Bimodal Chromoendoscopy with Confocal Laser Endomicroscopy for the Detection of Early Esophageal Squamous Cell Neoplasms

Background/Aims This study aimed to evaluate the diagnostic accuracy of dual-focus narrow-band imaging (dNBI) and Lugol’schromoendoscopy (LCE) combined with probe-based confocal laser endomicroscopy (pCLE) to screen for esophageal squamous cell neoplasms (ESCNs) in patients with a history of head and neck cancer. Methods From March to August 2016, dNBI was performed. Next, LCE was performed, followed by pCLE and biopsy. Histology has historically been the gold standard to diagnose ESCN. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of dNBI and LCE adjunct with pCLE were determined. Results Twenty-four patients were included. Ten ESCNs were found in 8 patients (33%). Forty percent of high-graded intraepithelial neoplasias and all low-grade intraepithelial neoplasias were overlooked by dNBI. The sensitivity, specificity, PPV, NPV, and accuracy of dNBI vs. LCE combined with pCLE were 50% vs. 80%, 62% vs. 67%, 36% vs. 44%, 75% vs. 91%, and 83% vs. 70%, respectively. Conclusions The use of dNBI to detect ESCN was suboptimal. LCE with pCLE following dNBI had additional value for detecting esophageal dysplasia not detected by dNBI. The use of pCLE to detect dNBI-missed lesions yielded a high NPV, while pCLE-guided biopsy could reduce the number of unnecessary biopsies

Real-time semantic segmentation of gastric intestinal metaplasia using a deep learning approach

Background/Aims Previous artificial intelligence (AI) models attempting to segment gastric intestinal metaplasia (GIM) areas have failed to be deployed in real-time endoscopy due to their slow inference speeds. Here, we propose a new GIM segmentation AI model with inference speeds faster than 25 frames per second that maintains a high level of accuracy. Methods Investigators from Chulalongkorn University obtained 802 histological-proven GIM images for AI model training. Four strategies were proposed to improve the model accuracy. First, transfer learning was employed to the public colon datasets. Second, an image preprocessing technique contrast-limited adaptive histogram equalization was employed to produce clearer GIM areas. Third, data augmentation was applied for a more robust model. Lastly, the bilateral segmentation network model was applied to segment GIM areas in real time. The results were analyzed using different validity values. Results From the internal test, our AI model achieved an inference speed of 31.53 frames per second. GIM detection showed sensitivity, specificity, positive predictive, negative predictive, accuracy, and mean intersection over union in GIM segmentation values of 93%, 80%, 82%, 92%, 87%, and 57%, respectively. Conclusions The bilateral segmentation network combined with transfer learning, contrast-limited adaptive histogram equalization, and data augmentation can provide high sensitivity and good accuracy for GIM detection and segmentation

H4K20me3 upregulated by reactive oxygen species is associated with tumor progression and poor prognosis in patients with hepatocellular carcinoma

Epigenetic alteration by oxidative stress is vitally involved in carcinogenesis and cancer progression. Previously, we demonstrated that oxidative stress was increased in hepatocellular carcinoma (HCC) patients and associated with tumor aggressiveness. Herein, we immunohistochemically investigated whether histone methylation, specifically H4K20me3, was upregulated in human hepatic tissues obtained from HCC patients (n = 100). Also, we experimentally explored if the H4K20me3 was upregulated by reactive oxygen species (ROS) and contributed to tumor progression in HCC cell lines. We found that H4K20me3 level was increased in HCC tissues compared with the adjacent noncancerous liver tissues. H3K9me3 and H3K4me3 levels were also increased in HCC tissues. Cox regression analysis revealed that the elevated H4K20me3 level was associated with tumor recurrence and short survival in HCC patients. Experimentally, H2O2 provoked oxidative stress and induced H4K20me3 formation in HepG2 and Huh7 cells. Transcript expression of histone methyltransferase Suv420h2 (for H4K20me3), Suv39h1 (for H3K9me3), and Smyd3 (for H3K4me3) were upregulated in H2O2-treated HCC cells. H2O2 also induced epithelial-mesenchymal transition (EMT) in HCC cells, indicated by decreased E-cadherin but increased α-SMA and MMP-9 mRNA expression. Migration, invasion, and colony formation in HCC cells were markedly increased following the H2O2 exposure. Inhibition of H4K20me3 formation by A196 (a selective inhibitor of Suv420h2) attenuated EMT and reduced tumor migration in H2O2-treated HCC cells. In conclusion, we demonstrated for the first time that H4K20me3 level was increased in human HCC tissues, and it was independently associated with poor prognosis in HCC patients. ROS upregulated H4K20me3 formation, induced mRNA expression of EMT markers, and promoted tumor progression in human HCC cells. Inhibition of H4K20me3 formation reduced EMT and tumor aggressive phenotypes in ROS-treated HCC cells. Possibly, ROS-induced EMT and tumor progression in HCC cells was epigenetically mediated through an increased formation of repressive chromatin H4K20me3

Validation of models using basic parameters to differentiate intestinal tuberculosis from Crohn's disease: A multicenter study from Asia.

BackgroundData on external validation of models developed to distinguish Crohn's disease (CD) from intestinal tuberculosis (ITB) are limited. This study aimed to validate and compare models using clinical, endoscopic, and/or pathology findings to differentiate CD from ITB.MethodsData from newly diagnosed ITB and CD patients were retrospectively collected from 5 centers located in Thailand or Hong Kong. The data was applied to Lee, et al., Makharia, et al., Jung, et al., and Limsrivilai, et al. model.ResultsFive hundred and thirty patients (383 CD, 147 ITB) with clinical and endoscopic data were included. The area under the receiver operating characteristic curve (AUROC) of Limsrivilai's clinical-endoscopy (CE) model was 0.853, which was comparable to the value of 0.862 in Jung's model (p = 0.52). Both models performed significantly better than Lee's endoscopy model (AUROC: 0.713, pConclusionsScoring systems with more parameters and diagnostic modalities performed better; however, application to clinical practice is still limited owing to high rate of misdiagnosis of ITB as CD. Models integrating more modalities such as imaging and serological tests are needed

A germline STAT6 gain-of-function variant is associated with early-onset allergies

Background: The signal transducer and activator of transcription 6 (STAT6) signaling pathway plays a central role in allergic inflammation. To date, however, there have been no descriptions of STAT6 gain-of-function variants leading to allergies in humans. Objective: We report a STAT6 gain-of-function variant associated with early-onset multiorgan allergies in a family with 3 affected members. Methods: Exome sequencing and immunophenotyping of T-helper cell subsets were conducted. The function of the STAT6 protein was analyzed by Western blot, immunofluorescence, electrophoretic mobility shift assays, and luciferase assays. Gastric organoids obtained from the index patient were used to study downstream effector cytokines. Results: We identified a heterozygous missense variant (c.1129G>A;p.Glu377Lys) in the DNA binding domain of STAT6 that was de novo in the index patient's father and was inherited by 2 of his 3 children. Severe atopic dermatitis and food allergy were key presentations. Clinical heterogeneity was observed among the affected individuals. Higher levels of peripheral blood TH2 lymphocytes were detected. The mutant STAT6 displayed a strong preference for nuclear localization, increased DNA binding affinity, and spontaneous transcriptional activity. Moreover, gastric organoids showed constitutive activation of STAT6 downstream signaling molecules. Conclusions: A germline STAT6 gain-of-function variant results in spontaneous activation of the STAT6 signaling pathway and is associated with an early-onset and severe allergic phenotype in humans. These observations enhance our knowledge of the molecular mechanisms underlying allergic diseases and will potentially contribute to novel therapeutic interventions