• The Korean Journal of Nuclear Medicine
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• v.38 no.4
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• pp.294-299
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• 2004

Purpose: Both human NIS and mutant $D_2R$ transgenes are proposed as reporting system in transplanted cell tracking. Using hepatoma cell lines, we constructed a dual reporter system containing human sodium-iodide symporter (hNIS) and dopamine 2 receptor ($D_2R$) and compared its characteristics. Materials and Methods: The recombinant plasmid ($pIRES-hNIS/D_2R$) was constructed with IRES (internal ribosome entry site) under control of the CMV promoter $pIRES-hNIS/D_2R$ was transfected to human hepatoma SK-Hep1 cell line with lipofectamine. HEP-ND ($SK-Hep1-hNIS/D_2R$) cells stably expressing hNIS and $D_2R$ was established by selection with G418 for two weeks. RT-PCR was performed to investigate the expression of both hNIS and $D_2R$ genes. The expressions of hNIS and $D_2R$ were measured by $^{125}I$ uptake assays and receptor binding assays. Specific binding of $D_2R$ to $[^3H]spiperone$ was verified by Scatchard plot with (+) butaclamol as a specific inhibitor. $K_d\;and\;B_{max}$ values were estimated. The correlation between hNIS and $D_2R$ expression was compared by using each clone. Results: Similar quantities of hNIS and $D_2R$ genes were expressed on HEP-ND as RT-PCR assays. HEP-ND cells showed 30 to 40 fold higher radioiodine uptakes than those of parental SK-Hep1 cells. $^{125}I$ uptake in HEP-ND cells was completely inhibited by $KClO_4$, a NIS inhibitor Specific binding to HEP-ND cells was saturable and the $K_d\;and\;B_{max}$ values for HEP-ND cells were 2.92 nM, 745.25 fmol/mg protein and 2.91nM, 1323 fmole/mg protein in two clones, respectively. The radioiodine uptake by hNIS activity and $D_2R$ binding was highly correlated. Conclusion: We developed a dual positron and gamma imaging reporter system of hNIS and $D_2R$ in a stably transfected cell line. We expect that $D_2R$ and hNIS genes can complement mutually as a nuclear reporting system or that $D_2R$ can be used as reporter gene when hNIS gene were used as a treatment gene.

• The Korean Journal of Nuclear Medicine
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• v.38 no.4
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• pp.300-305
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• 2004

Purpose: We underwent this study to evaluate the factors which influence labeling efficiency when modified in vivo erythrocyte labeling technique was used. Materials and methods: Thirty healthy volunteers (M:F=19:11, age:$25{\pm}2$ yrs) were enrolled in this study. Totally, two hundred ten samples were obtained from them. The 1 mg of stannous pyrophosphate was injected intravenously at the beginning of labeling. After suitable tinning time (5 min, 20 min, 35 min) passed by, blood (5 mL, 3 mL or 1 mL) was withdrawn into 10 mL syringe previously containing Tc-99m (740 MBq) and anticoagulant (heparin, ACD or CPDA) through 19-gauged scalp needle. The generator ingrowth time of Tc-99m was within 24 hrs in each case. The blood samples were placed on rotating invertor during incubation (10 min, 25 min, 40 min) but some of them were not. Immediately after the conclusion of incubation, the labeled blood specimens to analyze were centrifuged. and then %Unbound Tc-99m was calculated. Statical analysis was used paired T-test and one way ANOVA with SPSS 10.0. Results: The binding efficiency at 1 mL of blood volume was $73{\pm}32%,\;91{\pm}10%$ at 3 mL and $96{\pm}7%$ at 5 mL (p<0.01). The binding efficiency at 5 min of tinning time was $45{\pm}23%,\;98{\pm}6%$, at 20 min and $97{\pm}8%$ at 35 min (p<0.001). The binding efficiency at 10 min of incubation time was $96{\pm}7%,\;95{\pm}12%$ at 25 min and $98{\pm}3%$ at 40 min (p>0.05). The binding efficiency in case of using rotating invertor was $96{\pm}7%$ and the binding efficiency in case of not using it was $87{\pm}18%$ (p>0.05). There was no significant difference between them. In binding efficiency according to kinds of anticoagulants, ACD was $98{\pm}4%$, CPDA was $97{\pm}6%$ and heparin was $89{\pm}20%$ (p<0.001). Conclusion: When modified in vivo erythrocyte labeling technique is used with Tc-99m, the methods to obtain the highest labeling efficiency are as follow. The withdrawing blood volume should be over 3 mL, tinning time should be kept between 20 min and 35 min, and incubation time should be kept between 10 min and 40 min. ACD or CPDA have to be used as a anticoagulant except heparin and the blood samples should be placed on rotating invertor during incubation.

• Pediatric Infection and Vaccine
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• v.9 no.2
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• pp.163-174
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• 2002

Background : To delineate the changes in the causative agents of neonatal sepsis and their antimicrobial susceptibilities in the neonatal intensive care unit and nursery of Hanyang University Hospital during the past 10 years. Methods : Hospital records of 15,144 patients hospitalized at the NICU and nursery of Hanyang University Hospital from 1989 to 1998 were reviewed and neonates diagnosed of neonatal sepsis were sorted and included in the study. The study period was divided into Period A(the first 5 years) and Period B(the second 5 years) to analyse causative agents and their antimicrobial susceptibilities. Results : Neonatal sepsis was diagnosed in 170 patients(1.1%{Period A 1.2%, Period B 1.0%}) among the total of 15,144 inpatients. Two hundred isolates(Period A 109 isolates, Period B 91 isolates) were identified in 186 blood cultures(Period A 99 cultures, Period B 87 cultures) from 170 patients(Period A 91 patients, Period B 79 patients). The average age at the onset of the disease, when the initial blood culture was drawn, was 12.3 days old(Period A 8.8 days, Period B 16.3 days), and the proportion of the early onset disease was 34.7% in Period A and 23.0% in Period B, indicating that neonatal sepsis developed earlier during Period A. Among the isolated organisms including Gram positive bacteria[132(66.0%)], Gram negative bacteria [60(30.0%)], and fungi[8(4.0%)], coagulase negative Staphylococcus(CNS) was the most common organism(69/34.5%), followed by Staphylococcus aureus(36/18.0%), Klebsiella pneumoniae(17/8.5%), Enterococcus(12/6.0%), Enterobacter cloacae(8/4.0%), Escherichia coli(6/3.0%), and Pseudomonas aeruginosae(5/2.5%). The isolated fungi were Candida parapsilosis, Candida albicans, and Trichosporon pullulans. CNS, S. aureus and Acinetobacter baumannii were isolated more frequently in Period A compared to Period B. Antimicrobial susceptibilities of CNS and S. aureus to methicillin and the first generation cephalo sporins were decreased in Period B compare to Period A, those to aminoglycosides were increased in Period B, and vancomycin resistant strains were not identified. K. pneumoniae, Enterococcus, E. coli, and P. aeruginosa were isolated less frequently in Period B, compared to Period A. For K. pneumoniae, antimicrobial susceptibilities to the first generation cephalosporins were low in both Periods A and B, those to tobramycin and gentamicin were increased in Period B, and those to amikacin, ceftriaxone, and trimethoprim-sulfamethoxazole were high in both Periods A and B. Antimicrobial susceptibilities of Enterococcous to ampicillin, penicillin, and the first generation cephalosporins were decreased in Period B, but vancomycin resistant strains were not identified. Conclusion : The occurrence rate of neonatal sepsis during the past 10 years in the NICU and nursery of the Hanyang University hospital was 1.1%, and the most common causitive agents were CNS and S. aureus, to which the antimicrobial susceptibilities to the first line drugs decreased in the later half of the study period with no vancomycin resistant isolates identified. Group B Streptococcus known to be the most common agent causing neonatal sepsis was not identified, and K. pneumoniae was isolated more commonly during the later half of the study period without decreased antimicrobial susceptibilities.

• Pediatric Infection and Vaccine
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• v.11 no.2
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• pp.158-169
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• 2004

Purpose : Although influenza is one of the most important cause of acute respiratory tract infections in children, virus isolation is not popular and there are only a few clinical studies on influenza and diagnostic methods. We evaluated the epidemiological and clinical features of influenza in children and rapid antigen detection test(QuickVue influenza test) on fist half of the year 2004 in Busan. Methods : From January 2004 to June 2004, throat swab and nasal secretion were obtained and cultured for the isolation of influenza virus and tested by rapid antigen detection test(QuickVue influenza test) in children with suspected influenza infections. The medical records of patients with influenza virus infection were reviewed retrospectively. Results : Influenza viruses were isolated in 79(17.2%) out of 621 patients examined. Influenza virus was isolated mainly from March to April 2004. The ratio of male and female with influenza virus infection was 1.2 : 1 with median age of 4 years 6month. The most common clinical diagnosis of influenza virus infection was bronchitis. There was no difference between influenza A and B infection in clinical diagnosis and symptoms. All patients recovered without severe complication. The sensitivity obtained for rapid antigen detection test (QuickVue influenza test) was 93.6% and the specificity was 80.2%, the positive predictive value 40.8%, the negative predictive value 98.8%. Conclusion : With rapid antigen detection test, it is possible early detection of influenza in children. reduction in use of antimicrobial agent and early use of antiviral agent.

• Childhood Kidney Diseases
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• v.8 no.1
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• pp.18-25
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• 2004

Purpose : Alport syndrome is clinically characterized by hereditary progressive nephritis causing ESRD with irregular thickening of the GBM and sensory neural hearing loss. The mutations of type IV collagen gene(COL4A5) located on the long arm of X chromosome is considered responsible for most of the structural abnormalities in the GBM of Alport patients. Since no definite clinical prognostic predictor has been reported in the disease yet, we designed this study to evaluate the significance of genetic polymorphism of the angiotensin converting enzyme in children with Alport syndrome as a prognostic factor for disease progression. Methods : ACE I/D genotype were examined by PCR amplification of the genomic DNA in 12 patients with Alport syndrome and 12 of their family members. Alport patients were divided into two groups; the conservative group, those who had preserved renal function for more than 10 years of age, the early CRF group, those who had progressed to CRF within 10 years of age. Results : The mean age of onset was $3.45{\pm}2.4$ years in the conservative group, $4.4{\pm}1.2$ years in the early CRF group. Sex ratios were 5:3 and 2:1 in each group. Among 12 cases of patients, 4 cases were in early CRF group and their mean duration of onset to CRF was 4.5 yews(8.9 years of age). Eight patients(67%) were in the conservative group and they had normal renal function for more than 10 years of age(mean duration of renal preservation was 10.6 years). The incidence of II type ACE gene were in 25.0%(3 cases), ID type in 41.7%(5 cases), DD type in 33.3%(4 cases). There was no significant difference between Alport patient and normal control(II type 44.3%, ID type 40.9%, DD type 14.8%). The incidence of DD type of early CRF group were higher than that of the conservative group(75% vs 12.5%)(p<0.05). There was no difference in ACE gene polymorphism between normal Alport family members and control group. Conclusion : Even though there was no significant difference of ACE polymorphism between Alport patients and the normal control group, the incidence of DD type is significantly increased in early CRF group which means DD type of ACE polymorphism has a possibility of being a predictor for early progression to CRF in Alport patients.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.316-322
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• 2002

Objective : A retrospective study was peformed to evaluate whether postoperative adjuvant radiotherapy can improve survival and decrease recurrence as compared with surgery alone in resected esophageal cancer. Materials and Methods : From Jan. 1985 to Dec. 1993, among 94 esophageal cancer Patients treated with surgery, fifty-one patients were included in this study. Transthoracic esophagectomy was peformed in 35 patients and transhiatal esophagectomy in 16. Postoperative adjuvant radiotherapy was peformed 4 weeks after surgery in 26 among 38 patients in stage II and III. A total dose of $30\~60\;Gy$ in 1.8 Gy daily fraction, median 54 Gy over 6 weeks, was delivered in the mediastinum+both supraclavicular lymph nodes or celiac lymph nodes according to the tumor location. Forty-seven patients$(92\%)$ had squamous histology. The median follow-up period was 38 months. Results : The overall 2-year and 5-year survival and median survival were $56.4\%,\;36.8\%$ and 45 months. Two-year and 5-year survival and median survival by stage were $92\%,\;60.3\%$ for stage I, $63\%,\;42\%$ and 51 months for stage II and $34\%,\;23\%$ and 19 months for stage III (p=0.04). For stage II and III patients, 5-year survival and median survival were $22.8\%$, 45 months for the surgery alone group and $37.8\%$, 22 months for the postoperative RT group (p=0.89). For stage III patients, 2-year survival and median survival were $0\%$, 11 months for the surgery alone group and $36.5\%$, 20 months for the postoperative RT group (p=0.14). Local and distant failure rates for stage II and III were $50\%,\;16\%$ for the surgery alone and $39\%,\;31\%$ for the postoperative RT group. For N1 patients, local failure rate was $71\%$ for the surgery alone group and $37\%$ for the postoperative RT group (p=0.19). Among 10 local failures in the postoperative RT group, in-field failures were 2, marginal failures 1, out-field 5 and anastomotic site failures 2. Conclusion : There were no statistically significant differences in either the overall survival or the patterns of failure between the surgery alone group and the postoperative RT group for resected stage II and III esophageal cancer. But this study showed a tendency of survival improvement and decrease in local failure when postoperative RT was peformed for stage III or N1 though statistically not significant. To decrease local failure, a more generous radiation field encompassing the supraclavicular, mediastinal, and celiac lymph nodes and anastomotic site in postoperative adjuvant treatment should be considered.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.343-352
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• 2002

Purpose : Radiotherapy is the main treatment modality for uterine cervix cancer. Since the rectum is in the radiation target volume, rectal bleeding is a common late side effect. This study evaluates the risk factors of radiation induced rectal bleeding and discusses its optimal management. Materials and Methods : total of 213 patients who completed external beam radiation therapy (EBRT) and intracavitary radiation (ICR) between September 1994 and December 1999 were included in this study. No patient had undergone concurrent chemo-radiotherapy. Ninety patients received radiotherapy according to a modified hyperfractionated schedule. A midline block was placed at a pelvic dose of between 30.6 Gy to 39.6 Gy. The total parametrial dose from the EBRT was 51 to 59 Gy depending on the extent of their disease. The Point A dose from the HDR brachytherapy was 28 Gy to 30 Gy $(4\;Gy\times7,\;or\;5\;Gy\times6)$. The rectal point dose was calculated either by the ICRU 38 guideline, or by anterior rectal wall point seen on radiographs, with barium contrast. Rectal bleeding was scored by the LENT/SOMA criteria. For the management of rectal bleeding, we opted for observation, sucralfate enema or coagulation based on the frequency or amount of bleeding. The median follow-up period was 39 months $(12\~86\;months)$. Results : The incidence of rectal bleeding was $12.7\%$ (27/213); graded as 1 in 9 patients, grade 2 in 16 and grade 3 in 2. The overall moderate and severe rectal complication rate was $8.5\%$. Most complications $(92.6\%)$ developed within 2 years following completion of radiotherapy (median 16 months). No patient progressed to rectal fistula or obstruction during the follow-up period. In the univariate analysis, three factors correlated with a high incidence of bleeding an icruCRBED greater than 100 Gy $(19.7\%\;vs.\;4.2\%)$, an EBRT dose to the parametrium over 55 Gy $(22.1\%\;vs.\;5.1\%)$ and higher stages of III and IV $(31.8\%\;vs.\;10.5\%)$. In the multivariate analysis, the icruCRBED was the only significant factor (p>0.0432). The total parametrial dose from the EBRT had borderline significance (p=0.0546). Grade 1 bleeding was controlled without further management (3 patients), or with sucralfate enema 1 to 2 months after treatment. For grade 2 bleeding, sucralfate enema for 1 to 2 months reduced the frequency or amount of bleeding but for residual bleeding, additional coagulation was peformed, where immediate cessation of bleeding was achieved (symptom duration of 3 to 10 months). Grade 3 bleeding lasted for 1 year even with multiple transfusions and coagulations. Conclusion : Moderate and several rectal bleeding occurred in $8.5\%$ of patients, which is comparable with other reports. The most significant risk factor for rectal bleeding was the accumulated dose to the rectum (icruCRBED), which corrected with consideration to biological equivalence. Prompt management of rectal bleeding, with a combination of sucralfate enema and coagulation, reduced the duration of the symptom, and minimized the anxiety/discomfort of patients.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.334-342
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• 2002

Purpose : The aim of this study was to determine if postoperative adjuvant chemotherapy (CT) alone and concurrent chemoradiation (CCRT), following radical surgery, improved the disease free survival (DFS) and overall survival (OS) in rectal cancer AJCC stage II and III patients. Materials and Methods : A total of 144 patients with AJCC stage II and III rectal cancer who had had radical surgery between 1989 and 1999 were included in the study. Of these patients, 72 had been treated with postoperative CT, and the other 72 with postoperative CCRT. The chemotherapy regimen consisted of oral UFT on a daily basis for $1\~12$ months (median 12 months) or 5-FU ($500\;mg/m^2$ for 5 days) intravenous (IV) chemotherapy with 4 week intervals for $1\~18$ cycles (median 6 cycles). Radiation of 4,500 cGy was delivered to the surgical bed and regional pelvic lymph nodes area, followed by $540\~1,440\;cGy$ (median 540 cGy) boost to the surgical bed. The follow-up period ranged from 20 to 150 months, with a median of 44 months. Results : The 5-year OS was $60.9\%\;and\;68.9\%$ (p=0.0915), and the 5-year DFS was $56.1\%\;and\;63.8\%$ (p=0.3510) for postoperative CT and postoperative CCRT, respectively. In the stage nm patients, the 5-year OS was $71.1\%\;and\;92.2\%$, and the 5-year DFS was $57.3\%\;and\;85.4\%$ for postoperative CT and CCRT, respectively. The OS was significantly improved (p=0.0379) but the DFS was not with postoperative CCRT compared to the postoperative CT (p=0.1482). In the stage III patients, the 5-year OS was $52.0\%\;and\;55.0\%$, and the 5-year DFS was $47.8\%\;and\;49.8\%$ for postoperative CT and postoperative CCRT. There were no statistically significant differences between postoperative CT and CCRT (p=0.4280 and p=0.7891) in OS and DFS. The locoregional relapses were $16.7\%\;and\;12.5\%$ for postoperative CT and CCRT, respectively. The distant relapses were $25.0\%\;and\;26.4\%$ for postoperative CT and CCRT, respectively. Conclusion : These results showed that postoperative CCRT compared with CT alone improved OS in stage II patients. Although there was no statistical significance, the addition of postoperative RT to CT reduced locoregional relapses compared to CT alone.

• Radiation Oncology Journal
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• v.15 no.4
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• pp.369-377
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• 1997

Purpose : This study was Performed to identify the histopathologic feature by the reevaluation of the Pathologic specimen of the cervical tumors and to evaluate the clinical findings and the treatment results of the patients with small cell carcinoma of the cervix treated by radiotherapy. Materials and Methods : 2890 patients with cervical carcinoma received radiotherapy at the Department of Radiation Oncology. Yonsei Cancer Center, Yonsei University College of Medicine between October 1981 and April 1995. Of the 2890 patients in this data base, sixty were found to have small cell carcinomas $(2.08\%)$. Among them thirty six patients were transferred from other hospitals. the biopsy specimens of those Patients were not available. So we could review the slides of the other twenty four patients who were diagnosed at our hospital. Twenty four patients with small cell carcinoma of the cervix were analyzed retrospectively based on the assessment of H & E staining and other four immunohistochemical stains for neuroendocrine differentiation (neuron specific enolase, chromogranin. synaptophysin and Grimelius stain). And we also evaluate the Patients and tumor characteristics. response to radiation. patterns of failures, 5 year overall and disease free survival rates. Results : Thirteen tumors were neuroendocrine carcinomas(13/24 = $54.2\%$) and eleven tumors were squamous carcinomas, small cell type (11/24 = $47.8\%$) based on the assessment of H & E staining and other four neuroendocrine marker studies. So we classified the Patients two groups as neuroendocrine carcinoma and small cell type of squamous carcinoma, Among the 13 neuroendocrine carcinomas, five were well to moderately differentiated tumors and the other eight were Poorly differentiated or undifferentiated ones. The median age was 54 years old (range 23-79 years). Eight Patients had FIGO stage IB disease, 12 had stage 11, 3 had stage III and one had stage IV disease, Pelvic lymph node metastases were found in five Patients $(20.8\%)$. three of them were diagnosed by surgical histologic examination and the other two were diagnosed by CT scan. There was no difference between two histopathologic groups in terms of patients and tumor characteristics. response to radiation. 5 year overall and disease free survival rates. However the distant metastases rate was higher in neuroendocrine carcinoma Patients (6/13:$46.2\%$) than in small cell type of squamous carcinoma Patients (2/11:$18.2\%$), but there was no statistically significant difference because of the small number of patients (P>0.05). Conclusion : More than half of the small cell carcinoma of the cervix patients were neuroendocrine carcinoma (13/24 : $54.1\%$) by reevaluation of the biopsy specimen of the cervical tumors. The tendency of distant metastases of the neurolndocrine carcinoma was greater than those of the small cell type of squamous carcinoma $(46.2\%\;vs.\;18.2\%)$. But there were no differences in the patients and tumor characteristics and other clinical treatment results in both groups. These data suggest that radical local treatment such as radiotherapy or radical surgery combined with combination systemic cytotoxic chemotherapy might provide these patients with the best chance for cure.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.295-301
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• 1993

Since Jan. 1991 a prospective randomized study for Stage III unresectable non small cell lung cancer (NSCLC) has been conducted to evaluate the response rate and tolerance of induction chemotherapy with MVP followed by hyperfractionated radiotherapy and evaluate the efficacy of maintenance chemotherapy in Asan Medical Center. All patients in this study were treated with hyperfractionated radiotherapy (120 cGy/fx BID, 6480 cGy/54 fx) following 3 cycles of induction chemotherapy, MVP (Mitomycin C 6 $mg/m^2,$ Vinblastin 6 $mg/m^2,$ Cisplatin 60 $mg/m^2$) and then the partial and complete responders from induction chemotherapy were randomized to 3 cycles of adjuvant MVP chemotherapy group and observation group. 48 patients were registered to this study until December 1992; among 48 patients 3 refused further treatment after induction chemotherapy and 6 received incomplete radiation therapy because of patient's refusal, 39 completed planned therapy. Twenty-three $(58\%)$ patients including 2 complete responders showed response from induction chemotherapy. Among the 21 patients who achieved a partial response after induction chemotherapy,1 patient rendered complete clearance of disease and 10 patients showed further regression of tumor following hyperfractionated radiotherapy. Remaining 10 patients showed stable disease or progression after radiotherapy. Of the sixteen patients judged to have stable disease or progression after induction chemotherapy, seven showed more than partial remission after radiotherapy but nine showed no response in spite of radiotherapy. Of the 39 patients who completed induction chemotherapy and radiotherapy, 25 patients $(64\%)$ including 3 complete responders showed more than partial remission. Nineteen patients were randomized after radio-therapy. Nine Patients were allocated to adjuvant chemotherapy group and 4/9 showed further regression of tumor after adjuvant chemotherapy. For the time being, there is no suggestion of a difference between the adjuvant chemotherapy group and observation group in distant metastasis rate and survival. Median survival time was 13 months. Actuarial survival rates at 6,12 and 18 months of 39 patients who completed this study were $84.6\%,\;53.7\%\;and\;40.3\%,$ respectively. The partial and complete responders from induction chemotherapy showed significantly better survival than non-responders (p=0.028). Incidence of radiation pneumonitis in this study group was less than that in historical control group inspite of induction chemotherapy. All patients tolerated hypertractionated radiotherapy without definite increase of acute complications compared with conventional radiotherapy group. The longer follow up is needed to evaluate the efficacies of induction and maintenance chemotherapy and survival advantage by hyperfractionated radiotherapy but authors are encouraged with an excellent tolerance, higher response rate and improvement of one year survival rate in patients of this study.