is 34$\%$. Organ preservation for more than five years is achieved in 12 patients (38$\%$). After neoadjuvant chemotherapy, 24 patients achieved more than partial remission (PR): the response rate was 75$\%$ (24/32). Five patients had complete remission (CR), 19 patients PR, and 8 patients no response (NR). Among the 19 patients who had PR to chemotherapy, 8 patients achieved CR after radiotherapy. Among the 8 non-responders to chemotherapy, 2 patients achieved CR, and 6 patients achieved PR after radiotherapy. There was no non-responder after radiotherapy. The overall survival rates were 60$\%$ for CR to chemotherapy group, 35.1$\%$ for PR to chemotherapy group, and 50$\%$ for NR to chemotherapy group, respectively (p=0.93). There were significant difference in five-year overall survival rates between the patients with CR and PR after neoadjuvant chemotherapy and radiotherapy (73.3$\%$ vs. 14.7$\%$, p<0.01). The prognostic factor affecting overall survival was the response to overall treatment (CR vs. PR, p<0.01). Conclusion :In this study, there were only five patients who achieved CR after neoadiuvant chemotherapy. Therefore the difference of overall survival rates between CR and PR to chemotherapy group was not statistically significant. Only the response to chemo-radiotherapy was the most important prognostic factor. There needs to be more effort to improve CR rate of neoadjuvant chemotherapy and consideration for future use of concurrent chemoradiotherapy.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.558-570
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• 1996

Background : The detection of Collapsible airways has important therapeutic implications in chronic airway disease and bronchial asthma. The distinction of a purely collapsible airways disease from that of asthma is important because the treatment of the dormer may include the use of pursed lip breathing or nasal positive pressure ventilation whereas in the latter, pharmacologic approaches are used. One form of irreversible airflow limitation is collapsible airways, which has been shown to be a Component of asthma or to emphysema, it can be assessed by the volume difference between what exits the lung as determined by a spirometer and the volume compressed as measured by the plethysmography. Method : To investigate whether volume difference between slow and forced vital Capacity(SVC-FVC) by spirometry may be used as a surrogate index of airway collapse, we examined pulmonary function parameters before and after bronchodilator agent inhalation by spirometry and body plethysmography in 20 cases of patients with evidence of airflow limitation(chronic obstructive pulmonary disease 12 cases, stable bronchial asthma 7 cases, combined chronic obstructive pulmonary disease with asthma 1 case) and 20 cases of normal subjects without evidence of airflow limitation referred to the Pusan National University Hospital pulmonary function laboratory from January 1995 to July 1995 prospectively. Results : 1) Average and standard deviation of age, height, weight of patients with airflow limitation was $58.3{\pm}7.24$(yr), $166{\pm}8.0$(cm), $59.0{\pm}9.9$(kg) and those of normal subjects was $56.3{\pm}12.47$(yr), $165.9{\pm}6.9$(cm), $64.4{\pm}10.4$(kg), respectively. The differences of physical characteristics of both group were not significant statistically and male to female ratio was 14:6 in both groups. 2) The difference between slow vital capacity and forced vital capacity was $395{\pm}317ml$ in patients group and $154{\pm}176ml$ in normal group and there was statistically significance between two groups(p<0.05). Sensitivity and specificity were most higher when the cut-off value was 208ml. 3) After bronchodilator inhalation, reversible airway obstructions were shown in 16 cases of patients group, 7 cases of control group(p<0.05) by spirometry or body plethysmography d the differences of slow vital capacity and forced vital capacity in bronchodilator response group and nonresponse group were $300.4{\pm}306ml$, $144.7{\pm}180ml$ and this difference was statistically significant. 4) The difference between slow vital capacity and forced vital capacity before bronchodilator inhalation was correlated with airway resistance before bronchodilator(r=0.307 p=0.05), and the difference between slow vital capacity and forced vital capacity after bronchodilator was correlated with difference between slow vital capacity and forced vital capacity(r=0.559 p=0.0002), thoracic gas volume(r=0.488 p=0.002) before bronchodilator and airway resistance(r=0.583 p=0.0001), thoracic gas volume(r=0.375 p=0.0170) after bronchodilator, respectively. 5) The difference between slow vital capacity and forced vital capacity in smokers and nonsmokers was $257.5{\pm}303ml$, $277.5{\pm}276ml$, respectively and this difference did not reach statistical significance(p>0.05). Conclusion : The difference between slow vital capacity and forced vital capacity by spirometry may be useful for the detection of collapsible airway and may help decision making of therapeutic plans.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.369-377
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• 1997

Purpose : This study was Performed to identify the histopathologic feature by the reevaluation of the Pathologic specimen of the cervical tumors and to evaluate the clinical findings and the treatment results of the patients with small cell carcinoma of the cervix treated by radiotherapy. Materials and Methods : 2890 patients with cervical carcinoma received radiotherapy at the Department of Radiation Oncology. Yonsei Cancer Center, Yonsei University College of Medicine between October 1981 and April 1995. Of the 2890 patients in this data base, sixty were found to have small cell carcinomas $(2.08\%)$. Among them thirty six patients were transferred from other hospitals. the biopsy specimens of those Patients were not available. So we could review the slides of the other twenty four patients who were diagnosed at our hospital. Twenty four patients with small cell carcinoma of the cervix were analyzed retrospectively based on the assessment of H & E staining and other four immunohistochemical stains for neuroendocrine differentiation (neuron specific enolase, chromogranin. synaptophysin and Grimelius stain). And we also evaluate the Patients and tumor characteristics. response to radiation. patterns of failures, 5 year overall and disease free survival rates. Results : Thirteen tumors were neuroendocrine carcinomas(13/24 = $54.2\%$) and eleven tumors were squamous carcinomas, small cell type (11/24 = $47.8\%$) based on the assessment of H & E staining and other four neuroendocrine marker studies. So we classified the Patients two groups as neuroendocrine carcinoma and small cell type of squamous carcinoma, Among the 13 neuroendocrine carcinomas, five were well to moderately differentiated tumors and the other eight were Poorly differentiated or undifferentiated ones. The median age was 54 years old (range 23-79 years). Eight Patients had FIGO stage IB disease, 12 had stage 11, 3 had stage III and one had stage IV disease, Pelvic lymph node metastases were found in five Patients $(20.8\%)$. three of them were diagnosed by surgical histologic examination and the other two were diagnosed by CT scan. There was no difference between two histopathologic groups in terms of patients and tumor characteristics. response to radiation. 5 year overall and disease free survival rates. However the distant metastases rate was higher in neuroendocrine carcinoma Patients (6/13:$46.2\%$) than in small cell type of squamous carcinoma Patients (2/11:$18.2\%$), but there was no statistically significant difference because of the small number of patients (P>0.05). Conclusion : More than half of the small cell carcinoma of the cervix patients were neuroendocrine carcinoma (13/24 : $54.1\%$) by reevaluation of the biopsy specimen of the cervical tumors. The tendency of distant metastases of the neurolndocrine carcinoma was greater than those of the small cell type of squamous carcinoma $(46.2\%\;vs.\;18.2\%)$. But there were no differences in the patients and tumor characteristics and other clinical treatment results in both groups. These data suggest that radical local treatment such as radiotherapy or radical surgery combined with combination systemic cytotoxic chemotherapy might provide these patients with the best chance for cure.

• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.674-684
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• 1999

Background : It has been generally known that the incidence of lung cancer is higher in the patients with idopathic pumonary fibrosis (IPF) than those in general population. The reported incidence was variable from 4.8 to 43.2%. There were controversies on the most frequent cell type (squamous cell carcinoma vs. adenocarcinoma) and no study was done about the real concordance of cancer and the fibrotic lesion. And the pulmonary fibrosis may influence not only the development of cancer but also the treatment and prognosis of the cancer, but there was no report on that point. Method : Total 63 patients ($66.8{\pm}7.8$ year, M : F=61 : 2) were diagnosed as IPF combined with lung cancer (IFF-CA) at Asan Medical Center. A retrospective analysis was done about the risk factors of the lung cancer, pulmonary function test, the site of cancer(especially the relationship of the cancer with the fibrotic lesion), the histologic types, and the stage of cancer. The histologic types were compared with those of 2,660 patients with lung cancer who were diagnosed at the same institute for the same period. The effect of IPF on the treatment of the cancer was evaluated with the survival time after the detection of lung cancer. Results : The lung cancer was found in 63(22.9%) out of 281 patients with IPF. But in most of them(45 patients), lung cancer was detected at the same time with IPF and only in 18 patients, the cancer was diagnosed during the follow-up($25.2{\pm}17.7$ months) of IPF. So in our study, 6.7% of patients with IPF developed lung cancer during the course of the disease. The age ($66.8{\pm}7.84$ vs. $63.4{\pm}11.1$ years), percentage of smoker (88.9 vs. 67.2%), and the male gender (96.8 vs. 67.6%) were significantly higher in IPF-CA compared with lone IPF (p<0.05). The odds ratio of smoking was 4.7 compared with non smoking IPF controls. The lung cancer was located more frequently in the upper lobe and 55.5% was in the periphery of lung. The cancer was developed in the fibrotic lesion in 23 patients (35.9%), and in the majority of the patients, the cancer was separated from the fibrosis. The cell type of the lung cancer in IPF-CA was squamous cell carcinoma 34.9%, adenocarcinoma 30.2%, small cell carcinoma 19.0%, large cell undifferenciated carcinoma 6.3%, and others 9.5%. No significant difference in the distribution of histologic type of the lung cancer was found between IPF-CA and lone lung cancer. There was no significant difference in demographic features, cell types, location and the stage of the cancer between the group with concurrent IPF-CA and the group with cancer diagnosed during the follow up of IPF. There was a tendency (but statistically not significant : p=0.081) of higher incidence of adenocarcinoma among the cancers developed in the fibrotic area(43.5%) (F-CA) than in the cancers in non-fibrotic area (22.5%) (NF-CA). The prognosis of the patients with F-CA was poor (median survival : 4 months) compared with the patients with NF-CA (7 months, p=0.013), partly because the prevalence of severe IPF (the extent of fibrosis in HRCT 50%) was higher in F-CA group. Conclusion : These data suggest that the lung cancer in the patients with IPF has similar features to the ordinary lung cancer.

• Childhood Kidney Diseases
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• v.6 no.1
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• pp.75-84
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• 2002

Purpose Acute pyelonephritis of growing kidneys may result in renal scarring. TGF-${\beta}1$, inflammatory cytokine, has been suggested to play an important role in promoting renal scarring through apoptosis, suppression of cellular proliferation and fibrosis. We observed the effects of a potent anti-inflammatory agent, methylprednisolone on apoptosis and renal scarring in experimentally induced acute pyelonephritic weaning rats. Materials and Methods: To induce ascending pyelonephritis a saline solution containing Escherichia coli type ATCC No. 25922, pili- form (107 bacteria/mL) was infused into the bladder through the 16-guage silicone cannula for 48 hours to 102 three-week-old Sprague-Dawley rats (50-60g). Experimental groups were divided into three groups according to the treatment protocols, group I (ceftriaxone only, n=3l), group II (methylprednisolone+ceftriaxone n=28), control group (n=43) was not treated. Histopathologic scores of inflammatory changes, fibrosis and tubular atrophy, the apoptosis index and TGF-${\beta}1$ expression score were observed at post-infection 1 and 3 week. Datas were analysed using ANOVA test and P value below 0.05 was interpreted as significant. Results: The mortality rate ($21.4\%$) of group II was not different to the control group ($41.9\%$) and group I ($32.3\%$). The inflammatory score of group II ($0.8{\pm}0.87$) at week 1 was significantly lower than those of the control group ($2.3{\pm}0.87$) and Group I ($1.7{\pm}0.79$) (P<0.05). Apoptosis index of group II ($2.9{\pm}2.15$) at week 1 was significantly lower than those of the control group ($10.0{\pm}1.95$) and group 1 ($8.3{\pm}2.53$) (P<0.05). TCF-${\beta}1$ expression score of group II ($0.8{\pm}0.72$) at week 1 was significantly lower than those of the control group ($1.9{\pm}0.68$) and group I ($1.8{\pm}0.60$) (P<0.05). The fibrosis score of group II ($1.1{\pm}1.10$) at week 3 was significantly lower than that of the group I ($1.8{\pm}0.83$) (P<0.05) Conclusion: Conclusion Combined treatment with methylprednisolone and ceftriaxone reduced inflammation, fibrosis, apoptosis and TGF-${\beta}1$ expression in acute pyelonephritic weaning rats, compared to ceftriaxone alone. Anti-inflammatory agent supplemented to antibiotics could prevent renal scarring more effectively. (J Korean Soc Pediatr Nephrol 2002 ; 6 : 75-84)

• Radiation Oncology Journal
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• v.17 no.3
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• pp.209-216
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• 1999

Purpose : To evaluate the effectiveness of external radiation therapy and the prognostic factors, we retrospectively analyzed therapeutic results of malignant extrahepatic biliary obstruction (EHBO). Methods and Materials : We analyzed the results of the external radiation therapy in 59 patients of inoperable malignant EHBO who had been treated with more than 10 Gy of external radiation therapy from April 1984 to December 1990. There were 21 stomach cancer ($35.6\%$), 12 pancreas cancer ($20.3\%$), 15 extrahepatic biliary cancer ($18.0\%$) and 11 another cancer ($18.0\%$). Their pathologies were confirmed in 31 patients ($52.5\%$). They divided into 27 adenocarcinoma and 4 nonadenocarcinoma. Their chief complaints were jaundice in 47 patients ($79.7\%$) and abdominal pain in 15 patients ($49.2\%$). Twelve patients had slightly increased bilirubin level in liver function test without jaundice. We treated twenty four patients ($40.6\%$) with percutaneous transhepatic biliary drainage (PTBD) and 32 patients ($54\%$) with systemic chemotherapy (CT). We performed external radiation therapy (ERT) upto $10.8\~55.8$ Gy (median 37.8 Gy) with palliative aim. Results : Overall median survival duration was $7.80\pm1.15$ months. The response rates of jaundice were $81.8\%$ in PTBO group and $66.7\%$ in non-PTBD group without statistical significance. The improving rate of jaundice was not significantly different in decreased ratio of total bilirubin level. But abdominal pain was more decreased in CT group than non-CT group (p<0.05). The significant prognostic factors were high performance status (Karnofski Performance Status >70), total radiation dose more than 35 Gy and good response of pain after therapy. There were increased in bacterial cholagitis in PTBD group and gastrointestinal complications in CT group. Conclusion : External radiotheapy could improve jaundice and abdominal pain in malignant EHBO patients, Overall survival duration was prolonged in patients with higher performance status and patients who had been treated with more than 35 Gy of total radiation dose. In the future, we expect not only better palliative role but also the prolongation of survival of using the ERT combined with other treatment method. But to achieve certain conclusion, we need luther study consisted with many kinds of treatment methods including new technologies in RT.