Characteristics of cases for which esophageal endoscopic submucosal dissection under general anesthesia is recommended.

BACKGROUND/AIMS: Esophageal endoscopic submucosal dissection (ESD) performed under general anesthesia can potentially provide more stable treatment in difficult cases than that under sedation. We evaluated the clinical characteristics and outcomes of ESD performed under general anesthesia compared with those under propofol sedation and discussed the cases in which general anesthesia is recommended. PATIENTS AND METHODS: In total, 292 lesions in 265 consecutive patients undergoing esophageal ESD at Yamaguchi University Hospital from 2013 to 2023 were included in this retrospective study. RESULTS: ESD was performed under general anesthesia for 92 lesions in 81 patients and under propofol sedation for 200 lesions in 184 patients. Tumor long-axis diameter was larger (39.8 ± 14.4 mm vs. 32.4 ± 9.9 mm, p < 0.01) and dissection speed was faster (10.5 ± 5.9 mm2/min vs. 7.5 ± 4.2 mm2/min, p < 0.01) in the general anesthesia group versus the sedation group. In the sedation group, a treatment history of pharyngeal cancer was significantly associated with a slower dissection speed (p = 0.037). The sedation group showed higher frequencies of hypoxemia (0% vs 9.8%, p < 0.01), interruption due to body movement (0% vs 13%, p < 0.01), and acute adverse events (21.7% vs 33.5%, p = 0.05). A treatment history of pharyngeal cancer was shown to be the significant factor contributing to acute adverse events (p = 0.018). CONCLUSION: Esophageal ESD under general anesthesia can be a treatment option in patients with difficulty in performing stable procedures with propofol sedation. Especially in patients with a treatment history of pharyngeal cancer in whom ESD is more difficult to be performed and who are at higher risk for acute adverse events, general anesthesia can be considered.

A Novel Index Including Age, Sex, hTERT, and Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer.

INTRODUCTION: As the incidence of gastric cancer (GC) is increasing in East Asia including Japan, a simple blood test for early GC is needed as an alternative to upper gastrointestinal (UGI) endoscopy. We performed this study to address this issue. METHODS: We collected serum samples from 319 participants comprising 225 healthy subjects without GC (control group) and 94 patients with early GC (early GC group). After evaluating copy numbers of serum hTERT and methylated RUNX3 (m-RUNX3) using the combined restriction digital PCR (CORD) assay, which we developed, we assessed the diagnostic performance of hTERT and m-RUNX3 for early GC. RESULTS: Serum levels of hTERT and m-RUNX3 were significantly higher in the early GC group than in the control group. The area under the curve (AUC) was 0.89 for hTERT and 0.78 for m-RUNX3. Multivariate logistic regression analysis revealed age, sex, hTERT copy number, and m-RUNX3 copy number to be independent factors for early GC. We then established a prediction formula and named it the ASTEm-R3 (Age, Sex, hTERT, and m-RUNX3) index. The AUC of the ASTEm-R3 index was 0.93 with a sensitivity of 79.7% and specificity of 91.1%. CONCLUSION: We demonstrated excellent performance of the ASTEm-R3 index using the CORD assay to detect early GC. This index might be a promising alternative to UGI endoscopy.

A novel index combining fecal immunochemical test, DNA test, and age improves detection of advanced colorectal adenoma.

Although the fecal immunochemical test for hemoglobin (FIT) is a widely used screening test for colorectal cancer, it is not sensitive enough to detect advanced colorectal adenoma. To address this issue, we performed this study to investigate whether combining the FIT and fecal DNA testing of methylated somatostatin (SST) could improve diagnostic performance for advanced colorectal adenoma. We collected feces from 79 healthy subjects with negative results on colonoscopy, 43 patients with non-advanced colorectal adenoma, 117 patients with advanced colorectal adenoma, and 126 patients with colorectal cancer. After fecal DNA was incubated with methylation-sensitive restriction enzymes, SST methylation levels were measured by droplet digital PCR. Using logistic multivariate analysis, we established a prediction formula for detecting colorectal neoplasia and named it the FAMS (FIT, age, methylated SST) index. The diagnostic performance of a single use of FIT for advanced colorectal adenoma showed a sensitivity of 29.1% (34/117) and specificity of 89.3% (109/122). In contrast, the FAMS index showed a sensitivity of 56.4% (66/117) at a similar specificity point of 91.0% (111/122). Furthermore, even at the higher specificity point of 94.3% (115/122), the sensitivity was still higher than that of FIT, reaching 42.7% (50/117). As the FAMS index showed better diagnostic performance for advanced colorectal adenoma than a single use of FIT, the FAMS index could be a promising tool for detecting advanced colorectal adenoma.

A case of asymptomatic infection of Ascaris suum identified by PCR-restriction fragment length polymorphism and DNA sequence analysis.

Human ascariasis is a soil-transmitted helminthiasis and remains a neglected tropical disease. Ascaris suum has the potential to cause cross-infections between humans and pigs. In this study, we present a rare case of a patient with asymptomatic infection by Ascaris suum. A 66-year-old male underwent colonoscopy, and a white linear worm body was found in the hepatic curvature. The worm was collected by aspiration and submitted to the laboratory for parasite identification. The patient had no symptoms related to parasitic infection. The worm was highly suspected to be of the genus Ascaris. Because of the difficulty of morphological classification, genetic analysis was performed. From PCR-restriction fragment length polymorphism results and sequence analysis of the internal transcribed spacer-1 region, it was determined to be A. suum. The experience with rapid differentiation of A. suum by performing genetic analysis will be useful for future examinations of parasitic infections.

Cooperation between artificial intelligence and endoscopists for diagnosing invasion depth of early gastric cancer.

BACKGROUND AND STUDY AIMS: The diagnostic ability of endoscopists to determine invasion depth of early gastric cancer is not favorable. We designed an artificial intelligence (AI) classifier for differentiating intramucosal and submucosal gastric cancers and examined it to establish a diagnostic method based on cooperation between AI and endoscopists. PATIENTS AND METHODS: We prepared 500 training images using cases of mainly depressed-type early gastric cancer from 250 intramucosal cancers and 250 submucosal cancers. We also prepared 200 test images each of 100 cancers from another institution. We designed an AI classifier to differentiate between intramucosal and submucosal cancers by deep learning. We examined the performance of the AI classifier and the majority vote of the endoscopists as high confidence and low confidence diagnostic probability, respectively, and cooperatively combined them to establish a diagnostic method providing high accuracy. RESULTS: Internal evaluation of the training images showed that accuracy, sensitivity, specificity, and F1 measure by the AI classifier were 77%, 76%, 78%, and 0.768, and those of the majority vote of the endoscopists were 72.6%, 53.6%, 91.6%, and 0.662, respectively. A diagnostic method based on cooperation between AI and the endoscopists showed that the respective values were 78.0%, 76.0%, 80.0%, and 0.776 for the test images. The value of F1 measure was especially higher than those by AI or the endoscopists alone. CONCLUSIONS: Cooperation between AI and endoscopists improved the diagnostic ability to determine invasion depth of early gastric cancer.

The Evaluation of Transmural Healing by Low-dose Computed Tomography Enterography in Patients with Crohn's Disease.

Objective Transmural healing (TH) has been attracting attention as a new therapeutic target for Crohn's disease, but there are few clinical data on TH in Japan. We introduced low-dose computed tomography enterography (CTE) as a monitoring method for Crohn's disease and retrospectively investigated the accuracy of evaluating TH by CTE. Methods Among Crohn's disease patients who underwent low-dose CTE at our hospital from January 2009 to March 2021, 122 patients who underwent colonoscopy or balloon endoscopy within 2 weeks were included. Results of radiological and endoscopic examinations were reviewed independently by radiologists and gastrointestinal endoscopists, respectively. The concordance rate of the diagnosis between CTE and endoscopy was evaluated. Results Twenty-six patients (21.3%) achieved TH, and the kappa index was 0.743. On comparing the TH and non-TH groups, the Crohn's disease activity index (p=0.02), endoscopic healing rate (p<0.001), serum albumin (p=0.043), and serum C-reactive protein level (p=0.018) showed significant differences. Among the 122 patients, 69 (56.5%) showed concordance between the diagnosis of CTE and endoscopy, and 22 (18.0%) achieved both TH and endoscopic healing. Conclusion This study provides real-world data on Crohn's disease evaluated with low-dose CTE in Japan. The TH criterion used in this study has a high kappa coefficient and can be used reproducibly in many institutions.

MC180295 Inhibited Epstein-Barr Virus-Associated Gastric Carcinoma Cell Growth by Suppressing DNA Repair and the Cell Cycle.

DNA methylation of both viral and host DNA is one of the major mechanisms involved in the development of Epstein-Barr virus-associated gastric carcinoma (EBVaGC); thus, epigenetic treatment using demethylating agents would seem to be promising. We have verified the effect of MC180295, which was discovered by screening for demethylating agents. MC180295 inhibited cell growth of the EBVaGC cell lines YCCEL1 and SNU719 in a dose-dependent manner. In a cell cycle analysis, growth arrest and apoptosis were observed in both YCCEL1 and SNU719 cells treated with MC180295. MKN28 cells infected with EBV were sensitive to MC180295 and showed more significant inhibition of cell growth compared to controls without EBV infection. Serial analysis of gene expression analysis showed the expression of genes belonging to the role of BRCA1 in DNA damage response and cell cycle control chromosomal replication to be significantly reduced after MC180295 treatment. We confirmed with quantitative PCR that the expression levels of BRCA2, FANCM, RAD51, TOP2A, and CDC45 were significantly decreased by MC180295. LMP1 and BZLF1 are EBV genes with expression that is epigenetically regulated, and MC180295 could up-regulate their expression. In conclusion, MC180295 inhibited the growth of EBVaGC cells by suppressing DNA repair and the cell cycle.

Combined Use of Computed Tomography Enterography/Enteroclysis and Capsule Endoscopy Improves the Accuracy of Diagnosis of Small Bowel Bleeding.

Objective CT enterography/enteroclysis (CTE) is listed in the clinical practice guidelines as a method for diagnosing small bowel bleeding, as is capsule endoscopy (CE), but there are no real-world data yet available on CTE in Japan. This study aimed to investigate the diagnostic ability of CTE and long-term prognosis after CTE in Japan. Patients We conducted a retrospective cohort study of patients suspected of having small bowel bleeding who underwent both CTE and CE within 30 days between April 2008 and March 2019. The number of patients free from rebleeding for up to 24 months was thus determined. Results Seventy-one patients were extracted from the database. The 43 patients (60.6%) with a definite and suspicious source of bleeding in the small bowel were detected by CTE. When the 31 patients with a definite source of bleeding in the small bowel were analyzed, the sensitivity of CTE was 19/31 (61.3%) and that of CE was 24/31 (77.4%), thus indicating no significant difference (p=0.332). However, the sensitivity when CTE and CE were used in combination was 30/31 (96.8%), which was significantly higher than that of CE alone (p=0.0412). No rebleeding was observed in the CTE and CE negative group (p=0.0965). Conclusion The combined use of CTE and CE increased the detection rate of small bowel bleeding. Therefore, in patients with suspected tumor/polyp lesions, not only CE, but also CTE should be performed. This study provides the first real-world data on the diagnostic accuracy of CTE for small bowel bleeding in Japan.

Estimation of salt intake from spot urine may assist the risk assessment of gastric cancer.

Daily salt intake can be estimated by measuring sodium and creatinine concentrations in spot urine. Excessive salt intake is risk factor for gastric cancer. We examined the correlation between estimated salt intake from spot urine and risk of gastric cancer. This study included gastric cancer patients who underwent treatment at our hospital and patients in whom esophagogastroduodenoscopy was performed but gastric cancer was not observed. The history of H. pylori infection was known in these patients. Spot urine was collected, and daily salt intake was estimated from urine sodium and urine creatinine. Mean estimated salt intake was significantly higher in 120 gastric cancer patients (9.18 g/day) than in 80 non-gastric cancer patients (8.22 g/day). Multivariate analysis revealed estimated salt intake and H. pylori infection to be independent risk factors for gastric cancer. Among H. pylori-infected patients, salt intake was significantly higher in gastric cancer patients (9.25 g/day) than in non-gastric cancer patients (8.01 g/day). In conclusion, salt intake estimated from spot urine was high in patients with gastric cancer, especially in H. pylori infected patients. Spot urine is a simple examination and it may be applied as a new risk assessment of gastric cancer.