• Journal of Chest Surgery
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• v.33 no.9
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• pp.697-706
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• 2000

Background: Isolated lung perfusion(ILP) was developed as a new treatment approach to non-resectable primary or metastatic lung cancer, because of its ability to reduce systemic toxicity while delivering high-dose chemotherapeutic agents to the target organs. This research was planned to evaluate the direct toxic effect of high-dose cisplatin to the lung tissue during isolated lung perfusion. Material and Method: Fifteen mongrel dogs were divided in the perfusate for 40 minutes. The second group was composed of 5 mongrel dogs which underwent ILP with cisplatin 2.5 mg/Kg added to the perfusate for 30 minutes and 10 minutes with washing solution without cisplatin. The third group underwent the same procedure as the second group except cisplatin 5.0 mg/Kg in the perfusate. Activities of serum angiotensin converting enzyme(ACE), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and concentration of serum lactate dehydrogenase(LDH) and blood urea nitrogen/creatinine (BUN/Cr) were analyzed in each groups at the time of pre-perfusion, 1 hour, 1 day, 1 week, and 2 weeks after ILP. Result: Serum ACE activities before and 1 hour, 1 day, 1 week, and 2 weeks after ILP in control group were 45.1$\pm$6.3, 44.6$\pm$9.3, 46.7$\pm$9.5, 50.8$\pm$9.1, 46.1$\pm$4.3 U/L. Those in cisplatin 2.5 and 5.0 mg/Kg groups were 49.4$\pm$12.6, 39.0$\pm$8.6, 42.3$\pm$15.9, 50.0$\pm$2.6, 53.8$\pm$8.3 and 55.5$\pm$12.3, 47.0$\pm$6.3, 45.1$\pm$6.9, 74.8$\pm$19.5, 60.2$\pm$12.0 U/L, respectively. Serum TNF-$\alpha$ activities in each group before and after ILP were 5.0$\pm$1.5 / 7.7$\pm$2.2 / 6.6$\pm$2.5 / 4.3$\pm$1.3 / 5.2$\pm$1.1(control), 8.7$\pm$1.6 / 9.9$\pm$2.2 / 7.9$\pm$1.5 / 6.3$\pm$2.2 / 7.4$\pm$2.4 (cisplatin 2.5 mg/Kg), and 6.9$\pm$0.7 / 8.9$\pm$3.4 / 7.9$\pm$4.0 / 3.3$\pm$0.9 / 5.8$\pm$1.3 pg/ml(cisplatin 5.0 mg/Kg). Mean LDH levels of each group were 225.7 / 271.3 / 328.9 / 350.8 / 255.7(control), 235.7 / 265.7 / 336.0 / 379.5 / 299.2 (cisplatin 2.5 mg/Kg), and 259.6 / 285.2 / 340.6 / 433.4 / 292.4 IU/L(cisplatin 5.0 mg/Kg). So there was no significant difference in serum ACE, TNF-$\alpha$, and LDH activity changes after ILP between the 3 groups. And, there was no significant changes in BUN/Cr in each groups, which was independent of ILP and perfused concentration of cisplatin. In addition, all dogs survived the ILP and there was no significant evidence of pulmonary vascular injury after 2 weeks of ILP with cisplatin. Conclusion: There was no harmful effect of cisplatin to the lund tissue of the mongrel dog up to 5.0 mg/Kg in perfusate. Therefore, it is perceived to be safe and effective to deliver high-dose cisplatin to the lung without pulmonary toxicity and renal damage with ILP.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.909-921
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• 2000

Background : Defects in apoptotic signaling pathways play important role in tumor initiation, progression, metastasis and resistance to treatment. Several proteins which may promote tumorigenesis by inhibiting apoptosis were identified. The survivin protein is the member of inhibitor of apoptosis protein(IAPs) family which inhibits apoptosis. Unlike other IAPs, it is expressed in during the fetal period but not in adult differentiated tissues. Many reports have stated that survivin is selectively expressed in many cancer cell lines and cancer tissues. We performed immunohistochemical analysis for survivin expression in non-mall cell lung cancer to get evaluate its clinical implication. Methods : Twenty nine surgically resected lung cancers were examined. Immunohistochemical staining were performed by immuno-peroxidase technique using avidin-biotinylated horseradish pemxidase complex in the formalin-fixed, paraffin-embedded tissue $4{\mu}m$ section. Anti-survivin polyclonal antibody was used for primary antibody and anti-p53 monoclonal antibody was also used to analyze the correlation between survivin and p53 expression. The survivin expression scores were determined by as the sum of the stained area and intensity. Results : Immunohistochemical analysis showed cancer specific expression of survivin in 20 of 29 cases (69.0%). Western blot analysis also showed the selective survivin expression in tumor tissue. There was no correlation between survivin expression and clinicopathological parameters and prognosis. We analyzed the ∞π'elation between survivin expression and p53 expression, but found none. Conclusion: We confirmed the tumor specific expression of survival in non-small cell lung canær. But this expression was not correlated with clinical parameters as well as histology, tumor stage, recurrence, and survival rate. Also it was not statistically correlated with the expression of p53.

• The Korean Journal of Nuclear Medicine Technology
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• v.28 no.1
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• pp.41-47
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• 2024

Purpose: ¹⁸F-FET, a radiopharmaceutical based on a Tyrosine amino acid derivative using the Sodium-Potassium Pump-independent Transporter (System L) for non-invasive evaluation of primary, recurrent, and metastatic brain tumors, exhibits distinct characteristics. Unlike the widely absorbed ¹⁸F-FDG in both tumor and normal brain tissues, ¹⁸F-FET demonstrates specific uptake only in tumor tissue while almost negligible uptake in normal brain tissue. This study aims to compare and evaluate the usefulness of ¹⁸F-FDG and ¹⁸F-FET Brain PET/CT quantitative analysis in brain tumor diagnosis. Materials and Methods: In 46 patients diagnosed with brain gliomas (High Grade: 34, Low Grade: 12), Brain PET/CT scans were performed at 40 minutes after ¹⁸F-FDG injection and at 20 minutes (early) and 80 minutes (delay) after ¹⁸F-FET injection. SUV_max and SUV_peak of tumor areas corresponding to MRI images were measured in each scan, and the SUV_max-to-SUV_peak ratio, an indicator of tumor prognosis, was calculated. Differences in SUV_max, SUV_peak, and SUV_max-to-SUV_peak ratio between ¹⁸F-FDG and ¹⁸F-FET early/delay scans were statistically verified using SPSS (ver.28) package program. Results: SUV_max values were 3.72±1.36 for ¹⁸F-FDG, 4.59±1.55 for ¹⁸F-FET early, and 4.12±1.36 for ¹⁸F-FET delay scans. The highest SUV_max was observed in ¹⁸F-FET early scans, particularly in HG tumors (4.85±1.44), showing a slightly more significant difference (P<0.0001). SUV_peak values were 3.33±1.13 for ¹⁸F-FDG, 3.04±1.11 for ¹⁸F-FET early, and 2.80±0.96 for ¹⁸F-FET delay scans. The highest SUV_peak was in ¹⁸F-FDG scans, while the lowest was in ¹⁸F-FET delay scans, with a more significant difference in HG tumors (P<0.001). SUV_max-to-SUV_peak ratio values were 1.11±0.09 for ¹⁸F-FDG, 1.54±0.22 for ¹⁸F-FET early, and 1.48±0.17 for ¹⁸F-FET delay scans. This ratio was higher in ¹⁸F-FET scans for both HG and LG tumors (P<0.0001), but there was no statistically significant difference between ¹⁸F-FET early and delay scans. Conclusion: This study confirms the usefulness of early and delay scans in ¹⁸F-FET Brain PET/CT examinations, particularly demonstrating the changes in objective quantitative metrics such as SUV_max, SUV_peak, and introducing the SUV_max-to-SUV_peak ratio as a new evaluation metric based on the degree of tumor malignancy. This is expected to further contributions to the quantitative analysis of Brain PET/CT images.

• Childhood Kidney Diseases
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• v.2 no.1
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• pp.26-33
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• 1998

This retrospective study was designed to evaluate the prognostic value and histologic correlation of sonography in childhood nephrotic syndrome. Sixty-nine patients with proteinuria over 2g per day at the time of presentation who were treated at the Korea University Hospital were included in this review. They were 1 to 15 years old(mean age, 7.8 years) with 49 males and 20 females. In each patient an ultrasound examination was done using SPA 1000(Diasonics, C.A., U.S.A.) on admission. Tissue specimens were obtained from 46 patients. The paraffin-embedded specimens were reviewed with special reference to interstitial edema, interstitial fibrosis, tubular atrophy, global sclerosis or inflammatory cell infiltrates. Biopsy proven renal disease were minimal change disease(n=20), focal segmental glomerulosclerosis(n=7), membranous glomerulonephritis(n=2), membranoproliferative glomerulonephritis(n=1), $Henoch-Sch\"{o}nlein$ purpura nephritis(n=6), IgA nephropathy(n=5), poststreptococcal glomerulonephritis(n=2), systemic lupus erythematosus(n=1) and Alport syndrome(n=2). There was a significant relationship between increased cortical echogenicity and global sclerosis or tubular atrophy(P<0.05). But no significant relationship was found between increased cortical echogenicity and interstitial fibrosis, interstitial edema, or inflammatory cell infiltration. In biopsy-proven primary nephrotic syndrome(n=30), no significant relationship was found between the increased conical echogenicity and the interstitial edema, interstitial fibrosis, global sclerosis, tubular atrophy or inflammatory cell infiltration. But there was a significant relationship between increased cortical echogenicity and resistance to corticosteroid (P<0.05). These results suggest that increased cortical echogenicity may be due to tubular atrophy or global sclerosis in patients with proteinuria and may be an effective indicator of resistance to corticosteroid in primary nephrotic syndrome.(J Korean Soc of Pediatr Nephrol 2:26-33, 1998)

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.3
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• pp.92-101
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• 2009

Purpose: Scintimammography is one of the screening tests for the early diagnosis of breast cancer. It has been widely accepted as very useful in assessing masses that have not been detected in breast scanning. This method is highly sensitive and specific with respect to the diagnosis of primary and relapsing breast cancer. It has some difficulties, however, in detecting tumors sized 1 cm and below due to the radioactivity around the breast and the geometrical structure of the equipment. The recent introduction of high-resolution Breast-specific Gamma Imaging (BSGI) has made it possible to more accurately discriminate between malignant and benign tumors than with any other test method. Thus, the possibility of an unnecessary biopsy being performed has decreased. The purpose of this study was to examine the diagnostic capacity of mammography, breast sonography, and scintimammography, which are used for the early diagnosis of known breast cancer, and of BSGI, and to evaluate the skillfulness of radiologists. Materials and Methods: The 53 volunteers participants who had no clinical manifestation of breast cancer underwent the BSGI in February 2009. In the BSGI procedure, scanning images were obtained from the craniocaudal projection (CC) and the mediolateral Oblique projection (MLO), as well as from the additional $80{\times}80$-matrix-sized views at various angles in the Present Time method, 10 minutes after the 25 mCi $^{99m}Tc$-MIBI was injected. Results: The results of the BSGI showed that two participants had masses in their breast tissue. As the results of the diagnosis of four participants were not clear, they were retested and the results of the second test were negative. The results of the clinical screening test for breast cancer showed that the sensitivity of BSGI, scintimammography, mammography, and breast sonography was 86.5%, 77.8%, 85~90%, and 66.7%, respectively, and that their specificity was 92.4%, 84.2%, 20~42%, and 68%, respectively. Conclusion: The autodiagnosis and breast cancer screening test are needed for the early diagnosis of breast cancer. It was not easy, however, to accurately determine the presence of a mass in the breast using the existing breast cancer screening test. The patients with unclear test findings were made to undergo a histologic biopsy for a more accurate diagnosis. It is expected that the BSGI can provide useful information for the early diagnosis of breast cancer and of primary breast cancer, and will reduce the performance of unnecessary biopsies because of its higher sensitivity and specificity than existing breast cancer screening tests.

• Radiation Oncology Journal
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• v.8 no.2
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• pp.219-223
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• 1990

This is a retrospective review of 33 patients with large cell lung carcinoma treated at Yonsei University Cancer Center between Jan.1985 and Dec.1989. Of the thirty-three patients, twenty eight were men and five women. Median age was 59 years. Large cell undifferentiated carcinoma was the most common pathologic type, $78.8\%$. Twenty one of thirty three patients had far advanced diseases, stage IIIB-IV at the time of initial diagnosis. Pleural effusion was initially presented in 12 patients, and SVC syndrome appeared in 5 patients. As to location of the primary tumor,19($57.6\%$) appeared in the right lung and 14 ($42.4\%$) in the left. Patients with a centrally located primary tumor mass were nearly the same as those peripherally located (17 vs.16). Fifteen of thirty three patients developed metastasis involving not only bone, brain, the opposite lung, adrenal gland but also soft tissue, skin, pancreas and appendix. Treatment was individualized with 19 treated radically and 14 palliatively. After treatment, only two patients showed a complete response. Long term survival was observed in 4 patients: 1 (24 mo.),2 (41 mo.) and 1 (54 mo.). The overall 2 year survival rate was $14.3\%$ while the median survival time was 6.0 months. Through the analysis of the various factors affecting survival, we observed that pleural effusion-absent group and complete response group had a statistical significant better survival rate (p<0.01).

• Journal of Chest Surgery
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• v.43 no.4
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• pp.394-398
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• 2010

Background: The overexpression of transforming growth factor-beta 1 receptor II (TGF-${\beta}1$RII) and transforming growth factor-beta 1 (TGF-${\beta}1$) ligand may be involved in the formation of a bulla. In this study, we tested if serum TGF-${\beta}1$ ligand levels correlated with the expression level of TGF-${\beta}1$RII and TGF-${\beta}1$ in bullous tissues from patients with spontaneous pneumothorax. Material and Method: Bullous lung tissues and blood samples were obtained from 19 patients with spontaneous pneumothorax, 18 males and 1 female, aged 17 to 35 years old. The bullous tissues were obtained by video-assisted thoracic surgery (VATS), fixed in formalin, embedded in paraffin, and cut into $5{\sim}6{\mu}m$ thick slices. Sections were immunohistochemically stained with primary antibodies against TGF-${\beta}1$ or TGF-${\beta}1$RII, and serum levels of TGF-${\beta}1$ in patients and normal controls was measured by enzyme-linked immunosorbent assay (ELISA). Result: Of the 19 patients, 16 were TGF-${\beta}1$ positive and 10 were TGF-${\beta}1$RII positive. Among the 16 TGF-${\beta}1$ positives, 9 were also TGF-${\beta}1RII$ positive. As seen previously, strong immunohistochemical staining of TGF-${\beta}1$RII and TGF-${\beta}$ was detected in the boundary region between the bullous and normal lung tissues. Average TGF-${\beta}1$ blood levels of both TGF-${\beta}1$ and TGF-${\beta}1$RII positive patients was $38.36{\pm}16.2ng/mL$, and that of five controls was $54.06{\pm}15ng/mL$. Conclusion: These results suggest that overexpression of TGF-${\beta}1$ and TGF-${\beta}1$RII expression may be involved in the formation of bullae. TGF-${\beta}1$ blood levels in patients with primary spontaneous pneumothorax is lower than normal people, suggesting that the high level of local TGF-${\beta}1$ expression in the bullous tissue region, but not in the whole blood, may contribute more in the formation of bullae.

• 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.

• Journal of Dental Rehabilitation and Applied Science
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• v.27 no.3
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• pp.267-275
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• 2011

This prospective study was designed to compare clinical outcomes of immediately loaded implant with delayed loaded implant in partially posterior edentulous patients. For test group, 42 GS III (Osstem, Korea) implants in 17 patients were loaded within 48 hours after the placement. Control group was 27 implants in 15 patients loaded at $2.6{\pm}1.7months$ from the placement surgery. Before loading, primary stability was evaluated by ISQ value. Clinical symptoms, mobility, soft tissue state was evaluated at baseline, 3 months, 6 months and 12 months of loading. Marginal bone level change was also measured with periapical radiographs. Mann-Whitney test (${\alpha}$=0.05) and repeated measured ANOVA (${\alpha}$=0.05) was used for marginal bone level change between two groups. At the baseline, mean ISQ value of test group and control group was $80.3{\pm}7.1$ and $69{\pm}17$ respectively. Test group showed 95.23% of success rate and 100% of control group was successful. At 3 and 6months of loading, significantly more bone resorption was observed in test group than in control group (p<0.05). However, there was no significant difference in the bone level change at 12months of loading between two groups (p>0.05). Marginal bone level change showed no significant difference with gender and location (p>0.05). Within the limitation of this study, when primary stability was obtained, immediate loading of GS III implant at posterior region could be predictable treatment option.