MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model.

OBJECTIVE: To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC). BACKGROUND: The incidence of esophageal adenocarcinoma (EAC) has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies. METHODS: The modified Levrat's surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA) along with upstream and downstream targets. miRNA-linked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5) and metastasis negative (n=28) primary tumors. RESULTS: The epithelial origin of distant metastasis was established by IF using villin (VIL1) and mucin 5AC (MUC5AC) antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-92a-3p (p=0.0001), miR-141-3p (p=0.0022), miR-451-1a (p=0.0181) and miR133a-3p (p=0.0304). Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2. CONCLUSION: In vivo metastasis was confirmed in the modified Levrat's model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized.

Patient participation in surgical site marking: can this be an additional tool to help avoid wrong-site surgery?

INTRODUCTION: Wrong-site surgery is defined as an operation conducted at the wrong site, on the wrong person, or resulting in the wrong procedure. Since 1993, more than 2200 wrong-site surgeries have been reported by the National Practitioner Data Base. A 2005 survey reported, 5.6% of replying academy fellows encountered a wrong-site surgery incident. Multiple interventions have been since suggested for prevention of these occurrences by the American Academy of Orthopaedic Surgeons and Joint Commission on Accreditation of Healthcare Organizations. MATERIALS AND METHODS: This institutional review board-approved study was conducted to investigate patient compliance and reliability in marking the surgical site. Two hundred patients undergoing orthopedic surgery who agreed to participate were enrolled at the time of preoperative testing and clearance for surgery. The patients received instructions to mark the surgical site with a "YES." Patient data collected included age, sex, procedure type and location, history of previous orthopedic surgeries, workmen's compensation status or motor vehicle collision involvement, employment status, primary language, level of education, presence of depression or toxic habits, and the time between enrollment and day of surgery. RESULTS: We achieved an overall compliance rate of 68.2%. There was no difference with respect to sex, tobacco use or history of depression, level of education or occupation, workmen's compensation, or government insurance status. The mean age of compliant patients was 48.6 years versus 53.3 years for those who did not comply (P = 0.05). About 72% of those who spoke English as a primary language complied, as opposed to 49% in others (P = 0.009). The time between enrollment and surgery was 10.4 days in compliant patients versus 23.1 days in noncompliant patients (P = 0.05). No statistically significant difference was noted with all other variables recorded. In no instance did patients mark the wrong side or make any marks likely to contribute to the wrong operation. CONCLUSIONS: Patient's ability to be involved in this preventative measure is independent of most demographic variables previously thought to be significant. However, in view of the 68.2% compliance, patient involvement in surgical site marking is unreliable and may not help in decreasing the chances of wrong-site surgery.