Integrated GWAS and mRNA Microarray Analysis Identified IFNG and CD40L as the Central Upstream Regulators in Primary Biliary Cholangitis.

Genome-wide association studies (GWASs) in European and East Asian populations have identified more than 40 disease-susceptibility genes in primary biliary cholangitis (PBC). The aim of this study is to computationally identify disease pathways, upstream regulators, and therapeutic targets in PBC through integrated GWAS and messenger RNA (mRNA) microarray analysis. Disease pathways and upstream regulators were analyzed with ingenuity pathway analysis in data set 1 for GWASs (1,920 patients with PBC and 1,770 controls), which included 261 annotated genes derived from 6,760 single-nucleotide polymorphisms (P < 0.00001), and data set 2 for mRNA microarray analysis of liver biopsy specimens (36 patients with PBC and 5 normal controls), which included 1,574 genes with fold change >2 versus controls (P < 0.05). Hierarchical cluster analysis and categorization of cell type-specific genes were performed for data set 2. There were 27 genes, 10 pathways, and 149 upstream regulators that overlapped between data sets 1 and 2. All 10 pathways were immune-related. The most significant common upstream regulators associated with PBC disease susceptibility identified were interferon-gamma (IFNG) and CD40 ligand (CD40L). Hierarchical cluster analysis of data set 2 revealed two distinct groups of patients with PBC by disease activity. The most significant upstream regulators associated with disease activity were IFNG and CD40L. Several molecules expressed in B cells, T cells, Kupffer cells, and natural killer-like cells were identified as potential therapeutic targets in PBC with reference to a recently reported list of cell type-specific gene expression in the liver. Conclusion: Our integrated analysis using GWAS and mRNA microarray data sets predicted that IFNG and CD40L are the central upstream regulators in both disease susceptibility and activity of PBC and identified potential downstream therapeutic targets.

A pilot study using an infrared imaging system in prevention of post-endoscopic submucosal dissection ulcer bleeding.

BACKGROUND: Endoscopic submucosal dissection (ESD) for superficial gastric neoplasm is a curative method. The aim of this study was to detect potential nonbleeding visible vessels (NBVVs) by using an infrared imaging (IRI) system. METHODS: A total of 24 patients (25 lesions) were consecutively enrolled between March 2010 and December 2010. The day after ESD, endoscopist A (K.M.), who was blinded to the actual procedure of ESD, performed esophagogastroduodenoscopy (EGD) of the post-ESD ulcer base using the IRI system. Endoscopist A marked gray/blue points in the hard-copy images with the IRI system. After the first procedure, endoscopist B (Y.Y.), who was blinded to the results recorded by endoscopist A, performed a second EGD with white light endoscopy and administered water-jet pressure with the maximum level of an Olympus flushing pump onto the post-ESD ulcer base. This test can cause iatrogenic bleeding via application of pressure to NBVV in the post-ESD ulcer. RESULTS: The IRI system detected 58 gray points and 71 blue points. The post-ESD ulcer was divided into the central area and the peripheral area. There were 14 gray points (24 %) in the central area and 44 gray points (76 %) in the peripheral area. There were 19 blue points (27 %) in the central area and 52 blue points (73 %) in the peripheral area. There was no significant difference when comparing the distribution of gray points and blue points. Bleeding occurred with a water-jet pressure in 11 of 58 gray points and in none of the blue points (P = 0.000478). Among the gray points, bleeding in response to a water-jet pressure occurred in 2 points in the central area and in 9 points in the peripheral area. CONCLUSION: The IRI system detects visible vessels (VVs) that are in no need of coagulation as blue points, and VVs have a potential risk of bleeding as gray points.

The benefit of using narrow-band imaging systems for observation of capillary networks before determining of treatments for early colon cancer.

INTRODUCTION: This study examined whether magnifying endoscopy with narrow-band Imaging observation could be useful selecting the appropriate treatment for early colon cancer. PATIENTS AND METHODS: We analyzed 551 cases of colon tumors excised endoscopically or surgically, comprising 68 with large hyperplastic polyps, 25 traditional serrated adenomas, 141 tubular adenomas, 177 intramucosal cancers and 140 submucosal invasive (SM) cancers. We classified capillary network pattern into four types according to the degree of dilatation, irregularity and distribution of microcapillary features. These results were then compared with the histological findings. RESULTS: The comparison of capillary pattern and histological features showed microcapillary networks by magnifying endoscopy with narrow-band imaging observation in intramucosal lesion or SM cancer with remnant neoplastic glands at the superficial layer. CONCLUSIONS: The remaining microcapillary network was designed to maintain the architecture of neoplastic glands, even in the presence of subumucosal invasion. Consequently, loss of this network could correlate with depth of tumor invasion and histological reaction. Therefore, even if the tumor, remained of network was diagnosed to invade into SM layer, it should be checked up further examination by using magnifying endoscopy with crystal violet staining.

Imaging by Magnifying Endoscopy with NBI Implicates the Remnant Capillary Network As an Indication for Endoscopic Resection in Early Colon Cancer.

Introduction. This study examined whether magnifying endoscopy with NBI observation (ME-NBI) could be useful selecting the appropriate treatment for submucosal invasive cancer (SM cancer). Patients and Methods. We analyzed 515 cases of colon tumors excised endoscopically or surgically. We classified capillary network pattern into four types according to the degree of dilatation, irregularity, and distribution of microcapillary features. Results. The comparison of capillary pattern and histological features revealed microcapillary networks by using confocal laser-scanning microscopy and ME-NBI in intramucosal lesion or SM cancer with remnant neoplastic glands at the superficial layer. In contrast, the network was absent in SM cancer with desmoplastic reactions, which invaded deeper into the submucosal layer. Conclusions. The remaining microcapillary network is designed to maintain the architecture of neoplastic glands. Consequently, loss of this network could correlate with depth of tumor invasion and desmoplastic reaction. Therefore, we can decide the appropriate treatment by using ME-NBI method.

[Case of lymphangioleiomyomatosis associated with protein-losing gastroenteropathy].

A 29-year-old woman was referred to our hospital for the intensive examination of leg edema and hypoproteinemia. CT scan of showed multiple thin-walled cysts in both lungs, suggesting lymphangioleiomyomatosis. CT scan of the abdomen, lymphoscintigraphy showed enlarged abdominal lymph nodes. Protein loss from the gastrointestinal tract was documented by measurement of the clearance of alpha-1 antitrypsin from the plasma using a 72 h stool collection and (99m)Tc human serum albumin scintigraphy. We thought that secondary lymphangiectasia with lymphangioleiomyomatosis caused protein-losing gastroenteropathy. Dietary therapy resulted in symptomatic improvement.