• Radiation Oncology Journal
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• v.16 no.4
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• pp.367-375
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• 1998

Purpose : Xerostomia is a complication met by almost all patients who have radiotherapy for cancers of head and neck. Many studies for prevention of xerostomia will be necessary. Radiation-induced acute response of salivary glands has been defined as interphase death or apoptosis. Increased intracellular calcium level have an important role in radiation-induced apoptosis. Calcium channel blocker may prevent radiation-induced apoptosis of salivary glands. This study was designed to evaluate the effectiveness of diltiazem known as calcium channel blocker and pentoxifylline with inhibition of inflammatory response on the apoptosis as an acute response of radiation in rat salivary glands. Materials and Methods : Sprague-Dawley rats with about body weight 200-250 g were divided into 5 study groups : control, radiation alone, diltiazem with radiation, pentoxifylline with radiation, and diltiazem and pentoxifylline with radiation. The diltiazen and pentoxifylline were injected intraperitoneally 20 mg/kg and 50 mg/kg, 30 and 20 mimute before irradiation. respectively. Irradiation was given with a 4 MV linear accelerator. The 1600 cGy of radiation was delivered in a single fraction through a single anterior portal encompassing the entire neck. After 24 h of irradiation, rats were sacrificed and parotid and submandibular glands were removed and stained with hematoxylin and eosin. The quantification of apoptosis was performed by microscopic examination of stained tissue sections at a magnification of 200X and the percentage of apoptotic cell was calculated. Results : On parotid glands, the percentage of apoptosis by radiation alone, diltiazem with radiation, pentoxifylline with radiation, and diltiazem and pentoxifylline with radiation were 1.72$\%$ (8.35/486), 0.64$\%$ (2.9/453), 0.23$\%$ (1.2/516), and 0.28$\%$ (1.1/399), respectively. The apoptosis was markedly reduced in the groups receiving drugs compared with groups receivinge, radiation alone (p<0.05). In serous cell of submandibular glands, the percentages of apoptosis of radiation alone, diltiazem with radiation, pentoxifylline with radiation, and diltiazem and pentoxifylline with radiation were 1.94$\%$ (l1/567), 0.34$\%$ (1.9/554), 0.28$\%$ (1.8/637), and 0.22$\%$ (1.3/601), respectively. In the mucus cell of submandibular glands, the percentages of apoptosis were 0.92$\%$ (5.1/552), 0.41$\%$ (2.5/612), 0.29$\%$ (1.3/455), and 0.18$\%$ (1.0/562), respectively. The apoptosis was markedly reduced in the serous glands (p<0.05), but there was no difference in development of apoptosis in each group of mucus gland. Conclusion : These results suggest that radiation-induced apoptosis of serous cells of salivary glands may be decreased by diltiazem and pentoxifylline administration.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.216-223
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• 2001

Purpose : We evaluated retrospectively the outcomes of inoperable squamous cell lung cancer patients treated with radiotherapy to find out prognostic factors affecting survival. Materials and methods : Four hundred and eleven patients diagnosed as squamous cell lung cancer between November 1988 and December 1997 were the basis of this analyses. The planned dose to the gross tumor volume was ranged from 30 to 70.2 Gy. Chemotherapy was combined in 72 patients $(17.5\%)$ with the variable schedule and drug combination regimens. Follow-up period ranged from 1 to 113 months with the median of 8 months and survival status was identified in 381 patients $(92.7\%)$. Overall survival rate was calculated using the Kaplan-Meier method. Results : Age ranged from 23 years to 83 years with the median 63 years. The male to female ratio was about 16:1. For all 411 patients, the median overall survival was 8 months and the 1-year survival rate (YSR), 2-YSR, and 5-YSR were $35.6\%,\;12.6\%,\;and\;3.7\%$, respectively. The median and 5-YSR were 29 months and $33.3\%$ for Stage IA, 13 months and $6.3\%$ for Stage IIIA, and 9 months and $3.4\%$ for Stage IIIB, respectively(p=0.00). The median survival by treatment aim was 11 months in radical intent group and 5 months in palliative, respectively (p=0.00). Of 344 patients treated with radical intent, median survival of patients (N=247) who received planned radiotherapy completely was 12 months while that of patients (N=97) who did not was 5 months (p=0.0006). In the analyses of the various prognostic factors affecting to the survival outcomes in 247 patients who completed the planned radiotherapy, tumor location, supraclavicular LAP, SVC syndrome, pleural effusion, total lung atelectasis and hoarseness were statistically significant prognostic factors both in the univariate and multivariate analyses while the addition of chemotherapy was statistically significant only in multivariate analyses. The acute radiation esophagitis requiring analgesics was appeared in 49 patients $(11.9\%)$ and severe radiation esophagitis requiring hospitalization was shown in 2 patients $(0.5\%)$. The radiation pneumonitis requiring steroid medication was shown in 62 patients $(15.1\%)$ and severe pneumonitis requiring hospitalization was occurred in 2 patients $(0.5\%)$. During follow-up, 114 patients $(27.7\%)$ had progression of local disease with 10 months of median time to recur (range : $1\~87\;months$) and 49 patients $(11.9\%)$ had distant failure with 7 months of median value (range : $1\~52\;months$). Second malignancy before or after the diagnosis of lung cancer was appeared in 11 patients Conclusion : The conventional radiotherapy in the patients with locally advanced squamous cell lung cancer has given small survival advantage over supportive care and it is very important to select the patient group who can obtain the maximal benefit and to select the radiotherapy technique that would not compromise the life quality in these patients.

• Radiation Oncology Journal
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• v.19 no.3
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• pp.275-286
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• 2001

Purpose : To setup procedures of quality assurance (OA) for implementing intensity modulated radiation therapy (IMRT) clinically, report OA procedures peformed for one patient with prostate cancer. Materials and methods : $P^3IMRT$ (ADAC) and linear accelerator (Siemens) with multileaf collimator are used to implement IMRT. At first, the positional accuracy, reproducibility of MLC, and leaf transmission factor were evaluated. RTP commissioning was peformed again to consider small field effect. After RTP recommissioning, a test plan of a C-shaped PTV was made using 9 intensity modulated beams, and the calculated isocenter dose was compared with the measured one in solid water phantom. As a patient-specific IMRT QA, one patient with prostate cancer was planned using 6 beams of total 74 segmented fields. The same beams were used to recalculate dose in a solid water phantom. Dose of these beams were measured with a 0.015 cc micro-ionization chamber, a diode detector, films, and an array detector and compared with calculated one. Results : The positioning accuracy of MLC was about 1 mm, and the reproducibility was around 0.5 mm. For leaf transmission factor for 10 MV photon beams, interleaf leakage was measured $1.9\%$ and midleaf leakage $0.9\%$ relative to $10\times\;cm^2$ open filed. Penumbra measured with film, diode detector, microionization chamber, and conventional 0.125 cc chamber showed that $80\~20\%$ penumbra width measured with a 0.125 cc chamber was 2 mm larger than that of film, which means a 0.125 cc ionization chamber was unacceptable for measuring small field such like 0.5 cm beamlet. After RTP recommissioning, the discrepancy between the measured and calculated dose profile for a small field of $1\times1\;cm^2$ size was less than $2\%$. The isocenter dose of the test plan of C-shaped PTV was measured two times with micro-ionization chamber in solid phantom showed that the errors upto $12\%$ for individual beam, but total dose delivered were agreed with the calculated within $2\%$. The transverse dose distribution measured with EC-L film was agreed with the calculated one in general. The isocenter dose for the patient measured in solid phantom was agreed within $1.5\%$. On-axis dose profiles of each individual beam at the position of the central leaf measured with film and array detector were found that at out-of-the-field region, the calculated dose underestimates about $2\%$, at inside-the-field the measured one was agreed within $3\%$, except some position. Conclusion : It is necessary more tight quality control of MLC for IMRT relative to conventional large field treatment and to develop QA procedures to check intensity pattern more efficiently. At the conclusion, we did setup an appropriate QA procedures for IMRT by a series of verifications including the measurement of absolute dose at the isocenter with a micro-ionization chamber, film dosimetry for verifying intensity pattern, and another measurement with an array detector for comparing off-axis dose profile.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.485-495
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• 1998

Purpose : The major goal of the therapy in the soft tissue sarcoma is to control both local and distant tumor. However, the technique of obtaining local control has changed significantly over the past few decades from more aggressive surgery to combined therapy including conservative surgery and radiation and/or chemotherapy. We retrospectively analyzed the treatment results of the postoperative radiation therapy of soft tissue sarcoma and its prognostic factor. Materials and Methods : Between March 1983 and June 1994, 50 patients with soft tissue sarcoma were treated with surgery and postoperative radiation therapy at Kang-Nam St. Mary's hospital. Complete follow up was possible for all patients with median follow up duration 50 months (range 6-162 months). There were 28 male and 32 female patients. Their age ranged from 6 to 83 with a median of 44 years. Extremity (58$\%$) was the most frequent site of occurrence followed by trunk (20$\%$) and head and neck (12$\%$). Histologically malignant fibrous histiocytoma (23$\%$), liposarcoma (17$\%$), malignant schwannoma (12$\%$) constitute 52$\%$ of the patients. Daily radiation therapy designed to treat all areas at a risk for tumor spread upto dose of 4500-5000 cGy. A shrinking field technique was then used and total 55-65 Gy was delivered to tumor bed. Twenty-five patients (42$\%$) received chemotherapy with various regimen in the postoperative period. Results : Total 41 patients failed either with local recurrence or with distant metastasis. There were 29 patients (48$\%$) of local recurrence. Four patients (7$\%$) developed simultaneous local recurrence and distant metastasis and 8 patients (13$\%$) developed only distant metastasis. Local recurrence rate was rather higher than of other reported series. This study included patients of gross residual, recurrent cases after previous operation, trunk and head and neck Primary This feature is likely explanation for the decreased local control rate. Five of 29 Patients who failed only locally were salvaged by re-excision and/or re-irradiation and remained free of disease. Factors affecting local control include histologic type, grade, stage, extent of operation and surgical margin involvement, lymph node metastasis (p<0.05). All 21 patients who failed distantly are dead with progressive disease at the time of this report. Our overall survival results are similar to those of larger series. Actuarial 5 year overall survival and disease free survival were 60.4 $\%$, 30.6$\%$ respectively. Grade, stage (being close association with grade), residual disease (negative margin, microscopic, gross) were significant as a predictor of survival in our series (p<0.05). Conclusion : Combined surgery and postoperative radiation therapy obtained 5 year survival rate comparable to that of radical surgery.

• Radiation Oncology Journal
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• v.16 no.1
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• pp.17-25
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• 1998

Purpose : Although local recurrence rates of stomach cancer after radiocal surgery have been reported in the range of $30-70\%$, the role of postoperative adjuvant therapy has not been established. We report the result of radiotherapy in resected stomach cancer with positive surgical margin to elucidate the role of postoperative radiotherapy. Materials and Methods : From June 1991 to August 1996, twenty five patients with positive surgical margins after radical gastrectomy were treated with postoperative radiotherapy and chemotherapy. Median dose of radiation was 55.8Gy and the range was 44.6-59.4Gy. Second cycle of chemotherapy was delivered concurrently with radiation and total number of six cycles were delivered. Twenty three had adenocarcinoma and the other two had leiornyosarcoma. The numbers of patients with stage I B, II, III A, III B, and IV were 1, 2, 11, 10 and 1 respectively. Positive margins at distal end of the stomach were in 17 patients and proximal in 5. The other three patients had positive margin at the sites of adjacent organ invasion Minimum and median follow-up periods were 12 months and 18 months, respectively, Results : Twenty-four of 25 patients received prescribed radiation dose and RTOG grade 3 toxicity of UGI tract was observed in 3, all of which were weight loss more than $15\%$ of their pretreatment weight. But hematemesis. melena, intestinal obstruction or grade 4 toxicity were not found. Locoregional failure within the radiation field was observed in 7 patients, and distant metastasis in 10 patients. Sites of locoregional recurrences involve anastomosis/remnant stomach in 3, tumor bed/duodenal stump in 3, regional lymph node in 1 patient Peritoneal seeding occurred in 6, liver metastases months and median disease free survival time was 26 months. Stages andradiation dose were not significant prognostic factors for locoregional in 2, and distant nodes in 2 patients. Four year disease specificsurvival rate was $40\%$ and disease free survival was $48\%$. Median survival was 35 failures. Conculsion : Although all patients in this study had positive surgical margins, locoregional failure rate was $28\%$, and 4 year disease specific survival rate was $40\%$. Considering small number of patients and relatively short follow-up period, it is not certain that postoperative radiotherapy lowered locoregional recurrences. but we could find a Possibility of the role of postoperative radiotherapy in Patients with high risk factors.

• Journal of Preventive Medicine and Public Health
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• v.22 no.4 s.28
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• pp.555-577
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• 1989

This study was conducted to compare the delivery management including laboratory tests, medication and surgical procedures for the delivery in various medical facilities. Two university hospitals, two general hospitals, three hospitals, two private obstetric clinics, and two midwifery clinics in a large city were selected as they permitted the investigators to abstract the required data from the medical and accounting records. The total number of deliveries occurred at these 11 facilities between 15 January and 15 February, 1989 was 789 among which 606(76.8%) were vaginal deliveries and 183 (23.3%) were C-sections. For the normal vaginal deliveries, CBC, Hb/Hct level, blood typing, VDRL, hepatitis B antigen and antibody, and urinalysis were routinely done except the private clinics and midwifery clinics which did not test for hepatitis B and Hb/Hct level at all. In one university hospital ultrasonography was performed in 71.4% of the mothers and in one general hospital liver function test was done in 76.7% of the mothers. For the C-section, chest X-ray, bleeding/clotting time and liver function test were routinely done in addition to the routine tests for the normal vaginal deliveries. Episiotomy was performed in 97.2% of the vaginal deliveries. The type and duration of fluid infused and antibiotics administered showed a wide variation among the medical facilities. In one university hospital antibiotics was not administered after C-section at all while in the general hospitals and hospitals one or two antibiotics were administered for one week on the average. In one private clinic one pint of whole blood was transfused routinely. A wide variation was observed among the medical facilities in the use of vitamin, hemostatics, oxytocics, antipyreptics, analgesics, anti-inflammatory agents. sedatives. digestives. stool softeners. antihistamines. and diuretics. Mean hospital day for the normal vaginal deliveries of primipara was 2.6 days with little variation except one hospital with 3.5 days. Mean hospital day for the C-section of primipara was 7.5 days and that of multipara was 7.6 days and it ranged between 6.5 days and 9.4 days. Average hospital fee for a normal vaginal delivery without the medical insurance coverage was 182,100 Won for the primipara and 167,300 Won for the multipara. In case of the primipara covered by the medical insurance a mother paid 82,400 Won and a multiparous mother paid 75,600 Won. Average hospital fee for a C-section without the medical insurance was 946,500 Won for the primipara and 753,800 Won for the multipara. In case of the primipara covered by the medical insurance a mother paid 256,200 Won and a multiparous mother paid 253,700 Won. Average hospital fee for a normal vaginal delivery in the university hospitals showed a remarkable difference, 268,000 Won vs 350,000 Won, as well as for the C-section. A wide variation in the laboratory tests performed for a normal vaginal delivery and a C-section as well as in the medication and hospital days brought about a big difference in the hospital fee and some hospitals were practicing the case payment system. Thus, standardization of the medical care to a certain level is warranted for the provision of adequate medical care for delivery.

• The Korean Journal of Nuclear Medicine
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• v.39 no.1
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• pp.34-43
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• 2005

Purpose: $^{99m}Tc$-sestamibi(MIBI) and $^{99m}Tc$-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of $^{99m}Tc$-MIBI and $^{99m}Tc$-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. Materials and Methods: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. Results: RT-PCR, western blot analysis of the cells and irnrnunochemical staining revealed selective expression of Pgp and MRP for HCY15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p<0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. Conclusion: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.

• The Korean Journal of Nuclear Medicine
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• v.36 no.4
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• pp.244-254
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• 2002

Purpose: This study investigated the differences between technetium-99m ethyl cysteinate dimer (Tc-99m ECD) and technetium-99m hexamethylpropylene amine oxime (Tc-99m HMPAO) uptake in the normal brain by means of statistical parametric mapping (SPM) analysis. Materials and Methods: We retrospectively analyzed age and sex matched 53 cases of normal brain SPECT. Thirty-two cases were obtained with Tc-99m ECD and 21 cases with Tc-99m HMPAO. There were no abnormal findings on brain MRIs. All of the SPECT images were spatially transformed to standard space, smoothed and globally normalized. The differences between the Tc-99m ECD and Tc-99m HMPAO SPECT images were statistically analyzed using statistical parametric mapping (SPM'99) software. The differences bgetween the two groups were considered significant ant a threshold of corrected P values less than 0.05. Results: SPM analysis revealed significantly different uptakes of Tc-99m ECD and Tc-99m HMPAO in the normal brains. On the Tc-99m ECD SPECT images, relatively higher uptake was observed in the frontal, parietal and occipital lobes, in the basal ganglia and thalamus, and in the superior region of the cerebellum. On the Tc-99m HMPAO SPECT images, relatively higher uptakes was observed in subcortical areas of the frontal region, temporal lobe, and posterior portion of inferior cerebellum. Conclusion: Uptake of Tc-99m ECD and Tc-99m HMPO in the normallooking brain was significantly different on SPM analysis. The selective use of Tc-99m ECD of Tc-99m HMPAO in brain SPECT imaging appears especially valuable for the interpretation of cerebral perfusion. Further investigation is necessary to determine which tracer is more accurate for diagnosing different clinical conditions.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.4
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• pp.307-313
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• 2008

Purpose: Vascular endothelial growth factor (VEGF) and its receptor, fetal liver kinase 1 (Flk-1), play an important role in vascular permeability and tumor angiogenesis. The aim of this study is to evaluate the therapeutic efficacy of $^{131}I$ labeled anti-Flk-1 monoclonal antibody (DC101) on the growth of melanoma tumor, which is known to be very aggressive in vivo. Materials and Methods: Balb/c nude mice were injected subcutaneously with melanoma cells in the right flank. Tumors were allowed to grow up to $200-250\;mm^3$ in volume. Gamma camera imaging and biodistribution studies were performed to identify an uptake of $^{131}I$-DC101 in various organs. Mice with tumor were randomly divided into five groups (10 mice per group) and injected intravenously; control PBS (group 1), $^{131}I$-DC101 $50\;{\mu}g/mouse$ (group 2), non-labeled DC101 $50\;{\mu}g/mouse$ (group 3), $^{131}I$-DC101 $30\;{\mu}g/mouse$ (group 4) and $15\;{\mu}g/mouse$ (group 5) every 3 or 4 days for 20 days. Tumor volume was measured with caliper twice a week. Results: In gamma camera images, the uptake of $^{131}I$-DC101 into tumor and thyroid was increased with time. Biodistribution results showed that the radioactivity of blood and other major organ was gradually decreased with time whereas tumor uptake was increased up to 48 hr and then decreased. After 4th injection of $^{131}I$-DC101, tumor volume of group 2 and 4 was significantly smaller than that group 1. After 5th injection, the tumor volume of group 5 also significantly reduced. Conclusion: These results indicated that delivery of $^{131}I$ to tumor using FlK-1 antibody, DC101, effectively blocks tumor growth in aggressive melanoma xenograft model.

• Korean Journal of Ecology and Environment
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• v.35 no.4 s.100
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• pp.285-294
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• 2002

The purpose of this study was to evaluate the relationships between purification characteristics and hydraulic conditions, and to clarify the basic and essential factors required to be considered in the construction and management of artificial wetland system for the improvement of reservoir water quality. The artificial wetland system was composed of a pumping station and six sequential plants beds with five species of macrophytes: Oenanthe javanica, Acorus calamus, Zizania latifolia, Typha angustifolia, and Phragmites australis. The system was operated on free surface-flow system, and operation conditions were $3,444-4,156\; m^3/d$ of inflow rate, 0.5-2.0 hr of HRT, 0.1-0.2 m of water depth, 6.0-9.4 m/d of hydraulic loading, and relatively low nutrients concentration (0.224-2.462 mgN/L, 0.145-0.164 mgP/L) of inflow water. The mean purification efficiencies of TN ranged from 12.1% to 14.3% by showing the highest efficiency at the Phragmites australis bed, and these of TP were 6.3-9.5% by showing the similar ranges of efficiencies among all species. The mean purification efficiencies of SS and Chl-A ranged from 17.4% to 38.5% and from 12.0% to 20.2%, respectively, and the Oenanthe javanica bed showed the highest efficiency with higher concentration of influent than others. The mean purification amount per day of each pollutant were $9.8-4.1\;g{\cdot}m^{-2}{\cdot}d^{-1}$ in BOD, $1.299-2.343\;g{\cdot}m^{-2}{\cdot}d^{-1}$ in TN, $0.085-1.821\;g{\cdot}m^{-2}{\cdot}d^{-1}$ in TP, $17.9-111.6\;g{\cdot}m^{-2}{\cdot}d^{-1}$ in SS and $0.011-0.094\;g{\cdot}m^{-2}{\cdot}d^{-1}$ in Chl-a. The purification amount per day of TN revealed the hi링hest level at the Zizania latifolia bed, and TP showed at the Acrous calamus bed. SS and Chl-a, as particulate materials, revealed the highest purification amount per day at the Oenanthe javanica bed that was high on the whole parameters. It was estimated that the purification amount per day was increased with the high concentration of influent and shoot density of macrophytes, as was shown in the purification efficiency. Correlation coefficients between purification efficiencies and hydraulic conditions (HRT and inflow rate) were 0.016-0.731 of $R^2$ in terms of HRT, and 0.015-0.868 of $R^2$ daily inflow rate. Correlation coefficients of purification amounts per day with hydraulic conditions were 0.173-0.763 of Ra in terms of HRT, and 0.209-0.770 daily inflow rate. Among the correlation coefficients between purification efficiency and hydraulic condition, the percentages of over 0.5 range of $R^2$ were 20% in HRT and in daily inflow rate. However, the percentages of over 0.5 range of correlation coefficients ($R^2$) between purification amount per day and hydraulic conditions were 53% in HRT and 73% in daily inflow rate. The relationships between purificationamount per day and hydraulic condition were more significant than those of purifi-cation efficiency. In this study, high hydraulic conditions (HRT and inflow rate) are not likely to affect significantly the purification efficiency of nutrient. Therefore, the emphasis should be on the purification amounts per day with high hydraulicloadings (HRT and inflow rate) for the improvement of eutrophic reservoir withrelatively low nutrients concentration and large quantity to be treated.