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Role of MYH Polymorphisms in Sporadic Colorectal Cancer in China: A Case-control, Population-based Study

  • Yang, Liu;Huang, Xin-En;Xu, Lin;Zhou, Jian-Nong;Yu, Dong-Sheng;Zhou, Xin;Li, Dong-Zheng;Guan, Xin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6403-6409
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    • 2013
  • Purpose: Biallelic germline variants of the 8-hydroxyguanine (8-OG) repair gene MYH have been associated with colorectal neoplasms that display somatic $G:C{\rightarrow}T:A$ transversions. However, the effect of single germline variants has not been widely studied, prompting the present investigation of monoallelic MYH variants and susceptibility to sporadic colorectal cancer (CRC) in a Chinese population. Patients and Methods: Between January 2006 and December 2012, 400 cases of sporadic CRC and 600 age- and sex-matched normal blood donors were screened randomly for 7 potentially pathogenic germline MYH exons using genetic testing technology. Variants of heterozygosity at the MYH locus were assessed in both sporadic cancer patients and healthy controls. Univariate and multivariate analyses were performed to determine risk factors for cancer onset. Results: Five monoallelic single nucleotide polymorphisms (SNPs) were identified in the 7 exon regions of MYH, which were detected in 75 (18.75%) of 400 CRC patients as well as 42 (7%) of 600 normal controls. The region of exon 1 proved to be a linked polymorphic region for the first time, a triple linked variant including exon 1-316 $G{\rightarrow}A$, exon 1-292 $G{\rightarrow}A$ and intron 1+11 $C{\rightarrow}T$, being identified in 13 CRC patients and 2 normal blood donors. A variant of base replacement, intron 10-2 $A{\rightarrow}G$, was identified in the exon 10 region in 21 cases and 7 controls, while a similar type of variant in the exon 13 region, intron 13+12 $C{\rightarrow}T$, was identified in 8 cases and 6 controls. Not the only but a newly missense variant in the present study, p. V463E (Exon 14+74 $T{\rightarrow}A$), was identified in exon 14 in 6 patients and 1 normal control. In exon 16, nt. 1678-80 del GTT with loss of heterozygosity (LOH) was identified in 27 CRC cases and 26 controls. There was no Y165C in exon 7 or G382D in exon 14, the hot-spot variants which have been reported most frequently in Caucasian studies. After univariate analysis and multivariate analysis, the linked variant in exon 1 region (p=0.002), intron 10-2 $A{\rightarrow}G$ (p=0.004) and p. V463E (p=0.036) in the MYH gene were selected as 3 independent risk factors for CRC. Conclusions: According to these results, the linked variant in Exon 1 region, Intron 10-2 $A{\rightarrow}G$ of base replacement and p. V463E of missense variant, the 3 heterozygosity variants of MYH gene in a Chinese population, may relate to the susceptibility to sporadic CRC. Lack of the hot-spot variants of Caucasians in the present study may due to the ethnic difference in MYH gene.

Role of Radiation Therapy for Locally Advanced Gastric Carcinoma Management (재발성 또는 국소진행된 위암의 방사선치료 -35예의 치료성적 분석)

  • Yoon Sei Chul;Oho Yoon Kyeoung;Shinn Kyeong Sub;Bahk Yong Whee;Kim In Chul;Lee Kyung Sik
    • Radiation Oncology Journal
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    • v.6 no.1
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    • pp.41-47
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    • 1988
  • Thirty-five patients with locally advanced gastric carcinoma were treated with combined modalities of external radiation therapy (RT) and 5-FU based chemotherapy at the Division of Radiation Therapy, Department of Radiology, Kangnam 51. Mary's Hospital, Catholic University Medical College from May 1983 to May 1987. The purpose of this retrospective study is for the evaluation of the palliative response to RT. There were 25 men and 10 women. The age ranged from 38 to 80 years (median: 56 years). The pathologic classification showed $14(40\%)$ poorly differentiated, $12 (34\%)$ moderately differentiated, $3(9\%)$ well differentiated adenocarcinomas, 2 mucinous cystadenocarcinomas, 1 signet ring cell and 3 not specified ones. The time intervals from the initial surgicopathologic diagnosis to the starting day of RT was within 1 year for $18 (51\%)$, 1 to 2 years for $8 (23\%)$ and 2 to 3 years for $5 (14\%)$, respectively. The major symptoms to be treated were pain in $30 (80\%)$, mass for $29 (83\%)$, obstruction for $11 (31\%)$ and jaundice for $9 (20\%)$ patients. The response rate (patient number of positive response/total patient number) according to treated radiation doses were observed as follows; $14/16(88\%)$ for $40\~50Gy,\;8/10(80\%)$ for over $50Gy,6/8 (75\%)\;for\;30\~40Gy\;and\;8/10(53\%)\;for\;20\~30 Gy$ in decreasing order. The over ail survival was 3.0 months and that of 5FU+RT, FAM+RT and RT alone groups were 4.6 months, 3.7 months and 2.5 months respectively. Complications induced by RT were nausea and vomiting in $16(46\%)$, diarrhea in $7(20\%)$, leukopenia in $6(17\%)$ and anemia and intercurrent pneumonia in each $3(9\%)$ patients in decreasing order.

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The Prognostic Factors Affecting Survival in Muscle Invasive Bladder Cancer Treated with Radiotherapy (방사선치료를 받은 근 침윤성 방광암의 예후 인자)

  • Chung Woong-Ki;Oh Bong-Ryoul;Ahn Sung Ja;Nah Byung Sik;Kwon Dong-Deuk;Park Kwangsung;Ryu Soo-Bang;Park Yang-IL
    • Radiation Oncology Journal
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    • v.20 no.2
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    • pp.130-138
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    • 2002
  • Purpose : This study analyzed the prognostic factors affecting the survival rate and evaluated the role of radiation therapy in muscle-invading bladder cancer. Materials and Methods : Twenty eight patients with bladder cancer who completed planned definitive radiotherapy in the Departments of Therapeutic Radiology and Urology, Chonnam National University Hospital between Jan. 1986 to Dec. 1998 were retrospectively analyzed. The reviews were peformed based on the patients' medical records. There were 21 males and 7 females in this study. The median of age was 72 years old ranging from 49 to 84 years. All patients were confirmed as having transitional cell carcinoma with histological grade 1 in one patient, grade 2 in 15, grade 3 in 9, and uninformed in 3. Radiation therapy was peformed using a linear accelerator with 6 or 10 MV X-rays. Radiation was delivered daily with a 1.8 or 2.0 Gy fraction size by 4 ports (anterior-posterior, both lateral, alternatively) or 3 ports (Anterior and both lateral). The median radiation dose delivered to the isocenter of the target volume was 61.24 Gy ranging from 59 to 66.6 Gy. The survival rate was calculated by the Kaplan-Meier method. Multivariate analysis was peformed on the prognostic factors affecting the survival rate. Results : The survival rate was $76\%,\;46\%,\;33\%,\;33\%$ at 1, 2, 3, 5 years, respectively, with 19 months of median survival. The potential factors of age (less than 70 years vs above 70), sex, diabetes mellitus, hypertension, hydronephrosis, 1-stage (T3a vs T3b), TUR, chemotherapy, total duration of radiotherapy, radiation dose (less than 60 Gy vs above 60 Gy), and the treatment response were investigated with uniand multivariate analysis. Un univariate analysis, the T-stage (p=0.078) and radiation dose (p=0.051) were marginally significant, and the treatment response (p=0.011) was a statistically significant factor on the survival rate. Multivariate analysis showed there were no significant prognostic factors affecting the survival rate. Conclusion : The treatment response and radiation dose are suggested as th은 statistically significant factors affecting the survival rate of muscle invasive bladder cancer. A Further prospective randomized study is needed to confirm these prognostic factors.

Tertiary Cytoreduction for Recurrent Epithelial Ovarian Cancer: a Multicenter Study in Turkey

  • Arvas, Macit;Salihoglu, Yavuz;Sal, Veysel;Gungor, Tayfun;Sozen, Hamdullah;Kahramanoglu, Ilker;Topuz, Samet;Demirkiran, Fuat;Iyibozkurt, Cem;Bese, Tugan;Ozgu, Burcin Salman;Vatansever, Dogan;Tokgozoglu, Nedim;Berkman, Sinan;Turan, Hasan;Bengisu, Ergin;Sofiyeva, Nigar;Demiral, Irem;Meydanli, Mutlu
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1909-1915
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    • 2016
  • Background: The purpose of this study was to determine the benefit of tertiary cytoreductive surgery (TC) for secondary recurrent epithelial ovarian cancer (EOC), focusing on whether optimal cytoreduction has an impact on disease-free survival, and whether certain patient characteristics could identify ideal candidates for TC. Materials and Methods: Retrospective analysis of secondary recurrent EOC patients undergoing TC at three Turkish tertiary institutions from May 1997 to July 2014 was performed. All patients had previously received primary cytoreduction followed by intravenous platinum-based chemotherapy and secondary cytoreduction for first recurrence. Clinical and pathological data were obtained from the patients' medical records. Survival analysis was caried out using the Kaplan Meier method. Actuarial curves were compared by the two tailed Logrank test with a statistical significance level of 0.05. Results: Median age of the patients was 49.6 years (range, 30-67) and thirty-eight (72%) had stage III-IV disease at initial diagnosis. Twenty six (49%) had optimal and 27 (51%) suboptimal cytoreduction during tertiary debulking surgery. Optimal initial cytoreduction, time to first recurrence, optimal secondary cytoreduction, time interval between secondary cytoreduction and secondary recurrence, size of recurrence, disease status at last follow-up were found to be significant risk factors to predict optimal TC. Optimal cytoreduction in initial and tertiary surgery and serum CA-125 level prior to TC were independent prognostic factors on univariate analysis. Conclusions: Our results and a literature review clearly showed that maximal surgical effort should be made in TC, since patients undergoing optimal TC have a better survival. Thus, patients with secondary recurrent EOC in whom optimal cytoreduction can be achieved should be actively selected.

The Study on Concentration of Serum Selenium in Patients with Hepatoma (간암환자의 혈청내 셀레늄 농도에 관한 연구)

  • 신원식
    • Journal of Nutrition and Health
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    • v.24 no.6
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    • pp.506-515
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    • 1991
  • Serum concentration of selenium were measured ; Studying 36 patients with Hepatoma. 19 with Hepatitis 15 with Liver cirrhosis and 67 Normal control to discover the correlation between serum selenum and cancer. And it have tested also the serum protein and albumin to compare the nutrition status by researching the same persons above The results of those two experiments are as follow : 1) The mean of each group of patients resulting from mearsuing the serum protein content showing 6.91$\pm$0.10g/dl in the patients with hepatoma 7.05$\pm$0.17g/dl in the ones with hepatitis 6.42$\pm$0.13g/dl in the ones with liver cirrhosis and 7.46$\pm$0.06g/dl in the normal control is all being within the normal range such as 6.0-0.8(g/dl) while the distribution is revealin 10.5%, 13.3% in the patients with hepatitis and liver cirrhosis which are below the normal range and 47.2%, 96.9%, 80.0% in the low range of normal one ; therefore in could see that patientsw compared with normal control are in low level in the serum protein content 2) The mean based on the consquence of serum albumin measurement is 3.74$\pm$0.11g/dl. 4.26$\pm$0.13g/dl 4.73$\pm$0.06g/dl in the patients with hepatoma hepatits and normal control which are in between the normal range such as 3.5-5.5(g/dl) except the patients with liver cirrhosis(3/05$\pm$0.12g/dl) while the distribution of the patients with hepatoma an liver cirrhosis is showing 27.8% 73.3% which are below the normal one and 55.5%, 52.6% and 26.7% in the patients with hepatoma hepatits and liver cirrhosis which are in the low area of normal range ; as a result It could find that patients. compared with the normal control are in low level in serum albumin measurement. 3) The mean consulting the serum concentration is 430.86$\pm$26.06$\mu\textrm{g}$/1, 192.37$\pm$18.15$\mu\textrm{g}$/1 186.73$\pm$23.99$\mu\textrm{g}$/1, 196.94$\pm$8.94$\mu\textrm{g}$/1 in the patients with hepatoma hepatitis liver cirrhosis and noramal control ; it shows 2.19 times increasing of serum selenium concentra-tion in the patients with hepatoma 'compared with the normal control and patients with hepatoma spread out at a still higher range in serum selenium concentration test. 4) The serum selenium concentration is not quite dependent on sexes and doesn't show any correlation with age, serum protein, serum albumin. The nutrition status of patients, rested on the results of those experiments, stays in low level, which is caused by that they are in low stage of serum protein and serum albu¬min. In serum selenium concentration, patients with hepatitis and liver cirrhosis, specially, show the condition as good as normal control's; while patients with hepatoma are indicating a significant increasing compared with the three groups, which can be reasoned into that there is a possibility for the patients to take selenium and chemotherapy or radiation treatment, and have high serum selenium concentration by poor excreting of seleno methionine, which is caused by low serum protein content And another thing can be reasoned is that the difference in origination mechanism hetween korean and western people. As a result, It showed that the correlation between serum selenium and seses, age, serum protein, and serum albumin neither exists nor affects on each other.

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The Preliminary Results of Intensity-Modulated Radiotherapy for Tonsillar Cancer (편도암에 대한 세기조절방사선치료의 예비적 결과)

  • Park, Geum-Ju;Lee, Sang-Wook;Choi, Eun-Kyung;Kim, Jong-Hoon;Song, Si-Yeol;Youn, Sang-Min;Park, Sung-Ho;Park, Dong-Wook;Ahn, Seung-Do
    • Radiation Oncology Journal
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    • v.27 no.3
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    • pp.120-125
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    • 2009
  • Purpose: We wanted to present the preliminary results of intensity-modulated radiotherapy (IMRT) for the treatment of tonsillar cancer. Materials and Methods: We retrospectively analyzed 12 patients who underwent IMRT for tonsillar cancer at Asan Medical Center between November 2002 and February 2007. Seven patients (58%) received definitive treatment, and five (42%) were treated in the postoperative setting. Among the definitively treated patients, 6 patients received cisplatin-based chemotherapy regimens. Simultaneous modulated accelerated radiation therapy (SMART) was used in nine patients. The prescribed dose was 72 Gy at 2.4 Gy/fraction for the definitively treated cases and 61.6 Gy at 2.2 Gy/fraction for the postoperative cases. The median follow-up period was 34 months. Results: All twelve patients completed treatment without interruption, and eleven showed a complete response. One patient had persistent loco-regional disease after treatment. The three-year estimates of loco-regional control, disease-free survival and overall survival were 91.7%, 91.7%, and 100%. The worst acute mucositis was Grade 1 in four patients, Grade 2 in five patients, Grade 3 in two patients and Grade 4 in one patient. Grade 3 xerostomia was observed in six patients. Conclusion: Intensity-modulated radiotherapy was shown to be a safe and effective treatment modality for tonsillar cancer. Further studies with a larger number of patients and a longer follow-up period are needed to evaluate the ultimate tumor control and late toxicity of IMRT for treating tonsillar cancer.

Long-term Results of Breast-conserving Surgery and Radiation Therapy in Early Breast Cancer (초기 유방암의 유방보존수술과 방사선치료의 장기추적결과)

  • Kim, Jin-Hee;Byun, Sang-Jun
    • Radiation Oncology Journal
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    • v.27 no.3
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    • pp.153-162
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    • 2009
  • Purpose: To evaluate the long-term results after breast-conserving surgery and radiation therapy in early breast cancer in terms of failure, survival, and cosmesis. Materials and Methods: One hundred fifty-four patients with stage I and II breast cancer were treated with conservative surgery plus radiotherapy between January 1992 and December 2002 at the Keimyung University Dongsan Medical Center. According to TNM stage, 93 patients were stage I, 50 were IIa, and 11 were IIb. The affected breasts were irradiated with 6 MV photons to 50.4 Gy in 28 fractions over 5.5 weeks with a boost irradiation dose of 10~16 Gy to the excision site. Chemotherapy was administered in 75 patients and hormonal therapy in 92 patients with tamoxifen. Follow-up periods were 13~179 months, with a median of 92.5 months. Results: The 5- and 10-year overall survival rates were 97.3% and 94.5%, respectively. The 5- and 10-year disease-free survival (5YDFS and 10YDFS, respectively) rates were 92.5% and 88.9%, respectively; the ultimate 5YDFS and 10YDFS rates after salvage treatment were 93.9% and 90.2%, respectively. Based on multivariate analysis, only the interval between surgery and radiation therapy ($\leq$6 weeks vs. >6 weeks, p=0.017) was a statistically significant prognostic factor for DFS. The major type of treatment failure was distant failure (78.5%) and the most common distant metastatic site was the lungs. The cosmetic results were good-to-excellent in 96 patients (80.7%). Conclusion: Conservative surgery and radiation for early stage invasive breast cancer yielded excellent survival and cosmetic results. Radiation therapy should be started as soon as possible after breast-conserving surgery in patients with early breast cancer, ideally within 6 weeks.

Outcomes of the Initial Surgical Treatment without Neoadjuvant Therapy in Patients with Unexpected N2 Non-small Cell Lung Cancer (선행요법 없이 초기치료로서 수술을 시행했던 예측되지 않은 N2 비소세포폐암의 치료 성적)

  • Shim, Man-Shik;Kim, Jhin-Gook;Yoon, Yoo-Sang;Chang, Sung-Wook;Kim, Hong-Kwan;Choi, Yong-Soo;Kim, Kwhan-Mien;Shim, Young-Mog
    • Journal of Chest Surgery
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    • v.43 no.1
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    • pp.39-46
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    • 2010
  • Background: Preoperative chemotherapy has been adopted in our hospital as a standard treatment for non-small cell lung cancer patients with N2 disease. However, there have been cases of pathologic N2 disease that have been detected after curative-intent surgical resection. We retrospectively studied the outcomes of initial surgical treatment without neoadjuvant therapy in patients with unexpected N2 non-small cell lung cancer. Material and Method: Between January 1995 and June 2007, 225 patients were diagnosed with pathologic N2 disease after they underwent initial pulmonary resection without neoadjuvant therapy. Among them, 170 patients were preoperatively diagnosed with lymph node stage N0 or N1. We retrospectively reviewed their medical record and analyzed the outcomes. Result: The overall 5-year survival rate was 35.4%. The prognostic factors that were significantly associated with survival were no adjuvant therapy, histologic cell types other than adenocarcinoma or squamous cell carcinoma, a pathologic T stage more than T1, old age (${\geq}$70 years) and no mediastinoscopic biopsy. During the follow-up, 79 patients (46.5%) experienced tumor recurrence, including loco-regional recurrence in 20 patients (25.3%) and distant metastasis in 56 (70.9%). The 5-year recurrence-free survival rate was 33.7%. Conclusion: Based on our findings, the survival was good for patients with unexpected N2 non-small cell lung cancer and who underwent initial pulmonary resection without neoadjuvant therapy. A prospective comparative analysis is needed to obtain more conclusive and persuasive results.

Retrospective Cohort Study on the Administration of Sedative for Delirium in Terminally Ill Cancer Patients and Survival Time (말기암환자의 섬망으로 인한 진정제 투약과 생존기간에 관한 후향적 코호트 연구)

  • Park, Hyoung Sook;Kim, Dae Sook;Bae, Eun Hee;Kim, Jung Rim;Seo, Jung Hwa;Yun, Jung Mi
    • Journal of Hospice and Palliative Care
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    • v.19 no.2
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    • pp.119-126
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    • 2016
  • Purpose: This study analyzed the difference in survival time of patients with delirium according to sedative medication. Methods: From January 2012 through December 2013, a retrospective cohort study was performed using the electronic medical records (EMR) of Pusan National University Hospital. Among 900 patients who died from cancer, we selected 240 who suffered delirium based on the EMR. The Nu-DESC delirium screening test was used to diagnose delirium. Results: The median length of delirium period was five days. Delirium characteristics were dominated by inappropriate behaviors (35.0%). Sedatives were administered in 72.1% of the cases. The most frequently used sedative was haloperidol which was used in 59.6% of cases. The delirium period significantly differed by patients' age (F=3.96, P=0.021), cancer type (F=3.31, P=0.010), chemotherapy (t=-3.44 P=0.001). The average survival time was 16.85 days for the sedative medication group and 9.37 days for the non-medication group, which, however, was not significant (t=1.766, P=0.079). Conclusion: In this study, the use of sedatives did not affect patients' survival time. Thus, appropriate sedative medication can be positively recommended to comfort terminal cancer patients and their families.

The Role of Adjuvant Postoperative Radiotherapy in Curative Resectable Sigmoid Colon Carcinoma (에스자결장암에서 근치적 절졔술 후 방사선 치료의 역할)

  • Park, Won;Seong, Jin-Sil;Keum, Ki-Chang;Suh, Chang-Ok;Lee, Sang-Wook;Lim, Ji-Hoon;Min, Jin-Sik;Roh, Jae-Kyung;Kim, Joo-Hang;Chung, Hyun-Cheol;Lee, Kang-Kyu;Kim, Gwi-Eon
    • Radiation Oncology Journal
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    • v.15 no.4
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    • pp.339-348
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    • 1997
  • Purpose : To evaluate the role of postoperative radiation therapy after curative resection of sigmoid colon cancer Materials and Methods : From 1988 to 1993, a total of 93 Patients with curative resectable sigmoid colon cancer of modified Astler-Coiler (MAC) stage B2, B3, C2, C3 was divided into two groups on the basis of those who received radiation treatment and those who did not. Forty-three patients who treated by surgery alone were classified as postop RT (-) group The remaining 50 patients who underwent postoperative radiotherapy were classified as postop RT (+) group. In all patients in Postop RT (+) group. radiation therapy was delivered using 4 or 10 MV linear accelerators to treat the tumor bed with approximately 5cm margin to a total dose 50.4-61Gy(median 54Gy) in 1.8Gy per fraction. Thirty-two patients were treated. with 5-Fluorouracil based adjuvant chemotherapy at least 3 cycles. but these was no significant difference between two groups. Treatment failure Pattern, 5-year local failure-free survival rates (LFFS), and 5-year disease-free survival rates (DFS) were compared between two groups. Result : Five year LFFS and DFS were $85.1\%,\;68.5\%$, respectively, In Postop RT (-) group, LFFS was $76.2\%$ compared with $91.7\%$ in Postop RT (+) group. Improved LFFS and DFS were seen for patients with stage C3 sigmoid colon carcinoma with postoperative radiation therapy compared with postop RT (-) group (P=0.01, p=0.06 respectively), in stage B3, LFFS washigher in postop RT (+) group than that in Postop RT (-) group. although itwas not significant. Especially, local control was higher in stage 74 inpostop RT (+) group than that in postop RT (-) group, Conclusion : This studv showed significantly improved LFFS and DFS in MAC Stage C3 and improved tendency of LFFS and DFS in MAC Stage B3 disease. Large scale prospective study is required to verify the role of adjuvant radiation therapy in resectable sigmoid colon cancer.

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