• Journal of Gastric Cancer
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• v.6 no.2
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• pp.109-113
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• 2006

Purpose: Various minimally invasive surgical techniques, such as an endoscopic mucosal resection and a laparoscopic gastrectomy, are becoming common practice for some cases of early gastric cancer (EGC) defined in terms of the depth of invasion being limited to the mucosa or submucosa. However, there are rare cases of early gastric cancer with massive lymph-node metastasis. Materials and Methods: From 6 university hospitals of Korea, 2,772 EGC cases were resected during the various period of analysis (1,432 cases of mucosal cancer and 1,340 of submucosal cancer). Results: As control data, we used the data from a single institute, CHA University Hospital. There were nine cases of early gastric cancer (9/2,772, 0.32%) with N3 lymph node metastasis defined by more than 15 lymph nodes being metastasized according to the UICC-TNM classification (pT1N3, stage IV). Two cases were mucosal cancer (2/1,432, 0.1 4%), and seven cases were submucosal cancer (7/1,340, 0.52%). Metastasized lymph nodes varied in number from 18 to 52. There were three male and six female patients with a mean age of 57. This is a totally reversed sex ratio compared to the usual gastric cancer or EGC. Among the total of 9 EGC patients, there were 5 who had superficial spreading carcinomas with surface areas larger than $25\;cm^2$. This is a significantly higher proportion compared to the general EGC population. When we compared the tumor size according to the LN status, the N3 group was definitely larger than the other groups. 78% of the pT1N3 cases showed lymphatic invasion, which is very high compared to the 4.7% in general EGC cases. Among the 9 cases, 6 patients had too short a follow-up period to evaluate the correct prognosis, but there was one patient with a non-curative resection and two patients with early recurrence. Although the sample size is small and the follow-up period is short, we can expect a very poor prognosis when we consider the common prognosis of EGC that is widely known and accepted. Conclusion: From these results, we can a conclude that the risk factors for pT1N3 gastric cancer are female patients, submucosal invasion, larger tumor size, and lymphatic invasion. However rare, the existence of pT1N3 gastric cancer needs to be taken into consideration, especially during the diagnosis. Furthermore, minimally invasive treatment for EGC needs to be chosen with great precaution. Since the prognosis of pT1N3 gastric cancer is expected to be poor, aggressive adjuvant chemotherapy may be necessary. (J Korean Gastric Cancer Assoc 2006;6:109-113)

• Tuberculosis and Respiratory Diseases
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• v.48 no.5
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• pp.757-765
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• 2000

Background : Angiogenesis plays a critical role in human tumor growth and metastasis. Microvessel count as a measure of tumor angiogenesis, has been significantly correlated with invasive and metastatic patterns in breast. prostate and cutaneous carcinomas. Materials and Methods : Fifty patients with curatively resected non-small cell lung cancer were evaluated. Tumor tissues embedded in paraffin block were stained by anti CD 31 (PECAM, platelet endothelial cellular adhesion molecule) using immunohistochemical method to assess microvessel count. Microvessels were counted in the most active areas of neovascularization(microscopy, 200$\times$). Results: 1) Mean microvessel count was 47.1$\pm$17.7(per 200$\times$field) in total 50 cases. 2) Mean microvessel count of adenocarcinoma (54.4$\pm$19.9) was significantly higher than that of squamous cancer (43.9$\pm$16.2) (p<0.05), but there were no relationship between microvessel count and TNM stages. 3) Median survival time, 2-year and 5-year survival rates of the low microvascular group (microvessel count<45, 22 cases) were 61 months, 80% and 40%, respectively, and those of the high microvascular group(microvessel count$\geq$45, 28 cases) were 46 months, 75% and 12%, respectively. As results, prognosis of low microvascular group is statistically significantly superior to that of the high microvascular group (p=0.0162, Kaplan-Meier, log-rank). Conclusion : Angiogenesis assessed by microvessel count can be used as one of the significant prognostic factors in non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.108-121
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• 2001

Background : The $p16^{INK4a}$ (p16) twnor suppressor gene is frequently inactivated in hwnan non-small cell lung cancers (NSCLCs), predominantly through homozygous deletion or in association with aberrant promotor hypermethylation. Death-associated protein kinase (DAPK) gene influences interferon $\gamma$-induced apoptotic cell death and has important role in metastasis of lung cancer in animal model. Hypermethylation of promoter region of DAP kinase gene may suppress the expression of this gene. Methods : This study was performed to investigate the aberrant methylation of p16 or DAP kinase in 35 resected primary NSCLCs by methylation-specific PCR (MSP), and demonstrated frequency, diagnostic value and clinical implication of aberrant methylation of two genes. Results : Thirty-two cases were male patients, and 3 cases were female patients with an average age was 57. $8{\pm}10.5$ years. The histologic types of lung cancer were 22 of squamous cell carcinoma, 12 of adenocarcinoma, 1 of large cell carcinoma. Pathologic stages were 11 cases of stage I (1 IA, 10 IB), 13 cases of stage II (1 IIA, 12 IIB), and 11 cases of stage III (9 IIIA, 2 IIIB). Regarding for the cancer tissue, p16 aberrant methylation was noted in 13 case of 33 cases (39.4%), DAP kinase in 21 cases of 35 cases (60%). Age over 55 year was associated with p16 aberrant methylation significantly (p<0.05). Methylation status of two genes was not different by smoking history, histologic type, size of tumor, lymph node metastasis and disease progression of lung cancer. There was no correlation between p16 and DAP kinase hypermethylation. Conclusion: This investigation demonstrates that aberrant methylation of p16 tumor suppressor gene or DAP kinase showed relatively high frequency (74.3%) in NSCLCs, and that these genes could be a biologic marker for early detection of lung cancer.

• Radiation Oncology Journal
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• v.19 no.4
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• pp.301-305
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• 2001

Purpose : This study was peformed for the evaluation of the feasibility and toxicity of hypofractionated radiation therapy for early glottic cancer Methods and Materials : From February 1999 to February 2000, 20 patients with Histologically confirmed Stage I, II glottic cancer were enrolled into this study. There were 18 males and 2 females, the median age of the patients was 59 years. The distribution of stage distribution was as fellows; T1aN0-16 patients, T1bN0-1 patient, T2N0-3 patients. Eighteen patients underwent laryngomicroscopic biopsy only, and two patients underwent laser cordectomy. All patients received radical radiation therapy (2.5 Gy per fraction, 24 fractions, total 60 Gy). Median duration of treatment was 36 days (range $31\~45\;days$). Results : Radiation therapy were well tolerated. Most common acute reactions were odynophagia and hoarseness, and these reactions resolved after radiation therapy. There were one case of RTOG grade 3 odynophagia $(5\%)$, six cases of grade 3 hoarseness $(30\%)$. Response of radiation therapy was evaluated one month after completion of treatment. All patients revealed complete response. During follow up, total three cases of treatment failure were detected. two cases were local recurrence in 10 and 13 months of radiation therapy and one case was local recurrence and distant metastasis in 2 months of radiation therapy. Conclusion : This hypofractionated radiation therapy schedule was feasible and effective for control of early glottic cancer But longer follow up time would be required to assess the long-term disease control and the late complication by shortening radiation therapy duration.

• Tuberculosis and Respiratory Diseases
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• v.53 no.6
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• pp.644-649
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• 2002

Background : Pulmonary hamartomas are the most common form of benign tumors, occurring in approximately 0.2% of routine autopsies. However, only a few reports on the clinical characteristics of pulmonary hamartoma in Korea have been published. Materials and Methods : The charts, X-rays and pathological specimens of 29 pulmonary hamartoma patients who were diagnosed by a pathological examination from 1990 to 1999 at the Catholic Medical Center were retrospectively reviewed. Results : The peak incidence of the tumor occurred in the sixth decade of life (37.5%). Seventeen patients (58.6%) were asymptomatic and 12 patients (41.4%) had symptoms. Chest discomfort was the most common symptom (31.0%). A total of 25 tumors (86.2%) were parenchymal, and 4 (13.8%) were endobronchial. Twenty cases were in the right lung and 9 cases were in the left lung (approximately 1:2.2). The RLL was the most commonly involved lobe (31.0%). Calcification was noted in 5 cases(19.2%) on a plain X-ray and in 5 cases (29.4%) on chest CT. Accompanied neoplasms were observed in 2 cases. Twenty-four hamartomas (82.8%) were diagnosed by a surgical resection and 4 cases(13.8%) were diagnosed by a fine needle aspiration biopsy. Twenty-six hamartomas (89.7%) were managed by a surgical resection. The follow up ranged from 4 to 55 months (mean, 19.6 months) and no recurrent pulmonary hamartomas were noted. Conclusion : Pulmonary hamartoma is more common in females and more commonly in the right lung. Calcification was noted only in 19.2% on a plain chest X-ray and 29.4% on a chest CT. No recurrent hamartomas had developed during the follow up period.

• Tuberculosis and Respiratory Diseases
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• v.64 no.4
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• pp.278-284
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• 2008

Background: TRAIL is a promising anticancer agent which induces selective tumor cell death due to a unique receptor system that includes death receptors and decoy receptors. DR5 TRAIL receptor is an originally identified p53-regulated death receptor gene that was induced, by doxorubicine, only in cells with a wild-type p53 status. We investigated that focused on the correlation between the DR5 and p53 expressions in non-small cell lung cancer (NSCLC). Methods: Immunohistochemical analysis, with using avidin-biotinylated horseradish peroxidase complex, was carried out in 89 surgically resected NSCLC formalin-fixed paraffin-embedded tissue sections. As primary antibodies, we used anti-DR5 polyclonal antibody and anti-p53 monoclonal antibody. A negative control was processed with each slide. The positive tumor cells were quantified twice and these values were expressed as percentage of the total number of tumor cells, and the intensity of immunostaining was expressed. The analysis of the DR5 expression was done separately in tumor area and in a nearby region of normal tissue. Results: The DR5 expression was high in the bronchial epithelium (89% of cases) but this was almost absent in type I & II pneumocytes, lymphocytes and smooth muscle cells. High DR5 expression rate in tumor was seen in 28% (15/53) of squamous cell carcinomas, in 47% (15/32) of adenocarcinomas and, in 50% (2/4) of large cell carcinomas. The DR5 expression did not show any statistical significance relationship with the T stage, N stage, or survival. However, the DR5 expression showed significant inverse correlation with the p53 expression. (p< 0.01). Conclusion: We demonstrated that the DR5 expression in NSCLC via immunohistochemical analysis is relatively tumor-specific except for that in the normal bronchial epithelium and it is significantly dependent on the p53 status. This might be in vivo evidence for the significance of the DR5 gene as a p53 downstream gene.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.111-119
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• 2009

Purpose: This study aimed at assessing the value of fluorine-18 fluorodeoxyglucose positron emission tomography ($^{18}F$-FDG PET) for predicting the response of locally advanced rectal cancer to neoadjuvant CRT. Materials and Methods: Between August 2006 and January 2008, we prospectively enrolled 20 patients with locally advanced rectal cancer and who were treated with neoadjuvant CRT at the Korea Institute of Radiological and Medical Sciences. The treatment consisted of radiation therapy and chemotherapy, and this was followed by curative resection 6 weeks later. All the patients underwent $^{18}F$-FDG PET/CT both before CRT and 6 weeks after completing CRT. The measurements of the FDG uptake ($SUV_{max}$), the absolute difference (${\Delta}SUV_{max}$) and the percent $SUV_{max}$ difference (response index, $RI_{SUV}$) between the pre- and post-CRT $^{18}F$-FDG PET/CT scans were assessed. The measurements of the metabolic volume, the absolute difference (${\Delta}$metabolic volume) and the percent metabolic volume difference (response index, $RI_{metabolic\;volume}$) were also assessed. Results: Of the 20 patients who underwent surgery, 11 patients (55%) were classified as responders according to Dworak's classification. The post-CRT $SUV_{max}$ was significantly lower than the pre-CRT $SUV_{max}$. However, there were no significant differences in the $SUV_{max}$ and the metabolic volume reduction between the responders and non-responders. We used a minimum $SUV_{max}$ reduction of 67% as the cut-off value for defining a response, with a sensitivity of 45.5%, a specificity of 88.9%, a positive predictive value of 77% and a negative predictive value of 53.8%. Conclusion: Although there were no statistically significant results in this study, other studies have revealed that $^{18}F$-FDG PET/CT has the potential to assess the tumor response to neoadjuvant CRT in patients with locally advanced rectal cancer.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.684-690
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• 2004

Background: Primary thymic epithelial neoplasm is a type of mediastinal tumors that have various biologic and morphologic features. In this study, we reclassified 59 cases of thymic epithelial tumors by the new WHO classification. We inquired whether the new WHO classification has independent prognostic relevance by analyzing clinical characteristics of thymic epithelial tumors including Masaoka's clinical stage. Material and Method: From December 1986 to August 2003, 59. patients who underwent surgery in the Keimyung University Dongsan Medical Center with definite diagnosis of thymic epithelial tumor were studied. We analyzed the histologic subtype (WHO classification). clinical stage (Masaoka's clinical stage) and patient's characteristics (sex, age, myasthenia gravis, tumor size, invasion. recurrence, metastasis) as prognostic factors. We analyzed the relationship between histologic subtype and clinical stage. Result: 32 patients were male and 27 were female. Mean age was 50.1$\pm$14.2. From WHO A to C, all thymic epithelial tumors were reclassified by the new WHO classification. Six patients (10.2%) had Type A, 7 (11.9%) had Type AB, 7 (11.9%) had Type B$_1$, 10 (16.9%) had Type B$_2$ and 7 (11.9%) had Type B$_3$, 22 (37.3%) had Type C. Two factors were shown by multivariate analysis to be associated with a favorable prognosis: completeness of resection (p=0.003) and non-invasiveness (p=0.001). The overall 5-year survival of the 59 patients was 53%, subtype A and AB were 92.3%, B$_1$ and B$_2$ were 70.2%, and B$_3$ and C were 26.1%. The association between histologic subtype and invasive behavior (stage) was statistically significant (p<0.001). Conclusion: The WHO classfication is not only a histologic classfication of the thymic epithelial tumors but also a significant prognostic factor that influence the survival of thymic epithelial tumors.

• Radiation Oncology Journal
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• v.21 no.2
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• pp.143-148
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• 2003

Purpose: The purpose of this study was to evaluate treatment results in terms of the survival and failure patterns subsequent to radiation therapy in recurrent cervical cancer, fellowing primary surgery. Material and Methods: Between January 1990 and December 1999, 27 patients, with recurrent cervical cancer following primary surgery, were subsequently treated with radiation in the Department of Radiation Oncology, at the Keimyung University Dongsan Medical Center. Their median age was 48, ranging from 31 to 70 years old. With regard to the Initial FIGO stage on presentation, 20 and 7 patients were stages I and II, respectively. Twenty three patients had squamous cell carcinomas and 4 had adenocarcinomas. The time interval from the primary surgery to the recurrence ranged from 2 to 90 months with a median of 29 months. The recurrent sites were the vaginal cuff alone, the pelvic cavity and combined recurrence in 14, 9 and 4 patients, respectively. Radiation was peformed, with external and vaginal intracavitary radiation in 13 patients, external radiation alone in 13 and vaginal intracavitary radiation alone in another one. The median follow-up period was 55 months, ranging from 6 to 128 months. Results: The five year disease free survival (5y DFS) and five year overall survival (5y OS) rates were 68.2 and 71.9$\%$, respectively. There was a marginal statistically significant difference in the 5y DFS in relation to the recurrent site (5y DFS, 85.7$\%$ in vaginal cuff recurrence alone, 53.3$\%$ in pelvic cavity recurrence, p=0.09). There was no difference in the survival according to the time interval between the primary surgery and a recurrence. There was only a 7$\%$ local failure rate in the patients with a vaginal cuff recurrence. The major failure patterns were local failure in the patients with pelvic cavity recurrence, and distant failure in the patients with a combined recurrence. There were no complications above grade 3 after the radiation therapy. Conclusion: Radiation therapy was safe and effective treatment for a recurrent carcinoma of the uterine cervix following primary surgery, especially the external beam radiation and vaginal intracavitary irradiation achieved the best results in the patients with a vaginal cuff recurrence following primary surgery.

• Journal of Chest Surgery
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• v.40 no.2 s.271
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• pp.114-121
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• 2007

Background: Apoptosis plays a crucial role in carcinogenesis, as well as in development and tissue homeostasis. Terminal deoxyribonucleotidyl transferase mediated neck end labelling (TUNEL) and in situ nick end labelling (ISEL) have been used to investigate the apoptosis in tissues. Since the introduction of the M30 monoclonal antibody to overcome drawbacks of TUNEL and ISEL, the apoptosis in various tumors, with the exception of pulmonary carcinomas, has been studied. In this study, attempts were made to examine the correlation of apoptosis in non-small cell carcinomas, using both M30 and the expression of p53 protein, with the clinicopathological factors. Material and Method: Forty five patients with surgically resected non-small cell carcinomas were included. Immunohistochemical staining with M30 and p53 monoclonal antibody were peformed, and their expressions compared with the clinicopathological features. The overall survival time and recurrence-free survival time were calculated, and the factors influencing the survival time analyzed using a univariate analysis. The effects of the expression stati of M30 and p53 on the risks of cancer related to both death and recurrence were evaluated using a multivariate analysis. Result: The p53 positive group had many more M30 positive cells than the p53 negative group (p53 positive group; $61.7{\pm}26.8$ cells vs. p53 negative group; $45.6{\pm}29.6$ cells, p=0.005) and significantly more p53 positive patients showing at least 10 positive cells (apoptotic index, $Al{\ge}1$) on M30 staining (p53 positive group; 52.4% (11/21) vs. p53 negative group 16,7% (4/24), p=0.025). In the univariate analysis, the survival times in relation to smoking (pack-year), performance status (PS) and Al showed significant differences. The multivariate analysis demonstrated the relative risk (R.R) of cancer death increased almost 7.5-fold (R.R 7.482; 95% Cl $1.886{\sim}29.678$; p=0.004) and the risk of recurrence almost 3,8-fold (R.R 3.795; 95% Cl: $1.184{\sim}12.158$; p=0.025) in the high Al (${\ge}1$) compared to the low Al (<1) group. There was no prognostic effect of p53 expression on the survival time or risk of cancer death and recurrence. Conclusion: In non-small cell lung carcinomas, M30 immunohistochemistry was an excellent method for analyzing apoptosis; the high apoptotic index could be an adverse prognostic predictive factor.