• Radiation Oncology Journal
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• v.15 no.2
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• pp.121-128
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• 1997

Purpose : To evaluate the effect of postoperative adjuvant radiation therapy and chemotherapy on the survival, pattern of failure and complication for locally advanced rectal carcinoma Materials and Methods : From October 1992 to September 1995, twenty eight patients with rectal carcinoma were treated by postoperative adjuvant radiation therapy and chemotherapy Radiation therapy was delivered with 6MV and 15MV linear accelerator, 180c0y fractions 5 day per week. Total radiation doses were 5040cGy in $B_{2+3}$ and 5580cGy in $C_{2+3}$. Within 4 weeks after radical surgery. 5-FU$(400mg/m^2/day)\;and\;Leucovorin(20mg/m^2/day)$ were administered by intravenous injection for 4 days during the first and fifth week of radiation therapy. The median follow up was 19 months with a range 2 to 47 months. Results : The 2 year overall survival and disease free survival rates were $78.6\%\;and\;70.8\%$, respectively. The 2 year overall survival was $93.0\%\;in\;B_{2+3}$ and $76.2\%\;in\;C_{2+3}$(p=0.11) The 2 year disease free survival was $79.4\%\;in\;B_{2+3}\;and\;69.2\%\;in\;C_{2+3}(p=0.13)$. The overall failure rate was $21.42\%$(6/28) including $10.72\%$(3/28) locoregional recurrence, $3.62\%$(1/28) distant metastasis and $7.12\%$(2/28) locoregional recurrence with distant metastasis. The overall locoregional recurrence rate was $17.92\%$(5/28). The 2 year locoregional recurrence rates were $13.32\%(2/15)\;and\;23.12\%$(3/13) for respectively for $B_{2+3}\;and\;C_{2+3}$ The difference between the locoregional recurrence of $B_{2+3}\;and\;C_{2+3}$ patients was not significant(p=0.07). Complications developed in 13 patients$(46.42\%)$, including 8 dermatitis, 7 loose stool, 6 leukopenia, 4 tenesmus, 2 diarrhea. In Univariate analysis, there was no statistically significant factor except for tumor grade in locoregional recurrence, disease free survival and overall survival rate(p=0.04, 0.05, 0.04). Conclusion : This study sugges1s that postoperative adjuvant radiation therapy and chemotherapy is effective in patients with locally advanced rectal cancer. Therefore these results need to be confirmed with a long term follow-up and larger number of patients with the further clinical trials including prospective controlled studies.

• Radiation Oncology Journal
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• v.14 no.1
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• pp.1-8
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• 1996

Purpose: We tried to evaluate the role of conventional radiotherapy alone or with neoadjuvant chemotherapy in oropharyngeal cancer in terms of survival rates and to identify prognostic factors affecting survival by retrospective analysis. Materials and Methods: Forty seven patients of oropharyngeal cancer were treated by conventional radiotherapy in our hospital from Nov. 1985 to APr. 1993. Of these, twenty six patients were treated by conventional radio-therapy alone, and 21 patients with neoadjuvant chemotherapy of mostly two or more cycles of cisplatin and pepleomycin. The Patient characteristics of radiotherapy alone group and neoadjuvant chemotherapy group were not different generally. Radiotherapy was performed by 6MV-LINAC and the total radiation doses of Primary tumors were 54.0-79.2 Gy and cervical lymph nodes were 55.8-90.0 Gy with a fraction size of 1.8 or 2.0 Gy per day. The range of follow-up periods was 3-102 months and median was 20 months. The range of a9e was 33-79 years old and median was 58 years old. Results : Overall 3-year actuarial survival rate (3YSR) of all patients was $39\%$. The 3YSRS of stage I (n=5), II (n=11), III (n=12) and IV (n=19) were 60, 55, 33 and $32\%$, respectively The 3YSRS of Tl+2, T3+4 and No, N+ were 55, $18\%$ (p=0.005) and 43, $36\%$ (p>0.1), respectively. There was no difference in 3YSRS between radiotherapy alone group and neoadjuvant chemotherapy group (38 vs $43\%$, p>0.1). According to the original site of primary tumor, the 3YSRS of tonsil (n=32), base of tongue (n=8), soft palate or uvula (n=6) and pharyngeal wall (n=1) were 36 38, 67 and $0\%$, respectively The Patients of soft palate or uvular cancer had longer survival than other primaries but the difference was not significant statistically (p>0.1). Of 32 patients of tonsillar cancer, 22 Patients who had primary extension to adjacent tissue showed inferior survival rate to the ones who had not Primary extension, but the difference was marginally significant statistically (24 vs $60\%$, p=0.08). On Cox multivariate analysis in entire patients with variables of age, T stage, N stage, total duration of radiotherapy, the site of primary tumor and the use of neoadjuvant chemotherapy, only T stage was a significant Prognostic factor affecting 3YSR. Conclusion : The difference of 3YASRS of conventional radiotherapy alone group and neoadjuvant chemotherapy group was not significant statistically. These treatments could be effective in oropharyngeal cancer of early stage, especially such as soft palate, uvular or tonsillar cancer which did not extend to adjacent tissue. But in order to improve the survival of patients of most advanced oropharyngeal cancer, other altered fractionated radiotherapy such as hyperfractionation rather than conventional fractionation or multi-modal approach combining radiotherapy and accessible surgery or concurrent chemotherapy might be beneficial.

• Radiation Oncology Journal
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• v.27 no.3
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• pp.126-132
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• 2009

Purpose: We wanted to evaluate the prognostic factors for the pathologic N2 non-small cell lung cancer (NSCLC) patients who were treated by postoperative radiotherapy. Materials and Methods: We retrospectively reviewed 112 pN2 NSCLC patients who underwent surgery and postoperative radiotherapy (PORT) From January 1999 to February 2008. Seventy-five (67%) patients received segmentectomy or lobectomy and 37 (33%) patients received pneumonectomy. The resection margin was negative in 94 patients, and it was positive or close in 18 patients. Chemotherapy was administered to 103 (92%) patients. Nine (8%) patients received PORT alone. The median radiation dose was 54 Gy (range, 45 to 66), and the fraction size was 1.8~2 Gy. Results: The 2-year overall survival (OS) rate was 60.2% and the disease free survival (DFS) rate was 44.7% for all the patients. Univariate analysis showed that the patients with multiple-station N2 disease had significantly reduced OS and DFS (p=0.047, p=0.007) and the patients with an advanced T stage ($\geq$T3) had significantly reduced OS and DFS (p<0.001, p=0.025). A large tumor size ($\geq$5 cm) and positive lymphovascular invasion reduced the OS (p=0.035, 0.034). Using multivariate analysis, we found that multiple-station N2 disease and an advanced T stage ($\geq$T3) significantly reduced the OS and DFS. Seventy one patients (63.4%) had recurrence of disease. The patterns of failure were loco-regional in 23 (20.5%) patients, distant failure in 62 (55.4%) and combined loco-regional and distant failure in 14 (12.5%) patients. Conclusion: Multiple involvement of mediastinal nodal stations for the pN2 NSCLC patients with PORT was a poor prognostic factor in this study. A prospective study is necessary to evaluate the N2 subclassification and to optimize the adjuvant treatment.

• Radiation Oncology Journal
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• v.27 no.4
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• pp.181-188
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• 2009

Purpose: The aim of this study was to evaluate the results of postoperative radiotherapy in a case of perihilar cholagiocarcinoma by analyzing overall survival rate, patterns of failure, prognostic factors for overall survival, and toxicity. Materials and Methods: Between January 1998 and March 2008, 38 patients with perihilar cholangiocarcinoma underwent a surgical resection and adjuvant radiotherapy. The median patient age was 59 years (range, 28 to 72 years), which included 23 men and 15 women. The extent of surgery was complete resection in 9 patients, microscopically positive margins in 25 patients, and a subtotal resection in 4 patients. The tumor bed and regional lymphatics initially received 45 Gy or 50 Gy, but was subsequently boosted to a total dose of 59.4 Gy or 60 Gy in incompletely resected patients. The median radiotherapy dose was 59.4 Gy. Concurrent chemotherapy was administered in 30 patients. The median follow-up period was 14 months (range, 6 to 45 months). Results: The 3-year overall survival and 3-year progression free survival rates were 30% and 8%, respectively. The median survival time was 28 months. A multivariate analysis showed that differentiation was the only significant factor for overall survival. The 3-year overall survival was 34% in R0 patients and 20% in R1 patients. No statistically significant differences in survival were found between the 2 groups (p=0.3067). The first site of failure was local in 18 patients (47%). No patient experienced grade 3 or higher acute toxicity and duodenal bleeding developed in 2 patients. Conclusion: Our results suggest that adjuvant RT might be a significant factor in patients with a positive margin following a radical resection. However, there was still a high locoregional recurrence rate following surgery and postoperative radiotherapy. Further study is necessary to enhance the effect of the adjuvant radiotherapy.

• 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.

• Journal of Chest Surgery
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• v.39 no.10 s.267
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• pp.739-748
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• 2006

Background: The purpose of this study is to ascertain the neuroprotective effect of cyclosporin A on the 25-min surgical ischemia model in the spinal cords of rabbits with neuropathological correlation and histoimmunochemical analyses, Material and Method: Thirty-two New Zealand white rabbits were randomly divided into four groups: Rabbits were randomly divided into four groups: the control 12 group (n=8), the control 17 group (n=8), the cyclosporin Cs2 group (n=8), and the cyclosporin Cs7 group (n=8). The 12 group underwent a 25-min aortic cross- clamp without intervention and were sacrificed on the 2nd day postoperatively, while the 17 group underwent a 25- min of aortic cross-clamp without intervention and were sacrificed on the 7th day postoperatively. The Cs2 group received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed on the End day postoperatively, while the Cs7 group received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed on the 7th day postoperatively. The rabbits underwent 25-min surgical aortic cross-clamp. Neurologic functions were evaluated on the 2nd day and 7th postoperative day using Tarlov scoring system. After scoring neurologic function, all rabbits were sacrificed for histopathologic observation. Result: All rabbits survived the experimental procedure. The values of Tarlov score did not show any differences between the control and cyclosporin groups on the 2nd day. The scores of group Cs7 ($2.75{\pm}0.89$) were significantly higher than those of group 17 ($1.25{\pm}1.39$) on the 7th day (p<0,05). On the histologic exanminations, specimens of the spinal cord showed necrosis and apoptosis. The pathologic scores of group Cs7 ($1,0{\pm}0.53$) was less than those of group 17 ($2.13{\pm}1.36$, p<0.05). TUNEL staing showed apoptosis of the specimen in group 12 and Cs2 but there was no stastically significant difference between groups on the score. There were more overexpression of HSP70 and nNOS in cyclosporine group than in control group. Conclusion: We think that cyclosporin A may decrease neuronal cell death with induced upregulation of HSP70 against 25-min ischemia of the spiral cord in the rabbit.

• Journal of Chest Surgery
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• v.39 no.1 s.258
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• pp.18-27
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• 2006

Background: Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly, but is one of the most common causes of myocardial ischemia which would result in high mortality within the first year of life. This is our early result of the surgical management for these patients. Material and Method: From June 1989 to July 2003, 6 patients with ALCAPA and one patient with ARCAPA (Anomalous origin of the Right coronary artery from the pulmonary artery) underwent surgical repair. We have reviewed the all medical records, electrocardiogram, chest X-ray and echocardiography retrospectively. Result: Three of the patients were boys and four were girls. The median age at the operation was 5.4 months (Range: 3$\∼$33 months). The average body weight of at the operation was 6.7 kg (Range: 3.7$\∼$11.3 kg). A mean follow up period was 18 months. Only 3 patients were initially diagnosed as ALCAPA. And 3 patients had moderate mitral regurgitation. Immediate coronary artery reimplantation on diagnosis with the aim of restoring a two-coronary system circulation was done. The average bypass time was 114$\pm$37 minutes, and the average aortic cross clamping time was 55$\pm$22 minutes. The average stay of intensive care unit was 5$\pm$3 days, the mean mechanical ventilator time was 38$\pm$45 hours and the hospital stay after operation was 12$\pm$5 days. There were significant improvements in electrocardiogram and chest X-ray of the all patients except one late death patient. The ventricular function showed almost normal recovery after operation; the EF (Ejection Fraction) increased from 41.2$\pm$ 10.3$\%$ to 60.5$\pm$ 15.8$\%$ within 1 month and to 59.8$\pm$13.9$\%$ within 1 year after operation, the SF (Shortening Fraction) increased from 23.6$\pm$4.7$\%$ to 38.6$\pm$8.4$\%$ within 1 month and to 37.4$\pm$7.9$\%$ within 1 year after operation, LVEDDI (Left Ventricular End-diastolic Dimension Index) decreased from 100.8$\pm$25.6 mm/$m^{2}$ to 90.3$\pm$ 19.2 mm/$m^{2}$ within f month and to 79.3$\pm$ 15.8 mm/$m^{2}$ within 1 year after operation. Concomitant mitral repair was done in two patients with anterior mitral leaflet prolapse. In every patient, mitral valve showed less than mild regurgitation during follow up. One late death occurred in which patient Dor procedure was applied 10 months after initial operation due to the dilated cardiomyopathy Conclusion: In the management of this rare and could be fatal Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), early suspicion and correct diagnosis is of most important. But, after diagnosis, immediate restoration of 2 coronary systems could result in good outcome.

• 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.318-324
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• 2004

Purpose: Philips GEMINI is a newly introduced whole-body GSO PET/CT scanner. In this study, performance of the scanner including spatial resolution, sensitivity, scatter fraction, noise equivalent count ratio (NECR) was measured utilizing NEMA NU2-2001 standard protocol and compared with performance of LSO, BGO crystal scanner. Methods: GEMINI is composed of the Philips ALLEGRO PET and MX8000 D multi-slice CT scanners. The PET scanner has 28 detector segments which have an array of 29 by 22 GSO crystals ($4{\times}6{\times}20$ mm), covering axial FOV of 18 cm. PET data to measure spatial resolution, sensitivity, scatter fraction, and NECR were acquired in 3D mode according to the NEMA NU2 protocols (coincidence window: 8 ns, energy window: $409[\sim}664$ keV). For the measurement of spatial resolution, images were reconstructed with FBP using ramp filter and an iterative reconstruction algorithm, 3D RAMLA. Data for sensitivity measurement were acquired using NEMA sensitivity phantom filled with F-18 solution and surrounded by $1{\sim}5$ aluminum sleeves after we confirmed that dead time loss did not exceed 1%. To measure NECR and scatter fraction, 1110 MBq of F-18 solution was injected into a NEMA scatter phantom with a length of 70 cm and dynamic scan with 20-min frame duration was acquired for 7 half-lives. Oblique sinograms were collapsed into transaxial slices using single slice rebinning method, and true to background (scatter+random) ratio for each slice and frame was estimated. Scatter fraction was determined by averaging the true to background ratio of last 3 frames in which the dead time loss was below 1%. Results: Transverse and axial resolutions at 1cm radius were (1) 5.3 and 6.5 mm (FBP), (2) 5.1 and 5.9 mm (3D RAMLA). Transverse radial, transverse tangential, and axial resolution at 10 cm were (1) 5.7, 5.7, and 7.0 mm (FBP), (2) 5.4, 5.4, and 6.4 mm (3D RAMLA). Attenuation free values of sensitivity were 3,620 counts/sec/MBq at the center of transaxial FOV and 4,324 counts/sec/MBq at 10 cm offset from the center. Scatter fraction was 40.6%, and peak true count rate and NECR were 88.9 kcps @ 12.9 kBq/mL and 34.3 kcps @ 8.84 kBq/mL. These characteristics are better than that of ECAT EXACT PET scanner with BGO crystal. Conclusion: The results of this field test demonstrate high resolution, sensitivity and count rate performance of the 3D PET/CT scanner with GSO crystal. The data provided here will be useful for the comparative study with other 3D PET/CT scanners using BGO or LSO crystals.

• Pediatric Infection and Vaccine
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• v.13 no.2
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• pp.163-173
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• 2006

Purpose : To reduce the number of injections necessary to vaccinate young infants, various combined vaccines have been developed. The $Comvax^{TM}$ manufactured by Merck & Co. is a combination of Hepatitis B and PRP-OMP conjugate Haemophilus influenzae Type b vaccine. The purpose of this study is to evaluate the immunogenicity and safety of $Comvax^{TM}$ in Korean infants. Methods : The infants who were vaccinated at 0 months of age with Hepatitis B vaccine, were recruited for this study after parental informed consent was obtained. The subjects were vaccinated with $Comvax^{TM}$ at 2 and 4 months of age. At each visit, infants were also immunized with DTaP, inactivated poliovirus vaccine, and pneumococcal vaccine when indicated. The serum anti-PRP and anti-HBs were measured at 2 months after the 1st dose(4 months age), and the 2nd dose(6 months age) by the ELISA and chemiluminescent microparticle immunoassay method, respectively. The local and systemic adverse reactions of vaccination were monitored for 3 consecutive days after each immunization. Results : Among sixty-five healthy infants(35 male infants) enrolled in this study; fifty eight(32 male infants) completed the scheduled immunizations. The geometric mean titers (GMTs) of anti-PRP at 2 months after the 1st dose and the 2nd dose were 1.96 ${\mu}g/mL$ (95% CI; 1.38~2.78) and 10.02 ${\mu}g/mL$ (95% CI; 7.04~14.26), respectively. Anti-PRP ${\geq}1.0$ ${\mu}g/mL$, was obtained in 63.2%(95% CI; 53.75~72.65) after 1 dose, and 96.6%(95% CI; 93.05~100) after 2 doses. The GMTs of anti-HBs were 38.32 mIU/mL(95% CI; 22.42~65.51), and 101.17 mIU/mL(95% CI; 65.94~155.25) at 2 month after the 1st dose and 2nd dose of $Comvax^{TM}$, respectively. Anti-HBs ${\geq}10$ mIU/mL was observed in 73.7%(95% CI; 65.07~82.33) after 1 dose and 94.8%(95% CI; 90.45~99.15) after 2 doses. Most of the adverse reactions after vaccination were mild. Irritability, the most common systemic reaction, was observed in 24.8%, followed by drowsiness(19.2%), poor feeding(19.2%) and fever(7.2%). Among the local reactions tenderness was observed in 25.6%, redness(${\geq}5$ mm) in 19.2% and swelling(${\geq}5$ mm) in 4.8%. Conclusion : The $Comvax^{TM}$ vaccine was highly immunogenic for PRP and safe in Korean infants. Although the hepatitis B vaccine component was administered at 0, 2, 4 months, this study showed good immunogenicity against HBsAg.