Development and Feasibility Evaluation of Smart Cancer Care 2.0 Based on Patient-Reported Outcomes for Post-Discharge Management of Patients with Cancer.

Purpose: A "Smart Cancer Care" platform that integrates patient-reported outcomes (PROs) with management has been established in Korea. This study focused on improving health behaviors and connecting patients to welfare services by introducing and assessing the feasibility of "Smart Cancer Care 2.0," an enhanced version designed for monitoring complications post-cancer treatment. Materials and Methods: Smart Cancer Care 2.0 was developed by conducting a literature review and consulting with expert panels to identify symptoms or variables requiring monitoring and management guidelines based on the treatment type. Qualitative and quantitative surveys were conducted to assess the feasibility of the app and web system based on the experiences of patients with cancer and healthcare workers. Results: A total of 81 symptoms or variables (chemotherapy-, surgery-, radiotherapy-, rehabilitation-, and health management-related) were selected for management in Smart Cancer Care 2.0. PROs for these symptoms were basically categorized into three severity grades: (1) preventive management, (2) self-treatment, and (3) consultation with a healthcare worker or visit to a healthcare institution. The overall mean scores in the feasibility evaluation by patients and healthcare workers were 3.83 and 3.90 points, respectively, indicating high usefulness. Conclusion: Smart Cancer Care 2.0 leverages the existing ICT-based platform, Smart Cancer Care, and further includes health behaviors and welfare services. Smart Cancer Care 2.0 may play a crucial role in establishing a comprehensive post-discharge management system for patients with cancer as it provides suitable interventions based on patients' responses and allows the regularly collected PROs to be easily viewed for streamlined care.

Relevance Index Regional Variation by Each Disease and Its Essential Medical Field: A Retrospective Data Analysis From 2016-2020 in Korea.

BACKGROUND: To precisely build a healthcare delivery system at regional levels, local patients' healthcare service utilization patterns must be examined. Hence, this study utilized trend analysis of the relevance index of each disease of each essential medical service field at the municipal and provincial levels. METHODS: This study analyzed customized databases released by the National Health Insurance Service from 2016-2020. Diseases defined in the Korean National Burden of Disease (KNBD) study were categorized into the following essential medical service fields: trauma care, cardiocerebrovascular, maternal and neonatal, mental health, infection, cancer, older adults' care and rehabilitation, and others. Relevance index, the percentage of medical service utilization in a region by the residents of that region relative to their total medical service utilization, was examined by region (17 municipal and provincial regions) and disease area. The relevance index was determined based on the number of patients and the total out-of-pocket expenses. RESULT: Eight of the 17 regions showed over a 90.0% relevance index in the infection area. In the cancer area, 14 regions (not including Seoul, Daegu, and Busan) had a relevance index lower than 75.0%. Throughout the analysis period (2016-2020), there were no significant variations in the relevance index. Diseases such as bone and connective tissue cancer (39.0%), neural tube defects (16.7%), and autism (57.1%) had low relevance index in the essential medical service fields. In all 17 regions, the relevance index of inpatients was lower than that of outpatients, and that for out-of-pocket expenses was lower than that based on the number of patients. CONCLUSION: The relevance index of major diseases of each essential medical service field calculated in this study can provide good indicators for monitoring the level of an independent regional healthcare delivery system.

Challenge exposure to whole cigarette smoke condensate upregulates locomotor sensitization by stimulating α4ß2 nicotinic acetylcholine receptors in the nucleus accumbens of rats.

Nicotine, the primary addictive substance in tobacco, produces the psychomotor, rewarding, and reinforcing effects of tobacco dependence by stimulating nicotinic acetylcholine receptors (nAChRs) in the brain. The present study determined that α4ß2 nAChRs regulate locomotor sensitization by altering dopamine concentration in the nucleus accumbens (NAc) after systemic challenge exposure to whole cigarette smoke condensate (WCSC). Rats were administered subcutaneous injection of WCSC (0.2 mg/kg nicotine/day) for 7 consecutive days and then re-exposed to WCSC after 3 days of withdrawal. Challenge exposure to WCSC significantly increased locomotor activity. This increase was decreased by the subcutaneous injection of the α4ß2 nAChR antagonist, DHßE (3 mg/kg), but not by the intraperitoneal injection of the α7 nAChR antagonist, MLA (5 mg/kg). In parallel with a decrease in locomotor activity, blockade of α4ß2 nAChRs with DHßE decreased dopamine concentration in the NAc which was elevated by challenge exposure to WCSC. These findings suggest that challenge WCSC leads to the expression of locomotor sensitization by elevating dopamine concentration via stimulation of α4ß2 nAChRs expressed in neurons of the NAc in rats.

Surgical and Electrical Anatomy of the Inter-Nodal and Intra-Atrial Conduction System in the Heart.

An anatomical understanding of the atrial myocardium is crucial for surgeons and interventionists who treat atrial arrhythmias. We reviewed the anatomy of the inter-nodal and intra-atrial conduction systems. The anterior inter-nodal route (#1) arises from the sinus node and runs through the ventral wall of the atrial chambers. The major branch of route #1 approaches the atrioventricular node from the anterior aspect. Other branches of route #1 are Bachmann's bundle and a vestibular branch around the tricuspid valve. The middle inter-nodal route (#2) begins with a broad span of fibers at the sinus venarum and extends to the superior limbus of the oval fossa. The major branch of route #2 joins with the branch of route #1 at the anterior part of the atrioventricular node. The posterior inter-nodal route (#3) is at the terminal crest and gives rise to many branches at the pectinate muscles of the right atrium and then approaches the posterior atrioventricular node after joining with the vestibular branch of route #1. The branches of the left part of Bachmann's bundle and the branches of the second inter-nodal route form a thin myocardial network at the posterior wall of the left atrium. These anatomical structures could be categorized into major routes and side branches. There are 9 or more anatomical circles in the atrial chambers that could be structural sites for macro re-entry. The implications of normal and abnormal structures of the myocardium for the pathogenesis and treatment of atrial arrhythmias are discussed.

Serial ultrastructural evaluation of myocardial ischemic injury after infusion of del Nido cardioplegia in the human heart.

OBJECTIVES: The safe ischemic time after a single-dose del Nido cardioplegia (DNC) infusion has not yet been established. This study evaluated the progression of myocardial ischemic injury to establish the safe ischemic time after a single-dose DNC infusion in the human heart using a transmission electron microscope. METHODS: Seven hearts extracted from heart transplant recipients after infusion of 1000 mL single-dose DNC were evaluated. Serial left ventricular myocardial tissue samples were collected every 30 minutes for 180 minutes. Ischemic injuries in the mitochondria and nuclei were scored from 0 to 3 (0 = normal, 0.5 = slight, 1 = moderate, 2 = severe, and 3 = irreversible). RESULTS: At the time of extraction, 83.5% of the mitochondria were normal. The proportion of mitochondria with moderate ischemic injury increased gradually from 1.4% at extraction to 52.5% at 180 minutes. From 90 minutes to 180 minutes, the proportion of mitochondria with severe and irreversible injury increased from 0.8% to 4.4% and 0.3% to 1.3%, respectively. A significant linear correlation was identified between the average ischemic injury score of mitochondria and ischemic time (P < .001). Most nuclei showed moderate to severe ischemic injury at every time point (61.0%-85.2%). A significant linear correlation was also found between the average ischemic injury score of nuclei and ischemic time (P < .001). CONCLUSIONS: Myocardial ischemic injury progresses gradually, and irreversible ischemic injury begins to occur 90 minutes after initial DNC infusion in the adult human heart. Therefore, redosing of DNC may be required after 90 minutes of aortic crossclamp time during adult cardiac surgery.

Photo-Cross-Linkable Human Albumin Colloidal Gels Facilitate In Vivo Vascular Integration for Regenerative Medicine.

Biodegradable cellular and acellular scaffolds have great potential to regenerate damaged tissues or organs by creating a proper extracellular matrix (ECM) capable of recruiting endogenous cells to support cellular ingrowth. However, since hydrogel-based scaffolds normally degrade through surface erosion, cell migration and ingrowth into scaffolds might be inhibited early in the implantation. This could result in insufficient de novo tissue formation in the injured area. To address these challenges, continuous and microsized strand-like networks could be incorporated into scaffolds to guide and recruit endogenous cells in rapid manner. Fabrication of such microarchitectures in scaffolds is often a laborious and time-consuming process and could compromise the structural integrity of the scaffold or impact cell viability. Here, we have developed a fast single-step approach to fabricate colloidal hydrogels, which are made up of randomly packed human serum albumin-based photo-cross-linkable microparticles with continuous internal networks of microscale voids. The human serum albumin conjugated with methacrylic groups were assembled to microsized aggregates for achieving unique porous structures inside the colloidal gels. The albumin hydrogels showed tunable mechanical properties such as elastic modulus, porosity, and biodegradability, providing a suitable ECM for various cells such as cardiomyoblasts and endothelial cells. In addition, the encapsulated cells within the hydrogel showed improved cell retention and increased survivability in vitro. Microporous structures of the colloidal gels can serve as a guide for the infiltration of host cells upon implantation, achieving rapid recruitment of hematopoietic cells and, ultimately, enhancing the tissue regeneration capacity of implanted scaffolds.

Necessity of Assessing Biological Exposure to Arsenic Species by Two Representative Analytical Methods.

Arsenic (As) exists as highly toxic chemical species. Chronic exposure to its inorganic form can cause multiple organ failure and skin cancer in humans, warranting the need to determine the toxicity of each chemical species. This study evaluated the proportions of exposure to four chemical species of As (cAs), namely arsenite (AsIII), arsenate (AsV), monomethylarsinic acid (MMA), and dimethylarsenic acid (DMA), and it confirmed the necessity of evaluating biological exposure to cAs. Urine samples were collected from 457 subjects residing near 103 abandoned metal mines. Hydride generation atomic absorption spectroscopy (HG-AAS) was performed to measure the combined concentration of four cAs (hAsAAS). High-performance liquid chromatography and inductively coupled plasma-mass spectrometry (HPLC-ICP-MS) were performed to determine the concentrations of the individual cAs and the sum of the four cAs (hAsICP). The proportions of AsV and MMA were relatively higher in the low-hAsICP concentration section. These findings suggest that hAsAAS, which is mainly used for its cost-efficiency, is limited for evaluating exposure. Though hAsAAS was found to exist in a low concentration, highly toxic AsV and MMA could be observed in high concentrations. Therefore, HPLC-ICP-MS is recommended for assessing cAs in environmentally vulnerable areas such as abandoned metal mines.

Feasibility study on stereotactic radiotherapy for total pulmonary vein isolation in a canine model.

We tested the feasibility of pulmonary vein (PV) and left atrial (LA) posterior wall isolation using non-invasive stereotactic ablative body radiotherapy (SABR) and investigated pathological changes in irradiated lesions in a canine model. Seven male Mongrel dogs received single-fraction 33 Gy SABR. We designed the en-bloc circular target of total PVs and LA posterior wall to avoid the esophagus. The circular box lesion included the LA roof and ridge, low posterior wall, and posterior interatrial septum. At 6 weeks or 4 months post-SABR, electrical isolation of the SABR lesion was confirmed using LA posterior wall pacing, and histopathological review was performed. Electrical isolation of all PVs and the LA posterior wall was achieved in three of five dogs in the 4-month group. There was one target failure and one sudden death at 15 weeks. Although two dogs in the 6-week group failed to achieve electrical lesion isolation, the irradiated atrial myocardium showed diffuse hemorrhage with inflammatory cell infiltration. In successfully isolated 4-month model dogs, we observed transmural fibrotic scarring with extensive fibrosis on irradiated atrial tissue. The findings suggest that this novel circular box-design radiotherapy technique using SABR could be applied to humans after further studies are conducted to confirm safety.

Early Changes in Rat Heart After High-Dose Irradiation: Implications for Antiarrhythmic Effects of Cardiac Radioablation.

Background Noninvasive cardiac radioablation is employed to treat ventricular arrhythmia. However, myocardial changes leading to early-period antiarrhythmic effects induced by high-dose irradiation are unknown. This study investigated dose-responsive histologic, ultrastructural, and functional changes within 1 month after irradiation in rat heart. Methods and Results Whole hearts of wild-type Lewis rats (N=95) were irradiated with single fraction 20, 25, 30, 40, or 50 Gy and explanted at 1 day or 1, 2, 3, or 4 weeks' postirradiation. Microscopic pathologic changes of cardiac structures by light microscope with immunohistopathologic staining, ultrastructure by electron microscopy, and functional evaluation by ECG and echocardiography were studied. Despite high-dose irradiation, no myocardial necrosis and apoptosis were observed. Intercalated discs were widened and disrupted, forming uneven and twisted junctions between adjacent myocytes. Diffuse vacuolization peaked at 3 weeks, suggesting irradiation dose-responsiveness, which was correlated with interstitial and intracellular edema. CD68 immunostaining accompanying vacuolization suggested mononuclear cell infiltration. These changes were prominent in working myocardium but not cardiac conduction tissue. Intracardiac conduction represented by PR and QTc intervals on ECG was delayed compared with baseline measurements. ST segment was initially depressed and gradually elevated. Ventricular chamber dimensions and function remained intact without pericardial effusion. Conclusions Mononuclear cell-related intracellular and extracellular edema with diffuse vacuolization and intercalated disc widening were observed within 1 month after high-dose irradiation. ECG indicated intracardiac conduction delay with prominent ST-segment changes. These observations suggest that early antiarrhythmic effects after cardiac radioablation result from conduction disturbances and membrane potential alterations without necrosis.

Effects of Exposure to Lead and Cadmium on Health of Inhabitants of Abandoned Metal Mine Area in Korea.

People living near abandoned mines are at increased risk of exposure to toxic metals. We surveyed 4500 inhabitants with the mean age of 68.5 years old (male: 1768, female: 2732) living near 104 abandoned metal mines from 2013 to 2017 (the 2nd phase health survey in Korea). We conducted personal interviews, blood and urine sampling, and analyzed the concentrations of lead (Pb) and cadmium (Cd) in whole blood and Cd in urine using a graphite furnace atomic absorption spectrometer. The geometric means of blood Pb, blood Cd, and urine Cd were 2.27 µg/dL, 1.42 µg/L, and 1.66 µg/g creatinine, respectively. The level of metal exposure was lower than that reported from the first phase health survey in Korea (2008‒2011) but was higher than in the general population of Korea. Blood Pb was higher in males while blood Cd and urine Cd were significantly higher in females. Blood Pb was highest in the 40‒59 age group, while blood and urine Cd levels continuously increased until age 80 or older. The Cd levels in blood and urine were affected by consumption of locally produced rice and duration of residence near abandoned mines. Furthermore, negative correlations were observed between blood Pb and blood and urine Cd levels. Additionally, 252 of the 4500 subjects exceeded the thresholds of blood Cd or urine Cd levels. Together, these findings suggest that Cd has more sustainable and adverse health effects on the abandoned mine inhabitants, who are mostly aged. Therefore, continuous biomonitoring and risk assessment to environmental health risks are necessary for environmental pollution control and health promotion.

Indirect pathological indicators for cardiac sarcoidosis on endomyocardial biopsy.

BACKGROUND: The definitive pathologic diagnosis of cardiac sarcoidosis requires observation of a granuloma in the myocardial tissue. It is common, however, to receive a "negative" report for a clinically probable case. We would like to advise pathologists and clinicians on how to interpret "negative" biopsies. METHODS: Our study samples were 27 endomyocardial biopsies from 25 patients, three cardiac transplantation and an autopsied heart with suspected cardiac sarcoidosis. Pathologic, radiologic, and clinical features were compared. RESULTS: The presence of micro-granulomas or increased histiocytic infiltration was always (6/6 or 100%) associated with fatty infiltration and confluent fibrosis, and they showed radiological features of sarcoidosis. Three of five cases (60%) with fatty change and confluent fibrosis were probable for cardiac sarcoidosis on radiology. When either confluent fibrosis or fatty change was present, one-third (3/9) were radiologically probable for cardiac sarcoidosis. We interpreted cases with micro-granuloma as positive for cardiac sarcoidosis (five of 25, 20%). Cases with both confluent fibrosis and fatty change were interpreted as probable for cardiac sarcoidosis (seven of 25, 28%). Another 13 cases, including eight cases with either confluent fibrosis or fatty change, were interpreted as low probability based on endomyocardial biopsy. CONCLUSIONS: The presence of micro-granuloma could be an evidence for positive diagnosis of cardiac sarcoidosis. Presence of both confluent fibrosis and fatty change is necessary for probable cardiac sarcoidosis in the absence of granuloma. Either of confluent fibrosis or fatty change may be an indirect pathological evidence but they are interpreted as nonspecific findings.

A case of life-threatening valvulitis mimicking infective endocarditis in systemic juvenile idiopathic arthritis.

Differential diagnosis of an intracardiac mass is difficult when detected only by echocardiography before a biopsy is completed. However, treatment cannot be postponed until the biopsy results are obtained. We report the case of a 12-year-old girl who presented with an intracardiac mass in the mitral valve mimicking infective endocarditis and severe mitral regurgitation. The mass was finally diagnosed as valvulitis associated with systemic juvenile idiopathic arthritis, which was complicated with macrophage activation syndrome. After careful exclusion of acute infectious disease, we started steroid pulse therapy and administered tocilizumab to treat the cytokine storm before performing the surgery. Finally, we performed mass excision and mitral valve replacement after immunosuppressant therapy.

Pittsburgh B Compound Positron Emission Tomography in Patients With AL Cardiac Amyloidosis.

BACKGROUND: It remains unknown whether the noninvasive evaluation of the degree of amyloid deposition in the myocardium can predict the prognosis of patients with light chain (AL) cardiac amyloidosis. OBJECTIVES: The purpose of this study was to demonstrate that 11C-Pittsburgh B compound positron emission tomography (11C-PiB PET) is useful for prognostication of AL cardiac amyloidosis by noninvasively imaging the myocardial AL amyloid deposition. METHODS: This study consecutively enrolled 41 chemotherapy-naïve AL cardiac amyloidosis patients. The amyloid deposit was quantitatively assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial 11C-PiB uptake on PET. The primary endpoint was a composite of all-cause death, heart transplantation, and acute decompensated heart failure. RESULTS: The degree of myocardial 11C-PiB PET uptake was significantly higher in the cardiac amyloidosis patients compared with normal subjects and correlated well with the degree of amyloid deposit on histology (R2 = 0.343, p < 0.001). During follow-up (median: 423 days, interquartile range: 93 to 1,222 days), 24 patients experienced the primary endpoint. When the cardiac amyloidosis patients were divided into tertiles by the degree of myocardial 11C-PiB PET uptake, patients with the highest PiB uptake experienced the worst clinical event-free survival (log-rank p = 0.014). The degree of myocardial PiB PET uptake was a significant predictor of clinical outcome on multivariate Cox regression analysis (adjusted hazard ratio: 1.185; 95% confidence interval: 1.054 to 1.332; p = 0.005). CONCLUSIONS: These proof-of-concept results show that noninvasive evaluation of myocardial amyloid load by 11C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in AL cardiac amyloidosis patients.

Lower versus upper leg saphenous vein composite grafts based on the left internal thoracic artery: A randomized study.

OBJECTIVES: The "lower versus upper leg saphenous vein (SV) composite graft based on the left internal thoracic artery (ITA) for coronary artery bypass grafting" trial was designed to compare the histologic, immunohistochemical, and angiographic findings of lower versus upper leg SV composite grafts. METHODS: Twenty-six patients with multivessel coronary artery disease were prospectively randomized to undergo revascularization using a lower leg (n = 13) or upper leg (n = 13) SV composite graft based on the in situ left ITA. The SV was harvested with a "no-touch" technique, and 2 excess segments were removed from the distal and proximal portions of each SV conduit. Another proximal segment was removed from the reversed SV composite graft, which had been dilated by the native ITA pressure. Hematoxylin and eosin staining, immunohistochemistry, and early and 1-year postoperative angiographic results were compared. RESULTS: The histologic study showed that the proximal and dilated proximal SV conduit lumen diameters were smaller in the lower leg group than in the upper leg group (proximal, 623 ± 143 µm vs 858 ± 266 µm; P = .008; dilated proximal, 1138 ± 419 µm vs 1477 ± 353 µm; P = .047). However, there were no differences in the lumen diameters of the distal SV segments in terms of immunohistochemical comparisons, diameters, patency rates, or filling frame counts of the SV conduits on early and 1-year postoperative angiograms between the 2 groups. CONCLUSIONS: Although the proximal segment luminal diameters were smaller in the lower leg SV, there were no differences in the immunohistochemical results or patency rates on early and 1-year postoperative angiograms between the lower and upper leg "no-touch" SV conduits.

Automated extraction of Biomarker information from pathology reports.

BACKGROUND: Pathology reports are written in free-text form, which precludes efficient data gathering. We aimed to overcome this limitation and design an automated system for extracting biomarker profiles from accumulated pathology reports. METHODS: We designed a new data model for representing biomarker knowledge. The automated system parses immunohistochemistry reports based on a "slide paragraph" unit defined as a set of immunohistochemistry findings obtained for the same tissue slide. Pathology reports are parsed using context-free grammar for immunohistochemistry, and using a tree-like structure for surgical pathology. The performance of the approach was validated on manually annotated pathology reports of 100 randomly selected patients managed at Seoul National University Hospital. RESULTS: High F-scores were obtained for parsing biomarker name and corresponding test results (0.999 and 0.998, respectively) from the immunohistochemistry reports, compared to relatively poor performance for parsing surgical pathology findings. However, applying the proposed approach to our single-center dataset revealed information on 221 unique biomarkers, which represents a richer result than biomarker profiles obtained based on the published literature. Owing to the data representation model, the proposed approach can associate biomarker profiles extracted from an immunohistochemistry report with corresponding pathology findings listed in one or more surgical pathology reports. Term variations are resolved by normalization to corresponding preferred terms determined by expanded dictionary look-up and text similarity-based search. CONCLUSIONS: Our proposed approach for biomarker data extraction addresses key limitations regarding data representation and can handle reports prepared in the clinical setting, which often contain incomplete sentences, typographical errors, and inconsistent formatting.

Investigation of Health Effects According to the Exposure of Low Concentration Arsenic Contaminated Ground Water.

Recent epidemiological studies have reported adverse health effects, including skin cancer, due to low concentrations of arsenic via drinking water. We conducted a study to assess whether low arsenic contaminated ground water affected health of the residents who consumed it. For precise biomonitoring results, the inorganic (trivalent arsenite (As III) and pentavalent arsenate (As V)) and organic forms (monomethylarsonate (MMA) and dimethylarsinate (DMA)) of arsenic were separately quantified by combining high-performance liquid chromatography and inductively coupled plasma mass spectroscopy from urine samples. In conclusion, urinary As III, As V, MMA, and hair arsenic concentrations were significantly higher in residents who consumed arsenic contaminated ground water than control participants who consumed tap water. But, most health screening results did not show a statistically significant difference between exposed and control subjects. We presume that the elevated arsenic concentrations may not be sufficient to cause detectable health effects. Consumption of arsenic contaminated ground water could result in elevated urinary organic and inorganic arsenic concentrations. We recommend immediate discontinuation of ground water supply in this area for the safety of the residents.

Case-control study of chronic low-level exposure of inorganic arsenic species and non-melanoma skin cancer.

A significant relationship between arsenic exposure and non-melanoma skin cancer (NMSC) is well known. The toxicity of arsenics which develop NMSC is dependent on their species. Accordingly, total arsenic levels are unreliable for risk assessment of NMSC. However, there are few studies on quantitative exposure assessment of arsenic species in NMSC patients. To validate the contribution of each arsenic species to NMSC, we compared the creatinine-adjusted urinary concentration of arsenic species in NMSC patients and community controls. A total of 124 biopsy-proven NMSC cases and 125 age- and sex-matched community controls, drinking tap water with low-level arsenic concentration (<5 µg/L), were included in the study. High-performance liquid chromatography and inductively coupled plasma mass spectrometry were used for the measurement. The NMSC group was found to have significantly higher levels of total inorganic arsenic, trivalent and pentavalent arsenic and monomethylarsonic acid than the control group. Total arsenic, organic arsenic and dimethylarsonic acid levels were lower in the NMSC group. We suggest that inorganic arsenic species, trivalent arsenic and pentavalent arsenic may influence the prevalence of NMSC, in spite of these levels being lower than the Agency for Toxic Substances and Disease Registry-recommended standard or the levels reported by other highly contaminated areas and neighboring countries in East Asia. Furthermore, it also suggests that total arsenic level cannot represent the risk of NMSC.

Immunohistochemical Analysis of ATRX, IDH1 and p53 in Glioblastoma and Their Correlations with Patient Survival.

Glioblastoma (GBM) can be classified into molecular subgroups, on the basis of biomarker expression. Here, we classified our cohort of 163 adult GBMs into molecular subgroups according to the expression of proteins encoded by genes of alpha thalassemia/mental retardation syndrome X-linked (ATRX), isocitrate dehydrogenase (IDH) and TP53. We focused on the survival rate of molecular subgroups, depending on each and various combination of these biomarkers. ATRX, IDH1 and p53 protein expression were evaluated immunohistochemically and Kaplan-Meier analysis were carried out in each group. A total of 15.3% of enrolled GBMs demonstrated loss of ATRX expression (ATRX-), 10.4% expressed an aberrant IDH1 R132H protein (IDH1+), and 48.4% exhibited p53 overexpression (p53+). Survival differences were statistically significant when single protein expression or different combinations of expression of these proteins were analyzed. In conclusion, in the case of single protein expression, the patients with each IDH1+, or ATRX-, or p53- GBMs showed better survival than patients with counterparts protein expressed GBMs. In the case of double protein pairs, the patients with ATRX-/p53-, ATRX-/IDH1+, and IDH1+/p53- GBMs revealed better survival than the patients with GBMs with the remained pairs. In the case of triple protein combinations, the patients with ATRX-/p53-/IDH+ showed statistically significant survival gain than the patients with remained combination of proteins-expression status. Therefore, these three biomarkers, individually and as a combination, can stratify GBMs into prognostically relevant subgroups and have strong prognostic values in adult GBMs.

Analysis of Mutations in Epidermal Growth Factor Receptor Gene in Korean Patients with Non-small Cell Lung Cancer: Summary of a Nationwide Survey.

BACKGROUND: Analysis of mutations in the epidermal growth factor receptor gene (EGFR) is important for predicting response to EGFR tyrosine kinase inhibitors. The overall rate of EGFR mutations in Korean patients is variable. To obtain comprehensive data on the status of EGFR mutations in Korean patients with lung cancer, the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists initiated a nationwide survey. METHODS: We obtained 1,753 reports on EGFR mutations in patients with lung cancer from 15 hospitals between January and December 2009. We compared EGFR mutations with patient age, sex, history of smoking, histologic diagnosis, specimen type, procurement site, tumor cell dissection, and laboratory status. RESULTS: The overall EGFR mutation rate was 34.3% in patients with non-small cell lung cancer (NSCLC) and 43.3% in patients with adenocarcinoma. EGFR mutation rate was significantly higher in women, never smokers, patients with adenocarcinoma, and patients who had undergone excisional biopsy. EGFR mutation rates did not differ with respect to patient age or procurement site among patients with NSCLC. CONCLUSIONS: EGFR mutation rates and statuses were similar to those in published data from other East Asian countries.