Background: Accurate assessment of disease progression requires proper understanding of natural disease process which is often hidden and unobservable. For this purpose, disease status should be clearly detected. But in most diseases it is not possible to detect such status. This study, therefore, aims to present a model which both investigates the unobservable disease process and considers the error probability in diagnosis of disease states. Materials and Methods: Data from 330 patients with gastric cancer undergoing surgery at the Iran Cancer Institute from 1995 to 1999 were analyzed. Moreover, to estimate and assess the effect of demographic, diagnostic and clinical factors as well as medical and post-surgical variables on transition rates and the probability of misdiagnosis of relapse, a hidden Markov multi-state model was employed. Results: Classification errors of patients in alive state without a relapse ($e_{21}$) and with a relapse ($e_{12}$) were 0.22 (95% CI: 0.04-0.63) and 0.02 (95% CI: 0.00-0.09), respectively. Only variables of age and number of renewed treatments affected misdiagnosis of relapse. In addition, patient age and distant metastasis were among factors affecting the occurrence of relapse (state1${\rightarrow}$state2) while the number of renewed treatments and the type and extent of surgery had a significant effect on death hazard without relapse (state2${\rightarrow}$state3)and death hazard with relapse (state2${\rightarrow}$state3). Conclusions: A hidden Markov multi-state model provides the possibility of estimating classification error between different states of disease. Moreover, based on this model, factors affecting the probability of this error can be identified and researchers can be helped with understanding the mechanisms of classification error.
Journal of the Earthquake Engineering Society of Korea
/
v.11
no.4
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pp.53-63
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2007
Seismic design codes are developed mainly based on the observation of the behavior of structures in the high seismicity regions where structures may experience significant amount of inelastic deformations and major earthquakes may result in structural damages in a vast area. Therefore, seismic loads are reduced in current design codes for building structures using response modification factors which depend on the ductility capacity and overstrength of a structural system. However, structures in low seismicity regions, subjected to a minor earthquake, will behave almost elastically because of the larger overstrength of structures in low seismicity regions such as Korea. Structures in low seismicity regions may have longer periods since they are designed to smaller seismic loads and main target of design will be minor or moderate earthquakes occurring nearby. Ground accelerations recorded at stations near the epicenter may have somewhat different response spectra from those of distant station records. Therefore, it is necessary to verify if the seismic design methods based on high seismicity would he applicable to low seismicity regions. In this study, the adequacy of design spectra, period estimation and response modification factors are discussed for the seismic design in low seismicity regions. The response modification factors are verified based on the ductility and overstrength of building structures estimated from the farce-displacement relationship. For the same response modification factor, the ductility demand in low seismicity regions may be smaller than that of high seismicity regions because the overstrength of structures may be larger in low seismicity regions. The ductility demands in example structures designed to UBC97 for high, moderate and low seismicity regions were compared. Demands of plastic rotation in connections were much lower in low seismicity regions compared to those of high seismicity regions when the structures are designed with the same response modification factor. Therefore, in low seismicity regions, it would be not required to use connection details with large ductility capacity even for structures designed with a large response modification factor.
Purpose: Vascular endothelial growth factor (VEGF)-C and its tyrosine kinase receptor, VEGF receptor (VEGFR)-3 are recently known to have lymphangiogenic activities in various tumor types. In this study, we determined whether the expression of lymphangiogenic factors correlate with nodal metastasis or survival in a nude mouse model of oral squamous cell carcinoma (OSCC). Methods: Three OSCC cells (KB, SCC4, SCC9) were xenografted into the right mandibular gland of athymic nude mice. The mice were followed for tumor development and growth, and the mice were sacrificed when they had lost more than 20% of their initial body weight, or the diameter of the induced tumor exceeds 20 mm. After necropsy, the murine tumors were examined histologically and radiologically (micro-positron emission tomography computed tomography) for regional or distant metastasis. We performed immunohistochemical assays with anti-VEGF-C, VEGFR-3, CD105, and D2-40 antibodies. Immunofluorescence double staining for LYVE-1/CD31 was also performed. To quantify the VEGF-C and VEGFR-3 level in the cancer tissue, Western blotting was performed. Finally, we determined the correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time. Results: OSCC tumor cells into the mandibular gland of the nude mice successfully resulted in the formation of recapitulating orthotopic tumor. Tumor cells of the induced tumor did not express VEGF-C. VEGF-C/VEGFR-3 expression was mainly distributed in the endothelial cells of the stromal area. There were no correlation between the degree of expression of VEGF-C/VEGFR-3 and the mean survival time of mice injected with different OSCC cell lines. Conclusion: An recapitulating orthotopic model of OSCC in nude mice was established, which copies the cervical nodal metastasis of human OSCC. Overexpression of lymphangiogenic factors seems to have no effect on survival of hosts in this in vivo experiment.
Hallmarks of clinical behaviors of adenoid cystic carcinoma(ACC) of salivary glands are the delayed onset of vascular metastasis and poor responses to classical chemotherapeutic agents. Poor prognoses from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, cellular and molecular characteristics that influence the dissemination of metastatic cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of angiogenic proteins in benign (pleomorphic adenoma) and malignant (ACC, mucoepidermoid carcinoma) tumors of salivary glands and compared each other and to those in oral squamous cell carcinoma. Using surgical specimens, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), phosphorylated VEGFR-2 (pVEGFR-2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. Most angiogenic factors were overexpressed in malignant salivary tumors than in pleomorphic adenoma which is benign nature. Moreover, ACC demonstrated more expression of VEGFR-2 than that of squamous cell carcinoma which used as control. Conclusively, these data show those angiogenic factors produced by salivary gland tumors may affect the propagation and metastasis of malignant cells of salivary tumors, and could be used as biomarkers for the malignant transformation of salivary gland tumors. Prospectively, although further studies will be needed, these biomarkers related to angiogenesis can be molecular targets for the therapy of salivary ACC, which has propensity for delayed vascular metastasis.
Background and Purpose : Oral squamous cell carcinoma (OSCC) is one of the most aggressive tumors of the head and neck area. OSCC is known to preferentially metastasize via lymphatic system, and resulting cervical lymph node metastasis is the most reliable of treatment failure. But the biological mechanism of the regional nodal metastasis is not clear. So, we determined metastasis-related factors in orthotopic nude mouse models of OSCC. Experimental Design : Two cell lines-KB and YD-10B cells, established from human oral mucosal squamous cell carcinoma, were xenografted into the tissue space of athymic murine mouth floor. The mice were followed for tumor development and growth, the murine tumors were examined histopathologically for local invasion or regional or distant metastasis. Finally, we performed immunohistochemical assays with antiepithelial growth factor (EGF), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), and anti-vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, phosphorylated VEGFR-2/3 (pVEGFR-2/3) antibodies. We also determined the microvessel density. Results : Transplantation of human OSCC tumor cells into the mouth floor successfully resulted in the formation of orthotopic tumors. KB cell line showed significantly higher tumor proliferation and higher nodal metastatic potential than YD-10B cell line. Furthermore, immunohistochemical staining demonstrated higher expression of EGFR/pEGFR, VEGF, and pVEGFR-2/3 as well as higher microvessel density in KB murine tumors than in YD-10B murine tumors. Conclusion : An orthotopic model of OSCC in athymic mice was established which copies the cervical lymph nodal metastasis of human OSCC. Our mouth floor model should facillitate the understanding of the molecular pathogenesis of cervical nodal metastasis of OSCC.
Kim, Dae Hyeon;Na, Kwon Joong;Park, In Kyu;Kang, Chang Hyun;Kim, Young Tae;Park, Samina
Journal of Chest Surgery
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v.54
no.5
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pp.361-368
/
2021
Background: In general, a 2-cm surgical margin is recommended for limited resection to obtain equivalent oncologic outcomes to lobectomy for lung cancer. This study aimed to examine the patterns of recurrence and prognostic factors for recurrence in patients with a close parenchymal resection margin. Methods: From January 2009 to April 2017, 156 patients with stage I lung cancer who underwent segmentectomy with a close resection margin (<2 cm) were enrolled. Recurrence-free survival and overall survival were assessed. In addition, predisposing factors for recurrence were evaluated. Results: The mean tumor size was 1.7±0.8 cm and the parenchymal resection margin was 1.1±0.6 cm. Recurrence developed in 17 (10.7%) of the 156 patients, and the 5-year recurrence-free survival rate was 88.9%. Distant metastasis (7.7%) was the predominant recurrence pattern. The isolated local recurrence rate was 1.9%. Multivariate Cox regression analysis revealed that age, tumor size, mediastinal lymph node dissection, postoperative complications, and histologic type were significant predisposing factors for recurrence. However, parenchymal margin distance did not significantly affect the long-term prognosis. Conclusion: Segmentectomy with a close resection margin for early-stage lung cancer in selected patients resulted in acceptable recurrence and survival. However, patients with tumors larger than 2 cm, squamous cell carcinoma histology, and insufficient mediastinal evaluation should be carefully followed up for recurrence.
Yoon, Seung Hwan;Jung, Joon Chul;Park, In Kyu;Park, Samina;Kang, Chang Hyun;Kim, Young Tae
Journal of Chest Surgery
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v.52
no.3
/
pp.148-154
/
2019
Background: This study investigated the clinical outcomes of surgical treatment of primary chest wall soft tissue sarcoma (CW-STS). Methods: Thirty-one patients who underwent surgery for CW-STS between 2000 and 2015 were retrospectively reviewed. The disease-free and overall survival rates were estimated using the Kaplan-Meier method, and prognostic factors were analyzed using a Cox proportional hazards model. Results: The median follow-up duration was 65.6 months. The most common histologic type of tumor was malignant fibrous histiocytoma (29%). The resection extended to the soft tissue in 14 patients, while it reached full thickness in 17 patients. Complete resection was achieved in 27 patients (87.1%). There were 5 cases of local recurrence, 3 cases of distant metastasis, and 5 cases of combined recurrence. The 5-year disease-free rate was 49%. Univariate analysis indicated that incomplete resection (p<0.001) and stage (p=0.062) were possible risk factors for recurrence. Multivariate analysis determined that incomplete resection (p=0.013) and stage (p=0.05) were significantly associated with recurrence. The overall 5- and 10-year survival rates were 86.8% and 64.3%, respectively. No prognostic factor for survival was identified. Conclusion: Long-term primary CW-STS surgery outcomes were found to be favorable. Incomplete microscopic resection and stage were risk factors for recurrence.
KIM, O-Tae;JO, Hyun-Su;CHANG, Ho-Young;LEE, Yoo-Won
Journal of the Korean Society of Fisheries and Ocean Technology
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v.58
no.3
/
pp.251-261
/
2022
Tuna purse seine fishery (TPF) constitute more than 60% of distant water fishery production in Korea based on a statistic of 2018, and 28 ships from four different companies were under operation at the western and central Pacific Ocean. On this research, common risk factors during TPF were investigated via enumeration of five years Korean fisherman's insurance payment statement, followed by some counterplans to diminish the accident rate. The accident rate of TPF on the Pacific Ocean peaked by 43.0% in 2014 and constantly decreased to 23.0% until 2018, presenting an average of 33.6%. Meanwhile, the accident rate on the Indian Ocean reached the highest point 55.1% in 2014 and declined to 11.6% in 2016, having an average of 24.7%. The average accident rate of the Indian Ocean scored 8.9% lower than the rate of the Pacific Ocean, but no statistic significance was observed. Depending on the process of operation, 'casting or hauling of net' was the most frequent part that people received an injury (40.4%). When the accidents were classified by their types, 'falling down' was the most recurrent cause of the injuries (28.5%). At the point of severity, the worst injuries were induced by crush hazard. Considering aforementioned accident frequency and severity, all the factors on the accident type list were divided into three different groups including high risk, moderate risk, and common risk. This study is expected to contribute to the reduction of occupational accidents during the work of fishermen and establishment of a safety management system for distance water fishing vessels.
Guoxue Tang;Xin An;Huiling Xiang;Lixian Liu;Anhua Li;Xi Lin
Korean Journal of Radiology
/
v.21
no.5
/
pp.550-560
/
2020
Objective: To evaluate the interobserver agreement, diagnostic value, and associated clinical factors of automated breast ultrasound (ABUS) coronal features in differentiating breast lesions. Materials and Methods: This study enrolled 457 pathologically confirmed lesions in 387 female (age, 46.4 ± 10.3 years), including 377 masses and 80 non-mass lesions (NMLs). The unique coronal features, including retraction phenomenon, hyper- or hypoechoic rim (continuous or discontinuous), skipping sign, and white wall sign, were defined and recorded. The interobserver agreement on image type and coronal features was evaluated. Furthermore, clinical factors, including the lesion size, distance to the nipple or skin, palpability, and the histological grade were analyzed. Results: Among the 457 lesions, 296 were malignant and 161 were benign. The overall interobserver agreement for image type and all coronal features was moderate to good. For masses, the retraction phenomenon was significantly associated with malignancies (p < 0.001) and more frequently presented in small and superficial invasive carcinomas with a low histological grade (p = 0.027, 0.002, and < 0.001, respectively). Furthermore, continuous hyper- or hypoechoic rims were predictive of benign masses (p < 0.001), whereas discontinuous rims were predictive of malignancies (p < 0.001). A hyperechoic rim was more commonly detected in masses more distant from the nipple (p = 0.027), and a hypoechoic rim was more frequently found in large superficial masses (p < 0.001 for both). For NMLs, the skipping sign was a predictor of malignancies (p = 0.040). Conclusion: The coronal plane of ABUS may provide useful diagnostic value for breast lesions.
Purpose: The prognosis of stage IV gastric cancer is poor with the 5-year survival rate still being about 10%. We investigated the prognostic factors of stage IV gastric cancer patients who underwent resection. Materials and Methods: A retrospective study of 383 patients with stage IV gastric cancer who underwent surgery in our department between September 1983 to December 2000 was conducted. We classified the 383 patients into two groups: patients surviving 2 years or more (n=77) and those surviving less than 2 years (n=306). Clinicopathologic differences were analyzed between the two groups. We also performed univariate and multivariate analyses of various clinicopathologic factors concerning survival. Results: Statistically significant clinicopathologic differences between the two groups were observed in regard to macroscopic type, distant metastasis, lymph node dissection, curability, and histology. Curability and histology were significant survival factors in 2-year survival. The 5-year survival rate was 5.4% in stage IV gastric cancer. Significant differences in survival among macroscopic type, distant metastasis, lymph node dissection, curability and histology were observed in the univariate analysis. In the Multivariate analysis, Curability, lymph node dissection, and histology were significantly beneficial factors for survival. Conclusion: Lymph node dissection, curability, and histology were independent prognostic factors in stage IV gastric cancer, and radical treatment is recommended to improve survival.
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