• Journal of Chest Surgery
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• v.34 no.12
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• pp.917-923
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• 2001

Background : Bronchial sleeve resection for centrally located primary lung cancer is a lung-parenchyma-sparing operation in patients whose predicted postoperative lung function is expected to diminished markedly. Because of its potential bronchial anastomotic complications, it is considered to be an alternative to pneumonectomy. However, since sleeve lobectomy yielded survival results equal to at least those of pneumonectomy, as well as better functional results, it became and accepted standard procedure for patients with lung cancer who have anatomically suitable tumors, regardless of lung function. In this study, from analyzing of occurrence rate of postoperative complication and survival rate, we wish to investigate the validity of sleeve resection for primary lung cancer. Material and Method : From January 1989 to December 1998, 45 bronchial sleeve resections were carried out in the Department of Thoracic Surgery of Seoul National University Hospital. We included 40 men and 5 women, whose ages ranged from 23 to 72 years with mean age of 57 years. Histologic type was squamous cell carcinoma in 35 patients, adenocarcinoma in 7, and adenosquamous cell carcinoma in 1 patients. Right upper lobectomy was peformed in 24 patients, left upper lobectomy in 11, left lower lobectomy in 3, right lower lobectomy in 1, right middle lobecomy and right lower lobectomy in 3, right upper lobectomy and right middle lobecomy in 2, and left pneumonectomy in 1 patient. Postoperative stage was Ib in 11, IIa in 3, IIb in 16, IIIa in 13, and IIIb in 2 patients. Result: Postoperative complications were as follows; atelectasis in 9, persistent air leakage for more than 7 days was in 7 patients, prolonged pleural effusion for more than 2 weeks in 7, pneumonia in 2, chylothorax in 1, and disruption of anastomosis in 1. Hospital mortality was in 3 patients. During follow-up period, bronchial stricture at anastomotic site were found in 7 patients under bronchoscopy, Average follow-up duration of survivals(n=42) was 35.5$\pm$29 months. All of stage I patients were survived, and 3 year survival rate of stage II and III patients were 63%, 21%, respectively. According to Nstage, all of N0 patients were survived and 3 year survival rates of Nl and N2 were 63% and 28% respectively. Conclusion: We suggest that this sleeve resection, which is technically demanding, should be considered in patients with centrally located lung cancer, because ttlis lung-saving operation is safer than pneumonectomy and is equally curative.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.286-297
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• 2005

Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.17-23
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• 1996

Purpose : To evaluate the role of combination therapy of external radio-therapy and chemotherapy in the management of advanced esophageal cancer as a primary treatment compared with radiation therapy alone. Materials and Methods : A retrospective review of evaluable 55 esophageal cancer patients referred to the Department of Therapeutic Radiology, Paik Hospital for the external radiotherapy between Jul, 1983 and Dec. 1994 was undertaken. Combined therapy patients (A group) were 30 and radiation alone patients (B group) were 25. Median age was 60 years old in A group (ranges : 42-81) and 65 years old in B group (ranges : 50-81). The male patients were 53. The fifty patients had squamous cell carcinomas. Radiation doses of 2520-6480c0y were delivered over a period of 4-7weeks, using 4MV LINAC. Chemotherapy was administered in bolus injection before, after, or during the course of external radiotherapy. The local control rate and patterns of failure according to both treatment modalities and 1, 2 year survival rates according to prognostic factors (stage, tumor length, radiation dose etc.) were analysed. Resuts : Median follow up Period was 7 months (range : 2-73 months). Median survival was 7.5 months (20 days-29 months) in A group and 5 months (20 days-73 months) in B group. The 1, 2 YSRs were $26.7\%$, $8.9\%$ in A group, $12.7\%$, $4.3\%$ in B group (p>0.05), respectively. The 1, 2 YSRs according to stage(II/III), tumor length (5cm more or less). radiation dose (5000cGymore or less) of A and B group were analyzed and the differences of survival rates of both treatments were not statistically significant. But among group B, patients who received 5000cGy or more showed significant survival benefits (p<0.05). The treatment response rates of A and B group were $43.8\%$. $25.0\%$, respectively. Complete response rate of $25.0\%$ in A and $8.3\%$ in B were achieved. The local failure and distant metastsis were $52.4\%$. $23.8\%$ in A group, $64.3\%$, $14.3\%$ in 8 group, respectively. The combination therapy revealed more frequent leukopenia and nausea/vomiting than radiation alone group, but degree of side effects was only mild to moderate. Conclusion : The combined external radiotherapy and chemotherapy for advanced esophageal cancer appears to improve the response rate, local control rate and survival rate, but the improvement was not statistically significant. The side effects of combined modalities were mild to moderate without significant morbidity. Therefore it may be worthwhile to continue the present combined external radiotherapy and chemotherapy in the management of advanced esophageal cancer to confirm our result.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.323-327
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• 2002

Purpose : To evaluate the outcome of early stage non-small cell lung cancer patients who were treated with radiation therapy alone and define the optimal radiotherapeutic regimen for these patients. Materials and Methods : A retrospective review was peformed on patients with sage I or II non-small cell carcinoma of the lung that were treated at our institution between June, 1987 and May, 2000. A total of 21 patients treated definitively with radiation therapy alone were included in this study. The age of the patients ranged from 53 to 81 years with a median of 66 years. All the patients were male. The medical reasons for inoperability were lack of pulmonary reserve, cardiovascular disease, poor performance status, old age, and patient refusal in the decreasing order. Pathological evidence was not adequate to characterize the non-small cell subtype in two patients. Of the remaining 19 patients, 16 had squamous cell carcinoma and 3 had adenocarcinoma. Treatment was given with conventional fractionation, once a day, five times a week. The doses to the primary site ranged from 56 Gy to 59 Gy. No patients were lost to follow-up. Results : The overall survival rates for the entire group at 2, 3 and 5 years were 41, 30 and $21\%$, respectively. The cause specific survivals at 2, 3 and 5 years were 55, 36 and $25\%$, respectively. An intercurrent disease was the cause of death in two patients. The cumulative local failure rate at 5 years was $43\%$. Nine of the 21 patients had treatment failures after the curative radiotherapy was attempted. Local recurrences as the first site of failure were documented in 7 patients. Therefore, local failure alone represented $78\%$ of the total failures. Those patients whose tumor sizes were less than 4 cm had a significantly better 5 year disease free survival than those with tumors greater than 4 cm $(0\%\;vs\;36\%)$. Those patients with a Karnofsky performance status less than 70 did not differ significantly with respect to actuarial survival when compared to those with a status greater than 70 $(25\%\;vs\;26\%,\;p>0.05)$. Conclusion : Radiation therapy 리one is an effective and safe treatment for early stage non-small ceil lung cancer patients who are medically inoperable or refuse surgery. Also we believe that a higher radiation dose to the primary site could improve the local control rate, and ultimately the overall survival rate.

• Radiation Oncology Journal
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• v.22 no.3
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• pp.200-207
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• 2004

Purpose: An analysis was to compare the results of radiation alone with those of radiation with dally low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. Materials and Methods: A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was peformed. Thirty one patients received radiation alone and 28 patients received dally low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900$\~$l,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000$\~$3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4$\%$) and 8 (13.6$\%$) stages IIB and stage IIIB, respectively. Results: The overall 5 year survival rate was 65.65$\%$ and according to treatment modality were 56.75$\%$ and 73.42$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.180). The 5 year disease-free survival rates were 49.39$\%$ and 63.34$\%$ in the radiation alone and chemoradiatoin groups, respectively (p=0.053), The 5 year locoregional control rates were 52.34$\%$ and 73.58$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.013). The 5 year distant disease-free survival rates were 59.29$\%$ and 81.46$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.477), Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia $\geq$grade) occurred in 3.2$\%$and 28.5$\%$ of the radiation alone and chemoradiation groups, respectively (p=0.02). There were no statistical differences in the incidences of vesical, rectal and small bowel complications between two groups. Conclusion: Radiation therapy with low dose cisplatin did not improve the rates of survival and response rates, but did improve the rate of disease free survival and locoregional control rates In locally advanced cervical cancer. The incidence of bone marrow suppression was higher in the chemoradiation group.

• Radiation Oncology Journal
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• v.25 no.2
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• pp.70-78
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• 2007

[ $\underline{Purpose}$ ]: This study analyzed the tumor response, overall survival, progression free survival and related prognostic factors in patients with muscle invasive bladder cancer subjected to bladder preserving treatment. $\underline{Materials\;and\;Methods}$: Between August 1995 and June 2004, 37 patients with muscle invasive (transitional cell carcinoma, clinically stage T2-4) bladder cancer were enrolled for the treatment protocol of bladder preservation. There were 33 males and 4 females, and the median age was 67 years (range $38{\sim}86\;years$). Transurethral resection of the bladder (TURB) was performed in 17 patients who underwent complete resection. The median radiation dose administered was 64.8 Gy (range $55.8{\sim}67\;Gy$). The survival rate was calculated by the Kaplan-Meier method. $\underline{Results}$: An evaluation of the response rate was determined by abdomen-pelvic CT and cystoscopy at three months after radiotherapy. A complete response was seen in 17 patients (46%). The survival rate at three years was 54.7%, with 54 months of median survival (range $3{\sim}91$ months). During the study, 17 patients died and 13 patients had died from bladder cancer. The progression free survival rate at three years was 37.2%. There were 24 patients (64.9%) who had disease recurrence: 16 patients (43.2%) had local recurrence, 6 patients (16.2%) had a distant recurrence, and 2 patients (5.4%) had both a local and distant recurrence. The survival rate (p=0.0009) and progression free survival rates (p=0.001) were statistically significant when compared to the response rate after radiotherapy. $\underline{Conclusion}$: The availability of complete TURB and appropriate chemoradiotherapy were important predictors for bladder preservation and survival.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.30 no.2
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• pp.263-278
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• 2004

Ursolic acid (UA) and Oleanolic acid (ONA), known as urson, micromerol and malol, are pentacyclic triterpenoid compounds which naturally occur in a large number of vegetarian foods, medicinal herbs, and plants. They may occur in their free acid form or as aglycones for triterpenoid saponins, which are comprised of a triterpenoid aglycone, linked to one or more sugar moieties. Therefore UA and ONA are similar in pharmacological activity. Lately scientific research, which led to the identification of UA and ONA, revealed that several pharmacological effects, such as antitumor, hepato-protective, anti-inflammatory, anticarcinogenic, antimicrobial, and anti-hyperlipidemic could be attributed to UA and ONA. Here, we introduced the effect of UA and ONA on acutely barrier disrupted and normal hairless mouse skin. To evaluate the effects of UA and ONA on epidermal permeability barrier recovery, both flanks of 8-12 week-old hairless mice were topically treated with either 0.01-0.1mg/mL UA or 0.1-1mg/mL ONA after tape stripping, and TEWL (transepidermal water loss) was measured. The recovery rate increased in those UA or ONA treated groups (0.1mg/mL UA and 0.5mg/mL ONA) at 6h more than 20% compared to vehicle treated group (p < 0.05). Here, we introduced the effects of UA and ONA on acute barrier disruption and normal epidermal permeability barrier function. For verifying the effects of UA and ONA on normal epidermal barrier, hydration and TEWL were measured for 1 and 3 weeks after UA and ONA applications (2mg/mL per day). We also investigated the features of epidermis and dermis using electron microscopy (EM) and light microscopy (LM). Both samples increased hydration compared to vehicle group from 1 week without TEWL alteration (p < 0.005). EM examination using RuO4 and OsO4 fixation revealed that secretion and numbers of lamellar bodies and complete formation of lipid bilayers were most prominent (ONA=UA > vehicle). LM finding showed that thickness of stratum corneum (SC) was slightly increased and especially epidermal thickening and flattening was observed (UA > ONA > vehicle). We also observed that UA and ONA stimulate epidermal keratinocyte differentiation via PPAR Protein expression of involucrin, loricrin, and filaggrin increased at least 2 and 3 fold in HaCaT cells treated with either ONA (10${\mu}$M) or UA (10${\mu}$M) for 24 h respectively. This result suggested that the UA and ONA can improve epidermal permeability barrier function and induce the epidermal keratinocyte differentiation via PPAR Using Masson-trichrome and elastic fiber staining, we observed collagen thickening and elastic fiber elongation by UA and ONA treatments. In vitro results of collagen and elastin synthesis and elastase inhibitory activity measurements were also confirmed in vivo findings. These data suggested that the effects of UA and ONA related to not only epidermal permeability barrier functions but also dermal collagen and elastic fiber synthesis. Taken together, UA and ONA can be relevant candidates to improve epidermal and dermal functions and pertinent agents for cosmeseutical applications.

• Journal of Chest Surgery
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• v.38 no.2 s.247
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• pp.157-163
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• 2005

Background: Clinical outcomes of esophageal cancer have not been satisfactory in spite of the development of surgical skills and protocols of adjuvant therapy. We analyzed the results of corrective surgical patients for esophageal cancer from January 1992 to July 2002. Material and Method: Among 129 patients with esophageal cancer, this study was performed in 68 patients who received corrective surgery. The ratio of sex was 59 : 9 (male : female) and mean age was $61.07\pm7.36$ years old. Chief complaints of this patients were dysphagia, epigastric pain and weight loss, etc. The locations of esophageal cancer were 4 in upper esophagus, 36 in middle, 20 in lower, 8 in esophagogastric junction. 60 patients had squamous cell cancer and 7 had adenocarcinoma, and 1 had malignant melanoma. Five patients had neoadjuvant chemotherapy. Result: The postoperative stage I, IIA, IIB, III, IV patients were 7, 25, 12, 17 and 7, respectively. The conduit for replacement of esophagus were stomach (62 patients) and colon (6 patients). The neck anastomosis was performed in 28 patients and intrathoracic anastomosis in 40 patients. The technique of anastomosis were hand sewing method (44 patients) and stapling method (24 patients). One of the early complications was anastomosis leakage (3 patients) which had only radiologic leakage that recovered spontaneously. The anastomosis technique had no correlation with postoperative leakage, which stapling method (2 patients) and hand sewing method (1 patient). There were 3 respiratory failures, 6 pneumonia, 1 fulminant hepatitis, 1 bleeding and 1 sepsis. The 2 early postoperative deaths were fulminant hepatitis and sepsis. Among 68 patients, 23 patients had postoperative adjuvant therapy and 55 paitents were followed up. The follow up period was $23.73\pm22.18$ months ($1\~76$ month). There were 5 patients in stage I, 21 in stage 2A, 9 in stage IIB, 15 in stage III and 5 in stage IV. The 1, 3, 5 year survival rates of the patients who could be followed up completely was $58.43\pm6.5\%,\;35.48\pm7.5\%\;and\;18.81\pm7.7\%$, respectively. Statistical analysis showed that long-term survival difference was associated with a stage, T stage, and N stage (p<0.05) but not associated with histology, sex, anastomosis location, tumor location, and pre and postoperative adjuvant therapy. Conclusion: The early diagnosis, aggressive operative resection, and adequate postoperative treatment may have contributed to the observed increase in survival for esophageal cancer patients.

• 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.