• Journal of Applied Biological Chemistry
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• v.66
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• pp.416-423
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• 2023

Figs has known to have antioxidant, whitening, anti-inflammatory, and antibacterial effects in their leaves, roots, stems, latex, and fruits. In order to develop cosmetic materials based on natural products, we have studied on the skin activity of the ficin in latex as well as the whitening function of the fruit extract with 70% ethanol, and used it as a raw material for released cosmetic product. However, there is little research on the demand for the development of new eutectic solvent extraction methods and its ability to control skin inflammation and psoriasis regulation. Thus, in this study, we evaluated the effectiveness of fig fruit extracts and fractions using eutectic solvent extraction for skin inflammation control and psoriasis. First, fig fruits were extracted under optimal eutectic solvent conditions and fractionated with n-hexane, dichloromethane, ethyl acetate, and butanol. First, the antioxidant activity and inhibition of nitric oxide (NO) production were confirmed in mouse macrophage RAW264.7 cells. In addition, as a result of observing the mRNA expression through RT-PCR, pro-inflammatory cytokines such as TNF-α, IL1α, and IL-1β were suppressed significantly in the hexane, dichloromethane, and ethyl acetate fractions. In addition, it was confirmed in TNF-α stimulated HaCaT keratinocyte model. Finally, chemokine CC motif ligand 20 (CCL20), marker gene of human psoriasis skin disease, was significantly suppressed in the hexane, dichloromethane, and ethyl acetate fractions. These results suggested its anti-inflammatory and skin soothing effect and the possibility of development as an excellent skin soothing natural cosmetic material in the future through future clinical trials.

• Pediatric Infection and Vaccine
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• v.31 no.1
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• pp.12-24
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• 2024

The number of pediatric coronavirus disease 2019 (COVID-19) cases worldwide are increasing compared to the early phase of the pandemic, along with highly transmissible severe acute respiratory syndrome coronavirus variant and the increase in adult COVID-19 vaccination. We conducted a rapid systematic review and meta-analysis of published randomized clinical trials (RCTs) of the COVID-19 vaccines and the observational retrospective studies on adverse events after COVID-19 vaccination in adolescents. Seventeen studies were finally included in this systematic review. Meta-analysis showed that although vaccination in adolescents was significantly effective to prevent COVID-19 infection in retrospective studies (risk ratio [RR], 0.29; 95% confidence interval [CI], 0.22-0.37; I² =100%), however the effect of preventing COVID-19 infection was lower than in RCTs (RR, 0.05; 95% CI, 0.01-0.27). In five retrospective studies, the pooled estimated proportion of participants with myocarditis and/or pericarditis was 2.33 per 100,000 of the population (95% CI, 0.97-5.61 per 100,000). Sub-group analysis with sex and vaccine doses showed that male (5.35 per 100,000) and the second dose (9.71 per 100,000) had significantly higher incidence of myocarditis and/or pericarditis than female (1.09 per 100,000) and the first dose (1.61 per 100,000), respectively. Our study showed that mRNA COVID-19 vaccines in adolescent recipients were favorable and effective against COVID-19 in RCT as well as observational studies. The safety findings of BNT162b2 vaccine in adolescents were explored and we found the difference of safety according to sex and vaccine doses. The occurrence of adverse events after mRNA COVID-19 vaccination should be monitored.

• Journal of Chest Surgery
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• v.37 no.3
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• pp.201-209
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• 2004

Extracorporeal life support (ECLS) system is a device for respiratory and/or heart failure treatment, and there have been many trials for development and clinical application in the world. Currently, a non-pulsatile blood pump is a standard for ECLS system. Although a pulsatile blood pump is advantageous in physiologic aspects, high pressure generated in the circuits and resultant blood cell trauma remain major concerns which make one reluctant to use a pulsatile blood pump in artificial lung circuits containing a membrane oxygenator. The study was designed to evaluate the hypothesis that placement of a pressure-relieving compliance chamber between a pulsatile pump and a membrane oxygenator might reduce the above mentioned side effects while providing physiologic pulsatile blood flow. The study was performed in a canine model of oleic acid induced acute lung injury (N=16). The animals were divided into three groups according to the type of pump used and the presence of the compliance chamber, In group 1, a non-pulsatile centrifugal pump was used as a control (n=6). In group 2 (n=4), a single-pulsatile pump was used. In group 3 (n=6), a single-pulsatile pump equipped with a compliance chamber was used. The experimental model was a partial bypass between the right atrium and the aorta at a pump flow of 1.8∼2 L/min for 2 hours. The observed parameters were focused on hemodynamic changes, intra-circuit pressure, laboratory studies for blood profile, and the effect on blood cell trauma. In hemodynamics, the pulsatile group II & III generated higher arterial pulse pressure (47$\pm$ 10 and 41 $\pm$ 9 mmHg) than the nonpulsatile group 1 (17 $\pm$ 7 mmHg, p<0.001). The intra-circuit pressure at membrane oxygenator were 222 $\pm$ 8 mmHg in group 1, 739 $\pm$ 35 mmHg in group 2, and 470 $\pm$ 17 mmHg in group 3 (p<0.001). At 2 hour bypass, arterial oxygen partial pressures were significantly higher in the pulsatile group 2 & 3 than in the non-pulsatile group 1 (77 $\pm$ 41 mmHg in group 1, 96 $\pm$ 48 mmHg in group 2, and 97 $\pm$ 25 mmHg in group 3: p<0.05). The levels of plasma free hemoglobin which was an indicator of blood cell trauma were lowest in group 1, highest in group 2, and significantly decreased in group 3 (55.7 $\pm$ 43.3, 162.8 $\pm$ 113.6, 82.5 $\pm$ 25.1 mg%, respectively; p<0.05). Other laboratory findings for blood profile were not different. The above results imply that the pulsatile blood pump is beneficial in oxygenation while deleterious in the aspects to high pressure generation in the circuits and blood cell trauma. However, when a pressure-relieving compliance chamber is applied between the pulsatile pump and a membrane oxygenator, it can significantly reduce the high circuit pressure and result in low blood cell trauma.

• Tuberculosis and Respiratory Diseases
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• v.42 no.3
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• pp.361-369
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• 1995

Background: A number of different weaning techniques can be employed such as spontaneous breathing trial, Intermittent mandatory ventilation(IMV) or Pressure support ventilation(PSV). However, the conclusive data indicating the superiority of one technique over another have not been published. Usually, a conventional spontaneous breathing trial is undertaken by supplying humidified $O_2$ through T-shaped adaptor connected to endotracheal tube or tracheostomy tube. In Korea, T-tube trial is not popular because the high-flow oxygen system is not always available. Also, the timing of extubation is not conclusive and depends on clinical experiences. It is known that to withdraw the endotracheal tube after weaning is far better than to go through any period. The tube produces varying degrees of resistance depending on its internal diameter and the flow rates encountered. The purpose of present study is to evaluate the effectiveness of weaning and extubation following a 60 minutes spontaneous breathing trial with simple oxygen supply through the endotracheal tube. Methods: We analyzed the result of weaning and extubation following a 60 minutes spontaneous breathing trial with simple oxygen supply through the endotracheal tube in 18 subjects from June, 1993 to June, 1994. They consisted of 9 males and 9 females. The duration of mechanical ventilation was from 38 hours to 341 hours(mean: $105.9{\pm}83.4$ hours). In all cases, the cause of ventilator dependency should be identified and precipitating factors should be corrected. The weaning trial was done when the patient became alert and arterial $O_2$ tension was adequate($PaO_2$ > 55mmHg) with an inspired oxygen fraction of 40%. We conducted a careful physical examination when the patient was breathing spontaneously through the endotracheal tube. Failure of weaning trial was signaled by cyanosis, sweating, paradoxical respiration, intercostal recession. Weaning failure was defined as the need for mechanical ventilation within 48 hours. Results: In 19 weaning trials of 18 patients, successful weaning and extubation was possible in 16/19(84.2 %). During the trial of spontaneous breathing for 60 minutes through the endotracheal tube, the patients who could wean developed slight increase in respiratory rates but significant changes of arterial blood gas values were not noted. But, the patients who failed weaning trial showed the marked increase in respiratory rates without significant changes of arterial blood gas values. Conclusion: The result of present study indicates that weaning from mechanical ventilation following a 60 minutes spontaneous breathing with $O_2$ supply through the endotracheal tube is a simple and effective method. Extubation can be done at the same time of successful weaning except for endobronchial toilet or airway protection.

• Investigative Magnetic Resonance Imaging
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• v.8 no.1
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• pp.32-41
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• 2004

Purpose : To measure the NMR relaxation properties of MnPC, to observe the characteristics of liver enhancement patterns on MR images in experimentally implanted rabbit VX2 tumor model, and to estimate the possibility of tissue specific contrast agent for MnPC in comparison with the hepatobiliary agent. Materials and Methods : Phthalocyanine (PC) was chelated with paramagnetic ions, manganese (Mn). 2.01 g (5.2 mmol) of phthalocyanine was mixed with 0.37 g (1.4 nlmol) of Mn chloride at $310^{\circ}C$ for 36 hours and then purified by chromatography ($CHCl_3:\;CH_3OH=98:2$, volume ratio) to obtain 1.04 g $(46\%)$ of MnPC (molecular weight = 2000 daltons). The T1/T2 relaxivity (R1/R2) for MnPC were determined at a 1.5 T (64 MHz) MR spectrometer. VX2 tumor model was experimentally implanted in the liver parenchyma of rabbits. All MR studies were performed on 1.5 T. The human extremity radio frequency coil of a bird cage type was employed. MR images were acquired at 17 to 24 days after VX2 carcinoma implantation.4 mmol/kg MnPC and 0.01 mmol/kg Mn-DPDP were injected via the ear vein of rabbits. T1-weighted images were obtained with spin-echo (TR/TE=516/14 msec) and fast multiplanar spoiled gradient recalled (TR/TE : 80/4 msec, $60^{\circ}$ flip angle) pulse sequence. Fast spin-echo (TR/TE=1200/85 msec) was used to obtain the T2-weighted images. Results : The value of T1/T2 relaxivity (R1/R2) of MnPC was $7.28\;mM^{-1}S^{-1}$ and $55.56\;mM^{-1}S^{-1}$ respectively at 1.5 T (64 MHz). Because the T2 relaxivity of MnPC that bonded strongly, covalently manganese with phthalocyanine was very high, the signal intensity of liver parenchyma was decreased on postcontrast T2-weighted images and we could easily distinguish the VX2 carcinoma within the liver parenchyma. When MnPC was administrated intravenously, the tumor margin delineation was more remarkable than Mn-DPDP-enhanced images. The enhancement of liver parenchyma with MnPC persisted at relatively high levels over at least one hour after injection of the contrast agents. Conclusion : The hepatic uptake and biliary excretion of MnPC, which are similar to Mn-DPDP, suggest that this agent is a new liver-specific agent. Also, MnPC seems to be used as a dual contrast agent (T1 and T2) with high T2 relaxivity. However, it is warranted that MnPC needs further investigation as a potential contrast agent for MR imaging of the liver. That is, further characterizations of MnPC are needed in vivo and in vitro before clinical trials. The diagnostic potential of MnPC will also have to be examined more in the animal models of additional types.

• Radiation Oncology Journal
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• v.14 no.2
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• pp.95-103
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• 1996

Purpose : A retrospective analysis for patients with oropharyngeal carcinoma who were treated with radiation was performed to assess the results of treatment and patterns of failure, and to identify the factors that might influence survival. materials and methods : From March 1985 through June 1993, 53 patients with oropharyngeal carcinoma were treated with either radiation therapy alone or combination of neoadjuvant chemotherapy and radiation therapy at the Department of Radiation Oncology, Kyungpook National University Hospital. Patients' ages ranged from 31 to 73 years with a median age of 54 years. There were 47 men and 6 women, Forty-two Patients ($79.2\%$) had squamous cell carcinoma, 10 patients ($18.9\%$) had undifferentiated carcinoma and 1 patient ($19\%$) had adenoid cystic carcinoma. There were 2 patients with stage I, 12 patients with stage II, 12 Patients with stage III and 27 patients with stage IV. According to the TNM classification, patients were distributed as follows: T1 7, T2 28, T3 10, T4 7, TX 1, and N0 17, Nl 13, N2 21, N3 2. The primary tumor sites were tonsillar region in 36 patients ($67.9\%$), base of the tongue in 12 patients ($22.6\%$), and soft palate in 5 patients ($9.4\%$). Twenty-five patients were treated with radiation therapy alone and twenty-eight Patients were treated with one to three courses of chemotherapy followed by radiation therapy. Chemotherapeutic regimens used were either CF (cisplatin and 5-fluorouracil) or CVB (cisplatin, vincristine and bleomycin). Radiation therapy was delivered 180-200 cGy daily, five times a week using 6 MV X-ray with or without 8-10 MeV electron beams A tumor dose ranged from 4500 cGy to 7740 cGy with a median dose of 7100 cGy. The follow-up time ranged from 4 months to 99 months with a median of 21 months. Results : Thirty-seven patients ($69.8\%$) achieved a CR (complete response) and PR (partial response) in 16 patients ($30.2\%$) after radiation therapy. The overall survival rates were $47\%$ at 2 years and $42\%$ at 3 years, respectively. The median survival time was 23 months. Overall stage (p=0.02) and response to radiation therapy (p=0.004) were significant prognostic factors for overall survival. The 2-year disease-free survival rate was $45.5\%$. T-stage (p=0.03), N-stage (p=0.04) and overall stage (P=0.04) were significant prognostic factors for disease-free survival. Age, sex, histology, primary site of the tumor, radiation dose, combination of chemotherapy were not significantly associated with disease-free survival. Among evaluable 32 Patients with CR to radiation therapy, 12 patients were considered to have failed Among these, 8 patients failed locoregionally and 4 Patients failed distantly. Conclusion : T-stage, N-stage and overall stage were significant prognostic factors for disease-free survival in the treatment of oropharyngeal cancer Since locoregional failure was the predominant pattern of relapse, potential methods to improve locoregional control with radiation therapy should be attempted. More controlled clinical, trials should be completed before acceptance of chemotherapy as a part of treatment of oropharyngeal carcinoma.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.121-128
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• 1997

Purpose : To evaluate the effect of postoperative adjuvant radiation therapy and chemotherapy on the survival, pattern of failure and complication for locally advanced rectal carcinoma Materials and Methods : From October 1992 to September 1995, twenty eight patients with rectal carcinoma were treated by postoperative adjuvant radiation therapy and chemotherapy Radiation therapy was delivered with 6MV and 15MV linear accelerator, 180c0y fractions 5 day per week. Total radiation doses were 5040cGy in $B_{2+3}$ and 5580cGy in $C_{2+3}$. Within 4 weeks after radical surgery. 5-FU$(400mg/m^2/day)\;and\;Leucovorin(20mg/m^2/day)$ were administered by intravenous injection for 4 days during the first and fifth week of radiation therapy. The median follow up was 19 months with a range 2 to 47 months. Results : The 2 year overall survival and disease free survival rates were $78.6\%\;and\;70.8\%$, respectively. The 2 year overall survival was $93.0\%\;in\;B_{2+3}$ and $76.2\%\;in\;C_{2+3}$(p=0.11) The 2 year disease free survival was $79.4\%\;in\;B_{2+3}\;and\;69.2\%\;in\;C_{2+3}(p=0.13)$. The overall failure rate was $21.42\%$(6/28) including $10.72\%$(3/28) locoregional recurrence, $3.62\%$(1/28) distant metastasis and $7.12\%$(2/28) locoregional recurrence with distant metastasis. The overall locoregional recurrence rate was $17.92\%$(5/28). The 2 year locoregional recurrence rates were $13.32\%(2/15)\;and\;23.12\%$(3/13) for respectively for $B_{2+3}\;and\;C_{2+3}$ The difference between the locoregional recurrence of $B_{2+3}\;and\;C_{2+3}$ patients was not significant(p=0.07). Complications developed in 13 patients$(46.42\%)$, including 8 dermatitis, 7 loose stool, 6 leukopenia, 4 tenesmus, 2 diarrhea. In Univariate analysis, there was no statistically significant factor except for tumor grade in locoregional recurrence, disease free survival and overall survival rate(p=0.04, 0.05, 0.04). Conclusion : This study sugges1s that postoperative adjuvant radiation therapy and chemotherapy is effective in patients with locally advanced rectal cancer. Therefore these results need to be confirmed with a long term follow-up and larger number of patients with the further clinical trials including prospective controlled studies.

• Radiation Oncology Journal
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• v.26 no.2
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• pp.104-112
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• 2008

Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ dendritic cell(DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses($3{\times}10^6\;to\;12{\times}10^6$ DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The $12{\times}10^6$ DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The $DCVac/IR^{(R)}$ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.350-362
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• 1999

Background: Acute Respiratory failure which is developed after extubation in the weaning process from mechanical ventilation is an important cause of weaning failure. Once it was developed, endotracheal reintubation has been done for respiratory support. Noninvasive Positive Pressure Ventilation (NIPPV) has been used in the management of acute or chronic respiratory failure, as an alternative to endotracheal intubation, using via nasal or facial mask. In this study, we evaluated the usefulness of NIPPV as an alternative method of reintubation in patients who developed acute respiratory failure after extubation. Method: We retrospectively analyzed thirty one patients(eighteen males and thirteen females, mean ages $63\pm13.2$ years) who were developed acute respiratory failure within forty eight hours after extubation, or were extubated unintentionally at medical intensive care unit(MICU) of Asan Medical Center. NIPPV was applied to the patients. Ventilatory mode of NIPPV, level of ventilatory support and inspiratory oxygen concentration were adjusted according to the patient condition and results of blood gas analysis by the attending doctors at MICU. NIPPV was completely weaned when the patients maintained stable clinical condition under 8 $cmH_2O$ of pressure support level. Weaning success was defined as maintenance of stable spontaneous breathing more than forty eight hours after discontinuation of NIPPV. Respiratory rate, heart rate, arterial blood gas analysis, level of pressure support, and level of PEEP were monitored just before extubation, at thirty minutes, six hours, twenty four hours after initiation of NIPPV. They were also measured at just before weaning from NIPPV in success group, and just before reintubation in failure group. Results: NIPPV was successfully applied to thirty-one patients of thirty-two trials and one patient could not tolerated NIPPV longer than thirty minutes. Endotracheal reintubation was successfully obviated in fourteen patients (45%) among them. There was no difference in age, sex, APACHE III score on admission at MICU, duration of intubation, interval from extubation to initiation of NIPPV, baseline heart rate, respiratory rate, arterial blood gas, and $PaO_2/FiO_2$ between the success and the failure group. Heart rate and respiration rate were significantly decreased with increase $SaO_2$ after thirty minutes of NIPPV in both groups(p<0.05). However, in the patients of failure group, heart rate and respiratory rate were increased again with decrease in $SaO_2$ leading to endotracheal reintubation. The success rate of NIPPV treatment was significantly higher in the patients with COPD compared to other diseases(62% vs 39%) (p=0.007). The causes of failure were deterioration of arterial blood gas without aggravation of underlying disease(n=9), aggravation of undelying disease(n=5), mask intolerance(n=2), and retained airway secretion(n=l). Conclusion: NIPPV would be a useful therapeutic alternative which can avoid reintubation in patient who developed acute respiratory failure after extubation.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.322-332
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• 1998

Background: Accurate staging is important to determine treatment modalities and to predict prognosis for the patients with lung cancer. The simple two-stage system of the Veteran's Administration Lung Cancer study Group has been used for staging of small cell lung cancer(SCLC) because treatment usually consists of chemotherapy with or without radiotherapy. However, this system does not accurately reflect segregation of patients into homogenous prognostic groups. Therefore, a variety of new staging system have been proposed as more intensive treatments including either intensive radiotherapy or surgery enter clinical trials. We evaluate the prognostic importance of TNM staging, which has the advantage of providing a uniform detailed classification of tumor spread, in patients with SCLC. Methods: The medical records of 166 patients diagnosed with SCLC between January 1989 and December 1996 were reviewed retrospectively. The influence of TNM stage on survival was analyzed in 147 patients, among 166 patients, who had complete TNM staging data. Results: Three patients were classified in stage I / II, 15 in stage III a, 78 in stage IIIb and 48 in stage IV. Survival rate at 1 and 2 years for these patients were as follows: stage I / II, 75% and 37.5% ; stage IIIa, 46.7% and 25.0% ; stage III b, 34.3% and 11.3% ; and stage IV, 2.6% and 0%. The 2-year survival rates for 84 patients who received chemotherapy(more than 2 cycles) with or without radiotherapy were as follows: stage I / II, 37.5% ; stage rna, 31.3% ; stage IIIb 13.5% ; and stage IV 0%. Overall outcome according to TNM staging was significantly different whether or not received treatment. However, there was no significant difference between stage IIIa and stage IIIb though median survival and 2-year survival rate were higher in stage IIIa than stage IIIb. Conclusion: These results suggest that the TNM staging system may be helpful for predicting the prognosis of patients with SCLC.