• Radiation Oncology Journal
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• v.21 no.4
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• pp.261-268
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• 2003

Purpose: To report the results of curative treatment for patients with tonsil cancer by retrospective analysis. Materials and Methods: From Jan. 1995 till Dec. 2000, 27 patients with squamous cell carcinoma of the tonsil received curative treatment at Samsung Medical Center. Therapeutic decision was made through multidisciplinary conference, and curative radiation therapy was favored when, (1) the patient's condition was not fit for general anesthesia and surgery, (2) the patient refused surgery, (3) complete resection was presumed impossible, or (4) too severe disability was expected after surgery. Surgery was the main local modality in 17 patients (S$\pm$RT group), and radiation therapy in 10 (RT$\pm$CT group). The median follow-up period was 41 months. Results: AJCC stages were I/II in four, III in two, and IV in 21 patients. The 5-year disease-free survival rate was 73.3$\%$ in all patients, 70.6$\%$ in the S$\pm$RT group, and 77.8$\%$ in the RT$\pm$CT group. Treatment failure occurred in seven patients, all with stage III/IV, and all the failures occurred within 24 months of the start of treatment. Five patients among the S$\pm$CT group developed treatment failures; 2 local, 2 regional, and 1 distant (crude rate=29.4$\%$). Two patients among the RT$\pm$CT group developed failures; 1 synchronous local and regional, and 1 distant (crude rate=20.0$\%$). The 5-year overall survival rate was 77.0$\%$ in all patients, 80.9$\%$ in the S$\pm$RT group, and 70.0$\%$ in the RT$\pm$CT group. Conclusion: We could achieve favorable results that were comparable to previously reported data with respect to both the rates of local control and of survival by applying S$\pm$RT and RT$\pm$CT. RT$\pm$CT is judged to be an alternative option that can avoid the functional disability after surgical resection.

• Radiation Oncology Journal
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• v.21 no.1
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• pp.54-65
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• 2003

Purpose : To analyze the gene expression Profiles of uterine ceulcal cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a CDNA microarray. Materials and Methods :Sixteen patients, 8 with squamous ceil carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated w14h concurrent chemo-radiation, were Included in the study. Before the starling of the treatment, tumor biopsies were carried out, and the second time biopsies were peformed after a radiation dose of 16.2$\~$27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were peformed with 5 groups of the total RNAs extracted individually and then admixed as control, pre-radiation therapy alone, during-radiation therapy alone, pre-chemoradiation therapy, and during-chemoradlation therapy. The 33P-iabeled CDNAS were synthesized from the total RNAs of each group, by reverse transcription, and then they were hybridized to the CDNA microarray membrane. The gene expression of each microarrays was captured by the intensity of each spot produced by the radioactive isotopes. The pixels per spot were counted with an Arrayguage, and were exported to Microsoft Excel The data were normalized by the Z transformation, and the comparisons were peformed on the Z-ratio values calculated. Results : The expressions of 15 genes, including integrin linked kinase (ILK), CDC28 protein kinase 2, Spry 2, and ERK 3, were increased with the Z-ratio values of over 2.0 for the cervix cancer tissues compared to those for the normal controls. Those genes were involved In cell growth and proliferation, cell cycle control, or signal transduction. The expressions of the other 6 genes, Including G protein coupled receptor kinase 5, were decreased with the Z-ratio values of below -2.0. After the radiation thorapy, most of the genes, with a previously Increase expressions, represented the decreased expression profiles, and the genes, with the Z-ratio values of over 2.0, were cyclic nucleotlde gated channel and 3 Expressed sequence tags (EST). In the concurrent chemo-radiation group, the genes involved in cell growth and proliferation, cell cycle control, and signal transduction were shown to have increased expressions compared to the radiation therapy alone group. The expressions of genes involved in anglogenesis (angiopoietln-2), immune reactions (formyl peptide receptor-iike 1), and DNA repair (CAMP phosphodiesterase) were increased, however, the expression of gene involved In apoptosls (death associated protein kinase) was decreased. Conclusion : The different kinds of genes involved in the development and progression of cervical cancer were identified with the CDNA microarray, and the proposed theory is that the proliferation signal stalls with ILK, and is amplified with Spry 2 and MAPK signaling, and the cellular mitoses are Increased with the increased expression oi Cdc 2 and cell division kinases. After the radiation therapy, the expression profiles demonstrated 4he evidence of the decreased cancer cell proliferation. There was no sigificant difference in the morphological findings of cell death between the radiation therapy aione and the chemo-radiation groups In the second time biopsy specimen, however, the gene expression profiles were markedly different, and the mechanism at the molecular level needs further study.

• Radiation Oncology Journal
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• v.21 no.4
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• pp.253-260
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• 2003

Purpose: No general consensus has been reached regarding the necessity of postoperative radiation therapy (PORT) and the optimal techniques of its application for patients with chest wall invasion (pT3cw) and node negative (NO) non-small cell lung cancer (NSCLC). We retrospectively analyzed the PT3cwN0 NSCLC patients who received PORT because of presumed inadequate resection margin on surgical findings. Materials and Methods: From Aug. 1994 till June 2000, 21 pT3cwN0 NSCLC patients received PORT at Samsung Medical Center; all of whom underwent curative on-bloc resection of the primary tumor plus the chest wall and regional lymph node dissection. PORT was typically stalled 3 to 4 weeks after operation using 6 or 10 MV X-rays from a linear accelerator. The radiation target volume was confined to the tumor bed plus the immediate adjacent tissue, and no regional lymphatics were included. The planned radiation dose was 54 Gy by conventional fractionation schedule. The survival rates were calculated and the failure patterns analyzed. Results: Overall survival, disease-free survival, loco-regional recurrence-free survival, and distant metastases-free survival rates at 5 years were 38.8$\%$, 45.5$\%$, 90.2$\%$, and 48.1$\%$, respectively. Eleven patients experienced treatment failure: six with distant metastases, three with intra-thoracic failures, and two with combined distant and intra-thoracic failures. Among the five patients with intra-thoracic failures, two had pleural seeding, two had in-field local failures, and only one had regional lymphatic failure in the mediastinum. No patients suffered from acute and late radiation side effects of RTOG grade 3 or higher. Conclusion: The strategy of adding PORT to surgery to improve the probability, not only of local control but also of survival, was justified, considering that local control was the most important component in the successful treatment of pT3cw NSCLC patients, especially when the resection margin was not adequate. The incidence and the severity of the acute and late side effects of PORT were markedly reduced, which contributed to improving the patients' qualify of life both during and after PORT, without increasing the risk of regional failures by eliminating the regional lymphatics from the radiation target volume.

• Tuberculosis and Respiratory Diseases
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• v.52 no.3
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• pp.207-218
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• 2002

Background : Intensive care units (ICUs) are generally considered epicenters of antibiotic resistance and the principal sources of multi-resistant bacteria outbreaks. The antibiotic resistance in newly opened intensive care unit that has no microbial colonization on and around the devices was investigated. Materials and Methods : The authors analyzed the antibiotic resistance patterns for common hospital acquired-pneumonia pathogens in the ICUs(Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter spp.) at the newly opened ICU of Hanyang University Medical Center, Kuri Hospital during 6 years(1995-2000). Results : 1) Regarding Staphylococcus aureus, the resistance rate to methicillin was 15% at 1995, 21% at 1996, 20% at 1997, 23% at 1998, 22% at 1999, 55% at 2000. 2) Regarding Pseudomonas aeruginosa, the resistance rate to $3^{rd}$ cephalosporin was 50% at 1995, 50% at 1996, 78% at 1997, 40% at 1998, 77% at 1999, 39% at 2000. Imipenam was 0% at 1995, 27% at 1996, 65% at 1997, 12% at 1998, 16% at 1999, 12% at 2000. Ciprofloxacin was 0% at 1996, 56% at 1997, 36% at 1998, 57% at 1999, 58% at 2000. Tobramycin was 7% at 1995, 10% at 1996, 67% at 1997, 36% at 1998, 65% at 1999, 12% at 2000. Gentamycin was 14% at 1995, 36% at 1996, 67% at 1997, 36% at 1998, 65% at 1999, 12% at 2000. Amikacin was 14% at 1995, 30% at 1996, 61% at 1997, 16% at 1998, 39% at 1999, 18% at 2000. 3) Regarding Acinetobacter spp., the resistance rate to $3^{rd}$ cephalosporin was 92% at 1996, 89% at 1997, 88% at 1998,84% at 1999, 77% at 2000. Imipenem was 50% at 1996, 48% at 1997, 45% at 1998, 49% at 1999, 50% at 2000. Ciprofloxacin was 0% at 1996, 48% at 1997, 33% at 1998, 27% at 1999, 71% at 2000. Tobramycin was 67% at 1995, 100% at 1996, 89% at 1997, 95% at 1998, 87% at 1999, 77% at 2000. Gentamycin was 67% at 1995, 100% at 1996, 89% at 1997, 95% at 1998, 87% at 1999, 83% at 2000. Amikacin was 33% at 1995, 83% at 1996, 82% at 1997, 88% at 1998, 75% at 1999, 69% at 2000. Conclusion : The S.aureus resistance to methicillin, the Pseudomonas aeruginosa resistance to ciprofloxacin, and the Acinetobacter spp. resistance to ciprofloxacin have rapidly increased during 6 years. There is a need to pay speicial attention when using the the antibiotics for the above pathogens. This data may be useful in antibiotic therapy in newly opened intensive care units.

• Journal of Chest Surgery
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• v.40 no.4 s.273
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• pp.264-272
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• 2007

Background: Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, including stimulating the proliferation and migration of vascular smooth muscle cells (VSMCs). It has been known that diabetes is associated with accelerated cellular proliferation via VEGF, as compared to that under a normal glucose concentration. We investigated the effects of selective blockade of a VEGF receptor by using anti-Flt-1 peptide on the formation and hyperplasia of the neointima in balloon injured-carotid arteries of OLETF rats and also on the in vitro VSMCS' migration under high glucose conditions. Material and Method: The balloon-injury method was employed to induce neointima formation by VEGF. For f4 days beginning 2 days before the ballon injury, placebo or vascular endothelial growth factor receptor-1 (VEGFR-1) specific peptide (anti-Flt-1 peptide), was injected at a dose of 0.5mg/kg daily into the OLETF rats. At 14 days after balloon injury, the neointimal proliferation and vascular luminal stenosis were measured, and cellular proliferation was assessed by counting the proliferative cell nuclear antigen (PCNA) stained cells. To analyze the effect of VEGF and anti-Flt-1 peptide on the migration of VSMCs under a high glucose condition, transwell assay with a matrigel filter was performed. And finally, to determine the underlying mechanism of the effect of anti-Flt-1 peptide on the VEGF-induced VSMC migration in vitro, the expression of matrix metalloproteinase (MMP) was observed by performing reverse transcription-polymerase chain reaction (RT-PCR). Result: Both the neointimal area and luminal stenosis associated with neointimal proliferation were significantly decreased in the anti-Flt-1 peptide injected rats, ($0.15{\pm}0.04 mm^2$ and $ 36.03{\pm}3.78%$ compared to $0.24{\pm}0.03mm^2\;and\;61.85{\pm}5.11%$, respectively, in the placebo-injected rats (p<0.01, respectively). The ratio of PCNA(+) cells to the entire neointimal cells was also significantly decreased from $52.82{\pm}4.20%\;to\;38.11{\pm}6.89%$, by the injected anti-Flt-1 peptide (p<0.05). On the VSMC migration assay, anti-Flt-1 peptide significantly reduced the VEGF-induced VMSC migration by about 40% (p<0.01). Consistent with the effect of anti-Flt-1 peptide on VSMC migration, it also obviously attenuated the induction of the MMP-3 and MMP-9 mRNA expressions via VEGF in the VSMCS. Conclusion: Anti-Flt-1 peptide inhibits the formation and hyperplasia of the neointima in a balloon-injured carotid artery model of OLETF rats. Anti-Flt-1 peptide also inhibits the VSMCs' migration and the expressions of MMP-3 and MMP-9 mRNA induced by VEGF under a high glucose condition. Therefore, these results suggest that specific blockade of VEGFR-1 by anti-Flt-1 peptide may have therapeutic potential against the arterial stenosis of diabetes mellitus patients or that occurring under a high glucose condition.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.91-99
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• 1999

Propose : This study was performed to find out the prognostic factors affecting local control, survival and disease free survival rate in nasopharyngeal carcinomas treated with chemotherapy and radiation therapy. Materials and Methods : We analysed 47 patients of nasopharyngeal carcinomas, histologically confirmed and treated at Chonnam University Hospital between July 1986 and June 1996, retrospectively. Range of patients' age were from 16 to 80 years (median; 52 years). Thirty three (70$\%$) patients was male. Histological types were composed of 3 (6$\%$) keratinizing, 30 (64$\%$) nonkeratinizing squamous cell carcinoma and 13 (28$\%$) undifferentiated carcinoma. Histoiogicai type was not known in 1 patient (2$\%$). We restaged according to the staging system of 1997 American Joint Committee on Cancer Forty seven patients were recorded as follows: 71: 11 (23$\%$), T2a; 6 (13$\%$), T2b; 9 (19$\%$), 73; 7 (15$\%$), 74: 14 (30$\%$), and NO; 7 (15$\%$), Nl: 14 (30$\%$), N2; 21 (45%), N3: 5 (10%). Clinical staging was grouped as follows: Stage 1; 2 (4$\%$), IIA: 2 (4$\%$), IIB; 10 (21$\%$), III; 14 (30$\%$), IVA; 14 (30$\%$) and IVB; 5 (11$\%$). Radiation therapy was done using 6 MV and 10 MV X- ray of linear accelerator. Electron beam was used for the Iymph nodes of posterior neck after 4500 cGy. The range of total radiation dose delivered to the primary tumor was from 6120 to 7920 cGy (median; 7020 cGy). Neoadjuvant chemotherapy was performed with cisplatin +5-fluorouracil (25 patients) or cisplatin+pepleomycin (17 patients) with one to three cycles. Five patients did not received chemotherapy. Local control rate, survival and disease free suwival rate were calculated by Kaplan-Meier method. Generalized Wilcoxon test was used to evaluate the difference of survival rates between groups. multivariate analysis using Cox proportional hazard model was done for finding prognostic factors. Results: Local control rate was 81$\%$ in 5 year. Five year survival rate was 60$\%$ (median survival; 100 months). We included age, sex, cranial nerve deflicit, histologic type, stage group, chemotherapy, elapsed days between chemotherapy and radiotherapy, total radiation dose, period of radiotherapy as potential prognostic factors in multivariate analysis. As a result, cranial none deficit (P=0.004) had statistical significance in local control rate. Stage group and total radiation dose were significant prognostic factors in survival (P=0.000, P=0.012), and in disease free survival rates (P=0.003, P=0.008), respectively. Common complications were xerostomia, tooth and ear problems. Hypothyroidism was developed in 2 patients. Conclusion : In our study, cranial none deficit was a significant prognostic factor in local control rate, and stage group and total radiation dose were significant factors in both survival and disease free survival of nasopharyngeal carcinoma. We have concluded that chemotherapy and radiotherapy used in our patients were effective without any serious complication.

• Radiation Oncology Journal
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• v.25 no.4
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• pp.268-277
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• 2007

Purpose: Respiratory motion is a considerable inhibiting factor for precise treatment with stereotactic radiosurgery using the CyberKnife (CK). In this study, we developed a moving phantom to simulate three-dimensional breathing movement and investigated the distortion of dose profiles between the use of a moving phantom and a static phantom. Materials and Methods: The phantom consisted of four pieces of polyethylene; two sheets of Gafchromic film were inserted for dosimetry. Treatment was planned to deliver 30 Gy to virtual tumors of 20, 30, 40, and 50 mm diameters using 104 beams and a single center mode. A specially designed robot produced three-dimensional motion in the right-left, anterior-posterior, and craniocaudal directions of 5, 10 and 20 mm, respectively. Using the optical density of the films as a function of dose, the dose profiles of both static and moving phantoms were measured. Results: The prescribed isodose to cover the virtual tumors on the static phantom were 80% for 20 mm, 84% for 30 mm, 83% for 40 mm and 80% for 50 mm tumors. However, to compensate for the respiratory motion, the minimum isodose levels to cover the moving target were 70% for the $30{\sim}50$ mm diameter tumors and 60% for a 20 mm tumor. For the 20 mm tumor, the gaps between the isodose curves for the static and moving phantoms were 3.2, 3.3, 3.5 and 1.1 mm for the cranial, caudal, right, and left direction, respectively. In the case of the 30 mm tumor, the gaps were 3.9, 4.2, 2.8, 0 mm, respectively. In the case of the 40 mm tumor, the gaps were 4.0, 4.8, 1.1, and 0 mm, respectively. In the case of the 50 mm diameter tumor, the gaps were 3.9, 3.9, 0 and 0 mm, respectively. Conclusion: For a tumor of a 20 mm diameter, the 80% isodose curve can be planned to cover the tumor; a 60% isodose curve will have to be chosen due to the tumor motion. The gap between these 80% and 60% curves is 5 mm. In tumors with diameters of 30, 40 and 50 mm, the whole tumor will be covered if an isodose curve of about 70% is selected, equivalent of placing a respiratory margin of below 5 mm. It was confirmed that during CK treatment for a moving tumor, the range of distortion produced by motion was less than the range of motion itself.

• Radiation Oncology Journal
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• v.25 no.2
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• pp.70-78
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• 2007

[ $\underline{Purpose}$ ]: This study analyzed the tumor response, overall survival, progression free survival and related prognostic factors in patients with muscle invasive bladder cancer subjected to bladder preserving treatment. $\underline{Materials\;and\;Methods}$: Between August 1995 and June 2004, 37 patients with muscle invasive (transitional cell carcinoma, clinically stage T2-4) bladder cancer were enrolled for the treatment protocol of bladder preservation. There were 33 males and 4 females, and the median age was 67 years (range $38{\sim}86\;years$). Transurethral resection of the bladder (TURB) was performed in 17 patients who underwent complete resection. The median radiation dose administered was 64.8 Gy (range $55.8{\sim}67\;Gy$). The survival rate was calculated by the Kaplan-Meier method. $\underline{Results}$: An evaluation of the response rate was determined by abdomen-pelvic CT and cystoscopy at three months after radiotherapy. A complete response was seen in 17 patients (46%). The survival rate at three years was 54.7%, with 54 months of median survival (range $3{\sim}91$ months). During the study, 17 patients died and 13 patients had died from bladder cancer. The progression free survival rate at three years was 37.2%. There were 24 patients (64.9%) who had disease recurrence: 16 patients (43.2%) had local recurrence, 6 patients (16.2%) had a distant recurrence, and 2 patients (5.4%) had both a local and distant recurrence. The survival rate (p=0.0009) and progression free survival rates (p=0.001) were statistically significant when compared to the response rate after radiotherapy. $\underline{Conclusion}$: The availability of complete TURB and appropriate chemoradiotherapy were important predictors for bladder preservation and survival.

• Radiation Oncology Journal
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• v.26 no.2
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• pp.104-112
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• 2008

Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ dendritic cell(DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses($3{\times}10^6\;to\;12{\times}10^6$ DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The $12{\times}10^6$ DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The $DCVac/IR^{(R)}$ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.

• Journal of Chest Surgery
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• v.35 no.3
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• pp.188-198
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• 2002

Background: Reoperations on the aortic root or the ascending aorta are being performed with increasing frequency and remain a challenging problem. This study was performed to analyze the results of reoperations on the ascending aorta and aortic root. Material and Method: Between May 1995 and April 2001, 30 patients had reoperations on the ascending aorta and aortic root and were reviewed retrospectively. The mean interval between the previous repair and the actual reoperation was 56 months(range 3 to 142 months). Seven patients(23.3%) had two or more previous operations. The indications for reoperations were true aneurysm in 7 patients(23.3%), prosthetic valve endocarditis in 6(20%), false aneurysm in 5(16.7%), paravalvular leak associated with Behcet's disease in 4(13.3%), malfunction of prosthetic aortic valve in 4(13.3%), aortic dissection in 3(10%), and annuloaortic ectasia in 1(3.3%). The principal reoperations performed were aortic root replacement in 17 patients(56.7%), replacement of the ascending aorta in 8(26.7%), aortic and mitral valve replacement with reconstruction of fibrous trigone in 2(6.6%), patch aortoplasty in 2(6.6%), and aortic valve replacement after Bentall operation in 1 (3.3%). The cardiopulmonary bypass was started before sternotomy in 7 patients and the hypothermic circulatory arrest was used in 16(53.3%). The mean time of circulatory arrest, total bypass, and aortic crossclamp were 20$\pm$ 12 minutes, 228$\pm$56 minutes, and 143$\pm$62 minutes, respectively Result: There were three early deaths(10%). The postoperative complications were reoperation for bleeding in 7 patients(23.3%), cardiac complications in 5(16.7%), transient acute renal failure in 2(6.6%), transient focal seizure in 2(6.6%), and the others in 5. The mean follow-up was 22.8 $\pm$20.5 months. There were two late deaths(7.4%). The actuarial survival was 92.6$\pm$5.0% at 6 years. One patient required reoperation for complication of reoperation on the ascending aorta and aortic root(3.7%). The 1- and 6-year actuarial freedom from reoperation was 100% and 83.3$\pm$15.2%, respectively. One patient with Behcet's disease are waiting for reoperation due to false aneurysm, which developed after aortic root replacement with homograft. There were no thromboembolisms or anticoagulant related complications. Conclusions: This study suggests that reoperations on the ascending aorta and aortic root can be performed with acceptable early mortality and morbidity, and adequate surgical strategies according to the pathologi conditions are critical to the prevention of the reoperation.