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Efficacy and Safety of Long-Term Administration of Esomeprazole in Japanese Pediatric Patients Aged 1-14 Years with Chronic Gastric Acid-Related Disease

  • Masaaki Mori;Yoshiko Nakayama;Shigeo Nishimata;Tadafumi Yokoyama;Ryo Matsuoka;Reiko Hatori;Masaki Shimizu;Katsuhiro Arai;Yuri Etani;Tsuyoshi Sogo;Tomoko Ishizu;Masahiro Nii;Ryosuke Nakashima;Toshiaki Shimizu
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.27 no.5
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    • pp.274-285
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    • 2024
  • Purpose: To evaluate prolonged esomeprazole use in Japanese pediatric patients for reflux esophagitis (RE) maintenance therapy and prevention of gastric (GU) and/or duodenal ulcers (DU) while using non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA). Methods: This multicenter, open-label, parallel-group, phase III study (NCT03553563) included patients who were administered esomeprazole according to body weight (10 mg/day [Groups 1 and 3] and up to 20 mg/day [Groups 2 and 4] for patients weighing 10-20 kg and ≥20 kg, respectively). Efficacy outcomes for Groups 1 and 2 (maintenance therapy for healed RE) and Groups 3 and 4 (prevention of long-term NSAID/LDA use-associated GU/DU) were the presence/absence of RE relapse and GU/DU recurrence, respectively. Results: Esomeprazole as maintenance therapy was associated with a low RE recurrence rate, independent of body weight or dosage. Recurrence rates of RE were 0.0% and 5.3% for Groups 1 and 2, respectively. In patients previously diagnosed with GU and/or DU due to long-term NSAID/LDA use, the recurrence rates of GU/DU during weeks 0-32 were 11.1% and 0.0% in Groups 3 and 4, respectively. Conclusion: Long-term use of 10- or 20-mg, once-daily esomeprazole demonstrated a favorable benefit-risk balance in preventing RE and suppressing recurrence of GU and/or DU secondary to NSAID or LDA therapy in Japanese pediatric patients. No new safety concerns were identified. Esomeprazole may be a viable option for managing RE and preventing GU and DU in Japanese pediatric patients.

Radiation Dose-escalation Trial for Glioblastomas with 3D-conformal Radiotherapy (3차원 입체조형치료에 의한 아교모세포종의 방사선 선량증가 연구)

  • Cho, Jae-Ho;Lee, Chang-Geol;Kim, Kyoung-Ju;Bak, Jin-Ho;Lee, Se-Byeoung;Cho, Sam-Ju;Shim, Su-Jung;Yoon, Dok-Hyun;Chang, Jong-Hee;Kim, Tae-Gon;Kim, Dong-Suk;Suh, Chang-Ok
    • Radiation Oncology Journal
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    • v.22 no.4
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    • pp.237-246
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    • 2004
  • Purpose: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). Materials and Methods: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received $63\~70$ Gy (Median 66 Gy, fraction size $1.8\~2$ Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. Results: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were $15{\pm}1.65$ and $11{\pm}0.95$ months, respectively. The was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were $21{\pm}5.03$ and $12{\pm}1.59$ months, respectively, while for Arm 2 patients they were $14{\pm}0.94$ and $10{\pm}1.63$ months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; $44.7\%$ versus $19.2\%$. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. Conclusion: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.

The Neonatal Follow up and Correlative Analysis of Fetal Hydronephrosis (산전 수신증의 생후 추적 관찰)

  • Yoon Ho-Young;Kim Ji-Hong;Lee Jae-Seung;Kim Pyung-Kil;Kim Myung-Joon
    • Childhood Kidney Diseases
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    • v.2 no.1
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    • pp.60-68
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    • 1998
  • Purpose: To determine the various prenatal factors related to the prenatal hydronephrosis diagnosed on prenatal ultrasonography. We also attempted to correlate the prenatal and neonatal renal pelvic anteroposterior diameter with the outcome in infancy Methods: Between 1985 and 1997. We retrospectively reviewed 105 renal unit (75 patient) with fetal hydronphrosis persisting postnatally. Investigation consisted of renal ultrasonography, voiding cystourethrography, diurectic renogram, and DMSA scan. Results: The 75 patient assesed had the following underlying cause: UPJ(Ureteropelvic juction) obstruction(52%). multicystic dysplastic kidney(10%). UVJ (Ureterovesicai juction) obstruction (10%) and no underlying cause (25%). Of theses cases 36 cases (40 renal unit) underwent operation, while 28 cases (50 renal unit) resoled spontaneously. 12% of mild hydornephrosis deteriorated. whereas 50% of modrate hydrophrosis and 81% of severe hydronephrosis required surgical correction. Attempting to find the renal unit that were at risk for deterioration. our study showed that urinary tract infection group and calyceal blunting group had a predictive role. Conclusion: It is necessary to follow up after birth dilatation of caylx or urinary tract infection are present. Early operation is considered when prenatal pelvic AP diameter greater is than 22 mm and postnatal diameter greater than 17 mm. This may make it possible to prevent further progression of renal damage and prompt treatment of asymptomatic hydronephrosis before complications occur.

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Esophageal Atresia and Tracheoesophageal Fistula in Korea - A National Survey of Its Members by the Korean Association of Pediatric Surgeons - (선천성 식도 무공증 및 기관식도 누공 - 대한 소아외과학회 회원을 대상으로 한 전국 조사 -)

  • Park, W.H.;Kwon, S.I.;Kim, S.C.;Kim, S.K.;Kim, W.K.;Kim, I.K.;Kim, J.E.;Kim, H.H.;Park, K.W.;Park, Y.S.;Song, Y.T.;Yang, J.W.;Oh, S.M.;Yoo, S.Y.;Lee, D.S.;Lee, M.D.;Lee, S.C.;Lee, S.K.;Lee, T.S.;Chang, S.I.
    • Advances in pediatric surgery
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    • v.1 no.2
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    • pp.149-161
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    • 1995
  • The first national survey on esophageal atresia and tracheoesophageal fistula was conducted to access the current status of its incidence, clinical manifestation, preoperative diagnosis and management, type of its anomaly, associated anomalies, and surgical results and course. The 43 members of the Korea Association of Pediatric Surgeons received questionnaires and registration forms to be filled out on each patient who were born during the three years from January 1, 1992 through December 31, 1994. Questionnaires composed of six broad areas which include 1) preoperative diagnosis and management, 2) surgical technic, 3) long gap, 4) postoperative management, and 5) complications and courses. A total of 148 cases was returned by 28 members working at 23 institutions and 27 members returned questionnaires. We obtained the following results by analysis of the 148 cases of tracheoesophageal anomalies. The incidence of tracheoesophageal anomaly was about 1/10,000-11,000 in 1994, which is one third of that of anorectal malformations in Korea and the distribution of the patients was almost proportionate to the size of each province. Both sexes are about equally affected. Majority of the members make diagnosis of tracheoesophageal anomaly by taking a simple infantogram with a radiopaque tube in upper pouch and a little under half(46%) prefers to perform echocardiography as a part of preoperative management to identify congenital heart disease and lateralize the aorta. Esophageal atresia with distal TEF(87.5%) was by far the most common and there were pure esophageal atresia(5.6%), H-type TEF(2.1%), and so on. About half(49%) of the patients had one or more associated anomalies in addition to tracheoesophageal anomalies. Congenital heart disease was associated in 46 cases(31%), anorectral malfomations in 19 cases(13%), musculoskeletal anomalies in 15 cases(10%), genitourinary anomalies in 10 cases(7%) and gastrointestinal anomalies in 7 cases(5%). Postoperatively, parenteral nutrition and assisted ventilation were given in 66% and 52% of patients respectively. Ninety three(74%) of 126 cases who underwent sugical procedure, experienced one or more complications such as respiratory complication(65%), leak(22%), stricture(21%) and so on. The survival rates related to the Waterston risk categories were 90.2% in group A, 71.4-75% in $B_1$, $B_2$, and $C_1$, groups, and 28% in group $C_2$, and the overall survival rate was 71.4%. Thirty six(28.6%) of 126 cases died of pneumonia/sepsis(12 cases), respiratory failure(12 cases), and congenital heart disease(4 cases). With short term follow-up, 69% of patients have been excellent whereas remainders of the cases have suffered from some sort of morbidity related to gastroesophageal reflux, recurrent respiratory infection, and esophageal stricture.

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An Investigation of Microbial Contamination of Ready-to-Eat Products in Seoul, Korea (서울지역 유통판매 중인 즉석섭취.편의식품의 위해 미생물 오염도 조사)

  • Kim, Hee-Yun;Oh, Seon-Woo;Chung, So-Young;Choi, Seon-Hee;Lee, Ji-Won;Yang, Ji-Yeon;Seo, Eun-Chae;Kim, Yong-Hoon;Park, Hee-Ok;Yang, Cheul-Young;Ha, Sang-Chul;Shin, Il-Shik
    • Korean Journal of Food Science and Technology
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    • v.43 no.1
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    • pp.39-44
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    • 2011
  • This study was carried out to examine microbiological contamination of ready-to-eat products and to propose a draft-standard and specifications according to food types. RTE foods were classified into 6 groups including fish products, meat products, breads, rices, salads, and fresh cut foods. The prevalence rates of pathogens detected from all samples were compared among food categories. The pH ranges for all RTE samples were between 3.8 and 7.3. Total aerobic cell counts ranged from 2 to 6 log CFU/g. Bread, rice and fresh-cut foods showed significantly higher counts, which ranged above 4.0 log CFU/g among the samples. Two kinds of rice were above the level of the KFDA Food Code standard for Eschrichia coli. The prevalence rate of E. coli in the rice was 6.7%. For Staphylococcus aureus, one fish product and one bread-product had levels above 2 log CFU/g. Bacillus cereus counts for all samples were below the level of 3 log CFU/g. Listeria monocytogenes was not detected in the samples. Therefore, these data suggest that the primary microbial hazard factors for ready-to-eat foods and risk assessments should focus on E. coli, S. aureus, and B. cereus.

Innate Immunity and Genetic Susceptibility to Severe Respiratory Syncytial Virus Infection : Lack of an Association with Mannose Binding Lectin Gene Polymorphism (심한 Respiratory Syncytial Virus 감염증과 선천성 면역에 관련된 유전적 소인에 관한 연구 : Mannose Binding Lectin 유전자 다형성)

  • Choi, Eun Hwa;Kim, Hee Sup;Yun, Bo Young;Choi, Seung Eun;Nah, Song Yi;Kim, Dong Ho;Park, Ki Won;Lee, Hoan Jong
    • Pediatric Infection and Vaccine
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    • v.13 no.1
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    • pp.63-70
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    • 2006
  • Purpose : We hypothesized that mannose binding lectin gene(MBL2), a key molecule of innate immunity, may contirbute to the development and the outcome of respiratory syncytial virus(RSV) disease in early childhood. This study was performed to investigate the genetic basis of polymorphisms and haplotypes of MBL2 for RSV disease severity in Korean children. Methods : Cases with severe RSV diseases are 99 children with severe RSV lower respiratory tract infections, who were admitted to the Seoul National University Children's Hospital through 1993~2000. The control subjects consisted of 224 anonymous healthy Korean blood donors. The frequency of promoter variant(-221, X/Y) and structural variant(codon 54) were compared between the case patient group and the control subject group. Results : The mean age of patients was 11.8 months; 49% were <6 months, 39% were 6-24 months and 12% were >24 months. In the cohort of cases of severe RSV diseases, the genotypic frequencies of structural variant in codon 54 were 61% for AA, 34% for AB, and 5% for BB. Those of the promoter X/Y variant were 85% for YY and 15% for XY. There were no significant differences in overall distribution of both structural and promoter variants between the cases and the control subjects. We did not observe statistical difference in the haplotypic frequencies of MBL2. Conclusion : Common variants of MBL2 gene most likely do not contribute to the risk for severe RSV diseases in Korean children. Further genetic association studies should be conducted in a larger propsectively recruited cohort of children with RSV infection.

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Concurrent Weekly Cisplatin and Radiation Therapy for High risk group of Uterine Cervical Cancer (국소적으로 진행된 자궁경부암에 대한 방사선 치료와 Cisplatin의 동시 병행요법의 치료 결과)

  • Suh Hyun Suk;Kang Seung Hee;Kim Ju Ree;Lee Eung Soo;Kim Yong Bong;Park Sung Kwan
    • Radiation Oncology Journal
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    • v.10 no.2
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    • pp.213-217
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    • 1992
  • Locally advanced cervical carcinoma has shown high rate of local failure and poor survival rate despite the advances in modern radiation therapy techniques. Combination of chemotherapy and radiation therapy demonstrated benefit in improving local control and possibly the overall survival. Twelve patients with advanced stages (Figo stage III, IV) or 11b with bulky tumors (>5 cm in diameter) were treated with combination of radiation therapy and concurrent weekly cisplatin between May of 1988 and September of 1991 at Inje University Paik Hospital. Cisplatin was administered in bolus injections of 50 mg at weekly intervals during the courses of radiation therapy. Median follow-up period was 34 months with ranges from 3 to 53 months. Eleven patients were evaluable for the estimation of response. Response was noted in all the 11 patients: complete response (CR) in 7 ($64\%$), partial response (PR) in 4 ($36\%$). Of the 7 patients with CR, all maintained local control, whereas only 1 of 4 with PR showed local control. Six of 7 with CR are alive disease free on the completion of follow-up. Eight of 11 patients ($73\%$) maintained local control in the pelvis. The median survival for CR patient is 27 months and 9 months for the PR patients. Analysis of survival by stage shows 11 b 4/5, III 2/3 and IV 1/3. Overall survival rate was $61\%$. Three patients recurred: 1 at local, 1 in distant site and 1 with local and distant site. Toxicity for the combination therapy was not excessive. These results are preliminary, but definitely encouraging in view of markedly improved response rate compared with the results of historical control group.

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The Role of Radiation Therapy on Local Recurrence of Rectal Cancer (직장암에서 수술후 방사선치료의 역활)

  • Chung, Woong-Ki;Ahn, Sung-Ja;Nam, Taek-Keun;Nah, Byung-Sik;Kim, Young-Jin
    • Radiation Oncology Journal
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    • v.10 no.2
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    • pp.205-212
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    • 1992
  • Ninety five patients of rectal cancer treated with surgery with or without adjuvant radiation therapy since January 1982 to December 1990 at the Chonnam University Hospital were analysed retrospectively regarding local failure. Of these 95 patients 72 patients were treated with surgery alone and remaining 23 patients received postoperative radiation therapy to pelvis. There were 45 men and 50 women with 53 years of median age. Minimum follow-up period was 19 months and median was47 months (range, 19-125 months). Kaplan-Meier method was used to calculate actuarial risk of local recurrence and survival rate. Comparison between two groups was evaluated by Log rank test. Of total 95 patients twenty seven patients ($28.4\%$) developed local recurrence and 13 patients ($17.3\%$) developed local and distant metastasis concomitantly. Eighty nine percent (24/27) of patients developed local recurrence within 24 months. Pelvic organ adjacent to the primary tumor area was the most common site of initial local recurrence. Of 72 patients treated with surgery alone local recurrence developed in 24 patients. Of 17 patients with stage A and 81 (Gunderson-Sosin modification of Dukes' staging system) 6 patients experienced local recurrence ($31.2\%$). The local recurrence rate of B2 and B3 group was $29.9\%$ (7/33) and that of C2 and C3 was $54.7\%$ (11/19), respectively. There was statistically significant difference between two groups (p<0.05). Of 23 patients treated with definitive surgery and radiation therapy $10\%$ (1/10) recurred in B2 and B3 patients. This was slightly lower than C2 and C3 patients ($22.2\%$, 2/10) of similar policy, but revealed no statistically significant difference (p>0.05). In the patients of B2+3 local failure rate decreased when radiation therapy was added ($29.9\%$ vs $10\%$, p>0.05) and also similar results in C2+3 group ($34.7\%$ vs $22.2\%$, p<0.05). The local failure rate in relation to distance from the anal verge had no statistically significant difference.

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Bilateral retinoblastoma: Long-term follow-up results from a single institution (단일기관의 장기추적 결과)

  • Choi, Sang Yul;Kim, Dong Hwan;Lee, Kang Min;Lee, Hyun Jae;Kim, Mi-Sook;Lee, Tai-Won;Choi, Sang Wook;Kim, Dong Ho;Park, Kyung Duk;Lee, Jun Ah
    • Clinical and Experimental Pediatrics
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    • v.52 no.6
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    • pp.674-679
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    • 2009
  • Purpose : The authors aimed to analyze the long-term effects of treatments, especially external beam radiotherapy (EBRT), in bilateral retinoblastoma patients. Methods : This retrospective study analyzed the medical records of 22 bilateral retinoblastoma patients who were registered between October, 1987 and October, 1998 and followed-up for more than 10 years. They were treated by enucleation, EBRT, and systemic chemotherapy. Age at diagnosis, sex, delay prior to treatment, Reese-Ellsworth (RE) classification, and the local treatment modalities were analyzed in relation to recurrence-free survival (RFS) and complications. Results : Median age at diagnosis was 7.0 months (range 1.7-31.6 months). Leukocoria was the most common presenting feature. Two patients had a familial history. The RE classifications of the 44 eyes were group II in 4, III in 14, IV in 4, and V in 22. At the end of a median follow-up period of 141 months (range 55-218 months), 20 patients were alive. The 10-year ocular survival rate of the 44 eyes was $56.8{\pm}7.5%$. The 10-year RFS and ocular survival rate of the 29 eyes treated by combined EBRT and chemotherapy were 75.9% and 86.2%, respectively. Treatment delay (>3 months) was found to be related to higher risk of recurrence. Complications after EBRT were cataract, retinal detachment, phthisis bulbi, and facial asymmetry. No patient developed a second malignancy during the follow-up period. Conclusion : Early detection and prompt treatment can increase ocular survival rates. In addition, careful attention should be paid to possible long-term sequelae in these patients.

Assessment of the Quality of Esophago-gastric Anastomosis by Endoscopic Examination -Cervical Versus Intrathoracic Anastomosis- (내시경을 통한 식도-위 문합술의 질 평가-경부와 흉부 문합의 비교-)

  • Shim, Jae-Hoon;Kim, Hyun-Koo;Baek, Man-Jong;Kim, Hark-Jei;Choi, Young-Ho
    • Journal of Chest Surgery
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    • v.39 no.12 s.269
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    • pp.920-926
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    • 2006
  • Background: Mortality and morbidity of anastomotic complications after esophagectomy have gradually decreased in recent years. However, swallowing difficulties and reflux symptoms after esophagogastrostomy continue to be a burden jeopardizing the quality of life. In the present study, we evaluated the quality of esophagogastrostomy by analyzing anastomotic stenosis and reflux esophagitis. Material and Method: A retrospective analysis was made in 74 patients who underwent esophagogastrostomy after esophagectomy by one surgeon between January 1995 and December 2004. 53 patients of them received endoscopic examination during follow-up($29{\pm}23.6$ months, range $5{\sim}111$ months). Reflux esophagitis and stenosis at anastomostic site were analyzed according to the techniques and locations of esophagogastrostomy. Result: The median age at the time of repair was $60.3{\pm}8.87$ years(range $39{\sim}81$ years). 23 patients received a hand-sewn esophagogastric anastomosis and 30 patients a circular stapled one. There was no significant statistical difference in terms of anastomotic stenosis(p=0.64) and reflux esophagitis(p=0.41) between the two groups. Cervical anastomosis was peformed in 26 patients and intrathoracic anastomosis in 27 patients. No significant statistical difference in anastomotic stenosis between the two groups was found(p=0.44), but reflux esophagitis was noted in 3 patients in the cervical anastomosis group and 14 patients in the intrathoracic anastomosis group(p=0.003). Conclusion: Cervical anastomosis was supposed to have a better quality of esophagogastrostomy by lowering the risk of reflux esophagitis. In the future, the comprehensive study including a patient's subjective symptom and Barrett's metaplasia should be performed in larger cases.