The Role of Adjuvant Chemotherapy after Neoadjuvant Chemoradiotherapy Followed by Surgery in Patients with Esophageal Squamous Cell Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to investigate the efficacy of adjuvant chemotherapy after neoadjuvant chemoradiotherapy (CCRTx) followed by surgery in patients with esophageal squamous cell carcinoma (ESCC). @*Materials and Methods@#We retrospectively analyzed the data from 382 patients who received neoadjuvant CCRTx and esophagectomy for ESCC between 2003 and 2018. @*Results@#This study included 357 (93.4%) men, and the years median patient age was 63 (range, 40 to 84 years). Overall, 69 patients (18.1%) received adjuvant chemotherapy, whereas 313 patients (81.9%) did not. The median follow-up period was 28.07 months (interquartile range, 15.50 to 62.59). The 5-year overall survival (OS) and disease-free survival were 47.1% and 42.6%, respectively. Adjuvant chemotherapy did not improve OS in all patients, but subgroup analysis revealed that adjuvant chemotherapy improved the 5-year OS in patients with ypT+N+ (24.8% vs. 29.9%, p=0.048), whereas the survival benefit of adjuvant chemotherapy was not observed in patients with ypT0N0, ypT+N0, or ypT0N+. Multivariable analysis revealed that ypStage and adjuvant chemotherapy (hazard ratio, 0.601; p=0.046) were associated with OS in patients with ypT+N+. Freedom from distant metastasis was marginally different according to the adjuvant chemotherapy (48.3% vs. 41.3%, p=0.141). @*Conclusion@#Adjuvant chemotherapy after neoadjuvant therapy followed by surgery reduces the distant metastasis in ypT+N+ ESCC patients, thereby improving the OS. The consideration could be given to administration of adjuvant chemotherapy to ypT+N+ ESCC patients with tolerable conditions.

A case of esophagitis and mediastinitis developed in an infant with an esophageal duplication cyst

An esophageal duplication cyst (EDC) is a congenital anomaly of the foregut. EDCs are often asymptomatic, so they are found incidentally on chest radiographs. In symptomatic patients, EDCs present with cough, dyspnea, vomiting, dysphagia, and chest pain. Potential complications of EDCs include perforation, obstruction, bleeding, and infection. The rarity of this condition may hinder timely diagnosis, which may lead to life-threatening complications. This article describes a case of esophagitis and mediastinitis developed in a 12-month-old infant with an EDC. We emphasize that although rare, EDCs should be considered in the differential diagnosis of non-specific respiratory signs such as cough, dyspnea, and stridor.

Quantitative Proteomic Analysis Reveals Impaired Axonal Guidance Signaling in Human Postmortem Brain Tissues of Chronic Traumatic Encephalopathy

Chronic traumatic encephalopathy (CTE) is a distinct neurodegenerative disease that associated with repetitive head trauma. CTE is neuropathologically defined by the perivascular accumulation of abnormally phosphorylated tau protein in the depths of the sulci in the cerebral cortices. In advanced CTE, hyperphosphorylated tau protein deposits are found in widespread regions of brain, however the mechanisms of the progressive neurodegeneration in CTE are not fully understood. In order to identify which proteomic signatures are associated with CTE, we prepared RIPA-soluble fractions and performed quantitative proteomic analysis of postmortem brain tissue from individuals neuropathologically diagnosed with CTE. We found that axonal guidance signaling pathwayrelated proteins were most significantly decreased in CTE. Immunohistochemistry and Western blot analysis showed that axonal signaling pathway-related proteins were down regulated in neurons and oligodendrocytes and neuron-specific cytoskeletal proteins such as TUBB3 and CFL1 were reduced in the neuropils and cell body in CTE. Moreover, oligodendrocyte-specific proteins such as MAG and TUBB4 were decreased in the neuropils in both gray matter and white matter in CTE, which correlated with the degree of axonal injury and degeneration. Our findings indicate that deregulation of axonal guidance proteins in neurons and oligodendrocytes is associated with the neuropathology in CTE. Together, altered axonal guidance proteins may be potential pathological markers for CTE.

Metabolomic Analysis Identifies Alterations of Amino Acid Metabolome Signatures in the Postmortem Brain of Alzheimer's Disease

Despite significant advances in neuroscience research over the past several decades, the exact cause of AD has not yet fully understood. The metabolic hypothesis as well as the amyloid and tau hypotheses have been proposed to be associated with AD pathogenesis. In order to identify metabolome signatures from the postmortem brains of sporadic AD patients and control subjects, we performed ultra performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometer (UPLC-LTQ–Orbitrap-MS). Not only our study identified new metabolome signatures but also verified previously known metabolome profiles in the brain. Statistical modeling of the analytical data and validation of the structural assignments discovered metabolic biomarkers associated with the AD pathogenesis. Interestingly, hypotaurin, myo-inositol and oxo-proline levels were markedly elevated in AD while lutamate and N-acetyl-aspartate were decreased in the postmortem brain tissue of AD patients. In addition, neurosteroid level such as cortisol was significantly increased in AD. Together, our data indicate that impaired amino acid metabolism is associated with AD pathogenesis and the altered amino acid signatures can be useful diagnostic biomarkers of AD. Thus, modulation of amino acid metabolism may be a possible therapeutic approach to treat AD.

Genetic Ablation of EWS RNA Binding Protein 1 (EWSR1) Leads to Neuroanatomical Changes and Motor Dysfunction in Mice

A recent study reveals that missense mutations of EWSR1 are associated with neurodegenerative disorders such as amyotrophic lateral sclerosis, but the function of wild-type (WT) EWSR1 in the central nervous system (CNS) is not known yet. Herein, we investigated the neuroanatomical and motor function changes in Ewsr1 knock out (KO) mice. First, we quantified neuronal nucleus size in the motor cortex, dorsal striatum and hippocampus of three different groups: WT, heterozygous Ewsr1 KO (+/−), and homozygous Ewsr1 KO (−/−) mice. The neuronal nucleus size was significantly smaller in the motor cortex and striatum of homozygous Ewsr1 KO (−/−) mice than that of WT. In addition, in the hippocampus, the neuronal nucleus size was significantly smaller in both heterozygous Ewsr1 KO (+/−) and homozygous Ewsr1 KO (−/−) mice. We then assessed motor function of Ewsr1 KO (−/−) and WT mice by a tail suspension test. Both forelimb and hindlimb movements were significantly increased in Ewsr1 KO (−/−) mice. Lastly, we performed immunohistochemistry to examine the expression of TH, DARPP-32, and phosphorylated (p)-DARPP-32 (Thr75) in the striatum and substantia nigra, which are associated with dopaminergic signaling. The immunoreactivity of TH and DARPP-32 was decreased in Ewsr1 KO (−/−) mice. Together, our results suggest that EWSR1 plays a significant role in neuronal morphology, dopaminergic signaling pathways, and motor function in the CNS of mice.

Transcriptome analyses of chronic traumatic encephalopathy show alterations in protein phosphatase expression associated with tauopathy

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder that is associated with repetitive head injury and has distinctive neuropathological features that differentiate this disease from other neurodegenerative diseases. Intraneuronal tau aggregates, although they occur in different patterns, are diagnostic neuropathological features of CTE, but the precise mechanism of tauopathy is not known in CTE. We performed whole RNA sequencing analysis of post-mortem brain tissue from patients with CTE and compared the results to normal controls to determine the transcriptome signature changes associated with CTE. The results showed that the genes related to the MAP kinase and calcium-signaling pathways were significantly downregulated in CTE. The altered expression of protein phosphatases (PPs) in these networks further suggested that the tauopathy observed in CTE involves common pathological mechanisms similar to Alzheimer's disease (AD). Using cell lines and animal models, we also showed that reduced PPP3CA/PP2B phosphatase activity is directly associated with increases in phosphorylated (p)-tau proteins. These findings provide important insights into PP-dependent neurodegeneration and may lead to novel therapeutic approaches to reduce the tauopathy associated with CTE.

Astrocytes and Microglia as Non-cell Autonomous Players in the Pathogenesis of ALS

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder that leads to a progressive muscle wasting and paralysis. The pathological phenotypes are featured by severe motor neuron death and glial activation in the lumbar spinal cord. Proposed ALS pathogenic mechanisms include glutamate cytotoxicity, inflammatory pathway, oxidative stress, and protein aggregation. However, the exact mechanisms of ALS pathogenesis are not fully understood yet. Recently, a growing body of evidence provides a novel insight on the importance of glial cells in relation to the motor neuronal damage via the non-cell autonomous pathway. Accordingly, the aim of the current paper is to overview the role of astrocytes and microglia in the pathogenesis of ALS and to better understand the disease mechanism of ALS.

Concept and Neurobiology of Social Cognition in Schizophrenia / 신경정신의학

Recently, social cognition is becoming a hot issue in field of schizophrenia research. There are increasing demands for more clear definition of terms and knowledge about neurobiology of social cognition in schizophrenia. One of the reasons why it receives so much attention would be its role of predicting the functional outcomes of schizophrenia patients. The purpose of this article is to review and summarize the concepts and neural correlates of social cognition in schizophrenia. Functional brain imaging studies as well as behavioral studies were reviewed.

A Study of the Bloodstream Infections in one University Hospital Hemodialysis Patients / 병원감염관리

BACKGROUND: Hemodialysis patients are increasing every year and bloodstream infections (BSIs) are a major cause of morbidity and mortality in patients receiving hemodialysis. As the domestic studies have not explored the incidence of BSIs, the distribution and current situation of microorganism and so on this study was carried out to determine the incidence and epidemiological risk factors of the BSIs in hemodialysis patients. A distribution of pathogenic organism of the BSIs was investigated. METHODS: This study was carried out for those 275 patients with hemodialysis for 12 months the patients who underwent hemodialysis in the hemodialysis center within the university hospital. Data was collected by structural questionnaire, medical record review. The definition for BSIs was based on that of CDC. RESULTS: A total of 59 BSIs occurred during 123,502 dialysis sessions. The bloodstream infection rate per 1,000 dialysis sessions was 0.48 overall and varied markedly by the type of vascular access: 0.1 for arteriovenous fistulas, 0.54 for arteriovenous grafts. 2.57 for permanent catheters and 5.39 for temporary catheters. The most common pathogen isolated from the BSIs was MSSA and MRSA 18.0%, Streptococcus species 11.5%. In a logistic regression analysis, immunosuppressive therapy (OR=8.081, p=0.001), case of starting hemodialysis in the intensive care unit (OR=4.855, p=0.043) were associated independently with BSIs. CONCLUSION: Based on this study, continuous study and effort together with interest in BSIs, and the study on BSIs in hemodialysis patients should be further continued in the years to come. Surveillance for BSIs is recommended as a routine activity in hemodialysis center.

Feasibility Study for Dietitians' Roles as a Sanitation Consultant based on Managers' Self-Evaluation on Sanitation Management at Restaurants in Cheonan

The purpose of this study was to examine sanitation management practices of restaurant managers for the training needs analysis. A total of 26 restaurant managers participated in this study. A check list was consisted of three parts : facility, personal, and food hygiene. Two observers and one manager evaluated the same check list at same time and the results were compared. The results of this study suggested that most restaurants have needed for re-training programs in the view of facility, personal, food sanitation practices. Specially, proper washing and sanitizing methods for hands and utensils, proper cooking and holding temperature, and proper storing methods were needed to be trained. Based on this study, most independent restaurant managers in Cheonan were aware of training, but they had no effective training program manuals. Results of this study implicated that dietitians have new opportunity for consultants of independent restaurants in the region because they have practiced sanitation management manuals.