• Nuclear Medicine and Molecular Imaging
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• v.42 no.3
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• pp.192-200
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• 2008

To evaluate the hemodynamic changes and the predictive factors of the clinical outcome in pediatric patients with moyamoya disease, we analyzed pre/post basal/acetazolamide stress brain perfusion SPECT with automated volume of interest (VOIs) method. Methods: Total fifty six (M:F = 33:24, age $6.7{\pm}3.2$ years) pediatric patients with moyamoya disease, who underwent basal/acetazolamide stress brain perfusion SPECT within 6 before and after revascularization surgery (encephalo-duro-arterio-synangiosis (EDAS) with frontal encephalo-galeo-synangiosis (EGS) and EDAS only followed on contralateral hemisphere), and followed-up more than 6 months after post-operative SPECT, were included. A mean follow-up period after post-operative SPECT was $33{\pm}21$ months. Each patient's SPECT image was spatially normalized to Korean template with the SPM2. For the regional count normalization, the count of pons was used as a reference region. The basal/acetazolamide-stressed cerebral blood flow (CBF), the cerebral vascular reserve index (CVRI), and the extent of area with significantly decreased basal/acetazolamide- stressed rCBF than age-matched normal control were evaluated on both medial frontal, frontal, parietal, occipital lobes, and whole brain in each patient's images. The post-operative clinical outcome was assigned as good, poor according to the presence of transient ischemic attacks and/or fixed neurological deficits by pediatric neurosurgeon. Results: In a paired t-test, basal/acetazolamide-stressed rCBF and the CVRI were significantly improved after revascularization (p<0.05). The significant difference in the pre-operative basal/acetazolamide-stressed rCBF and the CVRI between the hemispheres where EDAS with frontal EGS was performed and their contralateral counterparts where EDAS only was done disappeared after operation (p<0.05). In an independent student t-test, the pre-operative basal rCBF in the medial frontal gyrus, the post-operative CVRI in the frontal lobe and the parietal lobe of the hemispheres with EDAS and frontal EGS, the post-operative CVRI, and ${\Delta}CVRI$ showed a significant difference between patients with a good and poor clinical outcome (p<0.05). In a multivariate logistic regression analysis, the ${\Delta}CVRI$ and the post-operative CVRI of medial frontal gyrus on the hemispheres where EDAS with frontal EGS was performed were the significant predictive factors for the clinical outcome (p =0.002, p =0.015), Conclusion: With probabilistic map, we could objectively evaluate pre/post-operative hemodynamic changes of pediatric patients with moyamoya disease. Specifically the post-operative CVRI and the post-operative CVRI of medial frontal gyrus where EDAS with frontal EGS was done were the significant predictive factors for further clinical outcomes.

• Journal of Chest Surgery
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• v.41 no.6
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• pp.703-709
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• 2008

Background: Diagnosis and treatment are often successful in the setting of cardiac myxomas. However, cardiac myxomas can lead to catastrophic complications, due to intracardiac obstruction and embolism preoperatively, and can recur postoperatively. Material and Method: We retrospectively reviewed the clinical characteristics, surgical treatment, and recurrence data of 85 patients who underwent cardiac myxoma surgery at Asan Medical Center between November 1994 and June 2007. We analyzed the morphologic characteristics of 58 patients with left atrial myxomas and determined the development of functional mitral valve stenosis and systemic embolism through reviewing the results of preoperative echo-cardiograms to find potential preoperative risk factors. Result: Twenty-seven (31.8%) patients were men, and 58 (68.2%) were women. The mean patient age was $54.5{\pm}14.3$ years. Preoperative symptoms included obstructive symptoms in 41 (48.2%) patients, signs of embolism in 19 (22.4%), constitutional symptoms in 8 (9.4%), and no symptoms in 19 (20.0%). Among the 58 patients with left atrial myxomas, the mean maximal tumor diameter was $4.3{\pm}1.8$ (range $1.1{\sim}8\;cm$)cm. Twenty-six (44.8%) patients had a prolapsing type, defined as a tumor mobile enough to move down. to the mitral. annular plane during diastole, and 32 (55.2%) had villous type, defined as a tumor consisting of multiple fine villous extensions on the surface. Twelve (20.7%) patients had severe functional mitral valve stenosis, and 15 (25.9%) had systemic embolism preoperatively. The incidence of severe functional mitral valve stenosis was significantly higher in patients with the prolapsing type than in those with the non-prolapsing type (p=0.001). The mean maximal tumor diameter in patients with severe functional mitral valve stenosis was $5.1{\pm}1.0\;cm$, significantly larger than that seen in patients without severe functional mitral valve stenosis (p=0.041). The incidence of systemic embolism was significantly higher in patients with the villous type than in those with the smooth type (p=0.006). Postoperative complications were noted in 6 (7.1%) patients, and early mortality was noted in 1 (1.2%). The mean postoperative follow-up duration was $36.2{\pm}37.5$ months, with recurrence reported in 2(2.4%) patients during the follow-up period. The disease free interval were 48, 12 months, respectively. Conclusion: Surgical treatment for cardiac myxomas was performed safely, and long-term prognosis was good. In patients with left atrial myxoma, close attention should be maintained and surgery should be performed promptly in those of prolapsing type, those with large maximal diameter in order to prevent severe functional mitral valve stenosis, and those of villous type in order to prevent systemic embolism. Echocardiography should be followed serially in order to detect recurrence.

• Journal of Gastric Cancer
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• v.5 no.2
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• pp.89-94
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• 2005

Purpose: Early gastric cancer (EGC) has an excellent prognosis compared to advanced gastric cancer. The 5-year survival rate for EGC now exceeds $90\%$, and EGC is recognized as a curable malignancy. The important prognostic factor in EGC is the status of lymph-node metastasis. Despite conserving surgery being suggested for EGC at present, it is of vital importance to select a surgical method appropriate to each individual case. This retrospective study was undertaken to clarify clinicopathologic features and factors related to lymph-node metastasis in submucosal gastric cancer in order to determine an appropriate therapy. Materials and Methods: This study analyzed the clinicopathologic features for 279 patients with a submucosal gastric carcinoma (Group I) and compared with those of patients with mucosal (Group II) or muscularis proprial gastric carcinoma (Group III). All patients were operated on from 1981 to 1999 at Chonnam University Hospital. There were no statistically significant differences among the groups with respect to age, gender, tumor location, hepatic metastasis, or peritoneal dissemination. Results: Positive lymph node metastasis was found in 47 ($16.8\%$) of the 279 patients with a submucosal gastric carcinoma. The incidence of lymph-node metastasis was significantly higher in patients with a submucosal gastric carcinoma than in patients with a mucosal gastric carcinoma ($16.8\%\;vs.\;3.9\%\;$; P<0.01). Therefore, depth of invasion was a significant factor affecting in lymph-node metastasis. The 5-year survival rates were $88.6\%$ for patients in Group I, $95.2\%$ for patients in Group II, and $72.7\%$ for patients in Group III (P<0.01 for Group I vs. Group II; Group I vs. Group III). In patients with a submucosal gastric carcinoma, the survival rate with positive lymph nodes was significantly poorer than that of patients without lymph-node metastasis ($87.3\%\;vs.\;94.2\%$; P<0.01). Conclusion: Gastrectomy with D2 lymph node dissection is an appropriate operative procedure for patients with a submucosal gastric carcinoma.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.108-115
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• 2002

Purpose : A retrospective study was undertaken to determine the role of conventional radiotherapy with or without surgery for treating a supraglottic carcinoma in terms of the local control and survival. Materials and Methods : From Jan. 1986 to Oct. 1996, a total of 134 patients were treated for a supraglottic carcinoma by radiotherapy with or without surgery. Of them, 117 patients who had completed the radiotherapy formed the base of this study. The patients were redistributed according to the revised AJCC staging system (1997). The number of patients of stage I, II, III, IVA, IVB were $6\;(5\%),\;16\;(14\%),\;53\;(45\%),\;32\;(27\%),\;10\;(9\%)$, respectively. Eighty patients were treated by radical radiotherapy in the range of $61.2\~79.2\;Gy$ (mean : 69.2 Gy) to the primary tumor and $45.0\~93.6\;Gy$ (mean : 54.0 Gy) to regional lymphatics. All patients with stage I and IVB were treated by radiotherapy alone. Thirty-seven patients underwent surgery plus postoperative radiotherapy in the range of $45.0\~68.4\;Gy$ (mean : 56.1 Gy) to the primary tumor bed and $45.0\~59.4\;Gy$ (mean : 47.2 Gy) to the regional lymphatics. Of them, 33 patients received a total laryngectomy (${\pm}lymph$ node dissection), three had a supraglottic horizontal laryngectomy (${\pm}lymph$ node dissection), and one had a primary excision alone. Results : The 5-year survival rate (5YSR) of all patients was $43\%$. The 5YSRs of the patients with stage I+II, III+IV were $49.9\%,\;41.2\%$, respectively (p=0.27). However, the disease-specific survival rate of the patients with stage I (n=6) was $100\%$. The 5YSRs of patients who underwent surgery plus radiotherapy (S+RT) vs radiotherapy alone (RT) in stage II, III, IVA were $100\%\;vs\;43\%$ (p=0.17), $62\%\;vs\;52\%$ (p=0.32), $58\%\;vs\;6\%$ (p<0.001), respectively. The 5-year actuarial locoregional control rate (5YLCR) of all the patients was $57\%$. The 5YLCR of the patients with stage I, II, III, IVA, IVB was $100\%,\;74\%,\;60\%,\;44\%,\;30\%$, respectively (p=0.008). The 5YLCR of the patients with S+RT vs RT in stage II, III, IVA was $100\%\;vs\;68\%$ (p=0.29), $67\%\;vs\;55\%$ (p=0.23), $81\%\;vs\;20\%$ (p<0.001), respectively. In the radiotherapy alone group, the 5YLCR of the patients with a complete, partial, and minimal response were $76\%,\;20\%,\;0\%$, respectively (p<0.001). In all patients, multivariate analysis showed that the N-stage, surgery or not, and age were significant factors affecting the survival rate and that the N-stage, surgery or not, and the ECOG performance index were significant factors affecting the locoregional control. In the radiotherapy alone group, multivariate analysis showed that the radiation response and N-stage were significant factors affecting the overall survival rate as well as locoregional control. Conclusion : In early stage supraglottic carcinoma, conventional radiotherapy alone is an equally effective modality compared to surgery plus radiotherapy and could preserve the laryngeal function. However, in the advanced stages, radiotherapy combined with concurrent chemotherapy for laryngeal preservation or surgery should be considered. In bulky neck disease, all the possible planned neck dissections after induction chemotherapy or before radiotherapy should be attempted.

• Journal of Chest Surgery
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• v.37 no.10
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• pp.845-855
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• 2004

Background: No general consensus has been available regarding the necessity of postoperative radiation therapy (PORT) and its optimal techniques in the patients with chest wall invasion (pT3cw) and node negative (N0) non-small cell lung cancer (NSCLC). We did retrospective analyses on the pT3cwN0 NSCLC patients who received PORT because of presumed inadequate resection margin on surgical findings. And we compared them with the pT3cwN0 NSCLC patients who did not received PORT during the same period. Material and Method: From Aug. of 1994 till June of 2002, 22 pT3cwN0 NSCLC patients received PORT-PORT (＋) group- and 16 pT3cwN0 NSCLC patients had no PORT-PORT (-) group. The radiation target volume for PORT (＋) group was confined to the tumor bed plus the immediate adjacent tissue only, and no regional lymphatics were included. The prognostic factors for all patients were analyzed and survival rates, failure patterns were compared with two groups. Result: Age, tumor size, depth of chest wall invasion, postoperative mobidities were greater in PORT (-) group than PORT (＋) group. In PORT (-) group, four patients who were consulted for PORT did not receive the PORT because of self refusal (3 patients) and delay in the wound repair (1 patient). For all patients, overall survival (OS), disease-free survival (DFS), loco-regional recurrence-free survival (LRFS), and distant metastases-free survival (DMFS) rates at 5 years were 35.3%, 30.3%, 80.9%, 36.3%. In univariate and multivariate analysis, only PORT significantly affect the survival. The 5 year as rates were 43.3% in the PORT (＋) group and 25.0% in PORT (-) group (p=0.03). DFS, LRFS, DMFS rates were 36.9%, 84.9%, 43.1 % in PORT (＋) group and 18.8%, 79.4%, 21.9% in PORT(-) group respectively. Three patients in PORT (-) group died of intercurrent disease without the evidence of recurrence. Few suffered from acute and late radiation side effects, all of which were RTOG grade 2 or lower. Conclusion: The strategy of adding PORT to surgery to improve the probability not only of local control but also of survival could be 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. Authors were successful in the marked reduction of the incidence as well as the severity of the acute and late side effects of PORT, without taking too high risk of the regional failures by eliminating the regional lymphatics from the radiation target volume.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.559-573
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• 1997

Background : Asthma causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough. These symptoms are usually associated with widespread but variable airflow limitation that is partly reversible either spontaneously or with treatment. The inflammation also causes an associated increase in airway responsiveness to a variety of stimuli. Method : Of the 403 adult bronchial asthma patients enrolled from March 1992 to March 1994 in Allergy Clinics of Severance Hospital in Yonsei University, this study reviewed the 97 cases to evaluate the treatment effects and to analyse prognostic factors. The patients were classified to five groups according to treatment responses ; group 1 (non control group) : patients who were not controlled during following up, group 2 (high step treatment group) : patients who were controlled longer than 3 months by step 3 or 4 treatment of "Global initiative for asthma, Global strategy for asthma management and prevention" (NHLBI/WHO) with PFR(%) larger than 80%, group 3 (short term control group) : patients who were controlled less than 1 year by step 1 or 2 treatment of NHLBI/WHO, group 4 (intermediate term control group) : patients who were controlled for more than 1 year but less than 2 years by step 1 or 2 treatment of NHLBI/WHO, group 5 (long term control group) : patients who were controlled for more than 2 years by step 1 or 2 treatment of NHLBI/WHO. Especially the patients who were controlled more than 1 year with negatively converted methacholine test and no eosinophil in sputum were classified to methacholine negative conversion group. We reviewed patients' history, atopy score, total IgE, specific IgE, methacholine PC20 and peripheral blood eosinophil count, pulmonary function test, steroid doses and aggrevation numbers after treatment. Results : On analysis of 98 patients, 20 cases(20.6%) were classified to group 1, 26 cases(26.8%) to group 2, 23 cases(23.7%) to group 3, 15 cases(15.5%) to group 4, and 13 cases(13.4%) to groups 5. There were no differences of sex, asthma type, family history, smoking history, allergic rhinitis and aspirin allergy among the groups. In long term control group, asthma onset age was younger, symptom duration was shorter, and initial pulmonary function was better. The long term control group required lower amounts of oral steroid. had less aggrevation during first 3months after starting treatment and shorter duration from enrollment to control Atopy, allergic skin test, sputum and blood eosinophil, total IgE, nonspecific bronchial responsiveness was not significantly different among the groups. Seven out of 28 patients who were controlled more than 1 years showed negatively converted methachloine test and no eosinophils in the sputum. The mean control duration was $20.3{\pm}9.7$ months and relapse did not occur. Conclusion : Patients who had asthma of onset age younger, shorter symptom duration, better PFT, lower treatment initial steps, lower amounts of steroid needs and less aggravation numbers after starting treatment were classified in the long term control groups compared to the others.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.237-245
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• 2002

Purpose : This study was conducted to evaluate the treatment results, prognostic factors, and complication rates after high dose rate (HDR) brachytherapy in patients with uterine cervix cancer who were treated with curative aim. Materials and Methods : Of 269 cervix cancer patients treated at the department of radiation oncology, Samsung Medical Center from September 1994 to July 1998, the 106 who were treated with radical radio-therapy were analyzed. The median age was 61 years (range 22 to 89). All patients except 4 with carcinoma in situ (CIS) were given external beam radiotherapy (range $30.6\~50.4\;Gy$ to whole pelvis) and HDR brachytherapy. The common regimens of HDR brachytherapy were a total dose of $24\~28\;Gy$ with $6\~7$ fractions to point A at two fractions per week. The median overall treatment time was 55 days (range 44 to 104) in patients given both external beam radiotherapy and HDR brachytherapy. Results : Early responses of radiotherapy were evaluated by gynecologic examination and follow-up MRI 1 month after radiotherapy. Treatment responses were complete remission in 72 patients, partial response in 33 and no response in 1. The overall survival (OS) rate of all patients was $82\%,\;and\;73\%$, and the disease free survival (DFS) rate was $72\%,\;and\;69\%$, at 3, and 5 years, respectively. The pelvic control rate (PCR) was $79\%$ at both 3 and 5 years. According to the FIGO stage,3 and 5 year OS were $100\%\;and\;50\%$ in CIS/IA, $100\%\;and\;100%$ in IB, $83\%\;and\;69\%$ in IIA, $87\%\;and\;80\%$ in IIB, and $62\%\;and\;62\%$ in III, respectively. The 3 year OS in 4 patients with stage IVA was $100\%$. Three-year DFS were $80\%$ in CIS/IA, $88\%$ in IB, $100\%$ in IIA, $64\%$ in IIB, $58\%$ in III, and $75\%$ in IVA. Three-year PCR were $100\%$ in CIS/IA, $94\%$ in IB, $100\%$ in IIA, $84\%$ in IIB, $69\%$ in III, and $50\%$ in IVA. By univariate analysis, FIGO stage and treatment response were significant factors for OS. The significant factors for DFS were age, FIGO stage, treatment response and overall treatment time (OTT). For pelvic control rate, treatment response and OTT were significant factors. By multivariate analysis, FIGO stage had a borderline significance for OS (p=0.0825) and treatment response had a borderline significance for DFS (0=0.0872). A total of 14 patients $(13\%)$ experienced rectal bleeding, which occurred from 3 to 44 months (median, 13 months) after the completion of radiotherapy. Conclusion : HDR brachytherapy protocol of Samsung Medical Center combined with properly optimal external beam pelvic irradiation is a safe and effective treatment for patients with uterine cervix cancer. The authors found that OTT of less than 55 days had a positive impact on pelvic control and survival rate.

• Journal of Chest Surgery
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• v.32 no.5
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• pp.448-455
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• 1999

Background: Recent developments in techniques of video-assisted thoracic surgery(VATS) and endoscopic equipment has expanded the application of video-assisted surgical procedures in the field of thoracic surgery. Especially, it will probably become the treatment of choice of spontaneous pneumothorax(SP). There is, however, a high recurrence rate, high cost, and paucity of long-term results. We report the results of postoperative follow-up and analyze perioperative parameters affected to recurrence, retrospectively. Material and Method: From march 1992 to march 1997, 276 patients with spontaneous pneumothorax underwent 292 VATS procedures. Conversion to open thoracotomy was necessitated in eight patients, and this patients excluded from the study. Result: The sex distribution was 249 males and 31 females. The mean age was 28.1 12.2 years(range, 15 to 69 years). Primary SP was 237cases(83.5%) and secondary SP was 47cases(16.5%). The major underlying lung diseases associated with secondary SP were tuberculosis 27cases(57.4%) and emphysema 8cases (38.3%). Operative indications included Ipsilateral recurrence 123(43.9%), persistent air-leak 53(18.9%), x-ray visible bleb 40(14.3%), tension 30(10.7%), contralateral recurrence 21(7.5%), uncomplicated first episode 8(2.9%), bilateral 3(1.1%), complicated episode 2(0.7%). Blebs were visualized in 247cases(87%) and 244cases(85.9%) performed stapled blebectomy. Early postoperative complications occurred in 33 cases(11.6%): 16 prolonged air-leak more than 5 days(four of them were required a second operation and found missed blebs); 5 bleeding; 5 empyema; 2 atelectasis; 1 wound infection. No deaths occured. The mean operative time was 52.8 23.1 minutes(range, 20 to 165 minutes). The mean d ration of chest tube drainage was 5.0 4.5 days(range, 2 to 37 days). The mean duration ofhospital stay was 8.2 5.5 days (range, 3 to 43days). At a mean follow-up 22.3 18.4 months(range, 1 to 65 months), 12 patients(4.2%) were lost to follow-up. There were 24 recurrences and seven patients underwent second operation and 6 patients(85.7%) were found the missed blebs. 12 perioperative parameters(age, sex, site, underlying disease, extent of collapse, operative indication, size of bleb, number of bleb, location of bleb, bleb management, pleural procedure, prolonged postoperative air-leak) were analyzed statistically to identify significant predictors of recurrence. The significant predictors of recurrence was the underlying disease[17.0%(8/47): 6.8%(16/237), p=0.038], prolonged postoperative air-leakage[37.5%(6/16): 6.7%(18/268), p=0.001], and pleural procedure [11.4%(19/167): 4.3%(5/117), p=0.034]. Blebectomy has less recurrence rate then non-blebectomy [8.2%(20/244) : 10.0%(4/40), p>0. 5]. However, this difference was not statistically significant(p=0.758). Conclusion: We conclude that it is important that we shoud careful finding of bleb during VATS due to reducing of recurrnece, and cases of no bleb identified and secondary spontaneous pneumothorax were indicated of pleurodectomy. VATS is a valid alternative to open procedure for the treatment of spontaneous pneumothorax with less pain, shorter hospital stay, more rapid return to work, high patient acceptance, less scar and exellent cosmetics. But, there is high recurrence rate and high cost, and than it is necessary to evaluate of long-term results for recurrence and to observate carefully during VATS.

• Journal of Chest Surgery
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• v.39 no.1 s.258
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• pp.1-11
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• 2006

Background: CD44 is a glycoprotein on the cell surface which is involved in the cell-to-cell and cell-to-matrix interaction. The standard form, CD44s and multiple isoforms are determined by alternative splicing of 10 exons. Recent studies have suggested that CD44 may help invasion and metastasis of various epithelial tumors as well as activation of Iymphocytes and monocytes. The expression pattern of CD44 can be different according to tumor types. The author studied the expression pattern of CD44s and one of its variants, CD44v6 in non-small cell lung carcinomas (NSCLC) to find their implications on clinicopathologic aspects, including the survival of the patients. Material and Method: A total of 89 primary NSCLSs (48 squamous cell carcinomas, 33 adenocarcinomas, and 8 undifferentiated large cell carcinomas) were retrieved during the years between 1985 to 1994. The immunohisto chemistry was done by using monoclonal antibodies and the CD44 expression for angiogenesis was evaluated by counting the number of tumor microvessels. Result: Seventy-one (79.8$\%$) and 64 (71 .9$\%$) among 89 NSCLSs revealed the expression of CD44s and CD44v6, respectively. The expression of CD44s was well correlated with that of CD44v6 (r=0.710, p < 0.0001). The expression of CD44s and CD44v6 was associated with the histopathologic type of the NSCLCs, and squamous cell carcinoma was the type that showed the highest expression of CD44s and CD44v6 (p < 0.0001). Microvessel count was the highest in adenocarcinomas (113.6$\pm$69.7 on 200-fold magnification and 54.8$\pm$41.1 on 400-fold magnification) and correlated with the tumor size of TNM system (r=0.217, p=0.043) and CD44s expression (r=0.218, p=0.040). In adenocarcinoma, the patients with higher CD44s expression survived shorter than those with lower CD44s expression (p=0.0194) but there was no statistical significance on multivariate analysis(p=0.3298). Conclusion: The expression of both CD44s and CD44v6 may be associated with the squamous differentiation in non-small cell lung carcinomas. The relationship of CD44s expression with micro-vessel density of the tumor suggests an involvement of CD44s in tumor angiogenesis, which in turn would help tumor growth.

• Radiation Oncology Journal
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• v.23 no.3
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• pp.143-156
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• 2005

Background: The best dose-fractionation regimen of the definitive radiotherapy for cervix cancer remains to be clearly determined. It seems to be partially attributed to the complexity of the affecting factors and the lack of detailed information on external and intra-cavitary fractionation. To find optimal practice guidelines, our experiences of the combination of external beam radiotherapy (EBRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT) were reviewed with detailed information of the various treatment parameters obtained from a large cohort of women treated homogeneously at a single institute. Materials and Methods: The subjects were 743 cervical cancer patients (Stage IB 198, IIA 77, IIB 364, IIIA 7, IIIB 89 and IVA 8) treated by radiotherapy alone, between 1990 and 1996. A total external beam radiotherapy (EBRT) dose of $23.4\~59.4$ Gy (Median 45.0) was delivered to the whole pelvis. High-dose-rate intracavitary brachytherapy (HDR-IBT) was also peformed using various fractionation schemes. A Midline block (MLB) was initiated after the delivery of $14.4\~43.2$ Gy (Median 36.0) of EBRT in 495 patients, while In the other 248 patients EBRT could not be used due to slow tumor regression or the huge initial bulk of tumor. The point A, actual bladder & rectal doses were individually assessed in all patients. The biologically effective dose (BED) to the tumor ($\alpha/\beta$=10) and late-responding tissues ($\alpha/\beta$=3) for both EBRT and HDR-ICBT were calculated. The total BED values to point A, the actual bladder and rectal reference points were the summation of the EBRT and HDR-ICBT. In addition to all the details on dose-fractionation, the other factors (i.e. the overall treatment time, physicians preference) that can affect the schedule of the definitive radiotherapy were also thoroughly analyzed. The association between MD-BED $Gy_3$ and the risk of complication was assessed using serial multiple logistic regression models. The associations between R-BED $Gy_3$ and rectal complications and between V-BED $Gy_3$ and bladder complications were assessed using multiple logistic regression models after adjustment for age, stage, tumor size and treatment duration. Serial Coxs proportional hazard regression models were used to estimate the relative risks of recurrence due to MD-BED $Gy_{10}$, and the treatment duration. Results: The overall complication rate for RTOG Grades $1\~4$ toxicities was $33.1\%$. The 5-year actuarial pelvic control rate for ail 743 patients was $83\%$. The midline cumulative BED dose, which is the sum of external midline BED and HDR-ICBT point A BED, ranged from 62.0 to 121.9 $Gy_{10}$ (median 93.0) for tumors and from 93.6 to 187.3 $Gy_3$ (median 137.6) for late responding tissues. The median cumulative values of actual rectal (R-BED $Gy_3$) and bladder Point BED (V-BED $Gy_3$) were 118.7 $Gy_3$ (range $48.8\~265.2$) and 126.1 $Gy_3$ (range: $54.9\~267.5$), respectively. MD-BED $Gy_3$ showed a good correlation with rectal (p=0.003), but not with bladder complications (p=0.095). R-BED $Gy_3$ had a very strong association (p=<0.0001), and was more predictive of rectal complications than A-BED $Gy_3$. B-BED $Gy_3$ also showed significance in the prediction of bladder complications in a trend test (p=0.0298). No statistically significant dose-response relationship for pelvic control was observed. The Sandwich and Continuous techniques, which differ according to when the ICR was inserted during the EBRT and due to the physicians preference, showed no differences in the local control and complication rates; there were also no differences in the 3 vs. 5 Gy fraction size of HDR-ICBT. Conclusion: The main reasons optimal dose-fractionation guidelines are not easily established is due to the absence of a dose-response relationship for tumor control as a result of the high-dose gradient of HDR-ICBT, individual differences In tumor responses to radiation therapy and the complexity of affecting factors. Therefore, in our opinion, there is a necessity for individualized tailored therapy, along with general guidelines, in the definitive radiation treatment for cervix cancer. This study also demonstrated the strong predictive value of actual rectal and bladder reference dosing therefore, vaginal gauze packing might be very Important. To maintain the BED dose to less than the threshold resulting in complication, early midline shielding, the HDR-ICBT total dose and fractional dose reduction should be considered.