• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6397-6403
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• 2014

Background: Aberrant promoter hypermethylation has been recognized in human breast carcinogenesis as a frequent molecular alteration associated with the loss of expression of a number of key regulatory genes and may serve as a biomarker. The E-cadherin gene (CDH1), mapping at chromosome 16q22, is an intercellular adhesion molecule in epithelial cells, which plays an important role in establishing and maintaining intercellular connections. The aim of our study was to assess the methylation pattern of CDH1 and to correlate it with the expression of E-cadherin, clinicopathological parameters and hormone receptor status in breast cancer patients of Kashmir. Materials and Methods: Methylation specific PCR (MSP) was used to determine the methylation status of CDH1 in 128 invasive ductal carcinomas (IDCs) paired with the corresponding normal tissue samples. Immunohistochemistry was used to study the expression of E-cadherin, ER and PR. Results: CDH1 hypermethylation was detected in 57.8% of cases and 14.8% of normal adjacent controls. Reduced levels of E-cadherin protein were observed in 71.9% of our samples. Loss of E-cadherin expression was significantly associated with the CDH1 promoter region methylation (p<0.05, OR=3.48, CI: 1.55-7.79). Hypermethylation of CDH1 was significantly associated with age at diagnosis (p=0.030), tumor size (p=0.008), tumor grade (p=0.024) and rate of node positivity or metastasis (p=0.043). Conclusions: Our preliminary findings suggest that abnormal CDH1 methylation occurs in high frequencies in infiltrating breast cancers associated with a decrease in E-cadherin expression. We found significant differences in tumor-related CDH1 gene methylation patterns relevant to tumor grade, tumor size, nodal involvement and age at diagnosis of breast tumors, which could be extended in future to provide diagnostic and prognostic information.

• Journal of Yeungnam Medical Science
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• v.12 no.1
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• pp.1-9
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• 1995

A monoclonal antibody to PCNA, which can be used on routinely processed tissue, was applied to 25 cases of gastric adenomas and 64 cases of gastric adenocarcinomas in order to diffentiate adenoma and adenocarcinoma and also to evaluate the prognostic value in adenocarcinoma. The results were summerized as follows: The peNA labelling index was $29.14{\pm}12.77%$ in control, $44.09{\pm}17.11%$ in adenoma and $80.15{\pm}10.69$ in adenocarcinoma, resulting in significant increase in adenocarcinoma compared to adenoma. In adenocarcinoma, no significant correlation was observed between PCNA labelling index and histologic grade, and there was increased tendency of PCNA labelling index in proportion to depth of invasion without statistical significance. The PCNA index was significantly increased in advanced adenocarcinoma compared to early gastric carcinoma, and also in positive nodal metastasis group than in negative group. From above results, the PCNA stain will be able to provide a helpful method for the differential diagnosis between gastric adenoma and adenocarcinoma, and could be a useful prognostic factor in adenocarcinoma if other factors are considered together.

• Journal of Gastric Cancer
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• v.4 no.4
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• pp.272-276
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• 2004

Purpose: The incidence of nodal metastases is as low as 2 to $20\%$ in early gastric cancer, so there is a trend to lessen the extent of surgery. In addition, the adequate range for a lymphadenectomy is controversial, especially in early gastric cancer. In this study, we tried to find the minimal range for a lymphadenectomy by analyzing sentinel-node and solitary lymph-node metastases in gastric cancer. Materials and Methods: The total of 78 patients who underwent a curative gastrectomy with a D2 lymphadenectomy for early gastric cancer between 2000 and 2002 in the Department of Surgery, Yonsei University, Seoul, Korea, were included for the evaluation of sentinel-node metastases.. After a laparotomy, 25 mg of indocyanine green was mixed in 5 ml of normal saline, and all the dye was injected into the subserosal layer around the primary tumor. All nodes stained within 5 minutes were marked. In addition, a total of 141 patients, who underwent a curative gastrectomy between 1997 and 2001 at the Department of Surgery, Yonsei University, Seoul, Korea, were analyzed for solitary lymph- node metastases. Results: Among the 78 patients, sentinel nodes were detected in 69 patients ($88.5\%$). The sentinel nodes in 60 cases ($87.0\%$) were located in the perigastric area. However, 9 cases ($13.0\%$) had sentinel nodes in the N2 group. In the 141 cases that had a solitary metastatic node, 125 cases ($88.6\%$) demonstrated the metastatic lymph node in the perigastric area, and 16 cases ($11.4\%$) showed that the metastatic node in the N2 group. Conclusion: Taken together, removal of a perigastric lymph node could miss early metastases in gastric cancer, so a D1 lymphadenectomy should not be the minimal range of dissection if a lymphadenectomy is necessary. (J Korean Gastric Cancer Assoc 2004;4:272-276)

• Journal of Gastric Cancer
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• v.9 no.3
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• pp.110-116
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• 2009

Purpose: The aim of this study was to examine the usefulness of positron emission tomography (PET)-computed tomography (CT) in the pre-operative staging of gastric cancer. Materials and Methods: Between February 2006 and August 2008, PET-CT and CT were performed on 70 patients diagnosed with gastric cancer by gastrofiberscopic biopsy. The sensitivities, specificities, Positive predictive value (PPV), and negative predictive value (NPV) of PET-CT and CT imaging for the detection of gastric cancer TNM staging were compared. Results: The detection rates for the primary tumor were as follows: PET-CT, 81.4% (57/70); and CT, 42.9% (30/70). For both early gastric cancer (EGC) and advanced gastric cancer (AGC), PET-CT was more accurate than CT in detecting the lesions. As the size of the tumor exceeded 3 cm, the detection rate increased. The sensitivities, specificities, PPV, and NPV of PET-CT for lymph node staging were 55.6%, 81%, 86.2%, and 45.9%, while the sensitivities, specificities, PPV, and NPV of CT were 40.0%, 85.7%, 85.7% and 40%, respectively. One case of multiple liver metastasis and two cases of dual primary cancer (rectal and pancreatic cancers) were detected by PET-CT. PET-CT also had a higher detection rate for all histologic types of primary tumors. PET-CT was more accurate than CT in detecting primary gastric cancer lesions. The detection of nodal metastasis by PET-CT was similar to CT; small-sized tumors or EGC detection rates were not high. However, PET-CT provided additional information to detect distant metastases and dual primary cancers and reduced unnecessary laparotomies to detect peritoneal seeding or carcinomatosis. Conclusion: It would be useful to make a pre-operative diagnosis of gastric cancer and determine treatment if PET-CT were added to other routine pre-operative studies.

• Radiation Oncology Journal
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• v.28 no.4
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• pp.205-210
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• 2010

Purpose: To evaluate the predictive factors for treatment response and prognostic factors affecting survival outcomes after concurrent chemoradiotherapy (CCRT) for patients with anal squamous cell carcinoma. Materials and Methods: Medical records of forty two patients with histologically confirmed analsquamous cell carcinoma, who had complete CCRT between 1993 and 2008, were reviewed retrospectively. Median age was 61.5 years (39~89 years), and median radiotherapy (RT) dose was 50.4 Gy (30.0~64.0 Gy). A total of 36 patients had equal to or less than T2 stage (85.7%). Fourteen patients (33.3%) showed regional nodal metastasis, 36 patients (85.7%) were treated with 5-fluorouracil (5-FU) plus mitomycin, and the remaining patients were treated by 5-FU plus cisplatinum. Results: The median follow-up time was 62 months (2~202 months). The 5-year overall survival, loco regional relapse-free survival, disease-free survival, and colostomy-free survival rates were 86.0%, 71.7%, 71.7%, 78.2%, respectively. Regarding overall survival, the Eastern Cooperative Oncology Group (ECOG) performance status and complete response were found to be significant prognostic factors on univariate analysis. For multivariate analysis, only the ECOG performance status was significant. No significant factor was found for locoregional relapse-free survival or disease-free survival and similarly for treatment response, no significant factor was determined on logistic regression analysis. There were 7 patients who had local or regional recurrences and one patient with distant metastasis. The only evaluable toxicity in all patients was radiation dermatitis of perianal skin (grade 3), which developed in 4 patients (9.5%) and grade 2 in 22 patients (52.4%). Conclusion: This study revealed that patients with a performance score of ECOG 0-1 survived significantly longer than those with a poorer score. Finally, there was no significant predicting factors tested for treatment response.

• Radiation Oncology Journal
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• v.9 no.2
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• pp.249-252
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• 1991

A Retrospective study to analyze the failure pattern in locally advanced stomach cancer, treated with radical surgery and post-op chemotherapy was perfomed. Among 107 patients who underwent radical gastrectomy in Asan Medical Center between June 1989 and August 1990. there were 20 stage II(T2NO, T2N1) and 87 stage III(T3N1, T3N2) and 91 patients were eligible for study. 57 patients treated with 6 cycles of postop adjuvant chemotherapy. Among 57 patients treated with postop adjuvant chemotherapy, local failure occurred in $21\%$ and distant failure in $12\%$. Among 34 patients who were not treated with postop chemotherapy, local failure occurred in $24\%$ and distant failure in $26\%$. Among 29 failures including 13 locoregional, 9 distant metastasis and 7 locoregional and distant metastasis, 11 cases recurred in the anastomotic site, 3 in the gastric bed,7 in the regional lymph nodes and peritoneal seeding occurred in 6 cases. The true incidences of gastric bed, nodal and peritoneal failures may be higher in the longer follow-up or reoperative or autopsy series. Our data sugest that postop chemocherapy is beneficial by reducing distant failure rate. Our data suggest that postop chemocherapy is beneficial by reducing distant failure rate. Postop adjuvant locoregional radiotherapy in addition to the systemic adjuvant therapy may reduce the local failure rate and potentially benefit in at least $20\%$ of patients who developed the local failure only.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.71-78
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• 2010

Purpose: To evaluate the result of neoadjuvant chemotherapy, surgery, and radiation therapy in locally advanced breast cancer as well as analyze the prognostic factors affecting survival. Materials and Methods: One hundred fifty-nine patients with breast cancer were treated by neoadjuvant chemotherapy between April 1995 and November 2006 at the Samsung Medical Center. Among these patients, we retrospectively reviewed 105 patients treated with neoadjuvant chemotherapy followed by surgery and radiation therapy for a cure with an initial tumor size >5 cm or clinically positive lymph nodes. All patients received anthracycline based chemotherapy except for 2 patients. According to clinical tumor stage, 3 patients (3%) were cT1, 26 (25%) were cT2, 39 (37%) were T3 and 37 (35%) were T4. Initially, 98 patients (93%) showed axillary lymph node metastasis. The follow-up periods ranged from 7~142 months (median, 41 months) after the beginning of neoadjuvant chemotherapy. Results: Locoregional failure free survival rate and distant metastasis free survival rate at 5 years were 82.1% and 69.9%, respectively. Disease free survival rate and overall survival rate at 5 years were 66.1% and 77.1%, respectively. The results of a univariate analysis indicate that clinical tumor stage, pathologic tumor stage, pathologic nodal stage and pathologic TNM stage were statistically significant factors for disease free survival rate and overall survival rate. Whereas, a multivariate analysis indicated that only hormone therapy was a statistically significant factor for survival. Conclusion: The current study results were comparable to other published studies for neoadjuvant chemotherapy for breast cancer. Hormone therapy was a statistically significant prognostic factor. The patients with early clinical or pathologic stage had a tendency to improve their survival rate.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.642-649
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• 1999

Background: It is very important to determine an accurate staging of the non-small cell lung cancer(NSCLC) for an assessment of operability and it's prognosis. However, it is difficult to evaluate tumor involvement of mediastinal lymph nodes accurately utilizing noninvasive imaging modalities. PET is one of the sensitive and specific imaging modality. Unfortunately PET is limited use because of prohibitive cost involved with it's operation. Recently hybrid SPECT/PET(single photon emission computed tomography/positron emission tomography) camera based PET imaging was introduced with relatively low cost. We evaluated the usefulness of coincidence detection(CoDe) PET in the detection of metastasis to the mediastinal lymph nodes in patients with NSCLC. Methods: Twenty one patients with NSCLC were evaluated by CT or MRI and they were considered operable. CoDe PET was performed in all 21 patients prior to surgery. Tomographic slices of axial, coronal and sagittal planes were visually analysed. At surgery, mediastinal lymph nodes were removed and histological diagnosis was performed. CoDe PET findings were correlated with histological findings. Results: Twenty of 21 primary tumor masses were detected by the CoDe PET. Thirteen of 21 patients was correctly diagnosed mediastinal lymph node metastasis by the CoDe PET. Pathological N0 was 14 cases and the specificity of N0 of CoDe PET was 64.3%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N1 node was 83.3%, 73.3%, 55.6%, 91.7%, and 76.2% respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of N2 node was 60.0%, 87.5%, 60.0%,87.5%, and 90.0% respectively. There were 3 false negative cases but the size of the 3 nodes were less than 1cm. The size of true positive nodes were 1.1cm, 1.0cm, 0.5cm respectively. There were 1 false positive among the 12 lymph nodes which were larger than 1cm. False positive cases consisted of 1 tuberculosis case, 1 pneumoconiosis case and 1 anthracosis case. Conclusion: CoDe PET has relatively high negative predictive value in the enlarged lymph node in staging of mediastinal nodes in patients with NSCLC. Therefore CoDe PET is useful in ruling out metastasis of enlarged N3 nodes. However, further study is needed including more number of patients in the future.

• Radiation Oncology Journal
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• v.28 no.3
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• pp.125-132
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• 2010

Purpose: To retrospectively assess the advantages and side effects of prophylactic Paraaortic irradiation in cervical cancer patients with common iliac nodal involvement, the results for survival, patterns of failure, and treatment-related toxicity. Materials and Methods: From May 1985 to October 2004, 909 patients with cervical carcinoma received postoperative radiotherapy at the Seoul National University Hospital. Among them, 54 patients with positive common iliac nodes on pathology and negative Paraaortic node were included in the study. In addition, 44 patients received standard pelvic irradiation delivered 50.4 Gy per 28 fractions (standard irradiation group), and chemotherapy was combined in 16 of them. The other 10 patients received pelvic irradiation at a dose of 50.4 Gy per 28 fractions in addition to Paraaortic irradiation at 45 Gy per 25 fractions (extended irradiation group). In addition, all of them received chemotherapy in combination with radiation. Follow-up times for pelvic and Paraaortic irradiation ranged from 6 to 201 months (median follow-up time, 58 months) and 21 to 58 months (median follow-up time, 47 months), respectively. Results: The 4-year overall survival, disease free survival, and distant metastasis free survival in the standard irradiation group and extended irradiation group were 67.2% vs. 90.0% (p=0.291), 59.0% vs. 70.0% (p=0.568) and 67.5% vs. 90.0% (p=0.196), respectively. The most common site of first failure for the standard irradiation group was the paraaortic lymph node, while no paraaortic failure was observed in the extended irradiation group. Relatively, hematologic toxicity grade 3 or greater was common in the extended irradiation group (2/10 extended vs. 2/44 standard), while gastrointestinal toxicity of grade 3 or greater was lower (2/10 extended vs. 6/44 standard), and urologic toxicity of grade 3 or greater was observed in the standard irradition group only (0/10 vs. 3/44). Conclusion: Concurrent chemotherapy and prophylactic Paraaortic irradiation in patients with common iliac nodal involvement showed slightly improved clinical outcomes aside from increased hematologic toxicity, which was statistically insignificant. Considering the relatively small number of patients and short follow-up times, additional studies are needed to obtain more conclusive outcomes.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.345-350
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• 2004

Background : To evaluate the frequency and clinical significance of lymph node micrometastasis in patients of non-small-cell lung cancer pathologically staged to be T1-2,N0. Method : From consecutive 29 patients of non-small-cell lung cancer who received curative operation and routine systemic nodal dissection, we immunohistochemically examined 806 lymph nodes from mediastinal, hilar and peribronchial lesion. All slides were stained with hematoxylin and eosin staining for one section and with cytokeratin AE1/AE3 antibody for another consecutive section of same lymph node to find out micrometastasis. Results : In 806 lymph nodes examined, no tumor cell was seen on hematoxylin and eosin staining and micrometastic foci were shown to be on 0.37%(3) of 806 lymph nodes, in which were upper paratracheal, interlobar and peribronchial lymph node. These three positive stains constitute 10.3%(3) of the 29 patients with non-small-cell lung cancer. Nine patients died from disease progression(4), postoperative complication(3) and concomitant diseases(2). The four patients with disease progression did not show evidence of micrometastasis on their lymph node examination. Conclusion : The frequency of lymph node micrometastasis was in 0.37% of 806 lymph nodes examined. The study results might suggested that routine analysis of micrometastasis on the lymph node didn't give any clinical implication on patients with non-small-cell lung cancer.