• Journal of Chest Surgery
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• v.56 no.6
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• pp.403-411
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• 2023

Background: The concept of oligo-recurrence has not been generally applied in esophageal cancer. This study aimed to determine the prognostic significance of the number of recurrences in esophageal cancer. Methods: Patients with squamous cell carcinoma who underwent curative esophagectomy with R0 or R1 resection and who experienced a confirmed recurrence were included. The study included 321 eligible participants from March 2001 to December 2019. The relationship between the number of recurrences and post-recurrence survival was investigated. Results: The mean age was 63.8±8.1 years, and the majority of the participants (97.5%) were men. The median time to recurrence was 10.7 months, and the median survival time after recurrence was 8.8 months. Multiple recurrences with simultaneous local, regional, and distant locations were common (38%). In terms of the number of recurrences, single recurrences were the most common (38.3%) and had the best post-recurrence survival rate (median, 17.1 months; p<0.001). Patients with 2 or 3 recurrences showed equivalent survival to each other and longer survival than those with 4 or more (median, 9.4 months; p<0.001). In the multivariable analysis, the significant predictors of post-recurrence survival were body mass index, minimally invasive esophagectomy, N stage, R0 resection, post-recurrence treatment, and the number of recurrences (p<0.05). Conclusion: After esophagectomy, the number of recurrences was the most significant risk factor influencing post-recurrence survival in patients with esophageal cancer. In esophageal cancer, oligo-recurrence can be defined as a recurrence with three or fewer metastases. More intensive treatment might be recommended if oligo-recurrence occurs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5455-5461
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• 2012

Luteolin is a plant flavonoid which exhibits anti-oxidative, anti-inflammatory and anti-tumor effects. However, the antiproliferative potential of luteolin is not fully understood. In this study, we investigated the effect of luteolin on cell cycling and apoptosis in human esophageal squamous carcinoma cell line Eca109 cells. MTT assays showed that luteolin had obvious cytotoxicity on Eca109 with an $IC_{50}$ of $70.7{\pm}1.72{\mu}M$ at 24h. Luteolin arrested cell cycle progression in the G0/G1 phase and prevented entry into S phase in a dose- and time-dependent manner. as assessed by FCM. Luteolin induced apoptosis of Eca109 cells was demonstrated by AO/EB staining assay and annexin V-FITC/PI staining. Moreover, luteolin downregulated the expression of cyclin D1, survivin and c-myc, and it also upregulated the expression of p53, in line with the fact that luteolin was able to inhibit Eca109 cell proliferation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7315-7319
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• 2013

Background: The metastasis gene osteopontin (OPN) is subject to alternative splicing, which yields three messages, osteopontin-a, osteopontin-b and osteopontin-c. Osteopontin-c is selectively expressed in invasive, but not in noninvasive tumors. In the present study, we examined the expression of OPN-c in esophageal squamous cell carcinomas (ESCCs) and assessed its value as a diagnostic biomarker. Methods: OPN-c expression was assessed by immunohistochemistry in 63 ESCC samples and correlated with clinicopathologic factors. Expression was also examined in peripheral blood mononuclear cells (PBMCs) from 120 ESCC patients and 30 healthy subjects. The role of OPN-c mRNA as a tumor marker was investigated by receiver operating characteristic curve (ROC) analysis. Results: Immunohistochemistry showed that OPN-c was expressed in 30 of 63 cancer lesions (48%)and significantly associated with pathological T stage (P=0.038) and overall stage (P=0.023). Real time PCR showed that OPN-c mRNA was expressed at higher levels in the PBMCs of ESCC patients than in those of healthy subjects (P<0.0001) with a sensitivity as an ESCC biomarker of 86.7%. Conclusion: Our findings suggest that expression of OPN-c is significantly elevated in ESCCs and this upregulation could be a potential diagnostic marker.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2345-2351
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• 2014

Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase (LOX) family, is a copper-dependent enzyme that catalyzes oxidative deamination of lysine residues on protein substrates. LOXL2 was found to be overexpressed in esophageal squamous cell carcinoma (ESCC) in our previous research. We later identified a LOXL2 splicing variant LOXL2-delta72 and we overexpressed LOXL2-delta72 and its wild type counterpart in ESCC cells following microarray analyses. First, the differentially expressed genes (DEGs) of LOXL2 and LOXL2-delta72 compared to empty plasmid were applied to generate protein-protein interaction (PPI) sub-networks. Comparison of these two sub-networks showed hundreds of different proteins. To reveal the potential specific roles of LOXL2- delta72 compared to its wild type, the DEGs of LOXL2-delta72 vs LOXL2 were also applied to construct a PPI sub-network which was annotated by Gene Ontology. The functional annotation map indicated the third PPI sub-network involved hundreds of GO terms, such as "cell cycle arrest", "G1/S transition of mitotic cell cycle", "interphase", "cell-matrix adhesion" and "cell-substrate adhesion", as well as significant "immunity" related terms, such as "innate immune response", "regulation of defense response" and "Toll signaling pathway". These results provide important clues for experimental identification of the specific biological roles and molecular mechanisms of LOXL2-delta72. This study also provided a work flow to test the different roles of a splicing variant with high-throughput data.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3825-3830
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• 2013

More studies are needed to clarify treatments and prognosis of early esophageal squamous cell carcinoma (ESCC). This retrospective study was designed to review the outcome of surgical treatment for early ESCC, evaluate the results of a left thoracotomy for selected patients with early ESCC, and identify factors affecting lymph node metastases and survival. The clinicopathological data of 228 patients with early ESCC who underwent transthoracic esophagectomy with lymphadenectomy without preoperative adjuvant treatment were reviewed. The ${\chi}^2$ test or Fisher's exact test were used to detect factors related to lymph node metastasis. Univariate and multivariate analyses were performed to identify prognostic factors. There were 152 males and 76 females with a median age of 55 years. Two hundred and eight patients underwent a left thoracotomy, and the remaining 20 patients with lymph nodes in the upper mediastinum more than 5 mm in short-axis diameter by computed tomography scan underwent a right thoracotomy. No lymph node metastasis was found in the 18 patients with carcinoma in situ, while lymph node metastases were detected in 1.6% (1/62) of patients with mucosal tumours and 18.2% (27/148) of patients with submucosal tumours. Only 7 patients showed upper mediastinal lymph node metastases in the follow-up. The 5- and 10-year overall survival rates were 81.4% and 70.1%, respectively. Only histologic grade (P<0.001) and pT category (P=0.001) significantly correlated with the presence of lymph node metastases. In multivariate analysis, only histologic grade (P=0.026) and pT category (P=0.008) were independent prognostic factors. A left thoracotomy is acceptable for selected patients with early ESCC. Histologic grade and pT category affected the presence of lymph node metastases and were independent prognostic factors for early ESCC.

• Journal of Chest Surgery
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• v.40 no.10
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• pp.685-690
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• 2007

Background: In the past, radiotherapy was the gold standard for the treatment of upper esophageal cancer, but the long-term follow-up was disappointing. There is still ongoing debate on the surgical management of these patients. This study was undertaker to update our experience with upper esophageal carcinoma and to evaluate the effectiveness of surgery. Material and Method: From May 1995 to December 2005, 147 patients with esophageal cancer underwent surgery at our hospital. They were divided into two groups: one group consisted of 23 patients with upper esophageal (cervical and upper thoracic) cancer and another group consisted of 424 patients with lower esophageal (middle thoracic, lower thoracic and abdominal) cancer. We evaluated the effectiveness of surgical treatment between the 2 groups by measuring the rate of complete surgical resection, the postoperative complications, the postoperative mortality, tumor recurrence, the average life expectancy and the long-term survival. Result: On comparing both groups, there was no significant difference in the distribution of the pathological stage and no significant difference in the percentage of performing complete surgical resection. The percentage of post-operative complications was 39.1% (9 out of 23 patients) in the upper esophageal cancer group, and this was significantly higher than 16.9% (21 out of 124 patients) in the lower esophageal cancer group (p<0.05). However, there was no significant statistical difference between the groups for the percentages of postoperative mortality, tumor recurrence or the postoperative average life expectancy. Conclusion: There was no significant difference in operative mortality or surgical effectiveness between the 2 groups. Therefore, we thought that surgical treatment is also effective for treating upper esophageal cancer, but further investigation with large patient populations will be required.

• Journal of Chest Surgery
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• v.41 no.2
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• pp.253-259
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• 2008

Background: The incidence of cervical esophageal cancer is low compared with that of thoracic esophageal cancer, and the role of surgery for cervical esophageal cancer is limited compared with that of radiotherapy or chemotherapy. This study was carried out to determine the outcome of surgery for cervical esophageal cancer. Material and Method: We analyzed retrospectively medical records of 43 patients who had undergone curative surgical resection for cervical esophageal cancer from January 1989 to December 2002. Follow-up loss was absent and the last follow-up was carried out in February 28, 2004. Result: The mean age was 60 years old and the male to female ratio was 40:3. Histologic types were squamous cell carcinoma 42 patients and malignant melanoma 1 patient. The methods used for esophageal reconstruction were gastric pull-up 32 patients, free jejunal graft 7 patients and colon interposition 4 patients. Postoperative complications occurred in 31 patients (72%), and operative mortality occurred in 7 patients (16%). Pathologic stages were I 3, IIa 14, IIb 1, III 19, and IVa 6 patients. Tumor recurrence occurred in 16 patients (44%), and the 3 and 5-year survival rates were 29.3% and 20.9%. Conclusion: The reported surgical results for cervical esophageal cancer showed somewhat high operative mortality, postoperative complication rates and recurrence rates and a low long-term survival rate. It is suggested that multimodality treatment including surgery is needed for the treatment of cervical esophageal cancer because radiotherapy or chemotherapy without surgery could not relieve dysphagia or resolve the tumor completely.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.441-446
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• 1998

Purpose : The incidence of esophageal carcinoma is increasing. Radical surgery is the treatment of choice, but large proportion of the esophageal cancer patients are with unresectable disease at the time of initial diagnosis, so radiation therapy has been the major treatment modality. We carried out retrospective analysis to see the outcome and prognostic factors of radiation therapy alone for esophageal carcinoma. Methods and Materials : From June of 1979 through December 1992, 289 patients with esophageal carcinoma were treated with radiation therapy alone at Department of Therapeutic Radiology, Seoul National University Hospital. Of these patients, 84 patients were excluded as they were ineligible for the current analyses. Twenty-two patients had distant metastasis other than supraclavicular lymph node metastasis, 52 patients received less than 45 Gy, and 10 patient were lost from follow-up. Therefore 205 patients constituted the base population of this study. According to AJCC s1aging system, there were 2 patients with stage 1, 104 with stage IIA, 26 with stage IIB, 48 with stage III, and 25 with stage IV Radiation dose ranged from 4500 cGy to 6980 cGy with median dose of 5940 cGy. Follow-up period of the alive patients ranged from 77 to 180 months. Results : The Median survival period of all the patients was II months and the 2-, 5-, and 10-year overall survival rates were 22.4$\%$, 10.2$\%$ and 5.3$\%$, respectively. Most of the failures were local recurrences. Of 169 failures, 134 had local failure as a component and 111 had local recurrence only. The Lymph node was most common distant metastatic site and the next was the lung. The stage, T-stage, N-stage, functional status, tumor size, and aim of treatment were statistically significant prognostic factors for survival by univariate analyses. But only tumor size and N-stage were significant by multivariate analyses. Conclusion : We could get 10.2$\%$ of 5 year survival rate and 5.3$\%$ of 10 year survival rate with radiation therapy alone. The size of tumor and N-stage were statistically significant prognostic factors for survival on multivariate analyses.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9417-9421
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• 2014

Background: Esophageal cancer is one of the most frequently occurring malignancies and the seventh leading cause of cancer-related deaths in the world. The esophageal squamous cell carcinoma (ESCC) is the most common histological type of esophageal cancer worldwide. Materials and Methods: Our goal in this study was to detect phospholipase A2 Group IIA (PLA2G2A) and cyclooxygenase-2 (COX-2) immuno-expression in ESCC in a high-risk population in China. Results: Positive expression of PLA2G2A protein was observed in 57.2% (166/290) of the cases, while COX-2 was found in 257 of 290 samples (88.6%), both PLA2G2A and COX-2 being expressed in 153 cases (52.8%), with a significant agreement (Kappa=0.091, p=0.031).Overexpression of PLA2G2A was significantly correlated with the depth of invasion (p=0.001). Co-expression of PLA2G2A and COX-2 not only significantly correlated with the depth of invasion (p=0.004) but also with TNM stage (p=0.04). Conclusions: Our results showed that in patients with ESCC, PLA2G2A overexpression and PLA2G2A co-expression with COX-2 is significantly correlated with advanced stage. The biological role and pathophysiologic regulation of PLA2G2A and COX-2 overexpression in ESCC deserve further investigation.

• Radiation Oncology Journal
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• v.3 no.1
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• pp.41-50
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• 1985

63 patients who were irradiated with a goal of long term control among 101 patients with esophageal cancer seen during an 11 fears period between Jan, 1970 and Dec, 1980 at Yonsei Cancer Center in Seoul, Korea have retrospectively analysed. 52(82.5%) among the 63 Patients were confirmed to have epidermoid carcinoma in the histology. 46 cases(73.0%) except 17 cases of $T_1$, were locally or far advanced extension. Tumor dose of radical radiation in the management of esophageal cancer had delivered from 50 Gy to 74 Gys. 2 Gys daily fractions, between 5weeks and 8 weeks. After 1 month from the completion of radiation, 23 of the 63 patients had a repeat barium esophagogram for the assessment of tumor response, there had showed 7 cases of complete response and 15 cases of partial response. 45(71.4%) patients were followed up and the remaining 18 patients were lost to follow-up within 1 year after the completion of irradiation. Actuarial overall 3 and 5 years survival rate of all 63 Patients were 11.8% and 8.8%, respectively. The actuarial 3 and 5 years survival rates of 17 cases of $T_1$, esophageal cancer were 24.7% and 20.8%. Statistically, there was no significant difference in survival rate according to tumor location (p>0.05). Radical Radiotherapy, Esophageal Cancer