• Radiation Oncology Journal
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• v.25 no.4
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• pp.242-248
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• 2007

Purpose: To study the effect of recombinant human epidermal growth factor (rhEGF) on oral mucositis induced by cisplatin and radiotherapy in a mouse model. Materials and Methods: Twenty-four ICR mice were divided into three groups-the normal control group, the no rhEGF group (treatment with cisplatin and radiation) and the rhEGF group (treatment with cisplatin, radiation and rhEGF). A model of mucositis induced by cisplatin and radiotherapy was established by injecting mice with cisplatin (10 mg/kg) on day 1 and with radiation exposure (5 Gy/day) to the head and neck on days $1{\sim}5$. rhEGF was administered subcutaneously on days -1 to 0 (1 mg/kg/day) and on days 3 to 5 (1 mg/kg/day). Evaluation included body weight, oral intake, and histology. Results: For the comparison of the change of body weight between the rhEGF group and the no rhEGF group, a statistically significant difference was observed in the rhEGF group for the 5 days after day 3 of. the experiment. The rhEGF group and no rhEGF group had reduced food intake until day 5 of the experiment, and then the mice demonstrated increased food intake after day 13 of the of experiment. When the histological examination was conducted on day 7 after treatment with cisplatin and radiation, the rhEGF group showed a focal cellular reaction in the epidermal layer of the mucosa, while the no rhEGF group did not show inflammation of the oral mucosa. Conclusion: These findings suggest that rhEGF has a potential to reduce the oral mucositis burden in mice after treatment with cisplatin and radiation. The optimal dose, number and timing of the administration of rhEGF require further investigation.

• Radiation Oncology Journal
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• v.26 no.2
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• pp.83-90
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• 2008

Purpose: For the first time, a nationwide survey of the Patterns of Care Study(PCS) for the various radiotherapy treatments of esophageal cancer was carried out in South Korea. In order to observe the different parameters, as well as offer a solid cooperative system, we compared the Korean results with those observed in the United States(US) and Japan. Materials and Methods: Two hundreds forty-six esophageal cancer patients from 21 institutions were enrolled in the South Korean study. The patients received radiation theraphy(RT) from 1998 to 1999. In order to compare these results with those from the United States, a published study by Suntharalingam, which included 414 patients[treated by Radiotherapy(RT)] from 59 institutions between 1996 and 1999 was chosen. In order to compare the South Korean with the Japanese data, we choose two different studies. The results published by Gomi were selected as the surgery group, in which 220 esophageal cancer patients were analyzed from 76 facilities. The patients underwent surgery and received RT with or without chemotherapy between 1998 and 2001. The non-surgery group originated from a study by Murakami, in which 385 patients were treated either by RT alone or RT with chemotherapy, but no surgery, between 1999 and 2001. Results: The median age of enrolled patients was highest in the Japanese non-surgery group(71 years old). The gender ratio was approximately 9:1(male:female) in both the Korean and Japanese studies, whereas females made up 23.1% of the study population in the US study. Adenocarcinoma outnumbered squamous cell carcinoma in the US study, whereas squamous cell carcinoma was more prevalent both the Korean and Japanese studies(Korea 96.3%, Japan 98%). An esophagogram, endoscopy, and chest CT scan were the main modalities of diagnostic evaluation used in all three countries. The US and Japan used the abdominal CT scan more frequently than the abdominal ultrasonography. Radiotherapy alone treatment was most rarely used in the US study(9.5%), compared to the Korean(23.2%) and Japanese(39%) studies. The combination of the three modalities(Surgery+RT+Chemotherapy) was performed least often in Korea(11.8%) compared to the Japanese(49.5%) and US(32.8%) studies. Chemotherapy(89%) and chemotherapy with concurrent chemoradiotherapy(97%) was most frequently used in the US study. Fluorouracil(5-FU) and Cisplatin were the most preferred drug treatments used in all three countries. The median radiation dose was 50.4 Gy in the US study, as compared to 55.8 Gy in the Korean study regardless of whether an operation was performed. However, in Japan, different median doses were delivered for the surgery(48 Gy) and non-surgery groups(60 Gy). Conclusion: Although some aspects of the evaluation of esophageal cancer and its various treatment modalities were heterogeneous among the three countries surveyed, we found no remarkable differences in the RT dose or technique, which includes the number of portals and energy beams.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.8 no.1
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• pp.21-30
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• 2005

Purpose: The aim of this study was to identify the clinical features and natural history of dietary protein induced proctocolitis (DPIPC) and to detect the causative foods of DPIPC, and to evaluate the effect of elimination of the foods on the course of the disease. Methods: Between March 2003 and July 2004, data from 30 consecutive patients with DPIPC who were followed for over 6 months, was reviewed. The diagnostic criterion used for DPIPC was an increase in the number of eosinophils in the lamina propria (${\geq}60per$ 10 high-power fields). In breast feeding mothers, 5 highly allergenic foods were eliminated from the maternal diet for 7 days, namely, allergenic food groups such as dairy products, eggs, nuts and soybean, fish and shellfish, and wheat and buckwheat. We observed the disappearance or appearance of hematochezia after elimination or challenge with the offending foods. Results: Before diagnosis infants were breast-fed (93.3%) or formula-fed (6.7%). Mean age at symptom onset was $11.5{\pm}5.1$ (5~24) weeks, and mean age at diagnosis was $17.8{\pm}9.5$ (8~56) weeks. Duration from symptom onset to diagnosis was $6.3{\pm}6.7$ (0~36) weeks. Mean peripheral blood eosinophil count was $478{\pm}320$ (40~1,790)/$mm^3$ and eosinophilia (> $250/mm^3$) was observedin 90.0% of patients. None of patients were found to have an increased serum IgE level. Of 15 patients that received sigmoidoscopy, nodular hyperplasia with erosion was observed in 93.3%. Of 27 patients whose mother ate the diet eliminated the 5 food groups, hematochezia diappeared in 74.1% of patients. Offending foods were identified as dairy products (37.5%), wheat and buckwheat (27.5%), fish and shellfish (20.0%), nuts and soybean (7.5%) and eggs (7.5%). A free maternal diet without patient's clinical symptoms was achieved at $29.4{\pm}8.7$ (9~44) weeks of patient's age, and a free baby diet without blood in stools was achieved at $37.5{\pm}9.7$ (12~56) weeks of age. Conclusion: DPIPC commonly occurs in exclusively breast-fed babies. Elimination of the above-mentioned 5 hyper-allergenic food groups from the maternal diet for 7days enables the detection of the offending foods. DPIPC is a transient disorder and 96.0% of patients can tolerate the offending foods at 12 months of age.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.763-773
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• 1996

Background : Behçet's syndrome is a chronic multisystemic disease affecting many organs such as skin, mucosa, eye, joint, central nervous system and blood vessels. Lung involvement occurs in 5% of Behçet's syndrome and is thought to be due to the pulmonary vasculitis leading to thromboembolism, aneurysm and arteriobronchial fistula. Pulmonary vasculitis in Behçet's syndrome is a unique clinical feature, differing from other vasculitis affecting the lung and is one of the major causes of death. Therefore, we examined the incidence, the clinical features, the radioloic findings and the clinical courses of the lung involvement in Behçet's syndrome. Methods: We retrospectively reviewed the medical records and radiologic studies of 10 cases of the lung involvement in Behçet's syndrome diagnosed at Yongdong Severance Hospital and Severance Hospital from 1986 to 1995. We analysed the clinical features, the radiological findings, the treatment modalities and the clinical courses. Results: 1) The incidence of the lung involvement in Behçet's syndrome was 2%(10/487). The male to female ratio was 8 : 2 and the mean age was 34 years. The presenting symptom was hemoptysis in 5 of 10 cases, and massive hemoptysis was noted in 2 cases. Other pulmonary symptoms were cough(6/10), dyspnea(4/10), and chest pain(2/10). Other manifestations were oral ulcers(10/10), genital ulcers(9/10), skin lesions(7/10), and eye lesions(6/10). 2) The laboratory findings were nonspecific. The posteroanterior views of chest radiographies showed multiple infiltrates(6/10), nodular or mass-like opacities(4/10), or normal findings(2/10). The chest CT scans showed multifocal consolidations(6/8), and aneurysms of the pulmonary aneries(4/8). The pulmonary angiographies were performed in 3 cases, and showed pulmonary artery aneurysms in 2 cases. The ventilation-perfusion scans in 2 cases of normal chest x-ray showed multiple mismatched findings. 3) The patients were treated with combination therapy consisting of corticosteroids, cyclophosphamide, and colchicine or anticoagulant agents. Surgical resection was performed in one case with a huge aneurysm. 4) We have followed up nine of ten cases. Three cases are well-being with medical therapy, two cases are severely disabled now and four cases died due to massive hemoptysis, massive pulmonary embolism, or sepsis. Conclusion : Pulmonary vasculitis is a main feature of the lung involvement of Behçet's syndrome, causing hemorrhage, aneurysmal formation, and/or thromboemboism. The lung involvement of Behçet's syndrome is uncommon but is one of the most serious prognostic factors of the disease. Therefore, an aggressive diagnostic work-up for early detection and proper treatment are recommended to improve the clinical course and the survival.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.33-44
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• 2003

Background : Mycobacterium avium complex(MAC) is the most common respiratory pathogen in nontuberculous mycobacterial pulmonary disease. This study described the clinical characteristics of the patients with pulmonary disease caused by MAC. Materials and Methods : The clinical characteristics of 24 patients with pulmonary disease caused by the MAC, who fulfilled the 1997 American Thoracic Society diagnostic criteria for nontuberculous mycobacterial pulmonary disease, were retrospectively analyzed. Results : Fourteen patients(58%) were male and the median age at diagnosis was 61 years(range 46-75). Of the 24 patients, 16(67%) had a M. intracellulare infection, 7(29%) had a M. avium infection and one patient was not identified. Coughing (92%) and sputum (88%) were most frequently observed symptoms. The sputum smear for acid-fast bacilli was positive in 17(71%) patients. Fourteen(58%) patients had the upper lobe cavitary form and 10(42%) patients had the nodular bronchiectatic form. In a comparison between the patients with the upper lobe cavitary form and those with the nodular bronchiectatic form, significant differences were found according to sex(male 86% vs. 20%, p=0.003), smoking history(79% vs. 10%, p=0.008), the presence of an underlying disease(64% vs. 20%, p=0.036), the pulmonary function(% forced vital capacity, median 71% vs. 88%, p=0.022; % forced expiratory volume in one second, median 69% vs. 89%, p=0.051) and bilateral disease at chest radiography(29% vs. 90%, p=0.005). The time from the onset of symptoms to diagnosis was longer in those with the nodular bronchiectatic form(median 72 months, range 8-132) than those with the upper lobe cavitary form(median 22 months, range 6-60) Conclusions : MAC pulmonary disease occurs in two distinct populations with two distinct clinical presentations. For a correct diagnosis of MAC pulmonary disease, knowledge of the diverse clinical and radiological findings is essential.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.57-70
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• 2003

Background : Small cell lung cancer represents approximately 20% of all carcinomas of the lung, and is recognized as having a poor long term outcome compared to non-small cell lung cancer. Therefore, this study investigated the prognostic factors in small cell lung cancer patients in order to improved the survival rate by using the proper therapeutic methods. Material and method : The clinical data from 394 patients who diagnosed with small cell lung cancer and treated from 1993 to 2001 at the Kosin University Gospel Hospital, were analyzed. Result : There were 314 male patients (79.7%), and 80 female patients (20.3%). The number of those with limited disease was 177 (44.9%), and the number of those with extensive disease was 217 (55.1%). Overall, 366 out of 394 enrolled patients had died. The median survival time was 215 days (95% CI : 192-237days). The disease stage, Karnofsky performance state, 5% body weight loss for the recent 3 months, chemotherapy regimens, and the additive chest radiotherapy were identified as being statistically significant factors for the survival time. The median survival times of the supportive care group, one anticancer therapy, and two or more treatment groups were 17 days, 211 days, and 419 day, respectively (p<0.001). These data emphasize the importance of anticancer treatment to improve survival time for patients. The group of concurrent chemoradiotherapy (30 patients) showed significantly longer survival time than the group given sequential chemoradiotherapy (55 patients) (528 days versus 373 days, p=0.0237). The favorable prognostic factors of laboratory study were groups of leukocyte =8,000/mm3, ALP=200 U/L, LDH=450 IU/L, NSE=15 ng/mL, s-GOT=40 IU/L. In extensive disease, there was no difference according to the number of metastatic site. However, the median survival time of patients with ipsilateral pleural effusion had longer than patients having other metastatic sites. According to the survey periods, three groups were divided into 1993-1995, 1996-1998, and 1999-2001. The median survival time was significantly prolonged after 1999 in comparison to previous groups (177 days, 194 days, 289 days, p=0.001, 0.002, respectively). Conclusion: Disease stage and 5% body weight loss for recent 3 months at diagnostic state were significant prognostic factors. In addition, the performance status, serum ALP, LDH, NSE, CEA levels also appear to be prognostic factors. The survival time of those patients with small cell lung cancer has been prologned in recent years. It was suggested that the used of the EP (etoposied and cisplatin) chemotherapy method and concurrent chemoradiotherapy for patients with a limited stage contributed to the improved survival time.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.275-282
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• 1998

Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.2
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• pp.99-110
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• 2008

Objectives: Preimplantation genetic diagnosis (PGD) has become an assisted reproductive technique for couples carrying genetic conditions that may affect their offspring. Osteogenesis imperfecta (OI) is an autosomal dominant disorder of connective tissue characterized by bone fragility and low bone mass. At least 95% of cases are caused by dominant mutations in the COL1A1 or COL1A2. In this study, we report on our experience clinical outcomes with 5 PGD cycles for OI in two couples. Methods: Before clinical PGD, we assessed the amplification rate and allele drop-out (ADO) rate of alkaline lysis and nested PCR protocol using heterozygous patient's single lymphocytes in the pre-clinical diagnostic tests for OI. We performed 5 cycles of PGD for OI by nested PCR for the causative mutation loci, COL1A1 c.2452G>A and c.3226G>A, in case 1 and case 2, respectively. The PCR products were analyzed by agarose gel electrophoresis, restriction fragment length polymorphism (RFLP) analysis with HaeIII restriction enzyme in the case 1 and direct DNA sequencing. Results: We confirmed the causative mutation loci, COL1A1 c.2452G>A in case 1 and c.3226G>A in case 2. In the pre-clinical tests, the amplification rate was 94.2% and ADO rate was 22.5% in case 1, while 98.1% and 1.9% in case 2, respectively. In case 1, a total of 34 embryos were analyzed and 31 embryos (91.2%) were successfully diagnosed in 3 PGD cycles. Eight out of 19 embryos diagnosed as unaffected embryos were transferred in all 3 cycles, and in the third cycle, pregnancy was achieved and a healthy baby was delivered without any complications in July, 2005. In case 2, all 19 embryos (100.0%) were successfully diagnosed and 4 out of 11 unaffected embryos were transferred in 2 cycles. Pregnancy was achieved in the second cycle and the healthy baby was delivered in March, 2008. The causative locus was confirmed as a normal by amniocentesis and postnatal diagnosis. Conclusions: To our knowledge, these two cases are the first successful PGD for OI in Korea. Our experience provides a further demonstration that PGD is a reliable and effective clinical techniques and a useful option for many couples with a high risk of transmitting a genetic disease.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.660-668
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• 1995

Background: It is said that tuberculous pleuritis responds well to anti-tuberculous drug in general, so no further aggressive therapeutic management is unnecesarry except in case of diagnostic thoracentesis. But in clinical practice, we often see some patients who need later decortication due to dyspnea caused by pleural loculation or thickening despite several months of anti-tuberculous drug therapy. Therefore, we want to know the clinical difference between a group who received decortication due to complication of tuberculous pleuritis despite of anti-tuberculous drug and a group who improved after 9 months of anti-tuberculous drug only. Methods: We reviewed 20 tuberculous pleuritis patients(group 1) who underwent decortication due to dyspnea caused by pleural loculation or severe pleural thickening despite of anti-tuberculous drug therapy for 9 or more months, and 20 other tuberculous pleuritis patients(group 2) who improved by anti-tuberculous drug only and had similar degrees of initial pleural effusion and similar age, sex distribution. Then we compared between the two groups the duration of symptoms before anti-tuberculous drug treatment and pleural fluid biochemistry like glucose, LDH, protein and pleural fluid cell count and WBC differential count, and we also wanted to know whether there was any difference in preoperative PFT value and postoperative PFT value in the patients who underwent decortication, and obtained following results. Results: 1) Group 1 patients had lower glucose level{$63.3{\pm}30.8$(mg/dl)} than that of the group 2{$98.5{\pm}34.2$(mg/dl), p<0.05}, and higher LDH level{$776.3{\pm}266.0$(IU/L)} than the group 2 patients{$376.3{\pm}123.1$(IU/L), p<0.05}, and also longer duration of symptom before treatment{$2.0{\pm}1.7$(month)} than the group 2{$1.1{\pm}1.2$(month), p<0.05}, respectively. 2) In group 1, FVC changed from preoperative $2.55{\pm}0.80$(L) to postoperative $2.99{\pm}0.78$(L)(p<0.05), and FEV1 changed from preoperative $2.19{\pm}0.70$(L/sec) to postoperative $2.50{\pm}0.69$(L/sec)(p<0.05). 3) There was no difference in pleural fluid protein level($5.05{\pm}1.01$(gm/dL) and $5.15{\pm}0.77$(gm/dl), p>0.05) and WBC differential count between group 1 and group 2. Conclusion: It is probable that in tuberculous pleuritis there is a risk of complication in the case of showing relatively low pleural fluid glucose or high LDH level, or in the case of having long duraton of symptom before treatment. We thought prospective study should be performed to confirm this.

• Tuberculosis and Respiratory Diseases
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• v.55 no.3
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• pp.250-256
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• 2003

Background : Anthracofibrosis, a descriptive term for multiple black pigmentation with fibrosis on bronchoscopic examination, has a close relationship with active tuberculosis (TB). However, TB activity is determined in the later stage by the TB culture results in some cases of anthracofibrosis. Therefore, it is necessary to identify early markers of TB activity in anthracofibrosis. There have been several reports investigating the serum levels of IL-2 $sR{\alpha}$, IFN-${\gamma}$ and TBGL antibody for the evaluation of TB activity. In the present study, we tried to measure the above mentioned serologic markers for the evaluation of TB activity in patients with anthracofibrosis. Methods : Anthracofibrosis was defined when there was deep pigmentation (in more than two lobar bronchi) and fibrotic stenosis of the bronchi on bronchoscopic examination. The serum of patients with anthracofibrosis was collected and stored under refrigeration before the start of anti-TB medication. The serum of healthy volunteers (N=16), patients with active TB prior to (N=22), and after (N=13), 6 month-medication was also collected and stored. Serum IL-2 $sR{\alpha}$, IFN-${\gamma}$ were measured with ELISA kit (R&D system, USA) and serum TBGL antibody was measured with TBGL EIA kit (Kyowa Inc, Japan). Results : Serum levels of IL-2 $sR{\alpha}$ in healthy volunteers, active TB patients before and after medication, and patients with anthracofibrosis were $640{\pm}174$, $1,611{\pm}2,423$, $953{\pm}562$, and $863{\pm}401$ pg/ml, respectively. The Serum IFN-${\gamma}$ levels were 0, $8.16{\pm}17.34$, $0.70{\pm}2.53$, and $2.33{\pm}6.67$ pg/ml, and TBGL antibody levels were $0.83{\pm}0.80$, $5.91{\pm}6.71$, $6.86{\pm}6.85$, and $3.22{\pm}2.59$ U/ml, respectively. The serum level of TBGL antibody was lower than of other groups (p<0.05). There was no significant difference of serum IL-2 $sR{\alpha}$ and IFN-${\gamma}$ levels among the four groups. Conclusion : The serum levels of IL-2 $sR{\alpha}$, IFN-${\gamma}$ and TBGL antibody were not useful in the evaluation of TB activity in patients with anthracofibrosis. More useful ways need to be developed for the differentiation of active TB in patients with anthracofibrosis.