• Journal of Gastric Cancer
• /
• v.6 no.1
• /
• pp.36-42
• /
• 2006

Purpose: The $p21^{Waf1/Cip1}$ protein Inhibits the cell cycle by Inhibiting the phosphorylation at the $G1{\rightarrow}S$ check point, and the $p27^{kip1}$ protein similarly performs the suppressor function by controlling the p27-mediated G1 arrest. In this study, we analysed the clinical status and survival rates in correlations with p21 and p27 expression patterns in gastric cancer. Materials and Methods: Between 1993 and 1997, 192 patients who underwent surgeries in Catholic Medical Center were analysed retrospectively in this study. Immunohistochemical staining was performed and if the nuclei of the tumor cells were stained, we assumed those as positive results. Statistical analysis was based on clinicopathological findings and differences in survival rates. Results: The expression rate of p27 was 28.1% and 15.6% in p21 each. The ratio of T1-2(80.0%) was significantly high in p21 (+), but the ratio of T3-4 (50.6%) was slightly high in p21 (-). There was no statistical significance regarding other factors. The results in p27 was not much different from expression rate of p21 in T-stage. In addition, p27 expression in diffuse type (91.3%) was higher than in intestinal type (62.7%) by Lauren's classification (P<0.05). Also, there was no statistical significance in other factors. In the correlation of p21 and p27, p27 was positive when p21 was positive (53.5%). Conversely, p27 was negative when p21 was negative (76.5%, p<0.05). In the p21 and p27 combination test, there was higher rate of T1-2 (87.5%) in p21 (+)/p27 (+), and higher rate of T3-4 (58.1%) in p21 (-)/p27 (-) (P<0.05). Results showed higher rate of intestinal type (100%) in p21 (+)/p27 (+), and diffuse type (87.0%) was dominant in p21 (-)/p27 (-) (P<0.05) by Lauren's classification. Moreover, there was no statistical significance in the 5-year survival rate in the expression of p21 and p27, and the 5-year survival rate was highest in the case of p21 (+)/p27 (+) without statistical significance. Conclusion: In our study, $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ expressed similar patterns. The expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ affected the degree of invasiveness of the tumor, and. Combined examination result revealed the correlation of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ with Lauren's classification and depth of invasion of the tumor. However, we assumed that little difference between the survival rates depending on expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ has limited their value as predictable prognostic indicators.

• The Journal of Korean Society for Radiation Therapy
• /
• v.24 no.2
• /
• pp.123-135
• /
• 2012

Purpose: It is essential to minimize the movement of tumor due to respiratory movement at the time of respiration controlled radiotherapy of non-small cell lung cancer patient. Accordingly, this Study aims to evaluate the usefulness of restricted respiratory period by comparing and analyzing the treatment plans that apply free and restricted respiration period respectively. Materials and Methods: After having conducted training on 9 non-small cell lung cancer patients (tumor n=10) from April to December 2011 by using 'signal monitored-breathing (guided- breathing)' method for the 'free respiratory period' measured on the basis of the regular respiratory period of the patents and 'restricted respiratory period' that was intentionally reduced, total of 10 CT images for each of the respiration phases were acquired by carrying out 4D CT for treatment planning purpose by using RPM and 4-dimensional computed tomography simulator. Visual gross tumor volume (GTV) and internal target volume (ITV) that each of the observer 1 and observer 2 has set were measured and compared on the CT image of each respiratory interval. Moreover, the amplitude of movement of tumor was measured by measuring the center of mass (COM) at the phase of 0% which is the end-inspiration (EI) and at the phase of 50% which is the end-exhalation (EE). In addition, both observers established treatment plan that applied the 2 respiratory periods, and mean dose to normal lung (MDTNL) was compared and analyzed through dose-volume histogram (DVH). Moreover, normal tissue complication probability (NTCP) of the normal lung volume was compared by using dose-volume histogram analysis program (DVH analyzer v.1) and statistical analysis was performed in order to carry out quantitative evaluation of the measured data. Results: As the result of the analysis of the treatment plan that applied the 'restricted respiratory period' of the observer 1 and observer 2, there was reduction rate of 38.75% in the 3-dimensional direction movement of the tumor in comparison to the 'free respiratory period' in the case of the observer 1, while there reduction rate was 41.10% in the case of the observer 2. The results of measurement and comparison of the volumes, GTV and ITV, there was reduction rate of $14.96{\pm}9.44%$ for observer 1 and $19.86{\pm}10.62%$ for observer 2 in the case of GTV, while there was reduction rate of $8.91{\pm}5.91%$ for observer 1 and $15.52{\pm}9.01%$ for observer 2 in the case of ITV. The results of analysis and comparison of MDTNL and NTCP illustrated the reduction rate of MDTNL $3.98{\pm}5.62%$ for observer 1 and $7.62{\pm}10.29%$ for observer 2 in the case of MDTNL, while there was reduction rate of $21.70{\pm}28.27%$ for observer 1 and $37.83{\pm}49.93%$ for observer 2 in the case of NTCP. In addition, the results of analysis of correlation between the resultant values of the 2 observers, while there was significant difference between the observers for the 'free respiratory period', there was no significantly different reduction rates between the observers for 'restricted respiratory period. Conclusion: It was possible to verify the usefulness and appropriateness of 'restricted respiratory period' at the time of respiration controlled radiotherapy on non-small cell lung cancer patient as the treatment plan that applied 'restricted respiratory period' illustrated relative reduction in the evaluation factors in comparison to the 'free respiratory period.

• Journal of Gastric Cancer
• /
• v.6 no.3
• /
• pp.146-153
• /
• 2006

Purpose: Gastrointestinal stromal tumorsm (GISTs) are the most common mesenchymal tumors that arise anywhere in the tubular GI tract. The prognosis for GSTIs is important because f GISTs may metastasiwx in the liver or the abdominal cavity in an early stage. For the reason we examined the tumor size, the mitotic number, ki 67, p53, and c-kit mutation as independent prognostic factor for GISTs. Materials and Methods: A retrospective study was conducted in 76 patients who had been re-evaluated for confirmation of diagnosis between Jan 1998 and Dec. 2001. at Catholic University of medicine. Results: There were significant difference between the turner size, mitotic indices, ki 67, c-kit mutations and the 5-years survival rates. Tumor size (${\geq}5\;cm$) and mitotic index (${\geq}5/50\;HPF$) were statistically related to a significantly poor prognosis (P=0.017 and P=0.042, respectively). c-kit mutations in exon 11 were found in 7 cases c-kit mutation was observed more frequently in high risk patients, and there was a significant difference between c-kit mutation and survival (P=0.037). Elevated ki 67 was noted in 34 out of the 76 cases. High risk patients showed elevated ki67 index more frequently and there was significant relation with the survival rate (P=0.0417). Conclusion: We think that tumor size, mitotic index, Ki 67 and c-kit mutation are as independent prognostic factors for GISTs, but more research is needed.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.5
• /
• pp.685-696
• /
• 1999

Background : Idiopathic pulmonary fibrosis (IPF) is a diffuse inflammatory and fibrosing process that occurs within the interstitium and alveolus of the lung with invariably poor prognosis. The major problem in management of IPF results from the variable rate of disease progression and the difficulties in predicting the response to therapy. The purpose of this retrospective study was to evaluate the short-term efficacy of steroid and immunosuppressive therapy for IPF and to identify the pre-treatment determinants of favorable response. Method : Twenty patients of IPF were included. Diagnosis of IPF was proven by thoracoscopic lung biopsy and they were presumed to have active progressive disease. The baseline evaluation in these patients included clinical history, pulmonary function test, bronchoalveolar lavage (BAL), and chest high resolution computed tomography (HRCT). Fourteen patients received oral prednisolone treatment with initial dose of 1mg/kg/day for 8 to 12 weeks and then tapering to low-dose prednisolone (0.25mg/kg/day). Six patients who previously had experienced significant side effects to steroid received 2mg/kg/day of oral cyclophosphamide with or without low-dose prednisolone. Follow-up evaluation was performed after 6 months of therapy. If patients met more than one of followings, they were considered to be responders : (1) improvement of more than one grade in dyspnea index, (2) improvement in FVC or TLC more than 10% or improvement in DLco more than 20% (3) decreased extent of disease in chest HRCT findings. Result : One patient died of extrapulmonary cause after 3 month of therapy, and another patient gave up any further medical therapy due to side effect of steroid. Eventually medical records of 18 patients were analyzed. Nine of 18 patients were classified into responders and the other nine patients into nonresponders. The histopathologic diagnosis of the responders were all nonspecific interstitial pneumonia (NSIP) and that of nonresponders were all usual interstitial pneumonia (UIP) (p<0.001). The other significant differences between the two groups were female predominance (p<0.01), smoking history (p<0.001), severe grade of dyspnea (p<0.05), lymphocytosis in BAL fluid ($23.8{\pm}16.3%$ vs $7.8{\pm}3.6%$, p<0.05), and less honeycombing in chest HRCT findings (0% vs $9.2{\pm}2.3%$, p<0.001). Conclusion : Our results suggest that patients with histopathologic diagnosis of NSIP or lymphocytosis in BAL fluid are more likely to respond to steroid or immunosuppressive therapy. Clinical results in large numbers of IPF patients will be required to identify the independent variables.

• Tuberculosis and Respiratory Diseases
• /
• v.46 no.6
• /
• pp.803-810
• /
• 1999

Background : The patient's work of breathing(WOBp) during assisted ventilation may vary according to many factors including ventilatory demand of the patients and applied ventilatory setting by the physician. Pressure-controlled ventilation(PCV) which delivers gas with decelerating flow may better meet patients' demand to improve patient-ventilator synchrony compared with volume-controlled ventilation(VCV) with constant flow. This study was conducted to compare the difference in WOBp in two assisted modes of ventilation, PCV and VCV with constant flow. Methods : Ten patients with respiratory failure were included in this study. Initially, the patients were placed on VCV with constant flow at low tidal volume($V_{T,\;LOW}$)(6-8 ml/kg) or high tidal volume($V_{T,\;HIGH}$)(10-12 ml/kg). After a 15 minute stabilization period, VCV with constant flow was switched to PCV and pressure was adjusted to maintain the same tidal volume($V_T$) received on VCV. Other ventilator settings were kept constant. Before changing the ventilatory mode, WOBp, $V_T$, minute ventilation($V_E$), respiratory rate(RR), peak airway pressure (Ppeak), peak inspiratory flow rate(PIFR) and pressure-time product(PTP) were measured. Results : The mean $V_E$ and RR were not different between PCV and VCV during the study period. The Ppeak was significantly lower in PCV than in VCV during $V_{T,\;HIGH}$. HIGH ventilation(p<0.05). PIFR was significantly higher in PCV than in VCV at both $V_T$ (p<0.05). During $V_{T,\;LOW}$ ventilation, WOBp and PTP in PCV($0.80{\pm}0.37\;J/min$, $164.5{\pm}74.4\;cmH_2O.S$) were significantly lower than in VCV($1.06{\pm}0.39J/mm$, $256.4{\pm}107.5\;cmH_2O.S$)(p<0.05). During $V_{T,\;HIGH}$ ventilation, WOBp and PTP in PCV($0.33{\pm}0.14\;J/min$, $65.7{\pm}26.3\;cmH_2O.S$) were also significantly lower than in VCV($0.40{\pm}0.14\;J/min$, $83.4{\pm}35.1\;cmH_2O.S$)(p<0.05). Conclusion : During assisted ventilation, PCV with decelerating flow was more effective in reducing WOBp than VCV with constant flow. But since individual variability was shown, further studies are needed to confirm these results.

• Tuberculosis and Respiratory Diseases
• /
• v.59 no.5
• /
• pp.522-529
• /
• 2005

Background : Several national societies have published guidelines for empirical antimicrobial therapy in patients with severe community-acquired pneumonia (SCAP). This study investigated the etiologies of SCAP in the Asan Medical Center and assessed the relationship between the initial empirical antimicrobial regimen and 30 day mortality rate. Method : retrospective analysis was performed on patients with SCAP admitted to the ICU between March 2002 and February 2004 in the Asan Medical Center. The basic demographic data, bacteriologic study results and initial antimicrobial regimen were examined for all patients. The clinical outcomes including the ICU length of stay, the ICU mortality rate, and 30 days mortality rates were assessed by the initial antimicrobial regimen. Results : One hundred sixteen consecutive patients were admitted to the ICU (mean age 66.5 years, 81.9 % male, 30 days mortality 28.4 %). The microbiologic diagnosis was established in 58 patients (50 %). The most common pathogens were S. pneumoniae (n=12), P. aeruginosae (n=9), K. pneumonia (n=9) and S. aureus (n=8). The initial empirical antimicrobial regimens were classified as: ${\beta}$-lactam plus macrolide; ${\beta}$-lactam plus fluoroquinolone; anti-Pseudomonal ${\beta}$-lactam plus fluoroquinolone; Aminoglycoside combination regimen; ${\beta}$-lactam plus clindamycin; and ${\beta}$-lactam alone. There were no statistical significant differences in the 30-day mortality rate according to the initial antimicrobial regimen (p = 0.682). Multivariate analysis revealed that acute renal failure, acute respiratory distress syndrome and K. pneumonae were independent risk factors related to the 30 day mortality rate. Conclusion : S. pneumoniae, P. aeruginosae, K. pneumonia and S. aureus were the most common causative pathogens in patients with SCAP and K. pneumoniae was an independent risk factor for 30 day mortality. The initial antimicrobial regimen was not associated with the 30-day mortality.

• Tuberculosis and Respiratory Diseases
• /
• v.49 no.2
• /
• pp.149-161
• /
• 2000

Background : Residual pleural thickening (RPT) develops in about 50% of tuberculous pleurisy ($PL_{TB}$). Some reports have suggested that elevated TNF-$\alpha$ and impaired fibrinolysis could be the cause of RPT, but until now, the mechanism and predictors of RPT have not been well known. TGF-$\beta$ has been known to promote fibrogenesis and is increased in tuberculous pleural fluid (PF). $PL_{TB}$ and malignant pleurisy ($PL_{MAL}$) manifest lymphocyte-dominant exudative pleural effusion, and it has clinical implications in the differentiation of the two diseases based on the findings of pleural effusion. We performed this study to compare pleural fluid TNF-$\alpha$ TGF-$\beta$, and fibrinolytic parameters between $PL_{TB}$ and $PL_{MAL}$, and to find the predictors of RPT in $PL_{TB}$. Methods : Thirty-five $PL_{TB}$ and 14 $PL_{MAL}$ patients who were admitted to the Asan Medical Center from February 1997 to August 1999 were enrolled. All $PL_{TB}$ patients were prescribed a primary, short-course, anti-tuberculosis regimen. INF-$\alpha$ tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), plasminogen, $\alpha$2-antiplasmin, and D-dimer were measured in both PF and PB. TGF-$\beta$was measured only in PF. Clinical characteristics, TNF-$\alpha$ TGF-$\beta$ and fibrinolytic parameters were compared between patients with RPT less than 2 mm and patients with more than 2 mm of the thirty patients who completed the anti-tuberculosis treatment. Results : The levels of TNF-$\alpha$ tPA, PAI-1, plasminogen, $\alpha$2-antiplasmin, and D-dimer in PF were higher than those in peripheral blood (PB) in $PL_{TB}$, whereas only plasminogen, $\alpha$2-antiplasmin, and D-dimer were higher in PF than in PB in $PL_{MAL}$. Pleural fluid TNF-$\alpha$ TGF-$\beta$, PAI-1, plasminogen, $\alpha$2-antiplasmin were increased in $PL_{TB}$ compared with $PL_{MAL}$, but these factors did not show any further advantages over ADA in differentiation between $PL_{TB}$ and $PL_{MAL}$. TNF-$\alpha$ TGF-$\beta$ and fibrinolytic parameters did not show any differences between patients with RPT less than 2 mm and patients with RPT more than 2 mm. Conclusion : Our data suggest that TNF-$\alpha$, TGF-$\beta$ and fibrinolytic parameters may play some role for the development of RPT in $PL_{TB}$, but they failed to predict the occurrence of RPT in $PL_{TB}$. Also these parameters did not seem to have any advantages over ADA in differentiating between two diseases.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.6
• /
• pp.1199-1213
• /
• 1998

Background : The number of immunocompromised hosts has been increasing steadily and a new pulmonary infiltrate in these patients is a potentially lethal condition which needs rapid diagnosis and treatment. In this study we sought to examine the clinical manifestations, radiologic findings, and therapeutic outcomes of pulmonary mycoses presenting as a new pulmonary infiltrate in immunocompromised hosts. Method : All cases presenting as a new pulmonary infiltrate in immunocompromised hosts and confirmed to be pulmonary mycoses by pathologic examination or by positive culture from a sterile site between October of 1996 and April of 1998 were included in the study and their chart and radiologic findings were retrospectively reviewed. Results : In all, 14 cases of pulmonary mycoses from 13 patients(male : female ratio = 8 : 5, median age 47 yr) were found. Twelve cases were diagnosed as aspergillosis while two were diagnosed as mucormycosis. Major risk factors for fungal infections were chemotherapy for hematologic malignancy(10 cases) and organ transplant recipients(4 cases). Three cases were receiving empirical amphotericin B at the time of appearance of new lung infiltrates. Cases in the hematologic malignancy group had more prominent symptoms : fever(9/10), cough(6/10), sputum(5/10), dyspnea(4/10), chest pain(5/10). Patients in the organ transplant group had minimal symptoms(p<0.05). On simple chest films, all of the cases presented as single or multiple nodules(6/14) or consolidations(8/14). High resolution computed tomograph showed peri-lesional ground glass opacities(14/14), pleural effusions(5/14), and cavitary changes(7/14). Definitive diagnostic methods were as follows : 10 cases underwent minithoracotomy, 2 underwent video-assisted thoracoscopic surgery, 1 underwent percutaneous needle aspiration and 1 case was diagnosed by culture of abscess fluid. All cases received treatment with amphotericin B with 1 case each being treated with liposomal amphotericin B and itraconazole due to renal toxicity. Lung lesion improved in 12 of 14 patient but 4 patients died before completing therapy. Conclusion : When a new lung infiltrate develops presenting either as a nodule or consolidation in a neutropenic patient with hematologic malignancy or in a transplant recipient, you should always consider pulmonary mycoses as one of the differential diagnosis. By performing aggressive work up and early treatment, we may improve prognosis of these patients.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.1
• /
• pp.128-139
• /
• 1998

Background: It is well known that various cytokines and growth factors secreted mainly from alveolar macrophages do the key role in the pathogenesis of IPF. But recently it has been known that structural cells like fibroblast can also release cytokines. So the phenotypic changes in fibroblasts of IPF may do a role in continuous progression of fibrosis. The aim of this study is to find out whether there is a change in the biologic properties of the lung fibroblasts of IPF. Subjects and Method: The study was done on 13 patients with IPF diagnosed by open or thoracoscopic lung biopsy and 7 control patients who underwent resectional surgery for lung cancer. Lung fibroblast cell lines (FB) were established by explant culture technique from the biopsy or resected specimen Result: Basal proliferation of the fibroblast of IPF(IFB) measured by BrdU uptake tended to be highter than control fibroblast(NFB) (0.212 0.107 vs $0.319{\pm}0.143$, p=0.0922), also there was no significant difference in proliferation after the stimulation with PDGF or 10% serum. On the contrary, the degree of inhibition in proliferation by PGE2 was significantly lower($33.0{\pm}13.1%$) in IFB than control($46.7{\pm}10.0%$, p=0.0429). The IFB secreted significantly higher amount of MCP-l($l574{\pm}1283$ pg/ml) spontaneously than NFB($243{\pm}100$ pg/ml) and also after the stimulation with TGF-$\beta$($3.23{\pm}1.31$ ng/ml vs $0.552{\pm}0.236$ ng/ml, p=0.0012). Similarly IL-8 and IL-6 seretion of IFB was significantly higher than NFB at basal state and with TGF-$beta$ stimulation. But after the maximal stimulation with IL-1,8, no significant difference in cytokine secretion was found between IFB and NFB. Conclusion : Above data suggest that the fibroblasts of IPF were phenotypically changed and these change may do a role in the pathogenesis of IPF.

• Tuberculosis and Respiratory Diseases
• /
• v.44 no.3
• /
• pp.592-600
• /
• 1997

Background : The level of imposed work of breathing (WOB) is important for patient-ventilator synchrony and during weaning from mechanical ventilation. Triggering methods and the sensitivity of demand system are important determining factors of the imposed WOB. Flow triggering method is available on several modern ventilator and is believed to impose less work to a patient-triggered breath than pressure triggering method. We intended to compare the level of imposed WOB on two different methods of triggering and also at different levels of sensitivities on each triggering method (0.7 L/min vs 2.0 L/min on flow triggering ; $-1\;cmH_2O$ vs $-2cm\;H_2O$ on pressure triggering). Methods : The subjects were 12 patients ($64.8{\pm}4.2\;yrs$) on mechanical ventilation and were stable in respiratory pattern on CPAP $3\;cmH_2O$. Four different triggering sensitivities were applied at random order. For determination of imposed WOB, tracheal end pressure was measured through the monitoring lumen of Hi-Lo Jet tracheal tube (Mallincrodt, New York, USA) using pneumotachograph/pressure transducer (CP-100 pulmonary monitor, Bicore, Irvine, CA, USA). Other data of respiratory mechanics were also obtained by CP-100 pulmonary monitor. Results : The imposed WOB was decreased by 37.5% during 0.7 L/min on flow triggering compared to $-2\;cmH_2O$ on pressure triggering and also decreased by 14% during $-1\;cmH_2O$ compared to $-2\;cmH_2O$ on pressure triggering (p < 0.05 in each). The PTP(Pressure Time Product) was also decreased significantly during 0.7 L/min on flow triggering and $-1\;cmH_2O$ on pressure triggering compared to $-2\;cmH_2O$ on pressure triggering (p < 0.05 in each). The proportions of imposed WOB in total WOB were ranged from 37% to 85% and no significant changes among different methods and sensitivities. The physiologic WOB showed no significant changes among different triggering methods and sensitivities. Conclusion : To reduce the imposed WOB, flow triggering with sensitivity of 0.7 L/min would be better method than pressure triggering with sensitivity of $-2\;cm\;H_2O$.