PURPOSE: Dysbiosis of gut microbiota has been reported to participate in the pathogenesis of colorectal cancer, but changes in microbiota due to radiotherapy have not been studied. In this study, we tried to elucidate the changes in the microbiome in rectal cancer after chemoradiotherapy using RNA sequencing analysis.MATERIALS AND METHODS: We included 11 pairs of human rectal cancer tissues before and after irradiation between August 2016 and December 2017 and performed RNA sequencing analysis. Mapped reads to human reference genomes were used for pair-wise transcriptome comparisons, and unmapped (non-human) reads were then mapped to bacterial marker genes using PathSeq.RESULTS: At microbiome level, interindividual variability of mucosal microbiota was greater than the change in microbial composition during radiotherapy. This indicates that rapid homeostatic recovery of the mucosal microbial composition takes place short after radiotherapy. At single microbe level, Prevotella and Fusobacterium, which were identified as important causative microbes of the initiation and progression of rectal cancer were decreased by radiotherapy. Moreover, changes in Prevotella were associated with changes in the human transcriptome of rectal cancer. We also found that there was a gene cluster that increased and decreased in association with changes in microbial composition by chemoradiation.CONCLUSION: This study revealed changes in tumor-associated microbial community by irradiation in rectal cancer. These findings can be used to develop a new treatment strategy of neoadjuvant therapy for locally advanced rectal cancer by overcoming radio-resistance or facilitating radio-sensitivity.
Chemoradiotherapy ; Colorectal Neoplasms ; Dysbiosis ; Fusobacterium ; Gastrointestinal Microbiome ; Genes, vif ; Genome ; Humans ; Microbiota ; Neoadjuvant Therapy ; Prevotella ; Radiotherapy ; Rectal Neoplasms ; Sequence Analysis, RNA ; Transcriptome

Background: The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway is involved in the regulation of cellular responses to oxidative stress. Nrf2 acts as a cell protector from inflammation, cellular damage, and tumorigenesis, whereas Keap1 is a negative regulator of Nrf2. Dysregulation of the Nrf2/ Keap1 pathway results in tumorigenesis and the active metabolism of tumor cells, leading to high resistance to radiotherapy. This study aimed to evaluate the predictive role of Nrf2 and Keap1 in the radiosensitivity and prognosis of locally advanced rectal cancer (LARC). Methods: In total, 90 patients with LARC underwent surgery after preoperative chemoradiotherapy (CRT). Endoscopic biopsies from the tumors were obtained before radiation, and the Nrf2 and Keap1 expressions were assessed by immunohistochemistry. The response to therapy was evaluated after surgery following CRT according to the pathologic tumor regression grade. The disease-free survival (DFS) and overall survival rates were also documented. The association between the Nrf2 and Keap1 immunoreactivity and the clinicopathological parameters was analyzed. Results: The overexpression of the nuclear Nrf2 before CRT showed a significant correlation with better DFS. The cytoplasmic Nrf2 expression was associated with more residual tumors after radiotherapy and a more unfavorable DFS, indicating lower radiosensitivity. Conclusion CRT is an important issue in LARC and is a major aspect of treatment. Thus, the Nrf2/Keap1 expression may be a potential predictor of preoperative therapeutic resistance.The Nrf2-Keap1 modulators that interact with each other may also be effectively applicable to CRT effect in LARC.

PURPOSE: Emergency procedures are highly dependent on the skill and experience of the physician performing them. Recent advances in light embalming techniques have enabled us to train students on more "realistic" cadavers. The purpose of this study was to report on or 3-year experience with lightly embalmed cadaver-based training and evaluate the student satisfaction with this approach. METHODS: Lightly embalmed cadavers were prepared by the Department of Anatomy. The course was held every March for 3 years. In 2007, we held a 6-hour course for 16 first-year emergency medicine residents from various hospitals. We had procedure and demonstration stations for airway management, tube thoracostomy, central venous catheterization, venous cutdown, pericardiocentesis, intraosseous insertion, open thoracostomy, and lumbar puncture. We evaluated the students' level of satisfaction with the course by giving pre- and post-course evaluations to all students. RESULTS: Based on our experience from the two prior courses, the 2007 curriculum was divided into three parts: didactic lecture, procedure stations and demonstration stations. Pre- and post-course scores were compared for the following: knowledge of the indications and contraindications for the procedures; ability and confidence in performing the procedures; and the ability to perform procedures on actual patients. For 26 items out of a total of 32 items(81.3%), the scores from the post-course evaluation were statistically higher than the scores from the pre-course evaluation. CONCLUSION: Lightly embalmed cadavers are excellent training models for emergency procedures. From our 3-year experience with this method, we were able to develop a training course that was satisfactory to students.
Airway Management ; Cadaver ; Catheterization, Central Venous ; Central Venous Catheters ; Curriculum ; Embalming ; Emergencies ; Emergency Medicine ; Humans ; Light ; Pericardiocentesis ; Spinal Puncture ; Thoracostomy ; Venous Cutdown

BACKGROUND: Careful consideration should be given administering a blood transfusion according to the transfusion criteria because blood components may cause various adverse reactions. In the future, a shortage of blood is inevitable due to strengthening the criteria of donor deferral and the increasing population of aged people, and this will cause a significant dearth of the blood supply. Therefore, we have developed a computerized blood auditing program for reducing the amount of blood transfused by changing the transfusion practices of clinicians. METHODS: The blood audit program was developed to automatically check the clinical information, the pretransfusion laboratory test results, the operation etc of patients who are undergoing transfusion based on the laboratory information system (LIS). The criteria for appropriateness were based on the national transfusion guideline and the transfusion criteria of Severance Hospital. We evaluated the transfusion appropriateness of transfusing red blood cells (RBCs) and fresh frozen plasma (FFP) from April, 2009 to June, 2009 using this audit program. RESULTS: RBCs were transfused to 2,353 patients over 5,652 episodes, and a total of 11,055 units were transfused. FFP was transfused to 574 patients over 1,228 episodes and a total of 4,258 units were transfused. We found that 1,120 (19.9%) RBC transfusion episodes and 377 (30.7%) FFP transfusion episodes were inappropriate. The proportion of inappropriate transfusion was higher in surgical departments than that in medical departments. CONCLUSION: Our computerized audit program evaluated a high number of transfusions in a short time, and we obtained results reflecting the entire past history of transfusions, and we can continuously audit transfusion using this program. We think that feedback to physicians who order transfusions would improve the appropriate use of transfusion.
Aged ; Blood Transfusion ; Clinical Laboratory Information Systems ; Erythrocytes ; Humans ; Plasma ; Tissue Donors