• Title/Summary/Keyword: ACUTE TOXICITY

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Combined Modality Treatment in Nasopharyngeal Carcinoma (비인강암의 병합요법)

  • Yun, Sang-Mo;Kim, Jae-Cheol;Park, In-Kyu
    • Radiation Oncology Journal
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    • v.19 no.2
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    • pp.100-106
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    • 2001
  • Purpose : We performed a retrospective analysis to compare short term results of induction chemotherapy-radiotherapy versus concurrent chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma. Materials and Methods : From Oct. 1989 to May 1998, 62 patients with locally advanced nasopharyngeal carcinoma were treated with induction chemotherapy followed by radiotherapy (induction group) or concurrent chemo-radiotherapy (concurrent group). Induction chemotherapy was done for 50 patients, and concurrent chemotherapy for 12 patients. Age, sex, performance status, and pathologic types were evenly distributed between two groups. Stage distribution showed $32\%$ with IIB, $32\%$ with III, and $38\%$ with IV in induction group, and $50\%,\;33.3\%,\;and\;16.7\%$ in concurrent group, respectively. Chemotherapy regimen was CF (cisplatin and 5-FU) in both groups, and drug delivery method also same. Cisplatin $100\;mg/m^2$ was intravenously infused on day 1, and 5-FU $1,000\;mg/m^2$ on day $2\~6$. This was repeated at 3 weeks interval. At the end of radiotherapy, total cycles of chemotherapy were $1\~3$ (median 2) in both groups. Conventionally fractionated radiotherapy with daily fraction size $1.8\~2.0\;Gy$ and 5 fractions/week was done. Total dose was $69.4\~86\;Gy$(median 73.4 Gy) for induction group, and $69.4\~75.4\;Gy$ (median 70.8 Gy) for concurrent group. Follow-up time was $9\~116$ months (median 40.5 months) for induction group, $14\~29$ months (median 21 months) for concurrent group, respectively. Results : Overall 2 year survival rate (2YSR) for all patients was $78.7\%$. According to treatment modality, 2YSR were $77\%$ for induction group, $87\%$ for concurrent group (p>0.05). 2 year disease-free survival rate were $56\%$ and $81\%\;(p>0.05)$, respectively. Complete response to treatment were $75.5\%$ for induction group and $91.7\%$ for concurrent group, but there was no statistical difference. The incidence of grade $3\~4$ hematologic toxicity during radiotherapy was not differ between two groups, but grade 2 leukopenia was more frequent in concurrent group $(18\%\;vs\;66.7\%)$Grade $3\~4$ mucositis was more frequent in concurrent group $(4.0\%\;vs\;33.3\%)$. Overall incidence of grade $3\~4$ acute toxicity during radiotherapy was more frequent in concurrent group $(6.0\%\;vs\;41.7\%,\;p=0.005)$. Conclusion : Concurrent chemo-radiotherapy showed a trend of improvement in short-term survival and in treatment response when compared with induction chemotherapy-radiotherapy in locally advanced nasopharyngeal carcinoma. More controlled randomized trial are needed.

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The Results of Postoperative Radiation Therapy for Perihilar Cholangiocarcinoma (간문부 담도암에서 수술 후 방사선 치료의 결과)

  • Lee, Yu-Sun;Park, Jae-Won;Park, Jin-Hong;Choi, Eun-Kyung;Ahn, Seung-Do;Lee, Sang-Wook;Song, Si-Yeol;Lee, Sung-Gyu;Hwang, Shin;Lee, Young-Joo;Park, Kwang-Min;Kim, Ki-Hun;Ahn, Chul-Soo;Moon, Deok-Bog;Chang, Heung-Moon;Ryu, Min-Hee;Kim, Tae-Won;Lee, Jae-Lyun;Kim, Jong-Hoon
    • Radiation Oncology Journal
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    • v.27 no.4
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    • pp.181-188
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    • 2009
  • Purpose: The aim of this study was to evaluate the results of postoperative radiotherapy in a case of perihilar cholagiocarcinoma by analyzing overall survival rate, patterns of failure, prognostic factors for overall survival, and toxicity. Materials and Methods: Between January 1998 and March 2008, 38 patients with perihilar cholangiocarcinoma underwent a surgical resection and adjuvant radiotherapy. The median patient age was 59 years (range, 28 to 72 years), which included 23 men and 15 women. The extent of surgery was complete resection in 9 patients, microscopically positive margins in 25 patients, and a subtotal resection in 4 patients. The tumor bed and regional lymphatics initially received 45 Gy or 50 Gy, but was subsequently boosted to a total dose of 59.4 Gy or 60 Gy in incompletely resected patients. The median radiotherapy dose was 59.4 Gy. Concurrent chemotherapy was administered in 30 patients. The median follow-up period was 14 months (range, 6 to 45 months). Results: The 3-year overall survival and 3-year progression free survival rates were 30% and 8%, respectively. The median survival time was 28 months. A multivariate analysis showed that differentiation was the only significant factor for overall survival. The 3-year overall survival was 34% in R0 patients and 20% in R1 patients. No statistically significant differences in survival were found between the 2 groups (p=0.3067). The first site of failure was local in 18 patients (47%). No patient experienced grade 3 or higher acute toxicity and duodenal bleeding developed in 2 patients. Conclusion: Our results suggest that adjuvant RT might be a significant factor in patients with a positive margin following a radical resection. However, there was still a high locoregional recurrence rate following surgery and postoperative radiotherapy. Further study is necessary to enhance the effect of the adjuvant radiotherapy.

Results of Preoperative Concurrent Chemoradiotherapy for the Treatment of Rectal Cancer (직장암의 수술 전 동시적 항암화학방사선치료 결과)

  • Yoon, Mee-Sun;Nam, Taek-Keun;Kim, Hyeong-Rok;Nah, Byung-Sik;Chung, Woong-Ki;Kim, Young-Jin;Ahn, Sung-Ja;Song, Ju-Young;Jeong, Jae-Uk
    • Radiation Oncology Journal
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    • v.26 no.4
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    • pp.247-256
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    • 2008
  • Purpose: The purpose of this study is to evaluate anal sphincter preservation rates, survival rates, and prognostic factors in patients with rectal cancer treated with preoperative chemoradiotherapy. Materials and Methods: One hundred fifty patients with pathologic confirmed rectal cancer and treated by preoperative chemoradiotherapy between January 1999 and June 2007. Of the 150 patients, the 82 who completed the scheduled chemoradiotherapy, received definitive surgery at our hospital, and did not have distant metastasis upon initial diagnosis were enrolled in this study. The radiation dose delivered to the whole pelvis ranged from 41.4 to 46.0 Gy (median 44.0 Gy) using daily fractions of $1.8{\sim}2.0\;Gy$ at 5 days per week and a boost dose to the primary tumor and high risk area up to a total of $43.2{\sim}54\;Gy$ (median 50.4 Gy). Sixty patients (80.5%) received 5-fluorouracil, leucovorin, and cisplatin, while 16 patients (19.5%) were administered 5-fluorouracil and leucovorin every 4 weeks concurrently during radiotherapy. Surgery was performed for 3 to 45 weeks (median 7 weeks) after completion of chemoradiotherapy. Results: The sphincter preservation rates for all patients were 73.2% (60/82). Of the 48 patients whose tumor was located at less than 5 cm away from the anal verge, 31 (64.6%) underwent sphincter-saving surgery. Moreover, of the 34 patients whose tumor was located at greater than or equal to 5 cm away from the anal verge, 29 (85.3%) were able to preserve their anal sphincter. A pathologic complete response was achieved in 14.6% (12/82) of all patients. The downstaging rates were 42.7% (35/82) for the T stage, 75.5% (37/49) for the N stage, and 67.1% (55/82) for the overall stages. The median follow-up period was 38 months (range $11{\sim}107$ months). The overall 5-year survival, disease-free survival, and locoregional control rates were 67.4%, 58.9% and 84.4%, respectively. The 5-year overall survival rates based on the pathologic stage were 100% for stage 0 (n=12), 59.1% for stage I (n=16), 78.6% for stage II (n=30), 36.9% for stage III (n=23), and one patient with pathologic stage IV was alive for 43 months (p=0.02). The 5-year disease-free survival rates were 77.8% for stage 0, 63.6% for stage I, 58.9% for stage II, 51.1% for stage III, and 0% for stage IV (p<0.001). The 5-year locoregional control rates were 88.9% for stage 0, 93.8% for stage I, 91.1% for stage II, 68.2% for stage III, and one patient with pathologic stage IV was alive without local recurrence (p=0.01). The results of a multivariate analysis with age (${\leq}55$ vs. >55), clinical stage (I+II vs. III), radiotherapy to surgery interval (${\leq}6$ weeks vs. >6 weeks), operation type (sphincter preservation vs. no preservation), pathologic T stage, pathologic N stage, pathologic overall stage (0 vs. I+II vs. III+IV), and pathologic response (complete vs. non-CR), only age and pathologic N stage were significant predictors of overall survival, pathologic overall stage for disease-free survival, and pathologic N stage for locoregional control rates, respectively. Recurrence was observed in 25 patients (local recurrence in 10 patients, distant metastasis in 13 patients, and both in 2 patients). Acute hematologic toxicity ($\geq$grade 3) during chemoradiotherapy was observed in 2 patients, while skin toxicity was observed in 1 patient. Complications developing within 60 days after surgery and required admission or surgical intervention, were observed in 11 patients: anastomotic leakage in 5 patients, pelvic abscess in 2 patients, and others in 4 patients. Conclusion: Preoperative chemoradiotherapy was an effective modality to achieve downstaging and sphincter preservation in rectal cancer cases with a relatively low toxicity. Pathologic N stage was a statistically significant prognostic factor for survival and locoregional control and so, more intensified postoperative adjuvant chemotherapy should be considered in these patients.

Effect of Cytarabine, Melphalan, and Total Body Irradiation as Conditioning for Autologous Stem Cell Transplantation for Patients with AML in First Remission (1차 관해된 급성 골수성 백혈병에서 자가 조혈모세포 이식을 위한 Cytarabine, Melphalan, 전신 방사선치료의 효과)

  • Kang Ki Mun;Choi Byung Ock;Chai Gyu Young;Kang Young Nam;Jang Hong Sek;Kim Hee Jae;Min Wo Sung;Kim Chun Choo;Choi Ihl Bohng
    • Radiation Oncology Journal
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    • v.21 no.3
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    • pp.192-198
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    • 2003
  • Purpose: Current results of autologous stem cell transplantation (SCT) suggest that this procedure may prolong disease free survival In patients with acute myeloid leukemia (AML). Autologous SCT is increasingly used as treatment for AML in first remission. The aim of this study was to evaluate the outcome of autologous SCT for patients with AML in first remission treated by autologous SCT using cytarabine, melphalan and total body irradiation (TBI) as the conditioning regimen. Materials and Methods: Between January 1995 and December 1999, 29 patients with AML in first remission underwent autologous SCT. The median age of patients was 33 years (range, 16 to 47). The conditioning regimen consisted of cytarabine ($3.0\;gm/m^2$ for 3 days), melphalan ($100\;gm/m^2$ for 1 day) and TBI (total 1000 cGy in five fractions over 3 days). Results: The median follow up was 40 months with a range of 3 to 58 months. The 4-year cumulative probability of disease free survival was 69.0%, and median survival was 41.5 months. The 4-year relapse rate was 27.6%. The factor Influencing disease free survival and relapse rate was the French-American-British (FAB) classification ($M_3$ group vs. other groups; p=0.048, p=0.043). One patient died from treatment-related toxicity. Conclusion:: Although the small number of patients does not allow us to draw any firm conclusion, our results were encouraging and suggest that the association of cytarabine, melphalan and TBI as a conditioning regimen for autologous SCT for AML on first remission appears to be safe and effective.

Effect of Lead Acetate on Pancreatico-biliary Secretion (납(Lead)이 취외분비 기능에 미치는 영향)

  • Sheen, Yhun-Yhong;Kim, Won-Joon
    • The Korean Journal of Pharmacology
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    • v.17 no.1 s.28
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    • pp.17-25
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    • 1981
  • No evidence has accumulated that lead compound is an essential component for biological function in animals. Lead is absorbed primarily through the epithelial mucosal cells in duodenum and the absorption can be enhanced by the substances which bind lead and increase its solubility. Iron, zinc and calcium ions, however, decrease the absorption of lead without affecting its solubility, probably by competing for shared absorptive receptors in the intestinal mucosa. Therefore, the absorption of lead is increased in iron deficient animals. Lead shows a strong affinity for ligands such as phosphate, cysteinyl and histidyl side chains of proteins, pterins and porphyrins. Hence lead can act on various active sites of enzymes, inhibiting the enzymes which has functional sulfhydryl groups. lead inhibits the activity of ${\delta}$-aminolevulinic acid dehydratase for the biosynthesis of hemoproteins and cytochrome, which catalyzed the synthesis of monopyrrole prophobilinogen from ${\delta}$-aminolevulinic acid. Accordingly lead decrease hepatic cytochrome p-450 content, resulting an inhibition of the activity of demethylase and hydroxylase in liver. Little informations are available on the effect of lead on digestive system although the catastrophic effects of lead intoxication are well documented. The present study was, therefore, attempted to investigate the effect of lead on pancreaticobiliary secretion in rats. Albino rats of both sexes weighing $170{\sim}230g$ were used for this study. The animals were divided into one control and three treated groups, i.e., control (physiologic saline 1.5ml/kg i.p.), lead acetate $(l0{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and EDTA$(each\;10{\mu}mole/kg/day\;i.p.)$, $Pb(Ac)_2$ and $FeSO_4(each\;l0{\mu}mole/kg/day\;hp)$. The pancreatico-biliary juice was collected under urethane anesthesia, and activities of amylase and lipase were determined by employing Sumner's and Cherry and Crandall's methods. The summarized results are follows. 1) In the experiment for acute toxicity of lead acetate, 20% of mortality was observed in rat treated with lead acetate as well as inhibition of the activity of amylase in the juice at the 3 rd day of the treatment. 2) No increases in body weight were observed in rats treated with lead acetate, while in control group the significant increases were observed. However, the body weights of animals were increased in the group lead acetate plus EDTA or $FeSO_4$. 3) Lead acetate decreased significantly the volume of pancreatico-biliary juice whereas additional treatment of EDTA and $FeSO_4$ prevented it. 4) Total activity of amylase was markedly reduced due to lead acetate treatment, but no change was showed following additional treatment with EDTA and $FeSO_4$. 5) No changes in the cholate and lipase output were observed in rats treated with lead acetate as compared with that of control rats. 6) Increase in bilirubin output in rats treated with lead acetate was shown on the 2nd and 3rd weeks treatment. 7) In the case of in vitro experiment, lead acetate also markedly inhibited release of amylase from pancreatic fragment. 8) Histologic finding indicated that acini vacuolation was induced in the pancreatic tissue of rat treated with lead acete. From the above results, it might be concluded that lead acetate decreases the volume of pancreatico-biliary secretion and inhibits the amylase activity, by acting directly on pancreatic cells.

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A Study on the Acute Toxicity of AF-2 (AF-2의 독성(毒性)에 관(關)한 연구(硏究)(급성중독(急性中毒)))

  • Park, Young-Ran;Lee, Yul;Sung, Nak-Eung
    • Korean Journal of Food Science and Technology
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    • v.8 no.1
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    • pp.53-60
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    • 1976
  • This study was undertaken to investigate the toxic effect of AF-2, 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide, in the diet of rats (Splague Dowley) for 4 weeks. Comparisons were made of weight gains, organ weights and the cholesterol, phospholipid and triglyceride content of the blood serum and liver tissue. Rats were divided into three groups, a control group which was fed on a standard diet and two groups were fed with 0.04% (group I) and 0.2% (group II) of AF-2. Male rats weighing 370-410 g, female rats weighing 240-250 g were used in this experiment and each group was composed of 24 Albino rats. The results were as follows. 1. Comparisons of weight gains, control and experimental groups did not show significant differences. 2. An examination of organ weights, liver weights of experimental groups showed higher than that of the control group. 3. In the lipid content of blood serum, phospholipid contents of experimental groups were lower than that of the control, while cholesterol and triglyceride content of experimental groups were higher than that of the control. 4. In the lipid content of liver tissue, phospholipid and triglyceride content of experimental groups did not show considerable changes, but cholesterol content was increased in proportion to AF-2 content. From these results, the authors could observe the significant changes in weight gains of liver and cholesterol content after feeding. It is concluded that the toxic effect of group II showed higher than that of group I and AF-2 had a toxic effect on rat liver to a certain extent.

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Improved Breast Irradiation Techniques Using Multistatic Fields or Three Dimensional Universal Compensators (Multistatic Field또는 3차원 공용보상체를 사용한 유방의 방사선 조사법의 평가)

  • Han Youngyih;Cho Jae Ho;Park Hee Chul;Chu Sung Sil;Suh Chang-Ok
    • Radiation Oncology Journal
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    • v.20 no.1
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    • pp.24-33
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    • 2002
  • Purpose : In order to improve dose homogeneity and to reduce acute toxicity in tangential whole breast radiotherapy, we evaluated two treatment techniques using multiple static fields or universal compensators. Materials and Methods : 1) Multistatic field technique : Using a three dimensional radiation treatment planning system, Adac Pinnacle 4.0, we accomplished a conventional wedged tangential plan. Examining the isodose distributions, a third field which blocked overdose regions was designed and an opposing field was created by using an automatic function of RTPS. Weighting of the beams was tuned until an ideal dose distribution was obtained. Another pair of beams were added when the dose homogeneity was not satisfactory. 2) Universal compensator technique : The breast shapes and sizes were obtained from the CT images of 20 patients who received whole breast radiation therapy at our institution. The data obtained were averaged and a pair of universal physical compensators were designed for the averaged data. DII (Dose Inhomogeneity Index : percentage volume of PTV outside $95\~105\%$ of the prescribed dose) $D_{max}$ (the maximum point dose in the PTV) and isodose distributions for each technique were compared. Results : The multistatic field technique was found to be superior to the conventional technique, reducing the mean value of DII by $14.6\%$ (p value<0.000) and the $D_{max}$ by $4.7\%$ (p value<0.000). The universal compensator was not significantly superior to the conventional technique since it decreased $D_{max}$ by $0.3\%$ (p value=0.867) and reduced DII by $3.7\%$ (p value=0.260). However, it decreased the value of DII by maximum $18\%$ when patients' breast shapes fitted in with the compensator geometry. Conclusion : The multistatic field technique is effective for improving dose homogeneity for whole breast radiation therapy and is applicable to all patients, whereas the use of universal compensators is effective only in patients whose breast shapes fit inwith the universal compensator geometry, and thus has limited applicability.

Inhibitory Substance on the Snake Venoms Produced by Penicillium sp. (사독의 조해물질에 관한 연구)

  • Seu, Jung-Hwn;Yi, Dong-Heui
    • Microbiology and Biotechnology Letters
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    • v.7 no.2
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    • pp.75-89
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    • 1979
  • One strain of Penicillium sp. (175-66-B), isolated from soil, was able to produce a substance that has a strong inibition activity against the Agkistrodon and Trimeresurus venoms. In this experiment, the chemical and biological properties of the sample were investigated. As an inhibitory substance, it was effective to the proteinase, hemorrhagic and lethal factors of Agkistrodon and Trimeresurus venoms, and also effective to several fractions of the proteinases and hemorrhagic factors of Agkistrodon halys blomhoffi venom. Moreover, in the addition of prednisotone, it was more effective for the cure of the mouse envenomated with the venom amount of two fold of MLD$_{100}$. This substance was very stable to the acid, alkali and heat. Its melting point was high enough to sublime at 222$^{\circ}C$ without any decomposition. This sample was easily dissolved only in hot water, but not in several organic solvents except for a little dissolution in elate. It did not have the chelating activity. It had very strong specificity to the snake venoms. but its activity was depressed by the addition of zinc or cupric salts. This sample had no acute toxicity to the mouse. Its chemical formula was $C_{16}$ $H_{12}$$N_2$ $O_{10}$ with the molecular weight of about 392. It has two epoxy groups and four carboxyl radicals, but amino, nitrite and nitrate radicals, unsaturated bonds and aromatic ring were not detected. Theuchemical configuration of this sample was suggested to be;

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Evaluation of cellular energy allocation (CEA) in the Manila clam, Ruditapes philippinarum as a tool for assessment of contaminated sediments (오염 퇴적물 평가 기법으로서의 바지락 (Ruditapes philippinarum) 세포내 에너지 할당 (cellular energy allocation, CEA) 적용성 검토)

  • Sung, Chan-Gyoung;Kang, Sin-Kil;Chung, Jiwoong;Park, Dong-Ho;Lee, Jong-Hyeon;Lee, Chang-Hoon
    • The Korean Journal of Malacology
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    • v.32 no.1
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    • pp.45-54
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    • 2016
  • To evaluate the applicability of cellular energy allocation (CEA) in the bivalves as a biomarker for the assessment of environmental contamination, the energy contents and energy consumption in several tissues of the Manila clam, Ruditapes philippinarum were analyzed. The contents of lipid, glucose, protein and electron transport system (ETS) activity in the foot, siphons, gills, and body of R. philippinarum exposed to crude oil-spiked sediments were measured at 1, 2, 4, 7, 10 days after exposure. The reserved energy (energy available, EA) in the lipid, glucose and protein decreased as contamination level and exposure time increased. In contrast, the ETS activity (energy consumed, EC) showed the reverse tendency. The order of available energy contents were foot > siphons > gill > body. Significant differences in both EA and EC were found only at the highest contamination level (58.3 mg TPAHs/kg DW). EA decreased significantly in the foot and gill at 1 day, in the body at 2 and 7 days after exposure. EC increased significantly in the body at 4 days after exposure. CEA showed higher sensitivity to the contamination than EA or EC. Especially, CEA in the foot and body decreased significantly at lower ranges of contamination level (as low as 6.5 mg TPAHs/kg DW) during 1 to 7 days after exposure. The CEA is more useful than EA or EC alone for the assessment of sediment contamination at lower level that acute toxicity could not be detected. CEA analyses in the body of R. philippinarum after 4 days' exposure to contaminated sediments seem to be the most sensitive and reliable.

Treatment Outcome of Postoperative Radiotherapy in Extrahepatic Bile Duct Cancer (간외담관암의 수술 후 방사선치료 성적)

  • Choi, Young-Min;Cho, Heung-Lae
    • Radiation Oncology Journal
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    • v.21 no.1
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    • pp.27-34
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    • 2003
  • Purpose : To evaluate the efficacy of radiotherapy, and the factors affecting survival in patients of extrahepatic bile duct cancer, by analyzing the results of postoperative radiotherapy Materials and Methods : Between October 1991 and July 2001, 21 patients with extrahepatic bile duct cancer, who received radiotherapy after a radical resection, were retrospectively reviewed. The patients' ages ranged from 39 to 75 years, with a median of 61 years, and a male to female ratio of 16 to 5. The numbers of patients with proximal and distal bile duct cancer were 14 and 7, respectively. From the postoperative pathological examination, 19 of the patients were found to have microscopic residues, and 7 to be lymph node positive. Patients with AJCC stages I, II and III were 10, 10 and 1, respectively. The total radiation dose administered was 4,500$\~$6,300 cGy, with a median dose of 5,040 cGy. The follow up period was 20$\~$81 months, with a median of 57.5 months. Results : The overall and disease free survival rates at 3 and 5 years were 41.0 and 29.3$\%$, and 41.6 and 29.7$\%$, respectively. The influences of age, sex, tumor location, differentiation, microscopic residue, neural invasion, 7 and N stage, the stage itself, the dose of radiation and chemotherapy, on survival were evaluated. The T stage and the stage itself were found to be significant from a univariate analysis (p<0.05), but the degree of significance was limited by the small number of patients. A recurrence occurred in 12 patients (57.1$\%$), 5 in locoregional sites, 4 in distant sites and 3 in a combination of locoregional and distant sites, and the sites of distant metastasis were the liver, 6, and the bone, 1 Grade 2 or 3 acute leucopenias occurred in 2 patients and grade 2 chronic peptic ulcers occurred in 4, who were all recovered by conservative management. Conclusion : Postoperative radiotherapy is feasigbls in extrah데atic bile duct cancer, with tolerable toxicity, but prospective studies, with a large patient enrollment, are needed for the evaluation of the effects of postoperative radiotherapy and the related prognostic factors.