• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.929-935
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• 2014

Two types of nanosized titanium dioxide, anatase ($anTiO_2$) and rutile ($rnTiO_2$), are widely used in industry, commercial products and biosystems. $TiO_2$ has been evaluated as a Group 2B carcinogen. Previous reports indicated that $anTiO_2$ is less toxic than $rnTiO_2$, however, under ultraviolet irradiation $anTiO_2$ is more toxic than $rnTiO_2$ in vitro because of differences in their crystal structures. In the present study, we compared the in vivo and in vitro toxic effects induced by $anTiO_2$ and $rnTiO_2$. Female SD rats were treated with $500{\mu}g/ml$ of $anTiO_2$ or $rnTiO_2$ suspensions by intra-pulmonary spraying 8 times over a two week period. In the lung, treatment with $anTiO_2$ or $rnTiO_2$ increased alveolar macrophage numbers and levels of 8-hydroxydeoxyguanosine (8-OHdG); these increases tended to be lower in the $anTiO_2$ treated group compared to the $rnTiO_2$ treated group. Expression of $MIP1{\alpha}$ mRNA and protein in lung tissues treated with $anTiO_2$ and $rnTiO_2$ was also significantly up-regulated, with $MIP1{\alpha}$ mRNA and protein expression significantly lower in the $anTiO_2$ group than in the $rnTiO_2$ group. In cell culture of primary alveolar macrophages (PAM) treated with $anTiO_2$ and $rnTiO_2$, expression of $MIP1{\alpha}$ mRNA in the PAM and protein in the culture media was significantly higher than in control cultures. Similarly to the in vivo results, $MIP1{\alpha}$ mRNA and protein expression was significantly lower in the $anTiO_2$ treated cultures compared to the $rnTiO_2$ treated cultures. Furthermore, conditioned cell culture media from PAM cultures treated with $anTiO_2$ had less effect on A549 cell proliferation compared to conditioned media from cultures treated with $rnTiO_2$. However, no significant difference was found in the toxicological effects on cell viability of ultra violet irradiated $anTiO_2$ and $rnTiO_2$. In conclusion, our results indicate that $anTiO_2$ is less potent in induction of alveolar macrophage infiltration, 8-OHdG and $MIP1{\alpha}$ expression in the lung, and growth stimulation of A549 cells in vitro than $rnTiO_2$.

• Journal of Chest Surgery
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• v.33 no.9
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• pp.697-706
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• 2000

Background: Isolated lung perfusion(ILP) was developed as a new treatment approach to non-resectable primary or metastatic lung cancer, because of its ability to reduce systemic toxicity while delivering high-dose chemotherapeutic agents to the target organs. This research was planned to evaluate the direct toxic effect of high-dose cisplatin to the lung tissue during isolated lung perfusion. Material and Method: Fifteen mongrel dogs were divided in the perfusate for 40 minutes. The second group was composed of 5 mongrel dogs which underwent ILP with cisplatin 2.5 mg/Kg added to the perfusate for 30 minutes and 10 minutes with washing solution without cisplatin. The third group underwent the same procedure as the second group except cisplatin 5.0 mg/Kg in the perfusate. Activities of serum angiotensin converting enzyme(ACE), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and concentration of serum lactate dehydrogenase(LDH) and blood urea nitrogen/creatinine (BUN/Cr) were analyzed in each groups at the time of pre-perfusion, 1 hour, 1 day, 1 week, and 2 weeks after ILP. Result: Serum ACE activities before and 1 hour, 1 day, 1 week, and 2 weeks after ILP in control group were 45.1$\pm$6.3, 44.6$\pm$9.3, 46.7$\pm$9.5, 50.8$\pm$9.1, 46.1$\pm$4.3 U/L. Those in cisplatin 2.5 and 5.0 mg/Kg groups were 49.4$\pm$12.6, 39.0$\pm$8.6, 42.3$\pm$15.9, 50.0$\pm$2.6, 53.8$\pm$8.3 and 55.5$\pm$12.3, 47.0$\pm$6.3, 45.1$\pm$6.9, 74.8$\pm$19.5, 60.2$\pm$12.0 U/L, respectively. Serum TNF-$\alpha$ activities in each group before and after ILP were 5.0$\pm$1.5 / 7.7$\pm$2.2 / 6.6$\pm$2.5 / 4.3$\pm$1.3 / 5.2$\pm$1.1(control), 8.7$\pm$1.6 / 9.9$\pm$2.2 / 7.9$\pm$1.5 / 6.3$\pm$2.2 / 7.4$\pm$2.4 (cisplatin 2.5 mg/Kg), and 6.9$\pm$0.7 / 8.9$\pm$3.4 / 7.9$\pm$4.0 / 3.3$\pm$0.9 / 5.8$\pm$1.3 pg/ml(cisplatin 5.0 mg/Kg). Mean LDH levels of each group were 225.7 / 271.3 / 328.9 / 350.8 / 255.7(control), 235.7 / 265.7 / 336.0 / 379.5 / 299.2 (cisplatin 2.5 mg/Kg), and 259.6 / 285.2 / 340.6 / 433.4 / 292.4 IU/L(cisplatin 5.0 mg/Kg). So there was no significant difference in serum ACE, TNF-$\alpha$, and LDH activity changes after ILP between the 3 groups. And, there was no significant changes in BUN/Cr in each groups, which was independent of ILP and perfused concentration of cisplatin. In addition, all dogs survived the ILP and there was no significant evidence of pulmonary vascular injury after 2 weeks of ILP with cisplatin. Conclusion: There was no harmful effect of cisplatin to the lund tissue of the mongrel dog up to 5.0 mg/Kg in perfusate. Therefore, it is perceived to be safe and effective to deliver high-dose cisplatin to the lung without pulmonary toxicity and renal damage with ILP.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.91-99
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• 1999

Propose : This study was performed to find out the prognostic factors affecting local control, survival and disease free survival rate in nasopharyngeal carcinomas treated with chemotherapy and radiation therapy. Materials and Methods : We analysed 47 patients of nasopharyngeal carcinomas, histologically confirmed and treated at Chonnam University Hospital between July 1986 and June 1996, retrospectively. Range of patients' age were from 16 to 80 years (median; 52 years). Thirty three (70$\%$) patients was male. Histological types were composed of 3 (6$\%$) keratinizing, 30 (64$\%$) nonkeratinizing squamous cell carcinoma and 13 (28$\%$) undifferentiated carcinoma. Histoiogicai type was not known in 1 patient (2$\%$). We restaged according to the staging system of 1997 American Joint Committee on Cancer Forty seven patients were recorded as follows: 71: 11 (23$\%$), T2a; 6 (13$\%$), T2b; 9 (19$\%$), 73; 7 (15$\%$), 74: 14 (30$\%$), and NO; 7 (15$\%$), Nl: 14 (30$\%$), N2; 21 (45%), N3: 5 (10%). Clinical staging was grouped as follows: Stage 1; 2 (4$\%$), IIA: 2 (4$\%$), IIB; 10 (21$\%$), III; 14 (30$\%$), IVA; 14 (30$\%$) and IVB; 5 (11$\%$). Radiation therapy was done using 6 MV and 10 MV X- ray of linear accelerator. Electron beam was used for the Iymph nodes of posterior neck after 4500 cGy. The range of total radiation dose delivered to the primary tumor was from 6120 to 7920 cGy (median; 7020 cGy). Neoadjuvant chemotherapy was performed with cisplatin +5-fluorouracil (25 patients) or cisplatin+pepleomycin (17 patients) with one to three cycles. Five patients did not received chemotherapy. Local control rate, survival and disease free suwival rate were calculated by Kaplan-Meier method. Generalized Wilcoxon test was used to evaluate the difference of survival rates between groups. multivariate analysis using Cox proportional hazard model was done for finding prognostic factors. Results: Local control rate was 81$\%$ in 5 year. Five year survival rate was 60$\%$ (median survival; 100 months). We included age, sex, cranial nerve deflicit, histologic type, stage group, chemotherapy, elapsed days between chemotherapy and radiotherapy, total radiation dose, period of radiotherapy as potential prognostic factors in multivariate analysis. As a result, cranial none deficit (P=0.004) had statistical significance in local control rate. Stage group and total radiation dose were significant prognostic factors in survival (P=0.000, P=0.012), and in disease free survival rates (P=0.003, P=0.008), respectively. Common complications were xerostomia, tooth and ear problems. Hypothyroidism was developed in 2 patients. Conclusion : In our study, cranial none deficit was a significant prognostic factor in local control rate, and stage group and total radiation dose were significant factors in both survival and disease free survival of nasopharyngeal carcinoma. We have concluded that chemotherapy and radiotherapy used in our patients were effective without any serious complication.

• 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.14 no.2
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• pp.95-103
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• 1996

Purpose : A retrospective analysis for patients with oropharyngeal carcinoma who were treated with radiation was performed to assess the results of treatment and patterns of failure, and to identify the factors that might influence survival. materials and methods : From March 1985 through June 1993, 53 patients with oropharyngeal carcinoma were treated with either radiation therapy alone or combination of neoadjuvant chemotherapy and radiation therapy at the Department of Radiation Oncology, Kyungpook National University Hospital. Patients' ages ranged from 31 to 73 years with a median age of 54 years. There were 47 men and 6 women, Forty-two Patients ($79.2\%$) had squamous cell carcinoma, 10 patients ($18.9\%$) had undifferentiated carcinoma and 1 patient ($19\%$) had adenoid cystic carcinoma. There were 2 patients with stage I, 12 patients with stage II, 12 Patients with stage III and 27 patients with stage IV. According to the TNM classification, patients were distributed as follows: T1 7, T2 28, T3 10, T4 7, TX 1, and N0 17, Nl 13, N2 21, N3 2. The primary tumor sites were tonsillar region in 36 patients ($67.9\%$), base of the tongue in 12 patients ($22.6\%$), and soft palate in 5 patients ($9.4\%$). Twenty-five patients were treated with radiation therapy alone and twenty-eight Patients were treated with one to three courses of chemotherapy followed by radiation therapy. Chemotherapeutic regimens used were either CF (cisplatin and 5-fluorouracil) or CVB (cisplatin, vincristine and bleomycin). Radiation therapy was delivered 180-200 cGy daily, five times a week using 6 MV X-ray with or without 8-10 MeV electron beams A tumor dose ranged from 4500 cGy to 7740 cGy with a median dose of 7100 cGy. The follow-up time ranged from 4 months to 99 months with a median of 21 months. Results : Thirty-seven patients ($69.8\%$) achieved a CR (complete response) and PR (partial response) in 16 patients ($30.2\%$) after radiation therapy. The overall survival rates were $47\%$ at 2 years and $42\%$ at 3 years, respectively. The median survival time was 23 months. Overall stage (p=0.02) and response to radiation therapy (p=0.004) were significant prognostic factors for overall survival. The 2-year disease-free survival rate was $45.5\%$. T-stage (p=0.03), N-stage (p=0.04) and overall stage (P=0.04) were significant prognostic factors for disease-free survival. Age, sex, histology, primary site of the tumor, radiation dose, combination of chemotherapy were not significantly associated with disease-free survival. Among evaluable 32 Patients with CR to radiation therapy, 12 patients were considered to have failed Among these, 8 patients failed locoregionally and 4 Patients failed distantly. Conclusion : T-stage, N-stage and overall stage were significant prognostic factors for disease-free survival in the treatment of oropharyngeal cancer Since locoregional failure was the predominant pattern of relapse, potential methods to improve locoregional control with radiation therapy should be attempted. More controlled clinical, trials should be completed before acceptance of chemotherapy as a part of treatment of oropharyngeal carcinoma.

• Radiation Oncology Journal
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• v.28 no.4
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• pp.193-204
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• 2010

Purpose: To analyze the treatment outcomes, complications, prognostic factors after a long-term follow-up of patients with nasopharyngeal carcinoma treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Materials and Methods: Between December 1981 and December 2006, 190 eligible patients with non-metastatic nasopharyngeal carcinoma were treated at our department with a curative intent. Of these patients, 103 were treated with RT alone and 87 patients received CCRT. The median age was 49 years (range, 8~78 years). The distributions of clinical stage according to the AJCC 6th edition included I: 7 (3.6%), IIA: 8 (4.2%), IIB: 33 (17.4%), III: 82 (43.2%), IVA: 31 (16.3%), IVB: 29 (15.3%). The accumulated radiation doses to the primary tumor ranged from 66.6~87.0 Gy (median, 72 Gy). Treatment outcomes and prognostic factors were retrospectively analyzed. Acute and late toxicities were assessed using the RTOG criteria. Results: A total of 96.8% (184/190) of patients completed the planned treatment. With a mean follow-up of 73 months (range, 2~278 months; median, 52 months), 93 (48.9%) patients had relapses that were local 44 (23.2%), nodal 13 (6.8%), or distant 49 (25.8%). The 5- and 10-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 55.6% and 44.5%, 54.8% and 51.3%, in addition to 65.3% and 57.4%, respectively. Multivariate analyses revealed that CCRT, age, gender, and stage were significant prognostic factors for OS. The CCRT and gender were independent prognostic factors for both DFS and DSS. There was no grade 4 or 5 acute toxicity, but grade 3 mucositis and hematologic toxicity were present in 42 patients (22.1%) and 18 patients (9.5%), respectively. During follow-up, grade 3 hearing loss in 9 patients and trismus in 6 patients were reported. Conclusion: The results of our study were in accordance with findings of previous studies and we confirmed that CCRT, low stage, female gender, and young age were related to improvement in OS. However, there are limitations in the locoregional control that can be achieved by CCRT with 20 conventional radiation therapy. This observation has led to further studies on clarifying the efficacy of concurrent chemotherapy by intensity modulated radiation therapy.

• Journal of Chest Surgery
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• v.29 no.8
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• pp.916-922
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• 1996

In patients with pleural adhesion, video-assisted thoracic surgery (VATS) has been regarded as a contra- indication. When such adhesions were found during a thoracoscopic trial, the thoracotomy proceeded with for fear of parenchymal Injury and bleeding. We had a question whether or not thoracoscopic surgery should be done in such pleural adhesions. Of the 226 consecutive thoracoscopic surgeries from Jul. 1992 through Sep. 1995, pleural adhesions were detected intraoperatively in 50 cases (22.1%): a detailed breakdown is as follows: pneumothorax (16 cases), pleural disease (15), benign pulmonary nodule(7), mediastinal mass(5), hyperhidrosis (2), diffuse parenchymal or interstitial lung disease (2), bronchiectasis(2), and primary lung cancer(1). We classified pleural adhesions according to their extent and severity. Extent is categorized as the involved area of the lung: degree 1, II, or III; severity is given one of four grades: mild, moderate, severe, or ve y severe. In cases of very severe severity requiring decortication, the possibility of VATS was excluded. Of the 50 cases, mild adhesions were detected in 15 cases(30.0%), moderate in 29 (58.0%), and severe in 6 (12.0%). As for the extent of the adhesions, 8 cases (16.0%) were categorized as degree 1, 32 cases (64. 0%) as degree II, and 10 cases (20.0%) as degree III. For patients with pleural adhesions, the operation time, the chest tube indwelling time, and the postoperative hospital stay were all longer than for patients in the non-adhesion group. Postoperative complications, namely prolonged air-leakage and pleural drain- age, were more common (18.0% and 6.0%, respectively) than in the non-adhesion group (5.1% and 1.7%, respectively). Only two bronchiectatic patients (4%) were converted to an open thoracotomy because of in- ability to control bleeding. Although complications were encountered more frequently in the group with adhesions, patients were still able to enjoy the benefi s of thoracoscopic surgery. It is advisable to proceed with thoracoscopic surgery even in cases of unpredicted pleural adhesions.

• 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.