• Radiation Oncology Journal
• /
• v.10 no.2
• /
• pp.193-204
• /
• 1992

During the period between March 1983 and December 1990, 74 patients with esophageal carcinoma (EG) were treated with radiation therapy (RT) at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. Of these, 6 patients were lost to follow-up, and 13 patients were interrupted. So the remaining 55 patients were analyzed, retrospectively. 32 patients were irradiated with curative aim, 12 patients with palliative intent, 10 patients postoperatively, and 1 patient pre- and post-operatively. Among these 55 patients, 28 patients were treated with chemoradiation modality, and 27 patients with RT alone. All patients were followed for a minimum of 20 months or until death. Of 32 patients irradiated by curative aim, 22 patients (69%) showed partial remission (PR), 6 patients (19%) complete remission (CR). Overall mean survival and two-year survival rate were 15.6 months and 22%. With respect to sex, age, pathologic differentiation, tumor location, tumor size, stage, RT aim, RT response, RT dose, use of chemotherapy and functional categories (FC) of dysphagia at initiation of RT and at finishing RT: Tumor size, stage, RT response had great influences on prognosis and FC at finishing RT had a slight influence on prognosis. Especially, the mean survival and 2-year survival rate in patients with postoperative RT were 24.7 months and 63%, which could be compared with 29.1 months and 43% in radically treated patients with CR. And the mean survival duration and 2-year survival rate in patients irradiated with doses more than 60 Gy were 22.4 months and 29%, and 50~60 Gy were 12.2 months and 12%, respectively. However, no significant difference was shown statistically. Among 12 patients treated with palliative intent, 9 patients (75%) had good improvement in dysphagia and the mean duration of palliative response was 10.6 months.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.8
• /
• pp.3613-3618
• /
• 2014

Stathmin, also called oncoprotein 18, is a founding member of the family of microtubule-destabilizing proteins that play a critical role in the regulation of mitosis. At the same time stathmin has been recognized as one of responsible factors in cancer cells. The aim of this study was to assess stathmin status, its correlations with clinicopathological parameters and its role as a progosnostic marker in EC patients. The protein and mRNA levels of stathmin were examined byimmunohistochemistry (IHC) and in situ hybridization in 100EC tissues and adjacent noncancerous tissues. mRNA and protein expression of stathmin in three EC cell lines(EC9706, ECa109, EC1 commonly used in research) were also analyzed using immunocytochemistry, western blot and in situ hybridization. The prognostic value of Stathmin expression within the tumor tissues were assessed by Cox regression and Kaplan-Meier analysis. We showed that stathmin expression was significantly higher in EC tissues than in adjacent noncancerous tissues. High stathmin immunostaining score in the EC was positively correlated with tumor differentiation, Tumor invasion, Lymph node metastases, and TNM stage. In addition, we demonstrated that three EC cell lines examined, were constitutively expressing a high level of stathmin. Of those, EC-1 showed the strongest mRNA and protein expression for the stathmin analyzed. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in EC patients with high Stathmin expression, compared to those with low expression of Stathmin expression. Furthermore, multivariate Cox proportional hazard analyses revealed that Stathmin was an independent factors affecting the overall survival probability. In conclusion, our data provide a basis for the concept that stathmin might be associated with EC development and progression. High levels of Stathmin expression in the tumor tissues may be a good prognostic marker for patients with EC.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.5
• /
• pp.1981-1987
• /
• 2014

Objective: To establish the prevalence and distribution profile of esophageal squamous cell carcinomas (ESCCs) over a 22-yr period in North China. Methods: Using endoscopy for primary diagnosis and histological analysis for the further confirmation, a total of 74,854 ESCC patients aged 20-89 between January 1985 and December 2006 were investigated to analyze the epidemiological profile including prevalence rates, distribution of age-of-onset, gender and geographical area of ESCC in Luoyang, the highest incidence area of North China. Results: A total of 4092 cases of ESCC were finally diagnosed among 74,854 patients who had their first endoscopies. The prevalence among males was higher than that among females (p<0.01), resulting in an overall male:female OR of 1.2 (95%CI, 1.2-1.3). The prevalence in rural areas was higher than in urban areas (p<0.01), resulting in an overall rural:urban OR of 2.6 (95%CI, 2.4-2.9). The rural:urban ORs and the 95% CI increased continuously from 2.6, 2.3-3.0 to 2.7, 2.2-3.3, respectively, for 4 consecutive periods during the 22-yr study period. Moreover, the median age of onset among females was higher than that among males (p<0.01). For both sexes and in both areas, the prevalence rates declined and the median age of onset rose for 4 consecutive periods in the 22-yrs time frame (p<0.01). Conculsions: These data reveal the epidemiological profile of ESCC in the area of North China, and suggest that urban areas and rural people account for a growing proportion of the ESCC patients although the prevalence of ESCC significantly declined and the median age-of-onset postponed over the 22-yrs period. Moreover, the prevalence status of ESCC in rural areas also underlines the need for public health initiatives aimed at reducing risk factors of this fatal disease.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.4
• /
• pp.1797-1802
• /
• 2014

Background: The prostaglandin-endoperoxide synthase 2 (PTGS2) and phospholipase A2 group IIA (PLA2G2A) genes encode enzymes that are involved in arachidonic acid and prostaglandin biosynthesis. Dysregulation of both genes is associated with inflammation and carcinogenesis, including esophageal squamous cell carcinoma (ESCC). We therefore hypothesized that there is an association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to ESCC. Methods: We performed a gene-wide tag SNP-based association study to examine the association of SNPs in PTGS2 and PLA2G2A with ESCC in 269 patients and 269 healthy controls from Taihangshan Mountain, Henan and Hebei Provinces, the rural area of China which has the highest incidence of esophageal cancer in the world. Thirteen tag SNPs in PLA2G2A and 4 functional SNPs in PTGS2 were selected and genotyped using a high-throughput Mass Array genotyping platform. Results: We found a modest increased risk of ESCC in subjects with the PTGS2 rs12042763 AA genotype (OR=1.23; 95% CI, 1.00-3.04) compared with genotype GG. For PLA2G2A, a decreased risk of ESCC was observed in subjects with the rs11677 CT (OR=0.51, 95%CI, 0.29-0.85) or TT genotype (OR=0.51, 95%CI, 0.17-0.96) or the T carriers (CT+TT) (OR=0.52, 95%CI, 0.31-0.85) when compared with the CC genotype. Also for PLA2G2A, rs2236771 C allele carriers were more frequent in the control group (P=0.02). Subjects with the GC (OR=0.55, 95%CI, 0.33-0.93) or CC genotype (OR=0.38, 95% CI, 0.16-0.94) or the C carriers (GC+CC) (OR=0.52, 95%CI, 0.32-0.85) showed a negative association with ESCC susceptibility. Conclusions: Our results suggest that PTGS2 and PLA2G2A gene polymorphisms may modify the risk of ESCC development.

• Radiation Oncology Journal
• /
• v.22 no.1
• /
• pp.25-32
• /
• 2004

Purpose : Evaluate the efficacies and toxicities of concurrent chemoradiotherapy (CCRT), with or without intraluminal brachytherapy (ILB), using a retrospective analysis in esophageal carcinomas with respect to survival. Materials and Methods : From April 1995 to July 2001, a total of 65 patients, diagnosed with an esophageal carcinoma, were treated by CCRT, with 21 also treated by ILB after CCRT. External radiotherapy was peformed using 6 or 10 MV X-rays, with a dose range of $46.8~\69.6$ Gy (median; 59.4). The ILB was peformed using high-dose-rate brachytherapy with Ir-192. The fractionation of ILB was 3 Gy by 4, or 5 Gy by 2 fractions. Cisplatin $(75\;mg/m^2)$ was given on each first day of weeks 1, 5, 9 and 13, and 5-FU $(1,000\;mg/m^2)$ as a continuous infusion for the first 4 days of each course. Results : The median survival time of all patients was 15 months, and the 1, 2 and 3-year survival rates were 55.4, 29.2 and $20.7\%$, respectively. The 2-year survival rates of the patients with and without ILB were 33.3 and $27.3\%$, respectively (p=0.80). The 2-year survival rates of the patients with a complete, partial and no response were 44.1, 13.8 and $0\%$, respectively (p=0.02). The response to treatment was the only significant factor affecting the overall survival from a multivariate analysis. Conclusion : This study has shown that the survival outcomes of CCRT were much better than previous results with radiotherapy alone. However, the addition of ILB after CCRT showed no advantage over that of CCRT alone.

• Radiation Oncology Journal
• /
• v.16 no.4
• /
• pp.447-454
• /
• 1998

Purpose : This study evaluated the survival, local control, prognostic factor, and failure pattern of patients with esophageal cancer treated with operation and adjuvant radiation therapy to use as fundermental data of postoperative radiation therapy. Materials and Methods : A retrospective analysis was undertaken of 82 patients who had locally advanced esophageal cancer treated with operation and adjuvant radiation therapy from January 1988 to December 1995. According to AJCC staging, stage IIA were in 26 patients, stage IIB in 4 patients, and stage III in 52 patients. Squamous cell carcinoma were in 77 patients, adenosquamous carcinoma in 3 patients, and adenocarcinoma in 2 patients. The patients received radiation therapy ranging from 41.0 Gy to 64.8 Gy. Five patients received neoadjuvant chemotherapy. Results : Two-year survival and local control rates for all patients were 36.8$\%$ and 30.4$\%$ respectively. And they were 9.3$\%$ and 26.3$\%$ respectively at 5 years. According to stages, 2-year survival rates were 50.2$\%$ in IIA, 0$\%$ in IIB and 23.3$\%$ in III (p=0.004). Two-year local control rates were 49.2 $\%$ in IIA, 66.6$\%$ in IIB and 24.7$\%$ in III (p=0.01). Sixty patients developed recurrence, which were 3 tumor margin, 23 lymph node recurrence, 4 tumor margin and lymph node, 1 tumor margin and distant metastasis, 9 lymph node and distant metastasis, 17 distant metastasis and 3 unknown metastatic site. Prognostic factors affecting survival were smoking (p=0.02), T-staging (p=0.0092), N-staging (p=0.0045). Prognostic factors affecting local control were T-staging (p=0.019), N-staging (p=0.047). Conclusion : In spite of post-operative radiation therapy, predominant failure pattern was local failure. Especially regional lymph node failure was major cause of local failure. So strategy of aggresive adjuvant radiation therapy to regional lymph node area in post operative treatment should be proposed.

• Radiation Oncology Journal
• /
• v.26 no.2
• /
• pp.83-90
• /
• 2008

Purpose: For the first time, a nationwide survey of the Patterns of Care Study(PCS) for the various radiotherapy treatments of esophageal cancer was carried out in South Korea. In order to observe the different parameters, as well as offer a solid cooperative system, we compared the Korean results with those observed in the United States(US) and Japan. Materials and Methods: Two hundreds forty-six esophageal cancer patients from 21 institutions were enrolled in the South Korean study. The patients received radiation theraphy(RT) from 1998 to 1999. In order to compare these results with those from the United States, a published study by Suntharalingam, which included 414 patients[treated by Radiotherapy(RT)] from 59 institutions between 1996 and 1999 was chosen. In order to compare the South Korean with the Japanese data, we choose two different studies. The results published by Gomi were selected as the surgery group, in which 220 esophageal cancer patients were analyzed from 76 facilities. The patients underwent surgery and received RT with or without chemotherapy between 1998 and 2001. The non-surgery group originated from a study by Murakami, in which 385 patients were treated either by RT alone or RT with chemotherapy, but no surgery, between 1999 and 2001. Results: The median age of enrolled patients was highest in the Japanese non-surgery group(71 years old). The gender ratio was approximately 9:1(male:female) in both the Korean and Japanese studies, whereas females made up 23.1% of the study population in the US study. Adenocarcinoma outnumbered squamous cell carcinoma in the US study, whereas squamous cell carcinoma was more prevalent both the Korean and Japanese studies(Korea 96.3%, Japan 98%). An esophagogram, endoscopy, and chest CT scan were the main modalities of diagnostic evaluation used in all three countries. The US and Japan used the abdominal CT scan more frequently than the abdominal ultrasonography. Radiotherapy alone treatment was most rarely used in the US study(9.5%), compared to the Korean(23.2%) and Japanese(39%) studies. The combination of the three modalities(Surgery+RT+Chemotherapy) was performed least often in Korea(11.8%) compared to the Japanese(49.5%) and US(32.8%) studies. Chemotherapy(89%) and chemotherapy with concurrent chemoradiotherapy(97%) was most frequently used in the US study. Fluorouracil(5-FU) and Cisplatin were the most preferred drug treatments used in all three countries. The median radiation dose was 50.4 Gy in the US study, as compared to 55.8 Gy in the Korean study regardless of whether an operation was performed. However, in Japan, different median doses were delivered for the surgery(48 Gy) and non-surgery groups(60 Gy). Conclusion: Although some aspects of the evaluation of esophageal cancer and its various treatment modalities were heterogeneous among the three countries surveyed, we found no remarkable differences in the RT dose or technique, which includes the number of portals and energy beams.

• Journal of Chest Surgery
• /
• v.37 no.4
• /
• pp.356-363
• /
• 2004

Esophageal cancer is an aggressive disease with a poor prognosis. Recently, every effort has been made to improve the long term survival, but the general prognosis for patients with this disease remains poor. In this study, we reviewed 8 years of experiences with esophageal cancer patients managed in our department at Dong-A University Hospital and evaluated the effectiveness of cervical lymph node dissection performed selectively. Material and Method: From January 1995 to August 2003, 70 patients underwent esophagectomy for esophageal cancer in our department. Among them, 51 patients who underwent curative resection, had no double primary tumors and no neoadjuvant therapy were analyzed retrospectively. In most patients, intrathoracic esophagectomy and cervical esophago-gastrostomy was performed. Since 1997, 3-field lymph node dissection was performed selectively. Result: There were 46 men and 15 women. The median age was 60 years. The tumor was located in the upper third part in 10 patients (19%), middle third in 21 (41%), and lower third in 20 (40%). Majority of the patients (90%) had squamous cell carcinoma. Cervical anastomosis was made in 41 patients, and intrathoracic anastomosis in 10. 2-field lymph node dissection was done in 40 patients, and 3-field lymph node dissection in 11. The pathologic staging were as follows: stage I in 9 patients (17.6%), IIA in 20 (39.2%), IIIB in 7 (13.7%), III in 11 (21.6%), IVA in 2 (3.9%), and IVB in 2 (3.9%). The in-hospital mortality was 3.9% (2 patients) and complications occurred in 24 patients (47%). Overall actuarial 1, 3, and 5-year survival rates were 74.4%, 48.4%, and 48.4% including operative mortality. The 4-year survival rate did not differ significantly between 3-field lymph node dissection group (50.5%) and 2-field lymph node dissection group (48.9%). In 3-field lymph node dissection group, the respiratory complications were more frequent and operative time was significantly longer. Conclusion: We think that curative resection for esophageal cancer can be performed with acceptable mortality, and aggressive surgical approach may improve the long term survival. even for advanced stages. Effectiveness of 3-field lymph node dissection needs further investigations.

• Journal of Chest Surgery
• /
• v.32 no.9
• /
• pp.806-812
• /
• 1999

Background: Selection of reconstruction route in esophageal cancer surgery is based on the patient's status, characteristics of tumor, surgeon's preference and experience. Of the various routes, it has been documented that subcutaneous or substernal route may prolong operation time and may be vulnerable to postoperative respiratory complications. This study was designed to evaluate whether the selection of reconstruction route affects the surgical outcomes. Material and Method: Of 131 patients who have undergone resection and reconstruction for esophageal cancer, posterior mediastinal route(Group I, n=34), substernal route (Group II, n=31), and subcutaneous route(Group III, n=21) were retrospectively reviewed in 86 patients. Results of early operations and morbidities were compared between the groups. Result: There was a male prevalence(79 of males vs. 7 of females). There were 81 squamous cell cancers and 5 adenocarcinomas. There were no differences between groups in weight, height, age, cancer staging and location, and in the preoperative anesthetic risk evaluation and pulmonary function test(p=NS). Postoperative mechanical ventilation time was longer in Group I(20.6 hours) than in Group II(7.8 hours) or III(3.4 hours)(p=0.005). Duration of stay in the intensive care unit was prolonged in Group III(6.4 days) compared to Group I (3.9 days) or II(3.1 days)(p=0.043). No differences were noted in the duration of hospital stay between the groups(p=NS). Blood transfusion was needed in 30 out of 34 patients in Group I compared to 14/31 in Group II or 15/21 in Group III(p=0.001). The mean amount of transfusion for each patient was also higher in Group I(3,833 mL) than in Group II(1535 mL) or Group III(1419 mL)(p=0.04), but there was no difference in the inreoperation due to bleeding. Ea ly mortality rate was substantially higher in Group I(17.6%) but the differences between the groups were insignificant(p=NS). Although sepsis was a more prevalent cause of death in Group I, it was not related to anastomotic leak. Other morbidities did not differ between the groups(p=NS). Conclusion: In above results show that the reconstruction route does not affect the outcome of esophageal cancer surgery. We believe that the selection of reconstruction route can be based on the surgeon's preference and experience.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.6
• /
• pp.2629-2633
• /
• 2012

Background: Raw betel nut (RBN) chewing is an important contributing factor for esophageal squamous cell carcinoma (ESCC), although associated genomic changes remain unclear. One difficulty in assessing the effects of exclusively RBN induced genetic alterations has been that earlier studies were performed with samples of patients commonly using tobacco and alcohol, in addition to betel-quid. Both CDKN2A (at 9p21) and Rb1 gene (at 13q14.2) are regarded as tumor suppressors involved in the development of ESCC. Therefore, the present study aimed to verify the RBN's ability to induce ESCC and assess the involvement of CDKN2A and Rb1 genes. Methods: A panel of dinucelotide polymorphic markers were chosen for loss of heterozygosity studies in 93 samples of which 34 were collected from patients with only RBN-chewing habit. Promoter hypermethylation was also investigated. Results: Loss in microsatellite markers D9S1748 and D9S1749, located close to exon $1{\beta}$ of CDKN2A/ARF gene at 9p21, was noted in 40% ESCC samples with the habit of RBN-chewing alone. Involvement of a novel site in the 9p23 region was also observed. Promoter hypermethylation of CDKN2A gene in the samples with the habit of only RBN-chewing alone was significantly higher (p=0.01) than Rb1 gene, also from the samples having the habit of use both RBN and tobacco (p=0.047). Conclusions: The data indicate that the disruption of 9p21 where CDKN2A gene resides, is the most frequent critical genetic event in RBN-associated carcinogenesis. The involvement of 9p23 as well as 13q14.2 could be required in later stages in RBN-mediated carcinogenesis.