• Tuberculosis and Respiratory Diseases
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• v.49 no.1
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• pp.60-71
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• 2000

Backgrounds : Cathepsin D, an aspartic lysosomal proteinase, is believed to be involved in local invasion and metastasis of tumor cells by its proteolytic activity and has been described to be associated with tumor progression and prognosis in some human malignancies including breast cancer. But, its prognostic value for human lung cancer remains to be determined. The purpose of this study is to determine clinicopathological and prognostic significance of cathepsin D expression in non-small cell lung cancer. Method : Using a polyclonal antibody, immunohistochemical analysis of cathepsin D was performed on paraffin embedded sections of tumors obtained surgically from 54 patients with non-small cell lung cancer (37 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, and 1 undifferentiated carcinoma). Results : Eighteen patients (33.3%) showed positive immunoreactivities of cathepsin D in tumor cells. No significant correlation of cathepsin D expression in tumor cells was found in p-stage (surgical-pathologic stage), tumor size, tumor factor, nodal involvement, and differentiation. Of 54 patients, 29 (53.7%) patients showed moderate to massive cathepsin D-positive stromal cells within the tumor tissues, while the rest (46.3%) showed few cathepsin D-positive stromal cells within the tumor tissues. Cathepsin D expression in stromal cells was significantly associated with p-stage in non-small cell lung canær (p=0.031). No significant correlation of the degree of cathepsin D-positive stromal cells was found in tumor size, T -factor, nodal involvement, differentiation Cathepsin D expression status in tumor cells and stromal cells was not significantly associated with prognosis expressed by survival rate. The results of multivariate analyses of variables possibly associated with prognosis showed that nodal involvement was the only independent prognostic factor in all patients. Conclusion : Cathepsin D expression in stromal cells was significantly associated with p-stage in non-small cell lung cancer. However, it was not related to other clinicopathologic features and prognosis, and Cathepsin D expression in tumor was not related to p-stage and prognosis.

• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.962-974
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• 1998

Background: Alteration of p53 tumor suppressor genes is most frequently identified in human neoplasms, including lung carcinoma. It is well known that bcl-2 oncoprotein protects cells from apoptosis. Recent studies have demonstrated that bcl-2 expression is associated with favorable prognosis for patients with non-small cell lung carcinoma. However, the precise biologic role of bcl-2 in the development of these tumors is still obscure. p53 and bcl-2 have important regulatory influence in the apoptotic pathway and thus their relationship is of interest in tumorigenesis, especially lung cancer. Purpose: The author investigated to know the prognostic significance of the expression of p53 and bcl-2 in radically resected non-small cell lung cancer. Method: 84 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from 1980 to 1994 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for p53 and bcl-2. Results : The histologic classification of the tumor was based on WHO criteria., and the specimens included 45 squamous cell carcinomas(53.6%), 28 adeonocarcinomas(33.3%) and 11 large cell carcinomas(13.1 %). p53 immunoreactivity was noted in 47 cases of 84 cases(56.0%). bcl-2 immunoreactivity was noted in 15 cases of 84 cases(17.9%). The mean survival duration was $64.23{\pm}10.73$ months in bcl-2 positive group and $35.28{\pm}4$. 39 months in bcl-2 negative group. The bcl-2 expression was significantly correlated with survival in radically resected non-small cell lung cancer patients(p=0.03). The mean survival duration was $34.71{\pm}6.12$ months in p53 positive group and $45.35{\pm}6.30$ months in p53 negative group(p=0.21). The p53 expression was not predictive for survival. There was no correlation between combination of the different status of p53 and bcl-2 expression in our study. Conclusions : The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. bcl-2 overexpression is a good prognostic factor in non-small cell lung cancer and p53 expression is not significantly associated with the prognostic factor in non-small cell lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.52 no.4
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• pp.317-329
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• 2002

Background : Immunotherapy is another treatment modality for various cancers. There is little information on the antitumor effects of immunotherapy on implanted lung cancer mouse models. Toxoplasma gondii is able to potently induce a nonspecific stimulation of the host immune system. Therefore, this study evaluated the antitumor and antimetastatic effect of nonspecific immune stimulation by T. gondii in a Lewis lung cancer mouse model. Methods : Female C57BL/6 mice were injected with either Lewis lung cancer cells ($1{\times}10^6$ per mouse) or 5 cysts from the T. gondii Me49 strain with various schedules. The number of survival days, the tumor size of the implanted muscle and the histopathological findings of each group were noted. In addition to these mice, the Toxoplasma antigen($50{\mu}g$ per mouse) or a lymphokine (0.5 ml per mouse) was added to boost the immunotherapy. Results : No mouse in the Toxoplasma-infected group had died, whereas the mice receiving only the cancer cells (cancer control) survived for $29.1{\pm}4.4$ days. Cancer cells were revealed from 1 week after cancer cell inceulation in the muscle and from 3 weeks in the lung of the cancer control, whereas cancer cells were found in both the preinfection control and coinfection control groups from 2 weeks and 4 weeks in the lung respectively. The in the number of survival days were $32.4{\pm}3.3$ in the mice receiving T. gondii 2 weeks prior to the cancer cells inoculation (preinfection control), $30.9{\pm}5.1$ in mice received both simultaneously (coinfection control), and $34.9{\pm}2.9$ in mice received T. gondii 2 weeks after cancer cells implantation (postinfection control). These 3 infection groups had significantly longer survival days and suppressed tumor growth than those of the cancer control. In addition to these mice, and injection with the Toxoplasma antigen alone or in combination with lymphokine resulted in a significant increase in the number of survival days. Conclusion : These findings suggest that an injection with T. gondii can induce the antitumor and antimetastatic effects in Lewis lung cancer mouse models. Moreover, these effects were increased with an injection of the Toxoplasma antigen alone or in combination with lymphokine. However, this therapy can not prevent the development of cancer.

• Journal of Chest Surgery
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• v.40 no.1 s.270
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• pp.37-44
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• 2007

Background: It is known that long-term survival rate in patients underwent bronchial sleeve lobectomy for primary lung cancer is at least equal to that in patients underwent pneumonectomy, and bronchial sleeve lobectomy is performed in patients with suitable tumor location even in patients have adequate pulmonary function. Sleeve pneumonectomy is performed when carina was invaded by tumor or tumor location was near to the carina. We performed this study to know our results of sleeve resection for primary lung cancer. Material and Method: We analyzed retrospectively the medical records of 45 patients who underwent sleeve lobectomy or sleeve pneumonectomy for primary lung cancer by one thoracic surgeon from May 1990 to July 2003 in Department of Thoracic & Cardiovascular Surgery, College of Medicine, Kyung Hee University. Follow-up loss was absent and last follow-up was performed in April 5, 2005. Kaplan-Meyer method and log-lank test were used to know long-term survival rate and p-value. Result: Mean age was 60 years old and male to female ratio 41:1. Histologic types were squamous cell carcinoma were 39, adenocarcinoma were 4, and others were 2 patients. Pathologic stages were I 14, II 14, and III 17 patients. Nodal stages were N0 23, N1 13, and N2 9 patients. Types of operation were sleeve lobectomy 40 and sleeve pneumonectomy 5 patients. Operative mortality was 3 patients and its cause was respiratory complications. Early complications were pneumonia 4, atelectasis 8, air leakage more than 7 days 6, and atrial fibrillation 4 patients. In 19 patients tumor was recurred. Local recurrence was 10 and systemic metastasis was 9 patients. Overall 5, 10-year survival rate were 54.2%, 42.5%. The 5, 10-year survival rates according to the pathologic stage were 83.9%, 67.1% in stage I, 55%, 47.1% in II, 33.3%, 25% in III, and significance difference was present between stage I and III. The 5, 10-year survival rate according to the lymph node involvement were 63.9%, 54.6% in N0, 53,8%, 46.5% in N1, 28.5%, 14.2% in N2, and significance difference was present between N0 and N2. Conclusion: Because bronchial sleeve lobectomy for primary lung cancer could be performed safely and shows acceptable long-term survival rate, it could be considered primary in case of suitable tumor location if complete resection is possible. Although sleeve pneumonectomy for primary lung cancer shows somewhat high operative mortality rate, it could be considered in view of curative treatment.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.241-253
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• 1990

331 patients of stage IIb uterine cervix cancer trated by radiation alone at Kosin Medical Center between June 1980 and Dec. 1985 were analysed to determine parameters of radiotherapy associated to disease states. Survival rate was highest among the reported ($82.8{\%}$ for crude and $82.4{\%}$ for disease free survival). Pelvic control rate in 6 weeks after the end of radiotherapy was $93.6{\%}$ in the patients treated with ICR following total pelvic radiation and $71.6{\%}$ with small field additional external irradiation. 5 year survival rate in those who achieved pelvic control was $98.9{\%}$ and $12.9{\%}$ in those who had pelvic failure and/or metastasis after radiation. The survival rate figured maximal $88.5{\%}$ with dosage of $7500{\~}8500$ cGy to point A with acceptable incidence of complications ($4.9{\%}$) but without increasing survival above it and minimal $74.1{\%}$ with dosage of less than 6500 cGy. The treatment failure was counted $18.7{\%}$ (62 of 331 patients): Local failure $72.6{\%}$ (45 of 62 patients), locoregional failure $3.2{\%}$ (2 of 62 patients) and distant failure $24{\%}$ (15 of 62 patients). Late complications were found in 50 patients ($15.1{\%}$) and $42{\%}$ of them was rectal bleeding and stenosis. The dose of 8500 cGy to point A was found to be critical for complication and $70{\%}$ of complications occurred above it and was more serious one such as fistula. Rectal complications were developed above rectal dose 6500 cGy and bladder complication above bladder dose 7500 cGy. Major cause of death was cachexia due to locoregional failure ($73.7{\%}$ of death), next was due to metastasis to lung, liver and bone, and only 3 patients died of complication of intestinal perforations and obstruction. In conclusion higher external radiation dose for a bulky uterine cervix and barrel shaped uterus was essential for local control.

• Journal of Chest Surgery
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• v.40 no.11
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• pp.765-769
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• 2007

Background: The curative treatment of choice for empyema is decortication of the pleura. The risks of this treatment however are increased for the patient with reduced pulmonary function, complicated calcification or septic shock. In the past, open window thoracostomy was a final stage treatment for chronic empyema. Relatively safe treatment of empyema could be achieved in difficult cases with a closure of the open window after open drainage and use of a myocutaneous flap (one stage or staged). Material and Method: A retrospective study of the cause, progression and final outcome of empyema patients who received open window thoracostomy was performed. 21 patients were followed from 1995 to 2004 in the department of Thoracic and Cardiovascular Surgery in the College of Medicine, Pusan National University. Result: The average age of the patients was $57.5{\pm}15.5$ years (range $25{\sim}78$ years), of whom 16 (76.2%) were men and five (23.8%) were women. Pulmonary function test results showed an average FEV1 of $1.58{\pm}0.49 L$. The type of empyema was tuberculous empyema in 13 cases (61.9%), aspergillosis in three cases (14.3%), parapneumonic empyema in three cases (14.3%) and post-resectional empyema in two cases (10%). Bronchopulmonary fistula was seen in 14 cases. Eight cases were complicated by severe calcification of the pleura. For the four cases of bronchopulmonary fistula, the patients' serratus anterior muscle was covered in their first operation. The average number of ribs resected was $4{\pm}1$. Closure of the open window thoracostomy was performed in 12 cases. The average time to closure after open drainage was $10.22{\pm}3.11$ months and the average defect of the empyemal cavity before the final operation was $330{\pm}110 cc$. Among the 12 cases, there were two cases of spontaneous closure. In two cases closure was only achieved by using the reserved skin fold during the first surgery. Of the remaining eight cases, in seven we used the myocutaneous flap (four cases of lattisimus dorsi muscle and three cases of pectoralis major muscle), and in one case we used soft tissue. As regards complications of the closure, tissue necrosis occurred in one case, which led to failed closure, and there was one case of abdominal hernia in the rectus abdominis muscle flap. One patient died within 30 days of the surgery and one patient died of metastatic cancer. Conclusion: A staged operation with a final closure using open window thoracostomy, which consists of open drainage, transposition of the muscle and a myocutaneous flap, can be a safe and effective option for the chronic empyema patient who is difficult to cure with traditional surgical methods.

• Journal of Chest Surgery
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• v.32 no.6
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• pp.536-542
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• 1999

Background: The purpose of this study is to improve the quality of the diagnostic procedures in the preoperative evaluation so as to reduce the unnecessary thoracotomy and to ensure resectability in non-small cell lung cancer. Material and Method: Of 616 patients who underwent thoracotomy for primary lung cancer from January 1990 to December 1996, 59 patients(9.6%) turned out to have inoperable lesions after the thoracotomy. We reprospectively reviewed the bronchoscopic findings, methods of tissue diagnosis, CT scans, pulmonary function test and lung perfusion scan, reasons for nonresectability, and adjuvant therapy, and then followed up on the survival rate after exploratory thoracotomy. Result: The cell types were squamous cell carcinoma in 38, adenocarcinoma in 15, large cell carcinoma in 3 and others in 3. Primary loci were RUL in 20, RML in 6, RLL in 8, LUL in 13, LLL in 4 and others in 8. The reasons for non-resectability were various; direct tumor invaison to mediastinal structures(n=41), seeding on pleural cavity(n=8), poor pulmonary function(n=2), invasions to extranodal mediastinal lymph node(n=2), technical non- resectability due to extensive chest wall invasion (n=3), small cell carcinoma (n=1), malignant lymphoma(n=1), and multiple rib metastases(n=1). In the follow-up of 58 patients, 1-year survival rate was 55.2% and 2-year survival rate was 17.2% and the mean survival time was 14 months. When compared according to cell types or postoperative adjuvant therapeutic modalities, no significant difference in the survival rates were found. The squamous cell carcinoma was frequently accompanied by local extension to contiguous structures and was the main cause of non-resectability. In adenocarcinoma, pleural seeding with malignant effusion was frequently encountered, and was the major reason for non-resectability. Conclusion: These data revealed that if appropriate preoperative diagnostic tools had been available, many unnecessary thoracotomies could have been avoided. Both the use of thoracoscopy in selected cases of adenocarcinoma and the more aggressive surgical approach to the locally advanced tumor could reduce the incidence of unnecessary thoracotomies for non-small cell lung cancers.

• The Korean Journal of Nuclear Medicine
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• v.32 no.3
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• pp.298-304
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• 1998

Purpose: We evaluated the usefulness of Re-188 sulfur colloid for radiation synovectomy and therapy of intraperitoneal metastasis. Materials and Methods: We investigated the labeling efficiency of Re-188 sulfur colloid on various conditions. The stability of Re-188 sulfur colloid was observed at room temperature for 24 h and in human serum and synovial fluid for 72 h. The particle size distribution of Re-188 sulfur colloid was measured by filtering with various pore size filters. Animal experiment was performed in mice and rabbits. Results: The labeling efficiency of Re-188 sulfur colloid was $64.5{\pm}5.8%$ (n=5) at the conditions of sodium thiosulfate 40 mg, EDTA $Na_2.2H_2O$ 0.8 mg, $KReO_4$ 0.8 mg at pH 1. After purification, the radiochemical purity was higher than 99%. The stability of Re-188 sulfur colloid was high (>99%) at room temperature for 24 h and in human serum and synovial fluid for 72 h. The particle size distribution of Re-188 sulfur colloid was 0.3% ($<1{\mu}m$), 11.2% ($1{\sim}5{\mu}m$), 25.8% ($5{\sim}10{\mu}m$) and 52.8% ($>10{\mu}m$). In mice, 1 h postinjection of Re-188 sulfur colloid into tail vein, uptakes in lung, liver and muscle were $37.30{\pm}5.36$, $32.33{\pm}1.79$, $6.60{\pm}0.02%$ ID/organ respectively. After i.p. injection in mice, the uptakes of extraperitonial organs of Re-188 sulfur colloid at 1 and 24 h were $0.1{\pm}0.1$, $0.4{\pm}0.1%$ ID/organ, and the excretions through urine and feces (${\sim}70 h$) were low ($2.68{\pm}0.80$, $0.95{\pm}0.17%$). When Re-188 sulfur colloid was injected to synovial space of rabbit, the uptake in other organs except knee was very low. Conclusion: Re-188 sulfur colloid showed high labeling efficiency, stability and potency for clinical use.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.217-222
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• 1999

Purpose : To evaluate prognostic factors and survival rates of the patients who received radiation therapy for locally recurrent uterine cervical cancer after curative surgery. Materials and Methods : Between October 1983 and July 1990, fifty three patients who received radiation therapy for locally recurrent cervical cancer after curative surgery at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, The Catholic University of Korea were analysed retrospectively. Age at diagnosis ranged from 33 to 69 years (median 53 years). Pathological analysis showed that forty five ($84.9\%$) patients had squamous cell carcinoma, seven ($13.2\%$) patients had adenocarcinoma, and one (1.9%) patient had adenosquamous cell carcinoma. The interval between hysterectomy and tumor recurrence ranged from 2 months to 25 years (mean 34.4 months). The recurrent sites were vaginal stump in 41 patients ($77.4\%$) and pelvic side wall in 12 patients ($22.6\%$). Recurrent tumor size was devided into two groups : less than 3 cm in 43 patients ($81.1\%$) and more than 3 cm in 10 patients ($18.9\%$). External beam irradiation of whole pelvis was done first up to 46.8 Gy to 50.4 Gy in 5 weeks to 6 weeks, followed by either external beam boost to the recurrent site in 18 patients ($34\%$) or intracavitary irradiation in 24 patients ($45.3\%$). Total dose of radiation ranged from 46.8 Gy to 111 Gy (median 70.2 Gy). Follow up period ranged from 2 to 153 months with a median of 35 months. Results : Overall response rate was $66\%$ (35/53). Among them, six patients ($17.1\%$) relapsed between 7 months and 116 months after radiation therapy (mean 47.7 months), Therefore overall recurrence rate was $45.3\%$. Overall five-year actuarial survival rate was $78.9\%$ and distant failure rate was $10\%$ (5/50). The significant prognostic factors affecting survival rate were interval between primary surgery and tumor recurrence (p=0.0055), recurrent tumor size (p=0.0039), and initial response to radiation therapy (p=0.0428). Complications were observed in 10 ($20/%$) patients, which included mild to moderate lower gastrointestinal, genitourinary, or skin manifestations. One patient died of pulmonary embolism just after intracavitary irradiation. Conclustion : Radiation therapy is the effective treatment for the patients with locally recurrent cervical cancer after curative surgery. These results suggest that interval between primary surgery and tumor recurrence, recurrent tumor size, and initial response to radiation therapy were significant prognostic factors for recurrent cervical cancer.

• Radiation Oncology Journal
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• v.28 no.4
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• pp.193-204
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• 2010

Purpose: To analyze the treatment outcomes, complications, prognostic factors after a long-term follow-up of patients with nasopharyngeal carcinoma treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Materials and Methods: Between December 1981 and December 2006, 190 eligible patients with non-metastatic nasopharyngeal carcinoma were treated at our department with a curative intent. Of these patients, 103 were treated with RT alone and 87 patients received CCRT. The median age was 49 years (range, 8~78 years). The distributions of clinical stage according to the AJCC 6th edition included I: 7 (3.6%), IIA: 8 (4.2%), IIB: 33 (17.4%), III: 82 (43.2%), IVA: 31 (16.3%), IVB: 29 (15.3%). The accumulated radiation doses to the primary tumor ranged from 66.6~87.0 Gy (median, 72 Gy). Treatment outcomes and prognostic factors were retrospectively analyzed. Acute and late toxicities were assessed using the RTOG criteria. Results: A total of 96.8% (184/190) of patients completed the planned treatment. With a mean follow-up of 73 months (range, 2~278 months; median, 52 months), 93 (48.9%) patients had relapses that were local 44 (23.2%), nodal 13 (6.8%), or distant 49 (25.8%). The 5- and 10-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 55.6% and 44.5%, 54.8% and 51.3%, in addition to 65.3% and 57.4%, respectively. Multivariate analyses revealed that CCRT, age, gender, and stage were significant prognostic factors for OS. The CCRT and gender were independent prognostic factors for both DFS and DSS. There was no grade 4 or 5 acute toxicity, but grade 3 mucositis and hematologic toxicity were present in 42 patients (22.1%) and 18 patients (9.5%), respectively. During follow-up, grade 3 hearing loss in 9 patients and trismus in 6 patients were reported. Conclusion: The results of our study were in accordance with findings of previous studies and we confirmed that CCRT, low stage, female gender, and young age were related to improvement in OS. However, there are limitations in the locoregional control that can be achieved by CCRT with 20 conventional radiation therapy. This observation has led to further studies on clarifying the efficacy of concurrent chemotherapy by intensity modulated radiation therapy.