• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.441-452
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• 2000

Background : It is well known that the prevalence of lung cancer is higher in idiopathic pulmonary fibrosis (IPF) patients than in the general population. This high prevalence is explained by the concept of 'scar carcinoma'. There have been several reports on the prevalence of histologic typo of lung cancer in IPF with conflicting results. Despite of the high smoker rate in almost all previous reports, none considered the smoking history of patients. Therefore we performed a separate studies on fibrosis associated lung cancer and smoking associated lung cancer. The purpose of this study is to investigate the proportion of lung cancer in IPF that is fibrosis associated and to determine the most common histologic type in fibrosis associated lung cancer in IPF. Method : A retrospective review of medical records and radiologic studies was performed for cases of lung cancer with IPF. We investigated smoking history, sequence of diagnosis of lung cancer and IPF, histologic type of lung cancer and the cancer location, especially whether the location is associated with fibrosis. To evaluate the proportion of fibrous associated lung cancer, the lung cancer in IPF were categorized according to the presence of fibrosis at cancer location. Results : Fifty seven patients were subjects for this analysis. Six (11%) cases were diagnosed as lung cancer during follow-up for IPF, and both diseases were diagnosed simultaneously in the others. Ninety four percent of patients were smokers and the average smoking amount was 47.1$\pm$21.9 pack-year. Among the patients with IPF and lung cancer, 42(80.8%) cases were considered as "fibrosis associated". The remainder was "not fibrosis associated" and probably was due to smoking etc. Although the most frequent histologic type was squamous cell carcinoma as a whole, adenocarcinoma was the prominent histologic type in "fibrosis associated lung cancer." Conclusion : Considering the proportion of "fibrosis not associated lung cancer" in the patients with IPF and lung cancer, significant proportion of lung cancer in IPF may not be fibrosis induced. This may influence the distribution of histologic type of lung cancer in IPF.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.310-322
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• 2000

Background : Phospholipase C(PLC) plays an important role in cellular signal transduction and is thought to be critical in cellular growth, differentiation and transformation of certain malignancies. Two second messengers produced from the enzymatic action of PLC are diacylglycerol (DAG) and inositol 1, 4, 5-trisphosphate (IP3). These two second messengers are important in down stream signal activation of protein kinase C and intracellular calcium elevation. In addition, functional domains of the PLC isozymes, such as Src homology 2 (SH2) domain, Src homology 3 (SH3) domain, and pleckstrin homology (PH) domain play crucial roles in protein translocation, lipid membrane modificailon and intracellular memrane trafficking which occur during various mitogenic processes. We have previously reported the presence of PLC-${\gamma}1$, ${\gamma}2$, ${\beta}1$, ${\beta}3$, and ${\delta}1$ isozymes in normal human lung tissue and tyrosine-kinase-independent activation of phospholipase C-${\gamma}$ isozymes by tau protein and AHNAK. We had also found that the expression of AHNAK protein was markedly increased in various mstologic types of lung can∞r tissues as compared to the normallungs. However, the report concerning expression of various PLC isozymes in lung canærs and other lung diseases is lacking. Therefore, in this study we examined the expression of PLC isozymes in the paired surgical specimens taken from lung cancer patients. Methods : Surgically resected lung cancer tissue samples taken from thirty seven patients and their paired normal control lungs from the same patients, The expression of various PLC isozymes were studied. Western blot analysis of the tissue extracts for the PLC isozymes and immunohistochemistry was performed on typical samples for localization of the isozyme. Results : In 16 of 18 squamous cell carcinomas, the expression of PLC-${\gamma}1$ was increased. PLC-${\gamma}1$ was also found to be increased in all of 15 adenocarcinoma patients. In most of the non-small cell lung cancer tissues we had examined, expression of PLC-${\delta}1$ was decreased. However, the expression of PLC-${\delta}1$ was markedly increased in 3 adenocarcinomas and 3 squamous carcinomas. Although the numbers were small, in all 4 cases of small cell lung cancer tissues, the expression of PLC-${\delta}1$ was nearly absent. Conclusion : We found increased expression of PLC-${\gamma}1$ isozyme in lung cancer tissues. Results of this study, taken together with our earlier findings of AHNAK protein-a putative PLD-${\gamma}$, activator-over-expression, and the changes observed in PLC-${\delta}1$ in primary human lung cancers may provide a possible insight into the derranged calcium-inositol signaling pathways leading to the lung malignancies.

• 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.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.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.209-216
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• 1999

Purpose : To evaluate the effectiveness of external radiation therapy and the prognostic factors, we retrospectively analyzed therapeutic results of malignant extrahepatic biliary obstruction (EHBO). Methods and Materials : We analyzed the results of the external radiation therapy in 59 patients of inoperable malignant EHBO who had been treated with more than 10 Gy of external radiation therapy from April 1984 to December 1990. There were 21 stomach cancer ($35.6\%$), 12 pancreas cancer ($20.3\%$), 15 extrahepatic biliary cancer ($18.0\%$) and 11 another cancer ($18.0\%$). Their pathologies were confirmed in 31 patients ($52.5\%$). They divided into 27 adenocarcinoma and 4 nonadenocarcinoma. Their chief complaints were jaundice in 47 patients ($79.7\%$) and abdominal pain in 15 patients ($49.2\%$). Twelve patients had slightly increased bilirubin level in liver function test without jaundice. We treated twenty four patients ($40.6\%$) with percutaneous transhepatic biliary drainage (PTBD) and 32 patients ($54\%$) with systemic chemotherapy (CT). We performed external radiation therapy (ERT) upto $10.8\~55.8$ Gy (median 37.8 Gy) with palliative aim. Results : Overall median survival duration was $7.80\pm1.15$ months. The response rates of jaundice were $81.8\%$ in PTBO group and $66.7\%$ in non-PTBD group without statistical significance. The improving rate of jaundice was not significantly different in decreased ratio of total bilirubin level. But abdominal pain was more decreased in CT group than non-CT group (p<0.05). The significant prognostic factors were high performance status (Karnofski Performance Status >70), total radiation dose more than 35 Gy and good response of pain after therapy. There were increased in bacterial cholagitis in PTBD group and gastrointestinal complications in CT group. Conclusion : External radiotheapy could improve jaundice and abdominal pain in malignant EHBO patients, Overall survival duration was prolonged in patients with higher performance status and patients who had been treated with more than 35 Gy of total radiation dose. In the future, we expect not only better palliative role but also the prolongation of survival of using the ERT combined with other treatment method. But to achieve certain conclusion, we need luther study consisted with many kinds of treatment methods including new technologies in RT.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.217-222
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• 1999

Purpose : To evaluate prognostic factors and survival rates of the patients who received radiation therapy for locally recurrent uterine cervical cancer after curative surgery. Materials and Methods : Between October 1983 and July 1990, fifty three patients who received radiation therapy for locally recurrent cervical cancer after curative surgery at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, The Catholic University of Korea were analysed retrospectively. Age at diagnosis ranged from 33 to 69 years (median 53 years). Pathological analysis showed that forty five ($84.9\%$) patients had squamous cell carcinoma, seven ($13.2\%$) patients had adenocarcinoma, and one (1.9%) patient had adenosquamous cell carcinoma. The interval between hysterectomy and tumor recurrence ranged from 2 months to 25 years (mean 34.4 months). The recurrent sites were vaginal stump in 41 patients ($77.4\%$) and pelvic side wall in 12 patients ($22.6\%$). Recurrent tumor size was devided into two groups : less than 3 cm in 43 patients ($81.1\%$) and more than 3 cm in 10 patients ($18.9\%$). External beam irradiation of whole pelvis was done first up to 46.8 Gy to 50.4 Gy in 5 weeks to 6 weeks, followed by either external beam boost to the recurrent site in 18 patients ($34\%$) or intracavitary irradiation in 24 patients ($45.3\%$). Total dose of radiation ranged from 46.8 Gy to 111 Gy (median 70.2 Gy). Follow up period ranged from 2 to 153 months with a median of 35 months. Results : Overall response rate was $66\%$ (35/53). Among them, six patients ($17.1\%$) relapsed between 7 months and 116 months after radiation therapy (mean 47.7 months), Therefore overall recurrence rate was $45.3\%$. Overall five-year actuarial survival rate was $78.9\%$ and distant failure rate was $10\%$ (5/50). The significant prognostic factors affecting survival rate were interval between primary surgery and tumor recurrence (p=0.0055), recurrent tumor size (p=0.0039), and initial response to radiation therapy (p=0.0428). Complications were observed in 10 ($20/%$) patients, which included mild to moderate lower gastrointestinal, genitourinary, or skin manifestations. One patient died of pulmonary embolism just after intracavitary irradiation. Conclustion : Radiation therapy is the effective treatment for the patients with locally recurrent cervical cancer after curative surgery. These results suggest that interval between primary surgery and tumor recurrence, recurrent tumor size, and initial response to radiation therapy were significant prognostic factors for recurrent cervical cancer.

• Radiation Oncology Journal
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• v.26 no.2
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• pp.83-90
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• 2008

Purpose: For the first time, a nationwide survey of the Patterns of Care Study(PCS) for the various radiotherapy treatments of esophageal cancer was carried out in South Korea. In order to observe the different parameters, as well as offer a solid cooperative system, we compared the Korean results with those observed in the United States(US) and Japan. Materials and Methods: Two hundreds forty-six esophageal cancer patients from 21 institutions were enrolled in the South Korean study. The patients received radiation theraphy(RT) from 1998 to 1999. In order to compare these results with those from the United States, a published study by Suntharalingam, which included 414 patients[treated by Radiotherapy(RT)] from 59 institutions between 1996 and 1999 was chosen. In order to compare the South Korean with the Japanese data, we choose two different studies. The results published by Gomi were selected as the surgery group, in which 220 esophageal cancer patients were analyzed from 76 facilities. The patients underwent surgery and received RT with or without chemotherapy between 1998 and 2001. The non-surgery group originated from a study by Murakami, in which 385 patients were treated either by RT alone or RT with chemotherapy, but no surgery, between 1999 and 2001. Results: The median age of enrolled patients was highest in the Japanese non-surgery group(71 years old). The gender ratio was approximately 9:1(male:female) in both the Korean and Japanese studies, whereas females made up 23.1% of the study population in the US study. Adenocarcinoma outnumbered squamous cell carcinoma in the US study, whereas squamous cell carcinoma was more prevalent both the Korean and Japanese studies(Korea 96.3%, Japan 98%). An esophagogram, endoscopy, and chest CT scan were the main modalities of diagnostic evaluation used in all three countries. The US and Japan used the abdominal CT scan more frequently than the abdominal ultrasonography. Radiotherapy alone treatment was most rarely used in the US study(9.5%), compared to the Korean(23.2%) and Japanese(39%) studies. The combination of the three modalities(Surgery+RT+Chemotherapy) was performed least often in Korea(11.8%) compared to the Japanese(49.5%) and US(32.8%) studies. Chemotherapy(89%) and chemotherapy with concurrent chemoradiotherapy(97%) was most frequently used in the US study. Fluorouracil(5-FU) and Cisplatin were the most preferred drug treatments used in all three countries. The median radiation dose was 50.4 Gy in the US study, as compared to 55.8 Gy in the Korean study regardless of whether an operation was performed. However, in Japan, different median doses were delivered for the surgery(48 Gy) and non-surgery groups(60 Gy). Conclusion: Although some aspects of the evaluation of esophageal cancer and its various treatment modalities were heterogeneous among the three countries surveyed, we found no remarkable differences in the RT dose or technique, which includes the number of portals and energy beams.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.709-719
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• 1996

Background: Surgical resection is the only way to cure non-small cell lung cancer(NSCLC) and the prognosis of NSCLC in patients who undergo a complete resection is largely influenced by the pathologic stage. After surgical resection, recurrences in distant sites is more common than local recurrences. An effective postoperative adjuvant therapy which can prevent recurrences is necessary to improve long tenn survival Although chemotherapy and radiotherapy are still the mainstay in adjuvant therapy, the benefits of such therapies are still controversial. We initiated this retrospective study to evaluate the effects of adjuvant therapies and analyze the prognostic factors for survival after curative resection. Method: From 1990 to 1995, curative resection was perfomled in 282 NSCLC patients with stage I, II, IIIa, Survival analysis of 282 patients was perfonned by Kaplan-Meier method. The prognostic factors, affecting survival of patients were analyzed by Cox regression model. Results: Squamous cell carcinoma was present in 166 patients(59%) ; adenocarcinoma in 86 pmients(30%) ; adenosquamous carcinoma in II parients(3.9%); and large cell undifferentiated carcinoma in 19 patients(7.1%). By TNM staging system, 93 patients were in stage I; 58 patients in stage II ; and 131 patients in stage rna. There were 139 postoperative recurrences which include 28 local and 111 distant failures(20.1% vs 79.9%). The five year survival rate was 50.1% in stage I ; 31.3% in stage II ; and 24.1% in stage IIIa(p <0.0001). The median survival duration was 55 months in stage I ; 27 months in stage II ; and 16 months in stage rna. Among 131 patients with stage rna, the median survival duration was 19 months for 81 patients who received postoperative adjuvant chemotherapy only or cherne-radiotherapy and 14 months for the other 50 patients who received surgery only or surgery with adjuvant radiotherapy(p=0.2982). Among 131 patients with stage IIIa, the median disease free survival duration was 16 months for 21 patients who received postop. adjuvant chemotherapy only and 4 months for 11 patients who received surgery only(p=0.0494). In 131 patients with stage IIIa, 92 cases were in N2 stage. The five year survival rate of the 92 patients with N2 was 25% and their median survival duration was 15 months. The median survival duration in patients with N2 stage was 18 months for those 62 patients who received adjuvant chemotherapy and 14 months for the other 30 patients who did not(p=0.3988). The median survival duration was 16 months for those 66 patients who received irradiation and 14 months for the other 26 patients who did not(p=0.6588). We performed multivariate analysis to identify the factors affecting prognosis after complete surgical resection, using the Cox multiple regression model. Only age(p=0.0093) and the pathologic stage(p<0.0001) were significam prognostic indicators. Conclusion: The age and pathologic stage of the NSCLC parients are the significant prognostic factors in our study. Disease free survival duration was prolonged with statistical significance in patients who received postoperative adjuvant chemotherapy but overall survival duration was not affected according to adjuvant therapy after surgical resection.

• Radiation Oncology Journal
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• v.24 no.3
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• pp.171-178
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• 2006

[ $\underline{Purpose}$ ]: To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. $\underline{Materials\;and\;Methods}$: From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range $34{\sim}74$) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follows: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of $45{\sim}50.4\;Gy$ (median: 50.4 Gy) over $5{\sim}5.5$ weeks. Ir-192 HDR intracavitary brachytherapy (ICBT) was given after a total dose of 41.4 Gy. HDR-ICBT was performed twice a week, with a fraction point A dose of 4 Gy and median dose to point A was 28 Gy (range: $16{\sim}32\;Gy$) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT+ICBT) was $88\;Gy_{10}$ (range: $77{\sim}94\;Gy_{10}$). The median cumulative BED at ICRU 38 reference point (EBRT+ICBT) was $131\;Gy_3$ (range: $122{\sim}140\;Gy_3$) at point A, $109\;Gy_3$ (range: $88{\sim}125\;Gy_3$) at the rectum and $111\;Gy_3$ (range: $91{\sim}123\;Gy_3$) at the urinary bladder. Cisplatin ($60\;mg/m^2$) and 5-FU ($1,000\;mg/m^2$) was administered intravenously at 3 weeks interval from the first day of radiation for median 5 (range: $2{\sim}6$) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range: $8{\sim}50$ months). $\underline{: The complete response rate after concurrent chemoradiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic complications (RTOG grade 1-2) occurred in 3 patients (10%) and one patient had suffered from severe leukopenia (RTOG grade 4) during concurrent treatment. Acute minor enterocolitis (RTOG grade 1-2) occurred in 11 patients (37%) and one patient (3%) was suffered from colon perforation during radiation therapy. Late colitis of RTOG grade 1 occurred in 5 patients (15%). Acute cystitis of RTOG grade 1 occurred in 12 patients (40%) and late cystitis of RTOG grade 2 occurred in one patient (3%). No treatment related death was seen. $\underline{Conclusion}$: The results of this study suggest that the concurrent chemoradiation therapy with HDR brachytherapy could be accepted as an effective and safe treatment for cervical cancer.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.275-282
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• 1998

Purpose : The effect of hyperfractionated radiotherapy on locally advanced non-small lung cancer was studied by a retrospective analysis. Materials & Methods : We analyzed sixty one patients of biopsy-confirmed, IIIA and IIIB non-small cell lung cancer. Using the ECOG performance scale, all the patients were scored less than 2. They were treated by curative hyperfractionated radiotherapy alone from Oct. 1992 to Oct. 1995 at the Department of Radiation Oncology. All the patients received 120cGy b.i.d with more than 6 hours interval between each fraction. The total dose of radiation was reached up to 6400-7080 cGy with a mean dose of 6934 cGy. The results were analyzed retrospectively. Results : The overall survival rate was 53 1$\%$ in 1 year, 9.9$\%$ in 2 years with a median survival time (MST) of 13.9 months. The progression free survival (PFS) rate was 37.0$\%$ in 1 year, 8.9$\%$ in 2 years. Twenty two Patients were classified as complete responders to this treatment and their MST was 19.5 months When this was compared with that of partial responders (MST: 11 7months), it was statistically significant (p=0.0003). Twenty nine patients of stage IIIA showed a better overall survival rate (1yr 63.3$\%$, 2yr 16.8$\%$) than IIIB patients (1yr 43.3$\%$, 2yr 3.6$\%$), which was also statistically significant (p=0.003). Patients with adenocarcinoma showed a better survival rate (1yr 64.3$\%$, 2yr 21.4$\%$) than that of squamous cell counterpart (1yr 49.4$\%$, 2yr 7.4$\%$), although this was not significant statistically (p=0.61). Two patients developed fatal radiation-induced pneumonia right after the completion of the treatment which progressed rapidly and they all died within 2 months. One patient developed radiation-induced fibrosis after 13 months. He refused further treatment and died soon after the development of fibrosis. Conclusion : Among locally advanced NSCLC, hyperfractionated radiotherapy was effective on stage IIIA patients by increasing MST with acceptable toxicities. Acute radiation-induced pneumonia should be carefully monitored and must be avoided during or after this treatment.