• Radiation Oncology Journal
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• v.22 no.4
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• pp.288-297
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• 2004

Puporse: The aims of this study were to evaluate the change of $[^18F]fluoromisonidazole$($[^18F]FMISO$) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia ($42^{circ}C$) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. Methods and Materials: $[^18F]FMISO$ was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at $42^{circ}C$ for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air, The biodistribution of these agents were obtained at 3 h after $[^18F]FMISO$ injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10- um sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Results: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for $[^18F]FMISO$ ($1.56{\pm}1.03$ vs. $0.67{\pm}0.30$; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of $[^18F]FMISO$ uptake was significantly decreased. Conclusion: Mild hyperthermla and nicotinamide significantly improved tumor hypoxia using $[^18F]FMISO$ and this uptake reflected tumor hypoxic status.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.253-264
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• 2002

Background : It has been reported that the expression of protein which influences on the cell cycle is significantly involved in the development, progress, treatment response, and survival of cancer, and also that the degree of expression of p27 and CDK4 is related to the prognosis. Recent research has revealed that uteroglobin, tumor suppressor gene, is related to cell cycle. This study is focused on the relations between expression of proteins related to cell cycle and clinical index of and survival of NSCLC. Methods : We examined immunohistochemically specimens of 110 surgically resected NSCLCs for expression of p27, CDK, Uteroglobin. Tissue array slide were obtained from 110 surgically resected NSCLCs. Immunohistochemical staining was performed by immuno-peroxidase technique using avidin-biotinylated horseradish peroxidase complex. Results : In 110 patients with resected NSCLCs, the ratio of male to female was 87:13, the median age was $56.43{\pm}9.41$ yrs. The positive staining of p27 was detected in 75% of the cases. A non-statistically significant trend toward increased p27 expression was observed in smoker and squamous cell cancer. The positive staining of CDK4 was detected in 89%, which was the highest expression of protein among 3 types. The survival ratio of CDK4 negative staining group was higher than that of positive staining group, which was significant diffrernce(P<0.05). There was no association between p27 or uteroglobin expression and survival. Conclusion : The expression degree of CDK4 is related to the prognosis. This findings suggests that the measurement of CDK4 may be useful in identifying patient at high risk for disease recurrence and survival.

• Tuberculosis and Respiratory Diseases
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• v.44 no.6
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• pp.1285-1295
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• 1997

Background : EGFR is one of the initial step in signal transduction pathway about multistep carcinogenesis. It is homologous to oncogene erbB-2 and is the receptor for EGF and TGF alpha. EGFR has important role in the growth and differentiation of tumor cells. So, EGFR in non-small cell lung cancer was examined to search for possible evidence as clinical prognostic factor. Methods : To investigate the role of EGFR in lung cancer, the author performed immunohistochemical stain of EGFR on 57 resected primary non-small cell lung cancer specimens. And the author analyzed the correlation between EGFR expression, clinical parameters, Sand $G_1$ phase fraction and survival. Results : 1) EGFR were detected in 56% of total 57 patients (according to histologic type, squamous cancer 50%, adenocarcinoma 63%, large cell cancer 75%) (according to TNM stage, stage I 64%, stage II 38%, stage III 55%) (according to cellular differentiation, well 50%, moderately 52%, poorly 65%). All differences were insignificant 2) Using the flow cytometric analysis, mean S-phase fraction of EGFR (+) and (-) group were 22.3(${\pm}10.5$)%. 18.0(${\pm}10.9$)% (p>0.05), mean $G_1$-phase fraction of EGFR (+) and (-) group were 68.4(${\pm}11.6$)%, 71.1(${\pm}12.8$)%, (p>0.05) 3) Two-year survival rate of EGFR (+) and (-) group were 53%, 84%, median survival time of EGFR (+) and (-) group were 26, 53 months. (p<0.05, Kaplan-Meier, generalized Wilcox) Conclusion : EGFR immunostaining may be a simple and useful method for survival prediction in non-small cell lung cancer.

• Radiation Oncology Journal
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• v.20 no.4
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• pp.323-327
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• 2002

Purpose : To evaluate the outcome of early stage non-small cell lung cancer patients who were treated with radiation therapy alone and define the optimal radiotherapeutic regimen for these patients. Materials and Methods : A retrospective review was peformed on patients with sage I or II non-small cell carcinoma of the lung that were treated at our institution between June, 1987 and May, 2000. A total of 21 patients treated definitively with radiation therapy alone were included in this study. The age of the patients ranged from 53 to 81 years with a median of 66 years. All the patients were male. The medical reasons for inoperability were lack of pulmonary reserve, cardiovascular disease, poor performance status, old age, and patient refusal in the decreasing order. Pathological evidence was not adequate to characterize the non-small cell subtype in two patients. Of the remaining 19 patients, 16 had squamous cell carcinoma and 3 had adenocarcinoma. Treatment was given with conventional fractionation, once a day, five times a week. The doses to the primary site ranged from 56 Gy to 59 Gy. No patients were lost to follow-up. Results : The overall survival rates for the entire group at 2, 3 and 5 years were 41, 30 and $21\%$, respectively. The cause specific survivals at 2, 3 and 5 years were 55, 36 and $25\%$, respectively. An intercurrent disease was the cause of death in two patients. The cumulative local failure rate at 5 years was $43\%$. Nine of the 21 patients had treatment failures after the curative radiotherapy was attempted. Local recurrences as the first site of failure were documented in 7 patients. Therefore, local failure alone represented $78\%$ of the total failures. Those patients whose tumor sizes were less than 4 cm had a significantly better 5 year disease free survival than those with tumors greater than 4 cm $(0\%\;vs\;36\%)$. Those patients with a Karnofsky performance status less than 70 did not differ significantly with respect to actuarial survival when compared to those with a status greater than 70 $(25\%\;vs\;26\%,\;p>0.05)$. Conclusion : Radiation therapy 리one is an effective and safe treatment for early stage non-small ceil lung cancer patients who are medically inoperable or refuse surgery. Also we believe that a higher radiation dose to the primary site could improve the local control rate, and ultimately the overall survival rate.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.480-489
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• 2005

Background : Dysregulation of apoptosis plays an important role in carcinogenesis, tumor progression, and resistance to chemotherapy. X-linked inhibitor of apoptosis (XIAP) is considered to be the most potent caspase inhibitor of all known IAP (inhibitor of apoptosis) family members. This study was designed to assess the pattern of expression and the prognostic value of XIAP in radically resected non-small cell lung carcinoma (NSCLC) patients. Method : The expression of XIAP and its relationship with clinicopathologic parameters (patient age, TNM stage, TNM-pT, TNM-pN, histologic type, VEGF expression, microvessel density, PCNA index) and overall survival were analysed with formalin-fixed, paraffin-embedded blocks from eighty cases of NSCLC. In addition, the apoptotic index (AI) was also assessed. Results : In a regard to histologic type, squamous cell carcinoma (SCC) showed XIAP expression in 91.3%(42/46) and adenocarcinoma (AC) in 61.8%(21/34). The difference was significant(p=0.001). There was no correlation between XIAP expression and other parameters. In the group of AC, XIAP expression showed the signifcant correlation with older age group ${\geq}58years$ and VEGF expression(p=0.028, p=0.014, respectively). The AI in the group with or without XIAP expression were $2.5{\pm}4.9%$ and $18.5{\pm}28.9%$, respectively(p=0.001). Both groups just aforementioned showed no significant difference in median survival time (42.5 months, 29.8 months, respectively). Conclusion : This study suggests that the XIAP expression in NSCLCs could have relation to inhibition of apoptosis, and show differential expression according to histologic type. However, its prognostic role during the progression of NSCLC needs to be further defined.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.428-437
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• 2000

Background : Five year survival rate of postoperative stage I non-small cell lung cancer(NSCLC) reaches to 66%. In the remaining one third of patients, however, cancer recurs and the overall survival of NSCLC remains dismal. To evaluate clinical and pathologic characteristics of recurred NSCLC, the patterns and factors for postoperative recurrence in patients with staged I and II NSCLC were studied. Method : A retrospective analysis was performed in 234 patients who underwent radical resection for pathologic stage I and II NSCLC. All patients who were followed up for at least one year were included in this study. Results : 1) There were 177 men and 57 women The median age was 63. The median duration of the follow up period was 732 days (range 365~1,695 days). The overall recurrence rate was 26.5%, and the recurrence occurred $358.8{\pm}239.8$ days after operation. 2) The ages of recurred NSCLC patients were higher ($63.2{\pm}8.8$ years) than those of non-recurred patients ($60.3{\pm}9.8$ years)(p=0.043). The recurrence rate was higher in stage II (46.9%) than in stage I (18.8%) NSCLC p<0.001. The size of primary lung mass was larger in recurred ($5.45{\pm}3.22\;cm$) than that of non-recurred NSCLC ($3.74{\pm}1.75\;cm$, p<0.001). Interestingly, there were no recurrent cases when the resected primary tumor was less than 2cm. 3) Distant recurrence was more frequent than locoregional recurrence (66.1% vs. 33.9%). Distant recurrence rate was higher in females and in cases of adenocarcinoma. Brain metastasis was more frequent in patients with adenocarcinoma than in those with squamous cell carcinoma (p=0.024). Conclusion: The tumor size and stage were two important factors for determining the possibility of a recurrence. Because distant brain metastasis was more frequent in patients with adenocarinoma, a prospective study should be conducted to evaluate the effectiveness of preoperative brain imaging.

• Radiation Oncology Journal
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• v.4 no.1
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• pp.35-43
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• 1986

Study patients with head and neck carcinoma were studied retrospectively to assess the impact of treatment on survival and local control rate by stage in the Dept of Radiation Therapy, Korea University Hae Wha Hospital between March 1981 and March 1986. Prior to definite radiotherapy, patients were evaluated by physical examination and radiologic studies including chest, laryngogram and CT scan and then these patients were grouped according to the American Joint Committee (AJC) staging system. They were treated with RT alone or postoperative irradiation to the dose of 7,200 cGy/8 weeks and 6,000 cGy/7 weeks respectively. The results were obtained and as follows; 1. Overall male to female sex ratio was 3.6:1. The peak age of patients with head and neck cancer was 6th decade. 2. In all patients treated by RT, the ratio of squamous cell 1 carcinoma to non-squamous cell carcinoma was 3.5:1 (60/77 patients). 3. The incidence according to the anatomic site of primary tumor was 22 cases in the larynx, 12 cases in PNS, 7 cases in nasopharynx, 6 cases in oropharynx, and 3 cases in hypopharynx. 4. According to AJC staging system,4 cases were Stage 1,7 in Stage II, 19 in Stage III and 27 in Stage IV. 5. The overall incidence of cervical lymph node metastases was $43\%$ and subdigatric and submaxillary triangle lymph nodes were the most frequent site of metastases. 6. Local control was achieved in $48\%$ of patients treated by radio-therapy. 7. The lung was the most common site for distant metastases, comprising 4 cases among 7 cases in which distant metastases occured. 8. The overall estimated 5-year survival rate was $43\%$ in the head and neck cancer treated with radiotherapy by life-table analysis.

• Journal of Chest Surgery
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• v.16 no.2
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• pp.231-242
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• 1983

A clinical study was performed on 75 cases of the esophageal cancer and benign esophageal diseases experienced at Department of thoracic & cardiovascular surgery, School of Medicine, Keimyung University during 3 year period from 1978 to 1982. Of 75 cases of the surgical esophageal diseases, there were 35 patients of the esophageal cancer. 17 patients of benign esophageal stenosis, 10 patients of esophageal perforation, 4 patients of diverticulum. 3 patients of achalasia, 2 patients of congenital T-E fistula, one of upper esophageal web, one of esophageal foreign body, one of leiomyoma and patient of hemangioma. First, esophageal carcinoma was more frequent in men than in women by a ratio of five to one, and the peak incidence occurred in the 5th to 6th decade. Dysphagia was the most common symptom in 88.6 percent of our cases. The tumor was located mostly in the middle & the lower one third [91.4%]. The histological diagnosis was made in 35 cases. The squamous cell carcinoma was the most common [82.9%] and the rest was the adenocarcinoma in the lower one third [17.1%]. Thirty-five cases were operated and resection was feasible in the twenty-five patients [71.4%] with 2 cases of hospital mortality [5.7%]. All but two of the esophageal stenosis were caused by corrosive esophagitis and ages ranged from 7 to 70 years with average age of 32 years. Corrective operations were performed on 17 patients of esophageal stenosis of whom 12 patients had esophagocologastrostomy, 3 patients esophagogastrostomy and in non-corrosive esophageal stenosis one case and esophagoplasty and another case had release of external compression. There was one complication of stenosis of the esophageal perforation were traumatic in five cases, empyema in three cases, caustics in one case and postemetic in one case. 10 patients of the esophageal perforation underwent operation: primary closure in 5 cases, two staged colon interposition in 2, esophagogastrostomy in 1 and closed thoracotomy in 2 cases There were 2 complications of leakage of anastomosis sites in postoperative period. 4 patients of traction type of diverticulum underwent diverticulectomy & 3 patients of achalasia underwent modified Heller`s operation. 2 patients of congenital esophageal atresia had distal tracheoesophageal fistula & underwent one staged operation with the results of one death caused by pneumonia. Upper esophageal web had divulsion through the esophagoscope and foreign body in upper esophagus was removed through cervical esophagotomy. One case of leiomyoma in esophagus had esophagectomy and reconstruction with right colon. And one case of hemangioma in esophagus had esophagectomy & esophagogastrostomy.

• Radiation Oncology Journal
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• v.36 no.3
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• pp.192-199
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• 2018

Purpose: Use of radiotherapy combined with chemotherapy is increasing in hypopharyngeal cancer. However, many show residual tumor after radiotherapy. Timing for treatment evaluation and salvage therapy is essential. However, optimal timing for salvage surgery has not been suggested. In this study, we tried to evaluate optimal timing for salvage surgery. Methods and Materials: Patients who were diagnosed with hypopharyngeal squamous cell carcinoma between 2006 and 2015 were retrospectively analyzed. All patients received definitive radiotherapy with or without chemotherapy. Response of all treated patients were analyzed at 1, 3, and 6 months after radiotherapy. Any patients with progression before 6 months were excluded. Results: A total of 54 patients were analyzed. Complete remission (CR) rates at 1 month (CR₁), 3 months (CR₃) and 6 months (CR₆) were 66.7%, 81.5%, and 90.7%, respectively. Non-CR at 1 month (NCR₁), 3 months (NCR₃), and 6 months (NCR₆) showed poor locoregional recurrence-free survival rates (1-year rates of 63.7%, 66.7%, and 0.0%, respectively) compared to CR₁, CR₃, and CR₆ (1-year rates 94.3%, 88.0%, and 91.5%, respectively). Particularly significant differences were seen between CR₆ and NCR₆ (p < 0.001). Of 10 patients with NCR₃, 5 showed CR at 6 months (NCR₃/CR₆). There was no statistical difference in locoregional recurrence-free survival between CR₃ and NCR₃/CR₆ group (p = 0.990). Conclusion: Our data suggest half of patients who did not show CR at 3 months eventually achieved CR at 6 months. Waiting until 6 months after radiotherapy may be appropriate for avoiding additional salvage therapy.

• Tuberculosis and Respiratory Diseases
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• v.66 no.6
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• pp.444-450
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• 2009

Background: Biomarkers for cancer have several potential clinical uses, including the following: early cancer detection, monitoring for recurrence prognostication, and risk stratification. However, no biomarker has been shown to have adequate sensitivity and specificity. Many investigators have tried to validate biomarkers for the early detection and recurrence of lung cancer. To evaluate plasma G-CSF as such a biomarker, protein levels were measured and were found to correlate with the clinicopathological features of primary lung tumors. Methods: Between December 2006 and May 2008, 100 patients with histologically-validated primary lung cancer were enrolled into this study. To serve as controls, 127 healthy volunteers were enrolled into this study. Plasma G-CSF levels were measured in lung cancer patients using the sandwich ELISA system (R & D inc.) prior to treatment. Results: The mean plasma G-CSF levels were 12.2$\pm$0.3 pg/mL and 46.0$\pm$3.8 pg/mL (mean$\pm$SE) in the normal and in the cancer groups, respectively. In addition, plasma G-CSF levels were higher in patients with early lung cancer than in healthy volunteers (p<.001). Plasma G-CSF levels were higher in patients who were under 65 years old or smokers. Within the cancer group, plasma G-CSF levels were higher in patients with non small cell lung cancer than in patients with small cell lung cancer (p<.05). Overall, plasma G-CSF levels were shown to increase dependent upon the type of lung cancer diagnsosed. In the order from highest to lowest, the levels of plasma G-CSF tended to decrease in the following order: large cell carcinoma, squamous cell carcinoma, adenocarcinoma, and bronchioloalveolar carcinoma. Plasma G-CSF levels tended to be higher in patients with advanced TNM stage than in localized TNM stage (I, II