• Radiation Oncology Journal
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• v.13 no.4
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• pp.359-368
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• 1995

Purpose : This is a retrospective analysis for pattern of failure, survival rate and prognostic factors of 114 patients with histologically proven invasive cancer of the uterine cervix treated with definitive irradiation. Materials and Methods : One hundred fourteen patients with invasive carcinoma of the cervix were treated with a combination of intracavitary irradiation using Fletcher-Suit applicator and external beam irradiation by 6MV X-ray at the Ewha Womans University Hospital between March 1982 and Mar 1990. The median age was 53 years(range:30-77 years). FIGO stage distribution was 19 for IB, 23 for IIA, 42 for IIB, 12 for IIIA and 18 for IIIB. Summation dose of external beam and intracavitary irradiation to point A was 80-90 Gy(median:8580 cGy) in early stage(IB-IIA) and 85-100 Gy(median:8850 cGy) in advanced stage(IIB-IIIB). Kaplan-Meier method was used to estimate the survival rate and multivariate analysis for progrostic factors was performed using the Log likelihood for Weibull Results : The pelvic failure rates by stage were $10.5{\%}$ for IB. $8.7{\%}$ for IIA, $23.8{\%}$ for IIB, $50.0{\%}$ for IIIA and $38.9{\%}$ for IIIB. The rate of distant metastasis by stage were $0{\%}$ for IB, $8.7{\%}$ for IIA, $4.8{\%}$ for IIB. $0{\%}$ for IIIA and $11.1{\%}$ for IIIB. The time of failure was from 3 to 50 months and with median of 15 months after completion of radiation therapy. There was no significant coorelation between dose to point A($\leq$90 Gy vs >90 Gy) and pelvic tumor control(P>0.05). Incidence rates of grade 2 rectal and bladder complications were $3.5{\%}$(4/114) and $7{\%}$(8/114), respectively and 1 patient had sigmoid colon obstruction and 1 patient had severe cystitis. Overall 5-year survival rate was $70.5{\%}$ and disease-free survival rate was $53.6{\%}$. Overall 5-year survival rate by stage was $100{\%}$ for IB, $76.9{\%}$ for IIA, $77.6{\%}$ for IIB $87.5{\%}$ for IIIA and $69.1{\%}$ for IIIB. Five-rear disease-free survival rate by stage was $81.3{\%}$ for IB, $67.9{\%}$ for IIA, $46.8{\%}$ for IIB, $45.4{\%}$ for IIIA and $34.4{\%}$ for IIIB. The prognostic factors for disease-free survival rate by multivariate analysis was performance status(p= 0.0063) and response rate after completion of radiation therapy(p= 0.0026) but stage, age and radiation dose to point A were not siginificant. Conclusion : The result of radiation therapy for early stage of the uterine cervix cancer was relatively good but local control rate and survival rate in advanced stage were poor inspite of high dose irradiation to point A above 90 Gy. Prospective randomized studies are recommended to establish optimal tumor doses for various stages and volume of carcinoma of uterine cervix, And ajuvant chemotherapy or radiation-sensitizing agents must be considered to increase the pelvic control and survival rate in advanced cancer of uterine cervix.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.200-207
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• 2004

Purpose: An analysis was to compare the results of radiation alone with those of radiation with dally low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. Materials and Methods: A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was peformed. Thirty one patients received radiation alone and 28 patients received dally low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900$\~$l,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000$\~$3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4$\%$) and 8 (13.6$\%$) stages IIB and stage IIIB, respectively. Results: The overall 5 year survival rate was 65.65$\%$ and according to treatment modality were 56.75$\%$ and 73.42$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.180). The 5 year disease-free survival rates were 49.39$\%$ and 63.34$\%$ in the radiation alone and chemoradiatoin groups, respectively (p=0.053), The 5 year locoregional control rates were 52.34$\%$ and 73.58$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.013). The 5 year distant disease-free survival rates were 59.29$\%$ and 81.46$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.477), Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia $\geq$grade) occurred in 3.2$\%$and 28.5$\%$ of the radiation alone and chemoradiation groups, respectively (p=0.02). There were no statistical differences in the incidences of vesical, rectal and small bowel complications between two groups. Conclusion: Radiation therapy with low dose cisplatin did not improve the rates of survival and response rates, but did improve the rate of disease free survival and locoregional control rates In locally advanced cervical cancer. The incidence of bone marrow suppression was higher in the chemoradiation group.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.237-246
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• 2008

Purpose: Three-dimensional conformal radiation therapy (3DCRT) and intensity-modulated radiation therapy (IMRT) were found to reduce the incidence of acute and late rectal toxicity compared with conventional radiation therapy (RT), although acute and late urinary toxicities were not reduced significantly. Acute urinary toxicity, even at a low-grade, not only has an impact on a patient's quality of life, but also can be used as a predictor for chronic urinary toxicity. With bladder filling, part of the bladder moves away from the radiation field, resulting in a small irradiated bladder volume; hence, urinary toxicity can be decreased. The purpose of this study is to evaluate the impact of bladder volume on acute urinary toxicity during RT in patients with prostate cancer. Materials and Methods: Forty two patients diagnosed with prostate cancer were treated by 3DCRT and of these, 21 patients made up a control group treated without any instruction to control the bladder volume. The remaining 21 patients in the experimental group were treated with a full bladder after drinking 450 mL of water an hour before treatment. We measured the bladder volume by CT and ultrasound at simulation to validate the accuracy of ultrasound. During the treatment period, we measured bladder volume weekly by ultrasound, for the experimental group, to evaluate the variation of the bladder volume. Results: A significant correlation between the bladder volume measured by CT and ultrasound was observed. The bladder volume in the experimental group varied with each patient despite drinking the same amount of water. Although weekly variations of the bladder volume were very high, larger initial CT volumes were associated with larger mean weekly bladder volumes. The mean bladder volume was $299{\pm}155\;mL$ in the experimental group, as opposed to $187{\pm}155\;mL$ in the control group. Patients in experimental group experienced less acute urinary toxicities than in control group, but the difference was not statistically significant. A trend of reduced toxicity was observed with the increase of CT bladder volume. In patients with bladder volumes greater than 150 mL at simulation, toxicity rates of all grades were significantly lower than in patients with bladder volume less than 150 mL. Also, patients with a mean bladder volume larger than 100 mL during treatment showed a slightly reduced Grade 1 urinary toxicity rate compared to patients with a mean bladder volume smaller than 100 mL. Conclusion: Despite the large variability in bladder volume during the treatment period, treating patients with a full bladder reduced acute urinary toxicities in patients with prostate cancer. We recommend that patients with prostate cancer undergo treatment with a full bladder.

• Radiation Oncology Journal
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• v.14 no.3
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• pp.191-199
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• 1996

Purpose : To evaluate 5-year survival rate, patterns of failure and complications of cervical cancer treatment, fifty nine patients treated by curative radiotherapy for the uterine cervical cancer were analyzed retrospectively. Materials and Methods : From March 1986 to May 1990, fifty nine patients with histologically proven uterine cervical cancer were analyzed. According to FIGO stage, there were 2 patients ($3.4\%$) in stage Ib, 2 patients ($3.4\%$) in stage IIa, 31 patients ($52.5\%$) in stage IIb, 15 patients ($25.4\%$) in stage IIIb, 9 patients ($15.3\%$) in stage IV. External RT was per formed by 6 MVLINAC with daily 1.8 Gy, 5 times per week and followed by ICR. A point dose of ICR was calculated to 30-43.66 Gy (median: 34.6 Gy). These techniques delivered total A Point dose of 80.4 to 109.8 Gy (median: 85 Gy). Patients had been followed up from 2 to 110 months (median: 61 months) Results : The overall 5-year survival rate & disease free survival rate were $55.9\%$ and $55.0\%$ respectively. According to FIGO stage, the 5-year survival rate for less than IIa, IIb, IIIb, IV were $75.0\%$, $74.8\%$, $26.7\%$, $33.3\%$, respectively. In univariate analysis, the 5-year survival rate for stage IIb and below versus stage IIIa and above revealed $74.8\%$, $29.2\%$ respectively (P<0.005). According to the hemoglobin level during RT, the 5-rear survival rate of was $73.3\%$ for patients with Hg 10 gm/dL or higher, in contrast to $0\%$ for those with lower than 10 gm/dL (p<0.005). In 18 patients with nonbulky tumor (<5cm), the 5-year survival rates were $71.8\%$. The 5-rear survival rates for 18 patients with 5 cm or greater in tumor diameter were $22.2\%$ (p<0.005). The 5-year survival rate for Patient age of above 50 years and below were $65.3\%$ $34.2\%$ respectively (p<0.05). ECOG performance status. pathologic finding, total dose, total treatment time were not statistically significant factors. The significant prognostic factors affecting overall 5-year survival rate by multivariate analysis showed the hemoglobin level during RT (P=0.0001), tumor size (p=0.0390), FIGO stage (p=0.0468). Total recurrence rate was $23.7\%$ local failure $15.2\%$ (9/59), distant metastasis $6.8\%$ (4/59), local and distant metastasis $1.7\%$ (1/59). According to the RTOG/EORTC Soma Scales, the late complication rate was $23.8\%$ (14/59) The late complication rate of colorectum and genitourinary tract were $15.3\%$ (9/59), $8.5\%$ (5/59), respectively: 10 patients ($17.0\%$) were grade 2, 3 Patients ($5.1\%$) were grade 3 and one patient ($1.7\%$) was grade 4. The late complications were radiation proctitis, rectal bleeding, radiation colitis, diarrhea and radiation cystitis in decreasing order. Conclusion : For improvement of therapeutic results, prospective randomized trials are recomended to discover new prognostic factors and more aggressive radiation therapeutic methods are needed for poor prognostic patients. The adjuvant chemotherapy or radiation-sensitizing agents must be considered to inhibit regional and distant metastasis.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1343-1352
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• 1997

Background : Heat-treated cells are known to be protected from lysis by TNF, which is considered to play a central role in the pathogenesis of sepsis-induced acute lung injury. The objective of the study was to investigate the effect of heat shock response by heat-pretreatment on the acute lung injury of the rats induced by intratracheally administered TNF-$\alpha$, Methods : We intratracheally instilled either saline or TNF (R&D, 500ng) with and without heat pretreatment in Sprague-Dawley rats weighing 250~350 g. The heated rats were raised their rectal temperature to $41^{\circ}C$ and was maintained thereafter for 13 minutes at 18 h before intratracheal administration of saline or TNF. After 5 h of intratracheal treatment, lung leak, lung myeloperoxidase activity (MPO) and heat shock proteins were measured in rats. Lung leak index was defined as counts per minute of $I^{25}$ in the right lung divided by counts per minutes of $I^{25}$ in 1.0 ml of blood. All data are expressed as means ${\pm}$SE. Results : There is no difference in acute lung leak index ($0.099{\pm}0.024$ vs $0.123{\pm}0.005$) among the rats given saline intratracheally with and without heat pretreatment, but MPO activity showed a decreased tendency in heat-pretreated rats ($4.58{\pm}0.79\;U/g$) compared with heat-unpretreated rats ($7.32{\pm}0.97\;U/g$) (P=0.064). Rats administered TNF intratracheally with heat-pretreatment had decreased lung leak index ($0.137{\pm}0.012$) and lung MPO activity ($5.51{\pm}1.04\;U/g$) compared with those of heat-unpretreated and TNF-administered rats ($0.186{\pm}0.016$, $14.34{\pm}1.22\;U/g$) (P<0.05 in each). There were no significant difference of lung leak index and MPO activity between TNF-treated rats with heat-pretreatment and saline-treated rats with and without heat-pretreatment. Conclusion : The heat shock response attenuated neutrophil recruitment and acute lung leak induced by intratracheal instillation of TNF-in rats.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.237-245
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• 2002

Purpose : This study was conducted to evaluate the treatment results, prognostic factors, and complication rates after high dose rate (HDR) brachytherapy in patients with uterine cervix cancer who were treated with curative aim. Materials and Methods : Of 269 cervix cancer patients treated at the department of radiation oncology, Samsung Medical Center from September 1994 to July 1998, the 106 who were treated with radical radio-therapy were analyzed. The median age was 61 years (range 22 to 89). All patients except 4 with carcinoma in situ (CIS) were given external beam radiotherapy (range $30.6\~50.4\;Gy$ to whole pelvis) and HDR brachytherapy. The common regimens of HDR brachytherapy were a total dose of $24\~28\;Gy$ with $6\~7$ fractions to point A at two fractions per week. The median overall treatment time was 55 days (range 44 to 104) in patients given both external beam radiotherapy and HDR brachytherapy. Results : Early responses of radiotherapy were evaluated by gynecologic examination and follow-up MRI 1 month after radiotherapy. Treatment responses were complete remission in 72 patients, partial response in 33 and no response in 1. The overall survival (OS) rate of all patients was $82\%,\;and\;73\%$, and the disease free survival (DFS) rate was $72\%,\;and\;69\%$, at 3, and 5 years, respectively. The pelvic control rate (PCR) was $79\%$ at both 3 and 5 years. According to the FIGO stage,3 and 5 year OS were $100\%\;and\;50\%$ in CIS/IA, $100\%\;and\;100%$ in IB, $83\%\;and\;69\%$ in IIA, $87\%\;and\;80\%$ in IIB, and $62\%\;and\;62\%$ in III, respectively. The 3 year OS in 4 patients with stage IVA was $100\%$. Three-year DFS were $80\%$ in CIS/IA, $88\%$ in IB, $100\%$ in IIA, $64\%$ in IIB, $58\%$ in III, and $75\%$ in IVA. Three-year PCR were $100\%$ in CIS/IA, $94\%$ in IB, $100\%$ in IIA, $84\%$ in IIB, $69\%$ in III, and $50\%$ in IVA. By univariate analysis, FIGO stage and treatment response were significant factors for OS. The significant factors for DFS were age, FIGO stage, treatment response and overall treatment time (OTT). For pelvic control rate, treatment response and OTT were significant factors. By multivariate analysis, FIGO stage had a borderline significance for OS (p=0.0825) and treatment response had a borderline significance for DFS (0=0.0872). A total of 14 patients $(13\%)$ experienced rectal bleeding, which occurred from 3 to 44 months (median, 13 months) after the completion of radiotherapy. Conclusion : HDR brachytherapy protocol of Samsung Medical Center combined with properly optimal external beam pelvic irradiation is a safe and effective treatment for patients with uterine cervix cancer. The authors found that OTT of less than 55 days had a positive impact on pelvic control and survival rate.

• Journal of Chest Surgery
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• v.39 no.12 s.269
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• pp.879-890
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• 2006

Background: The dysfunction of multiple organs is found to be caused by reactive oxygen species as a major modulator of microvascular injury after hemorrhagic shock. Hemorrhagic shock, one of many causes inducing acute lung injury, is associated with increase in alveolocapillary permeability and characterized by edema, neutrophil infiltration, and hemorrhage in the interstitial and alveolar space. Aggressive and rapid fluid resuscitation potentially might increased the risk of pulmonary dysfunction by the interstitial edema. Therefore, in order to improve the pulmonary dysfunction induced by hemorrhagic shock, the present study was attempted to investigate how to reduce the inflammatory responses and edema in lung. Material and Method: Male Sprague-Dawley rats, weight 300 to 350 gm were anesthetized with ketamine(7 mg/kg) intramuscular Hemorrhagic Shock(HS) was induced by withdrawal of 3 mL/100 g over 10 min. through right jugular vein. Mean arterial pressure was then maintained at $35{\sim}40$ mmHg by further blood withdrawal. At 60 min. after HS, the shed blood and Ringer's solution or 5% albumin was infused to restore mean carotid arterial pressure over 80 mmHg. Rats were divided into three groups according to rectal temperature level($37^{\circ}C$[normothermia] vs $33^{\circ}C$[mild hypothermia]) and resuscitation fluid(lactate Ringer's solution vs 5% albumin solution). Group I consisted of rats with the normothermia and lactate Ringer's solution infusion. Group II consisted of rats with the systemic hypothermia and lactate Ringer's solution infusion. Group III consisted of rats with the systemic hypothermia and 5% albumin solution infusion. Hemodynamic parameters(heart rate, mean carotid arterial pressure), metabolism, and pulmonary tissue damage were observed for 4 hours. Result: In all experimental groups including 6 rats in group I, totally 26 rats were alive in 3rd stage. However, bleeding volume of group I in first stage was $3.2{\pm}0.5$ mL/100 g less than those of group II($3.9{\pm}0.8$ mL/100 g) and group III($4.1{\pm}0.7$ mL/100 g). Fluid volume infused in 2nd stage was $28.6{\pm}6.0$ mL(group I), $20.6{\pm}4.0$ mL(group II) and $14.7{\pm}2.7$ mL(group III), retrospectively in which there was statistically a significance between all groups(p<0.05). Plasma potassium level was markedly elevated in comparison with other groups(II and III), whereas glucose level was obviously reduced in 2nd stage of group I. Level of interleukine-8 in group I was obviously higher than that of group II or III(p<0.05). They were $1.834{\pm}437$ pg/mL(group I), $1,006{\pm}532$ pg/mL(group II), and $764{\pm}302$ pg/mL(group III), retrospectively. In histologic score, the score of group III($1.6{\pm}0.6$) was significantly lower than that of group I($2.8{\pm}1.2$)(p<0.05). Conclusion: In pressure-controlled hemorrhagic shock model, it is suggested that hypothermia might inhibit the direct damage of ischemic tissue through reduction of basic metabolic rate in shock state compared to normothermia. It seems that hypothermia should be benefit to recovery pulmonary function by reducing replaced fluid volume, inhibiting anti-inflammatory agent(IL-8) and leukocyte infiltration in state of ischemia-reperfusion injury. However, if is considered that other changes in pulmonary damage and inflammatory responses might induce by not only kinds of fluid solutions but also hypothermia, and that the detailed evaluation should be study.