• Radiation Oncology Journal
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• v.19 no.2
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• pp.118-126
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• 2001

Purpose : In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. Materials and Methods : From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was $48.2{\pm}7.9\;Gy$ in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at $4\~8$ weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. Results : An objective response was observed in 106 of 158 patients, giving a response rate of $67.1\%$. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only $29.2\%$ showed objective response in patients treated with dose less than 40 Gy, while $68.6\%\;and\;77.1\%$ showed major response in patients with $40\~50\;Gy$ and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Conclusion : Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver volume.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.853-860
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• 1997

Background : Chronic cough, defined as a cough persisting for three weeks or longer, is a common symptom for which outpatient care is sought. The most common etiologies of chronic cough are postnasal drip, asthma, and gastroesophageal reflux. Methacholine challenge is a useful diagnostic study in the evaulation of chronic cough, particularly useful in chronic cough patients with asthmatic symptom. Patients with chronic cough may have dysfunction of bronchial and extrathoracic airways. To evaluate if dysfunction of the bronchial and extrathoracic airways causes chronic cough, we assessed bronchial (BHR) and extrathoracic airway (EAHR) responsiveness to inhaled methacholine in patients with chronic cough. Method : 111 patients with chronic cough were enrolled in our study. Enrolled patients had no recorded diagnosis of asthma, bronchopulmonary disease, hypertension, heart disease or systemic disease and no current treatment with bronchodilator or corticosteroid. Enrolled patients consisted of 46 patients with cough alone, 24 patients with wheeze, 22 patients with dyspnea, 19 patients with wheeze and dyspnea. The inhaled methacholine concentrations causing a 20% fall in forced expiratory volume in 1s($PC_{20}FEV_1$) and 25% fall in maximal mid-inspiratory flow ($PC_{25}MIF_{50}$) were used as bronchial and extra thoracic hyperresponsiveness. Results : There were four response patterns to methacholine challenge study : BHR in 27 patients, EAHR in 16 patients, combined BHR and EAHR in 8 patients, and no hyperresponsiveness in 60 patients. In patients with cough alone, there were BHR in 3 patients, EAHR in 9 patients, and combined BHR and EAHR in 2 patients. In patients with wheeze and/or dyspnea, there were BHR in 24 patients, EAHR in 7 patients, and BHR and EAHR in 6 patients. Compared with patients with wheeze and/or dyspnea, patients with cough alone had more common EAHR than BHR. In patients with wheeze and/or dyspnea, BHR was more common than EAHR. Conclusion : These results show that among patients with hyperresponsiveness to methacholine, those with dyspnea and/or wheezing had mainly bronchial hyperresponsiveness, whereas those with chronic cough alone had mainly extrathoracic airway hyperresponsiveness.

• The Korean Journal of Nuclear Medicine
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• v.39 no.4
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• pp.224-230
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• 2005

Purpose: The maximal elastance ($E_{max}$) of myocardium has been established as a reliable load-independent contractility index. Recently, we developed a noninvasive method to measure the regional contractility using gated myocardial SPECT and arterial tonometry data. In this study, we measured regional $E_{max}(rE_{max}$ in the patients who underwent coronary artery bypass graft surgery (CABG), and assessed its relationship with other variables. Materials and Methods: 21 patients (M:F=17:4, $58{\pm}12$ y) who underwent CABG were enrolled. $^{201}TI$ rest/dipyridamole stress $^{99m}Tc$-sestamibi gated SPECT were performed before and 3 months after CABG. For 15 myocardial regions, regional time-elastance curve was obtained using the pressure data of tonometry and the volume data of gated SPECT. To investigate the coupling with myocardial function, preoperative regional $E_{max}$ was compared with regional perfusion and systolic thickening. In addition, the correlation between $E_{max}$ and viability was assessed in dysfunctional segments (thickening <20% before CABG). The viability was defined as improvement of postoperative systolic thickening more than 10%. Results: Regional $E_{max}$ was slightly increased after CABG from $2.41{\pm}1.64 (pre)\;to\;2.78{\pm}1.83 (post)$ mmHg/ml. $E_{max}$ had weak correlation with perfusion and thickening (r=0.35, p<0.001). In the regions of preserved perfusion (${\geq}60%$), $E_{max}$ was $2.65{\pm}1.67$, while it was $1.30{\pm}1.24$ in the segments of decreased perfusion. With regard to thickening, $E_{max}$ was $3.01{\pm}1.92$ mmHg/ml for normal regions (thickening ${geq}40%$), $2.40{\pm}1.19$ mmHg/ml for mildly dysfunctional regions (<40% and ${\geq}20%$), and $1.13{\pm}0.89$ mmHg/ml for severely dysfunctional regions (<20%). $E_{max}$ was improved after CABG in both the viable (from $1.27{\pm}1.07\;to\;1.79{\pm}1.48$ mmHg/ml) and non-viable segments (from $0.97 {\pm}0.59\;to\;1.22{\pm}0.71$ mmHg/ml), but there was no correlation between $E_{max}$ and thickening improvements (r=0.007). Conclusions: Preoperative regional $E_{max}$ was relatively concordant with regional perfusion and systolic thickening on gated myocardial SPECT. In dysfunctional but viable segments, $E_{max}$ was improved after CABG, but showed no correlation with thickening improvement. As a load-independent contractility index of dysfunctional myocardial segments, we suggest that the regional $E_{max}$ could be an independent parameter in the assessment of myocardial function.

• Journal of Oral Medicine and Pain
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• v.33 no.3
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• pp.279-294
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• 2008

This study aimed to make an analysis of the occlusion in the state of muscle fatigue produced by excessive mouth opening and clenching during the dental treatment to control the dental pain and to evaluate the sensory nerve in the muscle pain state. Most of the reasons why patients visit the dental office result in pain-either conceivably the dental origin pain or the non-dental origin pain. The dental offices have many therapeutic actions to produce the masticatory muscle fatigue for the treatment. Dental treatment with long minutes of mouth opening can cause some headaches, masticatory muscle pain and mouth opening difficulties. Patients with mastication problems who visits a dental office to alleviate pain run against another unexpected pain with other aspects. This study uses T-scan II system(Tekscan Co., USA) for the evaluation on the occlusal pattern in the experimental muscle fatigue after clenching, opening the mouth excessively and chewing gum. The occlusal contact pattern is analyzed by the contact timing, namely first, intercuspal, maximum and end point of contact. This inspection was performed at frequencies of 2000Hz, 250 Hz and 5 Hz before and after each experimental muscle pain was produced to 24 subjects who had normal occlusion without the orthodontic treatment or a wide range of the prosthesis by using $neurometer^{\circledR}$ CPT/C(Neurotron, Inc. Baltimore, Maryland, USA). The measuring sites were mandibular nerve experimental muscle fatigue respectively. This study could obtain the following results after the assessment of occlusion and sensory nerve of the experimental muscle fatigue. 1. There were the fastest expression after the excessive mouth opening in muscle fatigue and after tooth clenching in muscle pain. In the visual analog scale that records the subjective level, there was the highest scale after the clenching in the muscle fatigue in jumping off the point of pain. 2. Tooth contact time, contact force, relative contact force on the point of the first contact had no difference, and there were decreases in the contact force after the excessive mouth opening on intercuspal position point, after the excessive mouth opening and the gum chewing on the point of the maximum, and in the contact time after all the experimental muscle fatigue state on the point of the end contact. 3. There was no statistic significance in the current perception threshold before and after the experimental muscle fatigue. 4. There was no significant difference in the contact number, the maximal contact number on the point of the first contact, and the contact number after the mouth opening and gum chewing on the point of the intercuspal position and the contact number after the experimental muscle fatigue on the maximum point, and showed significant decreases. In conclusion, it was found that the occlusal pattern can cause the changes on the case of the clinical muscle weakness by intra-external oral events. It was important that the sedulous attention to details is required during dental treatment in case of excessive mouth opening, mastication and clenching.

• Journal of Periodontal and Implant Science
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• v.24 no.3
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• pp.581-596
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• 1994

This in vitro study was undertaken to obtain optimal tetracycline concentration that aids proliferation and spreading of human periodontal ligament cells, for clinical application in root surfaces of periodontally diseased teeth. Periodontal ligament cells used in this study were obtained from explants of periodontal ligament of 1st premolar teeth which were extracted for the purpose of orthodontic treatment. The cells were cultured in Dulbecco's Modified Eagle Medium(DMEM) supplemented with 100 U/ml penicillin, $100\;{\mu}g/ml$ streptomycin and 10% FBS at $37^{\circ}C$, 100% humidity, 5% $CO_2-95%$ air. Cells were used between the third to 4th passage. After root planing of periodontally extracted teeth, the root slabs were cut with carborundum disk. In the cell proliferation experiment, experimental groups were root planing only group, immersed groups in 25, 50, 75, 100, 150mg/ml aqueous solution of Tetracycline HCl followed by a vigorous rinse in PBS. Human PDL cells at concentration of $1{\times}10^5\;cells/ml$ were seeded in each culture well which contained root slabs and incubated for 6 hours. Then, all of the root slabs were moved into new 24 culture well and incubated 24, 48 and 72 hours. The cell counting was done by inverted phase contrast microscope after trypsinization. The following results were obtained. The cell number was increased in order root planing only group, 25, 150, 50, 75, 100mg/ml of Tetracycline HCl treated group in 24, 48 and 72 hours. The maximal cell number was obtained when the root slabs were immersed in solution with 100mg/ml of Tetracycline HCl. There were statistically significant between the root planing only group and 75, 100 mg/ml of Tetracycline HCl treated group in 24 hours, between the root planing only group and 100mg/ml of Tetracycline HCl treated group in 48 hours, between the root planing only group and 50, 75, 100mg/ml of Tetracycline HCl treated group, between 25 and 100mg/ml of Tetracycline HCl treated group in 72 hours(p<0.05). In the cell spreading experiment, after 30 minutes of incubated, in the root planing only group, the cells were generally round in shape. The cell surface was mostly covered with blebs. The cells started to attach to root surface by cytoplasmic extension in 50, 100mg/ml of Tetracycline HCl treated groups, more numerous cells attached to root surface than root planing only group. Many orifices of dentinal tubule were exposed, cells showed radially spreaded cytoplasm and unspreaded central region of the cell was covered with blebs. After 6 hours of incubation, in the root planing only group, cells showed radially spreaded cytoplasm and were attached flat appearance. In 50, 100mg/ml of Tetracycline HCl treated groups, cellular margin was concaved and cytoplasm showed elongated appearance with polarity. After 24 hours of incubation, in the root planing group, cells showed characteristic polarity. In 50, 100mg/ml of Tetracycline HCl treated groups, cells showed more elongated and spindle - like appearance.

• The Korean Journal of Physiology
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• v.18 no.2
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• pp.151-162
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• 1984

The mechanism of the contractile response of longitudial muscle of rabbit ileum to substance P (SP) has been investigated. The contractions in rabbit ileum under various conditions were recorded isometrically The following results were obtained. 1) The contractions by SP increased according to concentrations. SP·induced contraction was not sustained but faded rapidly at $10^{-7}M$. The response to the commutative addition of SP was decreased in comparison to the response to separate administration of each concentration . 2) The response to $10^{-8}M$ SP after 5 min application cf $10^{-7}M$ SP was increased with increasing the time interval between the administration of $10^{-7}$ and $10^{-8}M$ SP. 3) The treatment of rabbit ileum by $10^{-7}M$ SP for 5 min didn't decrease the response to $10^{-6}M$ acetylcholine. 4) $10^{-6}M$ atropine had no effect of the contractile response to $10^{-7}M$ SP. The response to $10^{-7}M$ SP was normal or subnormal in the presence of 3 mM tetraethylammonium(TEA). 5) 100k solution, $10^{-4}M$ ouabain, and Na-free solution inhibited the response to $10^{-8}M$ SP and 3 mM TEA completely, and to $10^{-7}M$ SP incompletely. 3 mM TEA induced a considerable contraction in K-free solution, but $10^{-8}M$ SP didn't induce the contraction. $10^{-6}M$ norepinephrine decreased the contractile responses to SP and TEA. 6) The contractile response to $10^{-7}M$ SP was dependent on the extracellular $Ca^{2+}$ concentrations to 1.8 mM. 7) The contractile response to $10^{-7}M$ SP remained 15% of the maximal response after bathing the ileum in a Ca-free solution for 2.5 min. 8) The responsiveness to SP was completely lost within 10 min of bathing in Ca-free solution, but was restored by the exposure to $Ca^{2+}$. The restorative effect of $Ca^{2+}$ depended on the concentration of $Ca^{2+}$, and on time for which the tissue exposed to this $Ca^{2+}$ concentration. These results suggest that there are two mechanisms of the action by which the low concentrations of substance P causes the contraction of intestinal smooth muscle: the reduction of K conductance and a mechanism dependent on the extracellular $Ca^{2+}$, and that high concentration of SP may elicit a contraction by releasing $Ca^{2+}$ from an intracellular store, which is not as sensitive to removal of extracellular $Ca^{2+}$ or as easily accessible to EGTA as the extracellular space of the muscle. The location of this store is not known; it may be associated with the internal side of the cell membrane.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.85-98
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• 2004

Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

• 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.6
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• pp.817-825
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• 1999

Background : Forceps biopsy, bronchial brushing, and bronchial washing are used in conjunction with bronchoscopy to provide specimens for histologic and cytologic analysis in patients with suspected lung cancer. This study was performed to evaluate how many times brushing should be done and how much fluid should be used during bronchial washing for increasing diagnostic yield, and to evaluate which combination of these procedures gives the highest diagnostic yield. Methods : Forty patients, with suspected lung cancer, who had bronchoscopically visible lesions were enrolled in this prospective study. During one bronchoscopic examination four forceps biopsies, four bronchial brushings, and bronchial washing were done in all patients. The patients were divided into four groups by the amount of normal saline used for bronchial washing; group I, 10 ml ; group II, 20ml ; group III 30ml, and group IV, 40ml. We analyzed the results in 36 patients confirmed as lung cancer. Results : The diagnostic sensitivity of bronchial washing before and after forceps biopsy and bronchial brushing were 36% and 28%, respectively. The cumulative diagnostic sensitivity of bronchial washing was 47% and significantly higher than that of bronchial washing before or after forceps biopsy and bronchial brushing (p<0.05). The diagnostic sensitivity of bronchial washing with saline of 30ml was significantly higher than that of bronchial washing with saline of 10ml or 20ml (p<0.05). The diagnostic sensitivity of the first brushing was 75%, the second brushing 78%, the third brushing 83%, and the fourth brushing 67%. With repeated brushing up to three times, the diagnostic sensitivity increased to 92% (p<0.05). However, inclusion of the fourth brushing did not give a further increase of the diagnostic sensitivity. The diagnostic sensitivity of forceps biopsy was 86%. The diagnostic sensitivities of forceps biopsy by the type of bronchial lesion were as follows: tumor, 88%; infiltration, 67%; infiltration with nodularity, 80%; and collapse, 100%. The combination of forceps biopsy and bronchial washing gave a diagnostic sensitivity of 89%. The diagnostic sensitivity of combining forceps biopsy with bronchial brushing was 97%. Addition of bronchial washing did not increase the diagnostic yield over forceps biopsy and bronchial brushing. Conclusion : In patients with central lung cancer, forceps biopsies and repeated brushings up to three times should be done for maximal diagnostic yield.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.57-67
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• 1998

Purpose : This study was undertaken to determine the preoperative predictors of mortality and morbidity after lung cancer resection. Method: During the period from October 1, 1995 to August 31, 1996, a prospective study was conducted in 92 lung resection candidates diagnosed as lung cancer. For preoperative predictors of nonpulmonary factors, we considered age, sex, weight loss, hematocrit, serum albumin, EKG and concomitant illness, and for those of pulmonary factors, smoking history, presence of pneumonia, dyspnea scale(1 to 4), arterial blood gas analysis with room air breathing, routine pulmonary function test. And predicted postoperative(ppo) pulmonary factors such as PPO-$FEV_1$, ppo-diffusing capacity(DLco), predicted postoperative product(PPP) of ppo-$FEV_1%{\times}ppo$-DLco% and ppo-maximal $O_2$ uptake($VO_2$max) were also considered. Results: There were 78 men and 14 women with a median age of 62 years(range 42 to 82) and a mean $FEV_1$ of $2.37\pm0.06L$. Twenty nine patients had a decreased $FEV_1$ less than 2.0L. Pneumonectomy was performed in 26 patients, bilobectomy in 12, lobectomy in 54. Pulmonary complications developed in 10 patients, cardiac complications in 9, other complications(empyema, air leak, bleeding) in 11, and 16 patients were managed in intensive care unit for more than 48hours. Three patients died within 30 days after operation. The ppo-$VO_2$max was less than 10ml/kg/min in these three patients, but its statistical significance could not be determined due to small number of patients. In multivariate analysis, the predictor related to postoperative death was weight loss(p<0.05), and as for pulmonary complications, weight loss, dyspnea scale, ppo-DLco and extent of resection(p<0.05). Conclusions: Based on this study, preoperative nonpulmonary factors such as weight loss and dyspnea scale are more important than the pulmonary factors in the prediction of postoperative mortality and/or morbodity in lung resection candidates, but exercise pulmonary fuction test may be useful Our study suggests that ppo-$VO_2$max value less than 10ml/kg/min is associated with death after lung cancer resection but further studies are needed to validate this result.