Temporal Change in the Use of Laboratory and Imaging Tests in One Week Before Death, 2006–2015

Background@#To analyze the trends in laboratory and imaging test use 1 week before death among decedents who died in Korean hospitals, tests used per decedents from 2006 to 2015 were examined by using the National Health Insurance Service-Elderly Sample Cohort (NHISESC) dataset. @*Methods@#The study population consisted of decedents aged ≥ 60 years old with a history of admission and death at a hospital, and tests recorded in the payment claims for laboratory and imaging tests according to the Healthcare Common Procedure Coding System codes were examined. Twenty-eight laboratory and 6 imaging tests were selected. For each year, crude rates of test use per decedents in each age and sex stratum were calculated. Regression analysis was used to examine the temporal changes in the test use. @*Results@#During the follow-up period, 6,638 subjects included in the sample cohort died.The number of total laboratory and imaging tests performed on the deceased increased steadily throughout the study year from 10.3 tests/deceased in 2006 to 16.6 tests/deceased in 2015. The use of tests increased significantly in general hospitals, however, not in nursing hospitals. Laboratory tests showed yearly increase, from 9.46/deceased in 2006 to 15.57/ deceased in 2015, an annual increase of 7.39%. On the other hand, the use of imaging increased from 0.86/deceased in 2006 to 1.01/deceased in 2015, which was not statistically significant. @*Conclusion@#The use of tests, especially laboratory tests, increased steadily over the years even among those elderly patients at imminent death. Reducing acute healthcare at the end of life would be one target not only to support the sustainability of the health care budget but also to improve the quality of dying and death.

Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. @*Materials and Methods@#To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. @*Results@#Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. @*Conclusion@#We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

Predicting Recurrence Using the Clinical Factors of Patients with Non-small Cell Lung Cancer After Curative Resection

We present a recurrence prediction model using multiple clinical parameters in patients surgically treated for non-small cell lung cancer. Among 1,578 lung cancer patients who underwent complete resection, we compared the early-recurrence group with the 3-yr non-recurrence group for evaluating those factors that influence early recurrence within one year after surgery. Adenocarcinoma and squamous cell carcinoma were analyzed independently. We used multiple logistic regression analysis to identify the independent clinical predictors of recurrence and Cox's proportional hazard regression method to develop a clinical prediction model. We randomly divided our patients into the training and test subsets. The pathologic stages, tumor cell type, differentiation of tumor, neoadjuvant therapy and age were significant factors on the multivariable analysis. We constructed the model for the training set with adenocarcinoma (n=236) and squamous cell carcinoma (n=305), and we applied it to the test set with adenocarcinoma (n=110) and squamous cell carcinoma (n=154). It was predictive for the in adenocarcinoma (P<0.001) and the squamous cell carcinoma (P=0.037), respectively. Our results showed that our recurrence prediction model based on the clinical parameters could significantly predict the individual patients who were at high risk or low risk for recurrence.

Activity of Matrix Metalloproteinase-2 and its Significance after Resection of Stage I Non-small Cell Lung Cancer / 대한흉부외과학회지

BACKGROUND: Matrix metalloproteinase-2 (MMP-2) is a class of proteolytic enzymes that digest collagen type IV and other components of the basement membrane. It plays a key role in the local invasion and the formation of distant metastases by various malignant tumors. The aim of this study was to evaluate the activity of MMP-2 and its significance as a prognostic marker in resected stage I non-small cell lung cancer (NSCLC). MATERIAL AND METHOD: In this study we obtained fresh-frozen samples of tumor and non-tumor tissues from 34 patients with stage I NSCLC who underwent resection without preoperative radiotherapy or chemotherapy. After the extraction of total protein from tissue samples, MMP-2 activities were assessed by gelatin-substrate-zymography. The activities were divided into the higher or lower groups. RESULT: The MMP-2 activities were higher in tumor tissues than in non-tumor tissues. The MMP-2 activity of non-tumor tissues in recurrent group was higher than in non-recurrent group (p<0.01). Also the patients with higher MMP-2 activity of non-tumor tissues showed poor 5 year survival (p<0.01). CONCLUSION: This result indicates that the higher level of MMP-2 activity in the non-tumor tissue is associated with the recurrence and survival after the resection of stage I NSCLC. Therefore, MMP-2 activity in the non-tumor tissue could be used as a potential prognostic marker for the resected stage I-NSCLC.

Expression of beta-catenin in Colorectal Cancer with Liver Metastasis

PURPOSE: Decreased expression of beta-catenin has been known to be associated with tumor metastasis. However, the clinical relationship between the degree of expression and the prognosis in colorectal cancer (CRC) remains unclear. In this study, we evaluated the prognostic value of beta-catenin expression in CRC patients with liver metastasis. METHODS: Paraffin embedded blocks were obtained from 70 patients who underwent potentially curative resection for CRC with liver metastasis. Samples from normal colon mucosa, primary CRC and metastatic liver lesion were prepared in tissue microarrays and were stained by immunohistochemistry with monoclonal antibody against beta- catenin. The membranous beta-catenin expression was assessed and the beta-catenin expression difference between primary CRC and metastatic liver lesion was analysed in relation to overall survival as well as disease free survival rates. RESULTS: In beta-catenin expression, preserved expression (score >6) was observed in 42.0%, and 21.9% of primary CRC tumor samples and tumor samples from metastatic liver lesion respectively. The degree of beta-catenin expression in metastatic liver lesion was significantly lower than that in primary CRC (P=0.022). According to the difference of beta-catenin expression score between primary CRC and liver metastasis, patients were classified as group 'A' and 'B'. Group 'A' was defined as patients showing remarkably decreased expression of beta-catenin in metastatic liver lesion in that the difference of the score was three or more. Group 'B' was defined as patients showing maintained or increased beta-catenin expression in metastatic liver lesion in comparison to primary CRC, in that the difference of beta-catenin expression score was less than three. Overall survival rate and disease free survival rate were significantly better in group 'B' than group 'A' (P=0.02, P=0.002). CONCLUSIONS: Decreased expression of beta-catenin in metastatic liver lesion may be a poor prognostic marker in colorectal cancers with liver metastasis. A further large-scaled investigation is necessary to define the role of beta-catenin in CRC.

Association between RASSF1A Methylation and Clinicopathological Factors in Patients with Squamous Cell Carcinoma of Lung / 결핵및호흡기질환

BACKGROUND: RASSF1A, which is one of tumor suppressor genes, is frequently inactivated by hypermethylation of the promoter region in a variety of human cancers, including lung cancer. This study was performed to investigate the association between RASSF1A methylation and the clinicopathological factors in patients with squamous cell carcinoma of the lung. METHODS: Eighty-one samples from the patients with squamous cell carcinoma of lung were examined. The promoter methyation of RASSF1A was analyzed by methylation specific PCR and sequencing. Statistical analysis was made to examine the association between RASSF1A methylation and the clinicopathological parameters. RESULTS: RASSF1A methylation was observed in 37.0 % (30 of 81) of the patients with squamous cell carcinoma of the lung. RASSF1A methylation was found to be associated with cellular differentiation(p=0.0097) and the overall survival(p=0.0635). However, there was no association between RASSF1A methylation and the other clini?copathological parameters, such as the pathological TNM stage, the recurrence rate, lymph node invasion and the amount of cigarettes smoked. CONCLUSION: RASSF1A methylation might be associated with a poor prognosis in patients with squamous carcinoma of the lung. A larger scale study is needed.