• Journal of Chest Surgery
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• v.38 no.1 s.246
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• pp.44-49
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• 2005

Although thymomas are relatively common mediastinal tumors, to date not only has a universal system of pathologic classification not been established but neither has a clearly defined predictable relationship between treatment and prognosis been made. Recently, a new guideline for classification was reported by WHO, and efforts, based on this work, have been made to better define the relationship between treatment and pro­gnostic outcome. In the present study a comparative analysis between the WHO classification and Masaoka stage system with the clinical disease pattern was conducted. Material and Method: A total of 98 patients undergoing complete resection for mediastinal thymoma between Juanuary 1993 and June 2003 were included in the present study. The male female ratio was 48 : 50 and the mean age at operation was $49.6{\pm}13.9\;years.$ A retrospective analytic comparison studying the relationship between the WHO classification and the Masaoka stage system with the clinical disease pattern of thymoma was conducted. Pathologic slide specimens were carefully examined, details of postoperative treatment were documented, and a relationship with the prognostic outcome and recurrence was studied. Result: There were 7 patients in type A according to the WHO system of classification, 14 in AB, 28 in B 1, 23 in B2, 18 in B3, and 9 in type C. The study of the relationship between the Masaoka stage and WHO classification system showed 4 patients to be in WHO system type A, 7 in type AB, 22 in B 1, 17 in B2, and 3 in type B3 among 53 $(54{\%})$ patients shown to be in Masaoka stage I. Among 28 $(28.5{\%})$ patients in Masaoka stage II system, there were 2 patients in type A, 7 in AB, 4 in B 1, 2 in B2, 8 in B3, and 5 in type C. Among 15 $(15.3{\%})$ in Masaoka stage III, there were 1 patient in type B1, 3 in B2, 7 in B3, and 4 in type C. Finally, among 2 $(2{\%})$ patients found to be in Masaoka stage IV there was 1 patient in type B1, and 1 in type B2. The mean follow up duration was $28{\pm}6.8$ months. There were 3 deaths in the entire series of which 2 were in type B2 (Masaoka stages III and IV), and 1 was in type C (Masaoka stage II). Of the patients that experienced relapse, 6 patients remain alive of which 2 were in type B2 (Masaoka III), 2 in type B3 (Masaoka I and III) and 2 in type C (Masaoka stage II). The 5 year survival rate by the Kaplan-Meier method was $90{\%}$ for those in type B2 WHO classification system, $87.5{\%}$ for type C. The 5 year freedom from recurrence rate was $80.7{\%}$ for those in WHO type B2, $81.6{\%}$ for those in type B3, and $50{\%}$ for those in type C. By the Log-Rank method, a statistically significant correlation between survival and recurrence was found with the WHO system of classification (p<0.05). An analysis of the relationship between the WHO classification and Masaoka stage system using the Spearman correction method, showed a slope=0.401 (p=0.023), showing a close correlation. Conclusion: As type C of the WHO classification system is associated with a high postoperative mortality and recurrence rate, aggressive treatment postoperatively and meticulous follow up are warranted. The WHO classification and Masaoka stage system were found to have a close relationship with each other and either the WHO classification method or the Masaoka stage system may be used as a predict prognostic outcome of Thymoma.

• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.674-684
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• 1999

Background : It has been generally known that the incidence of lung cancer is higher in the patients with idopathic pumonary fibrosis (IPF) than those in general population. The reported incidence was variable from 4.8 to 43.2%. There were controversies on the most frequent cell type (squamous cell carcinoma vs. adenocarcinoma) and no study was done about the real concordance of cancer and the fibrotic lesion. And the pulmonary fibrosis may influence not only the development of cancer but also the treatment and prognosis of the cancer, but there was no report on that point. Method : Total 63 patients ($66.8{\pm}7.8$ year, M : F=61 : 2) were diagnosed as IPF combined with lung cancer (IFF-CA) at Asan Medical Center. A retrospective analysis was done about the risk factors of the lung cancer, pulmonary function test, the site of cancer(especially the relationship of the cancer with the fibrotic lesion), the histologic types, and the stage of cancer. The histologic types were compared with those of 2,660 patients with lung cancer who were diagnosed at the same institute for the same period. The effect of IPF on the treatment of the cancer was evaluated with the survival time after the detection of lung cancer. Results : The lung cancer was found in 63(22.9%) out of 281 patients with IPF. But in most of them(45 patients), lung cancer was detected at the same time with IPF and only in 18 patients, the cancer was diagnosed during the follow-up($25.2{\pm}17.7$ months) of IPF. So in our study, 6.7% of patients with IPF developed lung cancer during the course of the disease. The age ($66.8{\pm}7.84$ vs. $63.4{\pm}11.1$ years), percentage of smoker (88.9 vs. 67.2%), and the male gender (96.8 vs. 67.6%) were significantly higher in IPF-CA compared with lone IPF (p<0.05). The odds ratio of smoking was 4.7 compared with non smoking IPF controls. The lung cancer was located more frequently in the upper lobe and 55.5% was in the periphery of lung. The cancer was developed in the fibrotic lesion in 23 patients (35.9%), and in the majority of the patients, the cancer was separated from the fibrosis. The cell type of the lung cancer in IPF-CA was squamous cell carcinoma 34.9%, adenocarcinoma 30.2%, small cell carcinoma 19.0%, large cell undifferenciated carcinoma 6.3%, and others 9.5%. No significant difference in the distribution of histologic type of the lung cancer was found between IPF-CA and lone lung cancer. There was no significant difference in demographic features, cell types, location and the stage of the cancer between the group with concurrent IPF-CA and the group with cancer diagnosed during the follow up of IPF. There was a tendency (but statistically not significant : p=0.081) of higher incidence of adenocarcinoma among the cancers developed in the fibrotic area(43.5%) (F-CA) than in the cancers in non-fibrotic area (22.5%) (NF-CA). The prognosis of the patients with F-CA was poor (median survival : 4 months) compared with the patients with NF-CA (7 months, p=0.013), partly because the prevalence of severe IPF (the extent of fibrosis in HRCT 50%) was higher in F-CA group. Conclusion : These data suggest that the lung cancer in the patients with IPF has similar features to the ordinary lung cancer.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.3 no.1
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• pp.30-40
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• 2000

Purpose: During the first year of life, cow's milk protein is the major offender causing food allergy. Cow's milk allergy (CMA) affects 2~7% of infants, of which approximately one-half show predominantly gastrointestinal symptoms. We studied the clinical types of cow's milk allergy with predominantly gastrointestinal symptoms (CMA-GI) of childhood. Methods: The retrospective study was performed on 30 (male 22, female 8) patients who had diagnosed as CMA-GI during 2 years and 3 months from March 1995 to June 1997. Results: 1) Children with CMA-GI presented in the three types of clinical manifestation on the basis of time to reaction to milk ingestion: Quick (Q) onset (5 cases), Slow (S) onset (20 cases), Quick & Slow (Q&S) (5 cases). 2) Age on admission of the three groups was significantly different (p<0.05): (Q onset: $81.4{\pm}67.1$ days, S onset: $31.9{\pm}12.7$ days, Q&S: $366.0{\pm}65.0$ days). Although the body weight at birth was 10~95 percentile in all patients, body weight on admission was different: (Q onset: 10~50 percentile, S onset: below 10 percentile, Q&S: 10~25 percentile). S onset group was significantly different compared with other groups (p<0.05) and 90% of this one was failure to thrive below 3 percentile. 3) Peripheral leukocyte counts were as followings: (Q onset: $5,700{\sim}12,300/mm^3$, S onset: $10,000{\sim}33,400/mm^3$, Q&S: $5,200{\sim}14,900/mm^3$). Slow onset group was significantly different compared with other groups (p<0.05). Serum albumin levels on admission were as followings: (Q onset: $4.2{\pm}0.4\;g/dl$, S onset: $3.0{\pm}0.3\;g/dl$, Q&S: $4.0{\pm}0.3\;g/dl$). S onset group was significantly different compared with other groups (p<0.05) and 85% of this one was below 3.5 g/dl. 4) Although morphometrical analysis on small intestinal mucosa did not show enteropathy in Q onset and Q&S groups, all cases of S onset revealed enteropathy: 45% of this one showed subtotal villous atrophy, 55 % showed partial villous atrophy. 5) Allergic reaction test to other foods was not performed in S onset group because of ethical problem and high risk in general condition. In Q onset group, allergic reaction to one or two other foods: soy formula, weaning formula and eggs. Q&S goup revealed allergic reactions to several foods or to most of all foods except protein hydrolysate formula: eggs, potatos, some kinds of sea food, apples, carrots, beef and chicken. 6) Serum IgE level, peripheral eosinophil counts, milk RAST, soy RAST, skin test were not significantly different among groups. Conclusion: CMA-GI may present in three clinical ways on the basis of time to reaction to milk ingestion, typical clinical findings and morphologic changes in the small bowel mucosal biopsy specimens. This clinical subdivision might be helpful in diagnostic and therapeutic approaches in CMA-GI. Early suspicion is mandatory especially in S onset type because of high risks with malnutrition and enteropathy.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.291-301
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• 1998

Purpose : A retrospective study was conducted comparing single daily fraction (SDF) thoracic radiotherapy (TRT) with twice daily (BID) TRT to determine the potential benefit of BID TRT in limited-stage small cell lung cancer (SCLC). Endpoints of the study were response. survival, pattern of failure, and acute toxicity. Materials and Methods : Between November 1989 to December 1996, 78 patients with histologically proven limited-stage SCLC were treated at the Department of Therapeutic Radiology, Chungnam National University Hospital. Of these, 9 were irradiated for palliative intent, and 1 had recurrent disease. Remaining 68 patients were enrolled in this study. There were 26 patients with a median age of 58 years, and 22 (85$\%$) ECOG performance score of less than 1 in SDF TRT. There were 42 patients with a median age of 57 years, and 36 (86$\%$) ECOG performance score of less than 1 in BID TRT By radiation fractionation regimen, there were 26 in SDF TRT and 42 in BID TRT. SDF TRT consisted of 180 cGy, 5 days a week. BID TRT consisted of 150 cGy BID, 5 days a week in 13 of 42 and 120 cGy BID, in 29 of 42. And the twice daily fractions were separated by at least 4 hours. Total radiotherapy doses were between 5040 and 6940 cGy (median, 5040 cGy) in SDF TRT and was between 4320 and 5100 cGy (median, 4560 cGy) in BID TRT. Prophylactic cranial irradiation (PCI) was recommended for patients who achieved a CR. The recommended PCI dose was 2500 cGy/10 fractions. Chemotherapy consisted of CAV (cytoxan 1000 mg/$m^2$, adriamycin 40 mg/$m^2$, vincristine 1 mg/$m^2$) alternating with VPP (cisplatin 60 mg/$m^2$, etoposide 100 mg/$m^2$) every 3 weeks in 25 (96$\%$) of SDF TRT and in 40 (95$\%$) of BID TRT. Median cycle of chemotherapy was six in both group. Timing for chemotherapy was sequential in 23 of SDF TRT and in 3 BID TRT, and concurrent in 3 of SDF TRT and in 39 of BID TRT Follow-up ranged from 2 to 99 months (median, 14 months) in both groups. Results : Of the 26 SDF TRT, 9 (35$\%$) achieved a complete response (CR) and 14 (54$\%$) experienced a partial response (PR). Of the 42 BID TRT, 18 (43$\%$) achieved a CR and 23 (55$\%$) experienced a PR. There was no significant response difference between the two arms (p=0.119). Overall median and 2-year survival were 15 months and 26.8$\%$, respectively. The 2-year survivals were 26.9$\%$ and 28$\%$ in both arm, respectively (p=0.51). The 2-rear survivals were 35$\%$ in CR and 24.2$\%$ in PR, respectively. The grade 2 to 3 esophageal toxicities and grade 2 to 4 neutropenias were more common in BID TRT (p=0.028 0.003). There was no difference in locoregional and distant metastasis between the two arms (p=0 125 and 0.335, respectively). The most common site of distant metastasis was the brain. Conclusion : The median survival and 2-year survival were 17 months and 20.9$\%$ in SDF TRT with sequential chemotherapy, and 15 months and 28$\%$ in BID TRT with concurrent chemotherapy, respectively. We did not observe a substantial improvement of long-term survival in the BID TRT with concurrent chemotherapy compared with standard schedules of SDF TRT with sequential chemotherapy. The grade 2 to 3 esophageal toxicities and glade 2 to 4 neutropenias were more common in BID TRT with concurrent chemotherapy. Although the acute toxicities were more common in BID TRT with concurrent chemotherapy than SDF TRT with sequential chemotherapy, a concurrent chemotherapy and twice daily TRT was feasible. However further patient accrual and long-term follow up are needed to determine the potential benefits of BID TRT in limited-stage SCLC.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.356-364
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• 1999

Backgrounds: Previous reports have revealed a high morbidity and mortality in fatal asthma patients, especially those treated in the medical intensive care unit(MICU). But it has not been well known about the predictable factors for the mortality of fatal asthma(F A) with acute respiratory failure. In order to define the predictable factors for the mortality of FA at the admission to MICU, we analyzed the relationship between the clinical parameters and the prognosis of FA patients. Methods: A retrospective analysis of all medical records of 59 patients who had admitted for FA to MICU at a tertiary care MICU from January 1992 to March 1997 was performed. Results: Over all mortality rate was 32.2% and 43 patients were mechanically ventilated. In uni-variate analysis, the death group had significantly older age ($66.2{\pm}10.5$ vs. $51.0{\pm}18.8$ year), lower FVC($59.2{\pm}21.1$ vs. $77.6{\pm}23.3%$) and lower $FEV_1$($41.4{\pm}18.8$ vs. $61.l{\pm}23.30%$), and longer total ventilation time ($255.0{\pm}236.3$ vs. $98.1{\pm}120.4$ hour) (p<0.05) compared with the survival group (PFT: best value of recent 1 year). At MICU admission, there were no significant differences in vital signs, $PaCO_2$, $PaO_2/FiO_2$, and $AaDO_2$, in both groups. However, on the second day of MICU, the death group had significantly more rapid pulse rate ($121.6{\pm}22.3$ vs. $105.2{\pm}19.4$ rate/min), elevated $PaCO_2$ ($50.1{\pm}16.5$ vs. $41.8{\pm}12.2 mm Hg$), lower $PaO_2/FiO_2$, ($160.8{\pm}59.8$ vs. $256.6{\pm}78.3 mm Hg$), higher $AaDO_2$ ($181.5{\pm}79.7$ vs. $98.6{\pm}47.9 mm Hg$), and higher APACHE III score ($57.6{\pm}21.1$ vs. $20.3{\pm}13.2$) than survival group (p<0.05). The death group had more frequently associated with pneumonia and anoxic brain damage at admission, and had more frequently developed sepsis during disease progression than the survival group (p<0.05). Multi-variate analysis using APACHE III score and $PaO_2/FiO_2$, ratio on first and second day, age, sex, and pneumonia combined at admission revealed that APACHE III score (40) and $PaO_2/FiO_2$ ratio (<200) on second day were regarded as predictive factors for the mortality of fatal asthma (p<0.05). Conclusions: APACHE III score ($\geq$40) and $PaO_2/FiO_2$ ratio (<200) on the second day of MICU, which might reflect the response of treatment, rather than initially presented clinical parameters would be more important predictable factors of mortality in patients with FA.

• Radiation Oncology Journal
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• v.16 no.4
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• pp.409-423
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• 1998

Purpose : This retrospective study was tried to evaluate the clinical characteristics of patients, patterns of failure, survival rates, prognostic factors affecting survival, and treatment related toxicities when non-small cell lung cancer patients was treated by definitive radiotherapy alone or combined with chemotherapy. Materials and Methods : We evaluated the treatment results of 70 patients who were treated by definitive radiation therapy for non-small cell lung cancer at the Department of Radiation Oncology, Ewha Womans University Hospital, between March 1982 and April 1996. The number of patients of each stage was 2 in stage I, 6 in stage II, 30 in stage III-A, 29 in stage III-B, 3 in stage IV. Radiation therapy was administered by 6 MV linear accelerator and daily dose was 1.8-2.0 Gy and total radiation dose was ranged from 50.4 Gy to 72.0 Gy with median dose 59.4 Gy. Thirty four patients was treated with combined therapy with neoadjuvant or concurrent chemotherapy and radiotherapy, and most of them were administered with the multi-drug combined chemotherapy including etoposide and cisplatin. The survival rate was calculated with the Kaplan-Meier methods. Results : The overall 1-year, 2-year, and 3-year survival rates were 63$\%$, 29$\%$, and 26$\%$, respectively. The median survival time of all patients was 17 months. The disease-free survival rate for 1-year and 2-year were 23$\%$ and 16$\%$, respectively. The overall 1-year survival rates according to the stage was 100$\%$ for stage I, 80$\%$ for stage II, 61$\%$ for stage III, and 50$\%$ for stage IV. The overall 1-year 2-year, and 3-year survival rates for stage III patients only were 61$\%$, 23$\%$, and 20$\%$, respectively. The median survival time of stage III patients only was 15 months. The complete response rates by radiation therapy was 10$\%$ and partial response rate was 50$\%$. Thirty patients (43$\%$) among 70 patients assessed local control at initial 3 months follow-up duration. Twenty four (80$\%$) of these 30 Patients was possible to evaluate the pattern of failure after achievement of local control. And then, treatment failure occured in 14 patients (58$\%$): local relapse in 6 patients (43$\%$), distant metastasis in 6 patients (43$\%$) and local relapse with distant metastasis in 2 patients (14$\%$). Therefore, 10 patients (23$\%$) were controlled of disease of primary site with or without distant metastases. Twenty three patients (46$\%$) among 50 patients who were possible to follow-up had distant metastasis. The overall 1-year survival rate according to the treatment modalities was 59$\%$ in radiotherapy alone and 66$\%$ in chemoirradiation group. The overall 1-year survival rates for stage III patients only was 51$\%$ in radiotherapy alone and 68$\%$ in chemoirradiation group which was significant different. The significant prognostic factors affecting survival rate were the stage and the achievement of local control for all patients at univariate- analysis. Use of neoadjuvant or concurrent chemotherapy, use of chemotherapy and the achievement of local control for stage III patients only were also prognostic factors. The stage, pretreatment performance status, use of neoadjuvant or concurrent chemotherapy, total radiation dose and the achievement of local control were significant at multivariate analysis. The treatment-related toxicities were esophagitis, radiation pneunonitis, hematologic toxicity and dermatitis, which were spontaneously improved, but 2 patients were died with radiation pneumonitis. Conclusion : The conventional radiation therapy was not sufficient therapy for achievement of long-term survival in locally advanced non-small cell lung cancer. Therefore, aggressive treatment including the addition of appropriate chemotherapeutic drug to decrease distant metastasis and preoperative radiotherapy combined with surgery, hyperfractionation radiotherapy or 3-D conformal radiation therapy for increase local control are needed.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.237-246
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• 2004

Purpose: To investigate the effects of radiation dose-escalation on the treatment outcome, complications and the other prognostic variables for glioblastoma patients treated with 3D-conformal radiotherapy (3D-CRT). Materials and Methods: Between Jan 1997 and July 2002, a total of 75 patients with histologically proven diagnosis of glioblastoma were analyzed. The patients who had a Karnofsky Performance Score (KPS) of 60 or higher, and received at least 50 Gy of radiation to the tumor bed were eligible. All the patients were divided into two arms; Arm 1, the high-dose group was enrolled prospectively, and Arm 2, the low-dose group served as a retrospective control. Arm 1 patients received $63\~70$ Gy (Median 66 Gy, fraction size $1.8\~2$ Gy) with 3D-conformal radiotherapy, and Arm 2 received 59.4 Gy or less (Median 59.4 Gy, fraction size 1.8 Gy) with 2D-conventional radiotherapy. The Gross Tumor Volume (GTV) was defined by the surgical margin and the residual gross tumor on a contrast enhanced MRI. Surrounding edema was not included in the Clinical Target Volume (CTV) in Arm 1, so as to reduce the risk of late radiation associated complications; whereas as in Arm 2 it was included. The overall survival and progression free survival times were calculated from the date of surgery using the Kaplan-Meier method. The time to progression was measured with serial neurologic examinations and MRI or CT scans after RT completion. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group neurotoxicity scores. Results: During the relatively short follow up period of 14 months, the median overall survival and progression free survival times were $15{\pm}1.65$ and $11{\pm}0.95$ months, respectively. The was a significantly longer survival time for the Arm 1 patients compared to those in Arm 2 (p=0.028). For Arm 1 patients, the median survival and progression free survival times were $21{\pm}5.03$ and $12{\pm}1.59$ months, respectively, while for Arm 2 patients they were $14{\pm}0.94$ and $10{\pm}1.63$ months, respectively. Especially in terms of the 2-year survival rate, the high-dose group showed a much better survival time than the low-dose group; $44.7\%$ versus $19.2\%$. Upon univariate analyses, age, performance status, location of tumor, extent of surgery, tumor volume and radiation dose group were significant factors for survival. Multivariate analyses confirmed that the impact of radiation dose on survival was independent of age, performance status, extent of surgery and target volume. During the follow-up period, complications related directly with radiation, such as radionecrosis, has not been identified. Conclusion: Using 3D-conformal radiotherapy, which is able to reduce the radiation dose to normal tissues compared to 2D-conventional treatment, up to 70 Gy of radiation could be delivered to the GTV without significant toxicity. As an approach to intensify local treatment, the radiation dose escalation through 3D-CRT can be expected to increase the overall and progression free survival times for patients with glioblastomas.