Pocket Creation Method of Endoscopic Submucosal Dissection to Ensure Curative Resection of Rectal Neuroendocrine Tumors

Purpose: Pancreatic/gastrointestinal tract neuroendocrine neoplasm (NEN) is divided into neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC) according to the grade of malignancy, and differences are seen in clinical prognosis. NET, and rectal NET in particular, is often treated endoscopically. Endoscopic mucosal resection (EMR) was previously the main intervention for rectal NET, but EMR with a ligation device (EMR-L) and endoscopic submucosal dissection (ESD) are now also used. However, complete resection with these therapies is not always achieved. The pocket creation method (PCM) is a safe ESD method for colon tumors that offers a high en bloc resection rate compared with conventional colonic ESD. We performed ESD using the PCM for rectal NET and evaluated the complete resection rate. Methods: We performed ESD using the PCM in 4 patients. This procedure was technically feasible in all patients. Results: Endoscopically, all cases were resected en bloc, and pathological complete resection was achieved in all cases. No complications such as perforation or delayed postoperative bleeding were encountered. Conclusions: PCM should be considered when treating NET of appropriate size

Evidence for Efficient Pathway to Produce Slow Electrons by Ground-state Dication in Clusters

We present an experimental evidence for a so-far unobserved, but potentially very important step relaxation cascades following inner-shell ionization of a composite system: Multiply charged ionic states created after Auger decay may be neutralized by electron transfer from a neighboring species, producing at the same time a low-energy free electron. This electron transfer-mediated decay (ETMD) called process is effective even after Auger decay into the dicationic ground state. Here, we report the ETMD of Ne2+ produced after Ne 1s photoionization in Ne-Kr mixed clusters

The Roles of Epigenetic Regulation and the Tumor Microenvironment in the Mechanism of Resistance to Systemic Therapy in Hepatocellular Carcinoma

Primary liver cancer is the sixth most common cancer and the third most common cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is a major histologic type with a poor prognosis owing to the difficulty in early detection, the chemotherapy resistance, and the high recurrence rate of the disease. Despite recent advancements in HCC prevention and diagnosis, over 50% of patients are diagnosed at Barcelona Clinic Liver Cancer Stage B or C. Systemic therapies are recommended for unresectable HCC (uHCC) with major vascular invasion, extrahepatic metastases, or intrahepatic lesions that have a limited response to transcatheter arterial chemoembolization, but the treatment outcome tends to be unsatisfactory due to acquired drug resistance. Elucidation of the mechanisms underlying the resistance to systemic therapies and the appropriate response strategies to solve this issue will contribute to improved outcomes in the multidisciplinary treatment of uHCC. In this review, we summarize recent findings on the mechanisms of resistance to drugs such as sorafenib, regorafenib, and lenvatinib in molecularly targeted therapy, with a focus on epigenetic regulation and the tumor microenvironment and outline the approaches to improve the therapeutic outcome for patients with advanced HCC

Fibrosis Staging Using Direct Serum Biomarkers is Influenced by Hepatitis Activity Grading in Hepatitis C Virus Infection

Background: Chronic liver diseases (CLDs) generally progress from inflammation to fibrosis and finally to carcinogenesis. Staging of liver fibrosis progression is inevitable for the management of CLD patients. The purpose of this study was to compare the diagnostic abilities of Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA-M2BP), Enhanced liver fibrosis (ELF) score, Fibrosis-4 index, and AST to platelet ratio index (APRI) based on histopathological analysis of liver biopsy samples, from patients with positive Hepatitis C Virus (HCV) infection. Methods: Japanese patients with HCV infection who underwent liver biopsy examinations were enrolled in this study. WFA-M2BP levels and ELF scores were calculated using preserved serum samples. The fibrosis staging and activity grading were assessed using a modified METAVIR score. Results: A total of 122 patients were enrolled; the cohort included 27 patients with stage 1, 66 with stage 2, 20 with stage 3, and nine with stage 4 fibrosis. All four biomarkers distinguished stage 3 and stage 2 fibrosis. ROC curves revealed that all four fibrosis biomarkers presented AUC values greater than 0.8. Each of the four biomarkers in stage 2 was significantly different between the activity grade 1 and 2 groups. Conclusion: Fib-4 index and APRI were comparable with WFA-M2BP and ELF score in the diagnosis of advanced liver fibrosis in Japanese patients with HCV infection. All four biomarkers of liver fibrosis were influenced by histopathological activity grading, which implies that liver biopsy should be the gold standard to evaluate liver fibrosis staging even though several noninvasive biomarkers have been investigated well