Diagnostic performance of linked color imaging for gastric cancer by Helicobacter pylori infection status: A subanalysis of the large-scale, multicenter randomized controlled trial LCI-FIND.

BACKGROUND: Linked color imaging (LCI) is a new image enhancement technology that facilitates the recognition of subtle differences in mucosal color. In the large-scale, multicenter randomized controlled trial LCI-FIND, LCI demonstrated good diagnostic performance for the detection of tumor lesions in the upper gastrointestinal tract. The aim of the present study was to exploratively evaluate the diagnostic performance of LCI according to H. pylori infection status as a subanalysis of LCI-FIND trial. METHODS: The patients were randomly allocated to receive white light imaging (WLI) first, followed by LCI (WLI group), or vice versa (LCI group), and the two groups were compared for the detection of tumors. Data from this trial were analyzed by the presence/absence of H. pylori infection and further analyzed by successful or unsuccessful eradication in the H. pylori infection group. RESULTS: The 752 patients in the WLI group and 750 patients in the LCI group who had participated in the LCI-FIND trial were included. In the successful eradication group, more gastric lesions were detected by primary mode in the LCI group than in the WLI group, indicating that more lesions were missed by WLI. Fisher's exact probability test for the comparison of the WLI and LCI groups yielded a p-value of 0.0068, with missed gastric lesions being detected 0.136 times (95% confidence interval: 0.020-0.923), significantly less with LCI than with WLI. CONCLUSION: The current study suggests that LCI should be used for gastric cancer screening, particularly in patients with successful H. pylori eradication.

Surveillance esophagogastroduodenoscopy using linked color imaging and narrow-band imaging: A multicenter randomized controlled trial.

BACKGROUND AND AIM: There has been no report on a direct comparison between linked color imaging (LCI) and second-generation narrow-band imaging (2G-NBI) for surveillance of epithelial neoplasms in the upper gastrointestinal tract (UGIT). The aim of this study was to verify the superiority of LCI to 2G-NBI for surveillance esophagogastroduodenoscopy and to clarify how each endoscopic system should be used. METHODS: This study was conducted as an open-label, two-arm-parallel (1:1), multicenter, randomized controlled trial at six institutions. Patients aged 20-85 years with a treatment history of epithelial neoplasms in the UGIT were recruited. Patients were assigned to a 2G-NBI group and an LCI group, and esophagogastroduodenoscopy was performed with primary image-enhanced endoscopy followed by white light imaging (WLI). The primary endpoint was the detection rate of one or more epithelial neoplasms in the primary image-enhanced endoscopy. A WLI-detected epithelial neoplasm was defined as a lesion that was detected in only WLI. RESULTS: A total of 372 patients in the 2G-NBI group and 378 patients in the LCI group were analyzed. Epithelial neoplasms in the UGIT were detected by 2G-NBI in 18 patients (4.6%) and were detected by LCI in 20 patients (5.3%) (P = 0.87). WLI-detected epithelial neoplasms were in 11 patients in the 2G-NBI group (3.0%) and in 1 patient in the LCI group (0.27%) (P = 0.003). CONCLUSIONS: Linked color imaging did not show superiority to 2G-NBI for the detection of epithelial neoplasms. Also, the percentage of WLI-detected epithelial neoplasms in primary NBI was significantly higher than that in primary LCI.

Antimicrobial-resistant Helicobacter pylori in Japan: Report of nationwide surveillance for 2018-2020.

BACKGROUND: Antimicrobial therapy is necessary to eradicate Helicobacter pylori infection. The emergence of antimicrobial-resistant bacteria poses a threat to continued treatment with antimicrobial agents. For those who prescribe antimicrobial therapy, it is necessary to constantly monitor the emergence of antimicrobial-resistant bacteria. METHOD: H. pylori clinical isolates were collected in Japan from August 2018 to December 2020 for antimicrobial susceptibility testing. The agar dilution method was used for the determination of the minimum inhibitory concentration (MIC) of clarithromycin (CLR), amoxicillin (AMX), metronidazole (MNZ), and sitafloxacin (STX). RESULTS: MICs for 938 H. pylori isolates were examined. The primary resistance rates of H. pylori clinical isolates for CLR, AMX, MNZ, and STX in Japan were 35.5%, 2.7%, 4.2%, and 27.6%, respectively. The primary resistance rates for CLR, AMX, and MNZ were significantly higher than those of the 2002-2005 isolates. The resistance rate for CLR was significantly higher in females (males: 30.7%, females: 41.5%, p < 0.001) and higher in the ≤29 years age group (54.8%) than in the other age groups, although there were no significant differences (p = 0.104). The MNZ resistance rate was significantly higher in the ≤29 years age group than in the other age groups (p = 0.004). The resistance rate for STX increased with age, but a significant difference was only seen between the 30-49 years age group and the ≥70 years age group (p < 0.001), and the resistance rate was significantly higher in strains isolated in the Kyushu region than in the other regions (p < 0.001). CONCLUSIONS: The primary resistance rates for CLR, AMX, and MNZ of H. pylori clinical isolates in Japan were higher than those of the 2002-2005 isolates. Continuous surveillance is needed to monitor the trends in antimicrobial-resistant H. pylori.

An Analysis of Delayed Bleeding in Cases of Colorectal Endoscopic Submucosal Dissection Due to Types of Direct Oral Anticoagulants in Japan.

BACKGROUND & AIMS: Reported rates of delayed bleeding (DB) after endoscopic resection using direct oral anticoagulants (DOACs) are high and heterogeneous. This large-scale multicenter study analyzed cases of DB after colorectal endoscopic submucosal dissection related to various types of DOACs in Japan (the ABCD-J study) with those associated with warfarin. METHODS: We retrospectively reviewed 1019 lesions in patients treated with DOACs and 459 lesions in patients treated with warfarin among 34,455 endoscopic submucosal dissection cases from 47 Japanese institutions between 2012 and 2021. The DB rate (DBR) with each DOAC was compared with that with warfarin. Risk factors for DB in patients treated with DOACs or warfarin were also investigated. RESULTS: The mean tumor sizes in the DOAC and warfarin groups were 29.6 ± 14.0 and 30.3 ± 16.4 mm, respectively. In the DOAC group, the DBR with dabigatran (18.26%) was significantly higher than that with apixaban (10.08%, P = .029), edoxaban (7.73%, P = .001), and rivaroxaban (7.21%, P < .001). Only rivaroxaban showed a significantly lower DBR than warfarin (11.76%, P = .033). In the multivariate analysis, heparin bridging therapy (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.27-3.73, P = .005), rectal location (2.01, 1.28-3.16, P = .002), and procedure time ≥55 minutes (2.43, 1.49-3.95, P < .001) were significant risk factors for DB in the DOAC group. The DB risk in the DOAC group (OR, (95% CI)) was 2.13 (1.30-3.50) and 4.53 (2.52-8.15) for 1 and 2 significant risk factors, respectively. CONCLUSIONS: Dabigatran was associated with a higher DBR than other DOACs, and only rivaroxaban was associated with a significantly lower DBR than warfarin.

Application of polyglycolic acid sheets and basic fibroblast growth factor to prevent esophageal stricture after endoscopic submucosal dissection in pigs.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been the first-line treatment for early-stage esophageal cancer. However, it often causes postoperative stricture in cases requiring wide dissection. Basic fibroblast growth factor (bFGF) reportedly has anti-scarring effects during cutaneous wound healing. We hypothesized that suppressing myofibroblast activation will prevent stricture after esophageal ESD. METHODS: We resected a complete porcine esophagus circumference section by ESD. To investigate the preventive effect of bFGF on esophageal stricture formation after ESD, we endoscopically applied bFGF-soaked poly-glycolic acid (PGA) sheets onto the wound bed after ESD and fixed them by spraying fibrin glue (PGA + bFGF group), PGA sheets alone onto the wound bed and fixed them by spraying fibrin glue (PGA group), or nothing (control group). After removing the esophagus on day 22, we evaluated the mucosal constriction rate. RESULTS: Compared with those in the control group, esophageal stricture was significantly reduced in the PGA + bFGF group, and the areas stained with α-SMA and calponin-1 antibodies were significantly inhibited in the PGA + bFGF and PGA groups. The thickness of the fibrous layer in the PGA + bFGF group was uniform compared to that of the other groups. Thus, PGA + bFGF inhibited the development of unregulated fibroblasts in the acute phase, leading to uniform wound healing. CONCLUSIONS: Stenosis after esophageal ESD is related to fibrosis in the acute phase. Administration of PGA and bFGF suppresses myofibroblast activation in the acute phase, thereby preventing esophageal constriction in pigs.

Novel endoscopic management of gastroenterological anastomosis leakage by injecting gel-forming solutions: an experimental animal study.

BACKGROUND: Anastomotic leakage (AL) after gastrointestinal surgery remains a challenging complication that requires surgical or non-surgical treatment. Although various therapeutic endoscopic techniques are available, no definitive interventions exist. We developed a therapeutic endoscopic submucosal injection method using novel gel-forming mixed solutions to close AL and evaluated the elasticity of the developed hydrogel. The safety and efficacy of the injection method were explored in porcine AL models. METHODS: We developed a novel gel-forming solution, and the formed gel lasted approximately one week within the gastrointestinal wall. An indentation test evaluated the elasticity of the novel hydrogel. After the confirmation of AL on porcine anterior gastric walls, sodium alginate was endoscopically injected into the submucosal layer around the leakage site circularly, followed by a calcium lactate/chitosan-based solution. After that, the outcomes data were collected, and histopathological effectiveness was evaluated. RESULTS: The increased sodium alginate elasticity with the addition of calcium lactate/chitosan-based solution facilitated long-lasting gel formation. Four pigs with AL underwent this intervention consecutively. Each endoscopic injection was completed in less than 5 min. No significant complications were observed for 3 weeks after the intervention. All AL sites were macroscopically healed. Histopathologic findings at 3 weeks showed that the wall defect was filled with collagen fibers that had grown around the site of the muscle layer tear. No tissue necrosis was observed. CONCLUSION: This preclinical study demonstrated that the therapeutic injection method for gastroenterological AL using gel-forming solutions could be an alternative endoscopic treatment, especially in patients with severe conditions or comorbidities. The optimal target of this treatment is small size and early AL without poor blood flow or intense hypertrophic scar lesions.

Instability of harmonized thyroid-stimulating hormone immunoassays in clinical practice.

OBJECTIVE: Thyroid-stimulating hormone (TSH) harmonization is effective in minimizing differences between the results of immunoassays in healthy subjects. However, the effectiveness of TSH harmonization in clinical practice has not been investigated. The aim of this study was to evaluate the instability of TSH harmonization in clinical practice. METHODS: We compared the reactivities of four harmonized TSH immunoassays using combined difference plots of 431 patients. We selected patients with statistically significant deviations in TSH levels and analyzed their thyroid hormone levels and clinical characteristics. RESULTS: The combined difference plots showed that one harmonized TSH immunoassay exhibited markedly different reactivity even after TSH harmonization compared with the other three immunoassays. Among 109 patients with mild-to-moderate elevation of TSH levels, we selected 15 patients with statistically significant deviations in TSH levels according to the difference plots of three harmonized TSH immunoassays, excluding one immunoassay that showed different reactivity. The thyroid hormone levels of three patients were misclassified as hypothyroidism or normal due to deviating TSH levels. In terms of clinical characteristics, these patients were in poor nutritional status and general condition, possibly due to their severe illness (e.g., advanced metastatic cancer). CONCLUSION: We have confirmed that TSH harmonization in clinical practice is relatively stable. However, some patients showed deviating TSH levels in the harmonized TSH immunoassays, indicating the need for caution, particularly in poorly nourished patients. This finding suggests the presence of factors that contribute to the instability of TSH harmonization in such cases. Further investigation is warranted to validate these results.

Quantitative diagnostic algorithm using endocytoscopy for superficial nonampullary duodenal epithelial tumors.

BACKGROUND AND AIM: Optical biopsy using endocytoscopy for superficial nonampullary duodenal epithelial tumors (SNADETs) is practical; however, a diagnostic algorithm has not been established. The aim of this study was to determine correlations of endocytoscopic findings of SNADETs with histology using computer analysis and to establish an algorithm. METHODS: Endocytoscopic images and histological images of duodenal lesions from 70 patients were retrospectively collected. The numbers of glands and densely stained areas with methylene blue (DSMs) per 1 mm2 and the percentage of DSMs per screen in endocytoscopy were determined. Moreover, correlations in DSMs and glands between endocytoscopy and histological images were analyzed. Histopathological diagnoses were assessed according to the revised Vienna classification. The primary outcome was correlation between the number of glands in endocytoscopy and that in histology. Finally, a diagnostic algorithm for endoscopic intervention of SNADETs with a statistical program command was established. RESULTS: The number of glands in endocytoscopic images was correlated with that in histopathological images (ρ 0.64, P < 0.001). There were significant differences in the mean number of glands between category 4/5 and category 3 (P = 0.03) and the mean percentage of DSMs between category 4/5 and category 1 (P < 0.001). When the cutoffs for the number of glands and percentage of DSMs were set at 47 per 1 mm2 and 20.8% in one screen, respectively, the area under the ROC curve was 0.89. CONCLUSIONS: Endocytoscopic images of SNADETs reflect histopathological atypia, and computer analysis provides a practical diagnostic algorithm for endoscopic intervention.

Improvement of detection sensitivity of upper gastrointestinal epithelial neoplasia in linked color imaging based on data of eye tracking.

BACKGROUND AND AIM: Linked color imaging (LCI) is useful for screening in the gastrointestinal tract; however, its true clinical benefit has not been determined. The aim of this study was to determine the objective advantage of LCI for detection of upper gastrointestinal neoplasms. METHODS: Nine endoscopists, including three novices, three trainees, and three experts, prospectively performed eye tracking. From 30 cases of esophageal or gastric neoplasm and 30 normal cases without neoplasms, a total of 120 images, including 60 pair images of white light imaging (WLI) and LCI taken at the same positions and angles, were randomly shown for 10 s. The sensitivity of tumor detection as a primary endpoint was evaluated and sensitivities by organ, size, and visual gaze pattern were also assessed. Color differences (ΔE using CIE1976 [L*a*b*]) between lesions and surrounding mucosa were measured and compared with detectability. RESULTS: A total of 1080 experiments were completed. The sensitivities of tumor detection in WLI and LCI were 53.7% (50.1-56.8%) and 68.1% (64.8-70.8%), respectively (P = 0.002). LCI provided higher sensitivity than WLI for the novice and trainee groups (novice: 42.2% [WLI] vs 65.6% [LCI], P = 0.003; trainee: 54.4% vs 70.0%, P = 0.045). No significant correlations were found between sensitivity and visual gaze patterns. LCI significantly increased ΔE, and the diagnostic accuracy with WLI depended on ΔE. CONCLUSIONS: In conclusion, LCI significantly improved sensitivity in the detection of epithelial neoplasia and enabled epithelial neoplasia detection that is not possible with the small color difference in WLI. (UMIN000047944).

Linked color imaging provides enhanced visibility with a high color difference in upper gastrointestinal neoplasms.

BACKGROUND AND AIM: The aim of this post-hoc analysis in a randomized, controlled, multicenter trial was to evaluate the visibility of upper gastrointestinal (UGI) neoplasms detected using linked color imaging (LCI) compared with those detected using white light imaging (WLI). METHODS: The visibility of the detected UGI neoplasm images obtained using both WLI and LCI was subjectively reviewed, and the median color difference (ΔE) between each lesion and the surrounding mucosa according to the CIE L*a*b* color space was evaluated objectively. Multivariate logistic regression analysis was performed to identify factors associated with neoplasms that were missed under WLI and detected under LCI. RESULTS: A total of 120 neoplasms, including 10, 32, and 78 neoplasms in the pharynx, esophagus, and stomach, respectively, were analyzed in this study. LCI enhanced the visibility 80.9% and 93.6% of neoplasms in pharynx/esophagus and stomach compared with WLI, respectively. LCI also achieved a higher ΔE of enhanced neoplasms compared with WLI in the pharynx/esophagus and stomach. The median WLI ΔE values for gastric neoplasms missed under WLI and later detected under LCI were significantly lower than those for gastric neoplasms detected under WLI (8.2 vs 9.6, respectively). Furthermore, low levels of WLI ΔE (odds ratio [OR], 7.215) and high levels of LCI ΔE (OR, 22.202) were significantly associated with gastric neoplasms missed under WLI and later detected under LCI. CONCLUSION: Color differences were independently associated with missing gastric neoplasms under WLI, suggesting that LCI has an obvious advantage over WLI in enhancing neoplastic visibility.

Long-term changes in aberrant DNA methylation and gastritis after Helicobacter pylori eradication focused on metachronous gastric cancer.

BACKGROUND: A persistently high methylation level in gastric mucosa after Helicobacter pylori (H. pylori) eradication is presumed to be a risk for metachronous gastric cancer (MGC); however, long-term changes in aberrant DNA methylation and histological gastritis have been unclear. Our aim was to examine changes in DNA methylation and histological gastritis according to the occurrence of MGC. METHODS: Subjects were classified into three groups: 25 patients in whom MGCs occurred after the initial endoscopic resection (ER) for early gastric cancer and H. pylori eradication (MGC group), 17 patients in whom MGC did not occur for more than 5 years after the initial ER and H. pylori eradication (non-MGC group) and 29 patients without a history of gastric cancer who succeeded in eradication more than 5 years ago (HP group). Aberrance of DNA methylation in three genes (miR-124a-3, EMX1, NKX6-1) and histological score of atrophy and intestinal metaplasia (IM) were evaluated using biopsy samples before and more than a mean of 5 years after H. pylori eradication. Also, the mean Z-score was calculated using Z-score values of the three genes. RESULTS: The methylation level of miR-124a-3 in the HP group and non-MGC group and that of EMX1 in the HP group significantly decreased in the long term after eradication. In the MGC group, H. pylori eradication did not improve aberrant methylation, and the mean Z-score significantly increased. There were significant positive correlations between methylation levels in miR-124a-3 and EMX1 and histological findings after eradication. CONCLUSIONS: A persistently high methylation level after H. pylori eradication reflected precancerous mucosal conditions and led to long-term MGC.

Optical biopsy for esophageal squamous cell neoplasia by using endocytoscopy.

BACKGROUND: Endocytoscopy (ECS) enables microscopic observation in vivo for the gastrointestinal mucosa; however, there has been no prospective study in which the diagnostic accuracy of ECS for lesions that have not yet undergone histological diagnosis was evaluated. We conducted a surveillance study for patients in a high-risk group of esophageal squamous cell carcinoma (ESCC) and evaluated the in vivo histological diagnostic accuracy of ECS. METHODS: This study was a multicenter prospective study. We enrolled 197 patients in the study between September 1, 2019 and November 30, 2020. The patients first underwent white light imaging and narrow band imaging, and ultra-high magnifying observation was performed if there was a lesion suspected to be an esophageal tumor. Endoscopic submucosal dissection (ESD) was later performed for lesions that were diagnosed to be ESCC by ECS without biopsy. We evaluated the diagnostic accuracy of ECS for esophageal tumorous lesions. RESULTS: ESD was performed for 37 patients (41 lesions) who were diagnosed as having ESCC by ECS, and all of them were histopathologically diagnosed as having ESCC. The sensitivity [95% confidence interval (CI)] was 97.6% (87.7-99.7%), specificity (95% CI) was 100% (92.7-100%), diagnostic accuracy (95% CI) was 98.9% (94.0-99.8%), positive predictive value (PPV) (95% CI) was 100% (91.4-100%) and negative predictive value (NPV) (95% CI) was 98.0% (89.5-99.7%). CONCLUSIONS: ECS has a high diagnostic accuracy and there were no false positives in cases diagnosed and resected as ESCC. Optical biopsy by using ECS for esophageal lesions that are suspected to be tumorous is considered to be sufficient in clinical practice.

Bleeding After Gastric Endoscopic Submucosal Dissection Focused on Management of Xa Inhibitors.

Purpose: The use of direct oral Xa inhibitors (DXaIs) to prevent venothrombotic events is increasing. However, gastrointestinal bleeding, including that related to endoscopic resection, is a concern. In this study, we evaluated bleeding and coagulation times during the perioperative period of gastric endoscopic submucosal dissection (ESD). Materials and Methods: Patients who consecutively underwent gastric ESD from August 2016 to December 2018 were analyzed. Bleeding rates were compared among the 3 groups (antiplatelet, DXaIs, and control). DXaI administration was discontinued on the day of the procedure. Prothrombin time (PT), activated partial thromboplastin time, and the ratio of inhibited thrombin generation (RITG), which was based on dilute PT, were determined before and after ESD. Results: During the study period, 265 gastric ESDs were performed in 239 patients, where 23 and 50 patients received DXaIs and antiplatelets, respectively. Delayed bleeding occurred in 17 patients (7.4%) and 21 lesions (7.1%). The bleeding rate in the DXaI group was significantly higher than that in the other groups (30.4%, P<0.01), and the adjusted odds ratio of bleeding was 5.7 (95% confidence interval, 1.4-23.7; P=0.016). In patients using DXaIs, there was a significant (P=0.046) difference in the median RITG between bleeding cases (18.6%) and non-bleeding cases (3.8%). Conclusions: A one-day cessation of DXaIs was related to a high incidence of bleeding after gastric ESD, and monitoring of residual coagulation activity at trough levels might enable the predicted risk of delayed bleeding in patients using DXaIs.

Diagnostic ability of linked color imaging in ultraslim endoscopy to identify neoplastic lesions in the upper gastrointestinal tract.

Background and study aims Linked color imaging (LCI) is a new image-enhancing technique that facilitates the differentiation of slight differences in mucosal color tone. We performed an exploratory analysis to evaluate the diagnostic capability of LCI in ultraslim endoscopy, using data from patients examined in the LCI-Further Improving Neoplasm Detection in upper gastrointestinal (LCI-FIND) trial, a large-scale, multicenter, randomized controlled trial that demonstrated the capability of LCI for detecting neoplastic lesions in the upper gastrointestinal tract. Patients and methods Data from the LCI-FIND prospective trial were used. In the LCI-FIND trial, 1502 patients with a history of gastrointestinal cancer were randomly assigned to two groups based on examination methods: white light imaging (WLI) followed by LCI (WLI group) and LCI followed by WLI (LCI group). The present exploratory analysis investigated the outcomes of patients who underwent ultraslim and standard endoscopies. Results Ultraslim endoscopes were used in 223 patients and standard endoscopes in 1279 patients. The primary endpoint of the LCI-FIND trial was the percentage of patients diagnosed with a neoplastic lesion using WLI or LCI. The corresponding percentage tended to be higher with LCI than with WLI among patients who underwent ultraslim endoscopy and among those who underwent standard endoscopy; the crude risk ratio was 2.21 [95 % confidence interval (CI): 1.06-4.67], and the adjusted odds ratio was 2.46 (95 % CI: 1.07-5.63). Conclusions Our exploratory analysis of data from the LCI-FIND trial showed that LCI is useful in identifying neoplastic lesions, when used in ultraslim endoscopy.

Eradication of Helicobacter pylori may improve dyspepsia in the elderly for the long term.

BACKGROUND: Therapy for eradication of Helicobacter pylori (H. pylori) improves symptoms of H. pylori-associated dyspepsia (HPD), but the effects of eradication in elderly patients are unclear. The aim of our study was to investigate dyspepsia symptoms and long-term effects of eradication in elderly patients. METHODS: This retrospective study included 496 patients who received H. pylori eradication therapy. The patients were divided into a group of elderly patients (group E: ≧ 65 years old) and a group of non-elderly patients (group N: < 65 years old). Abdominal symptoms were evaluated using a questionnaire about abdominal symptoms before eradication and after eradication (1-2 months and more than one year). Dyspepsia was defined as a score of 4 points or more for at least one of 4 items (postprandial fullness, early satiety, epigastric pain, and hunger pain). Improvement of symptoms was defined on the basis of changes in Global Overall Systems scores. RESULTS: There were no differences in abdominal symptoms before eradication between the two groups. Successful eradication improved symptoms in patients with dyspepsia within 2 months (in 75.6% (56/74) of the patients in group N and in 64.5% (20/31) of the patients in group E). The questionnaire showed that 80% (32/40) of the patients in group N and 60% (12/20) of the patients in group E had long-term relief of dyspepsia. The scores for abdominal symptoms in group E continued to improve for a mean period of 54.8 months after eradication. CONCLUSIONS: Eradication of H. pylori age-independently improved dyspepsia symptoms for the long term.

Genomic profiling of intestinal/mixed-type superficial non-ampullary duodenal epithelial tumors.

BACKGROUND AND AIM: The mechanism underlying carcinogenesis and the genomic features of superficial non-ampullary duodenal epithelial tumors (SNADETs) have not been elucidated in detail. In this study, we examined the genomic features of incipient SNADETs, such as small lesions resected via endoscopic treatment, using next-generation sequencing (NGS). METHODS: Twenty consecutive patients who underwent endoscopic treatment for SNADETs of less than 20 mm between January and December 2017 were enrolled. Targeted genomic sequencing was performed through NGS using a panel of 160 cancer-related genes. Furthermore, the alteration/mutation frequencies in SNADETs were examined. RESULTS: The maximum size of the SNADETs examined in this study was 12 mm in diameter. Five SNADETs were classified as low-grade dysplasia (LGD) tumors, while 14 SNADETs were classified as high-grade dysplasia tumors. Only one carcinoma in situ was detected. NGS data for 16 samples were obtained. APC alterations were detected in 81% of samples (13/16). KRAS, BRAF, and TP53 alterations were detected in 25% (4/16), 18.8% (3/16), and 6.3% (1/16) of cases, respectively. CONCLUSION: We detected APC alterations in most small SNADETs resected via endoscopic treatment, from LGD to carcinoma samples. Even in SNADETs classified as small LGD exhibited KRAS and BRAF alterations.

Gastric epithelial neoplasm of fundic-gland mucosa lineage: proposal for a new classification in association with gastric adenocarcinoma of fundic-gland type.

BACKGROUND: Gastric adenocarcinoma of fundic-gland type (GA-FG) is a rare variant of gastric neoplasia. However, the etiology, classification, and clinicopathological features of gastric epithelial neoplasm of fundic-gland mucosa lineage (GEN-FGML; generic term of GA-FG related neoplasm) are not fully elucidated. We performed a large, multicenter, retrospective study to establish a new classification and clarify the clinicopathological features of GEN-FGML. METHODS: One hundred GEN-FGML lesions in 94 patients were collected from 35 institutions between 2008 and 2019. We designed a new histopathological classification of GEN-FGML using immunohistochemical analysis and analyzed via clinicopathological, immunohistochemical, and genetic evaluation. RESULTS: GEN-FGML was classified into 3 major types; oxyntic gland adenoma (OGA), GA-FG, and gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM). In addition, GA-FGM was classified into 3 subtypes; Type 1 (organized with exposure type), Type 2 (disorganized with exposure type), and Type 3 (disorganized with non-exposure type). OGA and GA-FG demonstrated low-grade epithelial neoplasm, and GA-FGM should be categorized as an aggressive variant of GEN-FGML that demonstrated high-grade epithelial neoplasm (Type 2 > 1, 3). The frequent presence of GNAS mutation was a characteristic genetic feature of GEN-FGML (7/34, 20.6%; OGA 1/3, 33.3%; GA-FG 3/24, 12.5%; GA-FGM 3/7, 42.9%) in mutation analysis using next-generation sequencing. CONCLUSIONS: We have established a new histopathological classification of GEN-FGML and propose a new lineage of gastric epithelial neoplasm that harbors recurrent GNAS mutation. This classification will be useful to estimate the malignant potential of GEN-FGML and establish an appropriate standard therapeutic approach.

Experiment on endoscopic balloon dilation for esophageal stenosis after endoscopic submucosal dissection in pigs.

BACKGROUND AND AIM: Endoscopic balloon dilation (EBD) is effective for esophageal stenosis caused by ESD. However, an efficient EBD method has not been established. We, therefore, conducted EBD experiments on porcine esophageal stenosis models. METHODS: Study 1: in dilation models (day 22 after ESD), the thickness of the outer muscle layer (as an index of the extension effect) and the area of muscle fiber bundle necrosis in the inner muscle layer (as an index of thermal damage) were evaluated. Study 2: in restenosis models (day 43 after ESD), the thickness of the fibrous plexus (as an index of restenosis) was evaluated. In total, 12 porcine models were created. RESULTS: Study 1: the thickness of the outer muscle layer was 1243 ± 322 µm in surrounding locations and it was 803 ± 145 µm beneath the laceration (p = 0.005). In cases of muscular layer injury, the area of necrosis was 15,500 ± 10400 µm2 in surrounding locations and it was 40,200 ± 12900 µm2 at the laceration site (p < 0.001). Study 2: the thickness of the fibrous plexus was 1359 ± 196 µm in surrounding locations and it was 1322 ± 136 µm2 in the laceration scar site (p = 0.74). CONCLUSION: Since thermal damage persists until the completion of stenosis, EBD in the initial stage should be carefully performed. An extension effect was observed only at the laceration site and it later returned to a status similar to that of surrounding locations. Additional intervention would be required for preventing restenosis.

Optical effect of spraying l-menthol on gastric intestinal metaplasia visualized by linked color imaging.

OBJECTIVE: Linked color imaging (LCI) enables noninvasive detection of gastric intestinal metaplasia (GIM) as a lavender color sign (LCS), and there has been a recent report that l-menthol enhanced GIM with LCI. We measured color values of GIM and surrounding mucosa with white light imaging (WLI), LCI and LCI after spraying l-menthol (Mint-LCI) and investigated the effect of l-menthol on gastric mucosa. METHODS: Endoscopic images of the antrum with WLI, LCI and Mint-LCI from 18 patients were prepared. Each of six regions of interest (three points of GIM and three points of surrounding mucosa) was selected for each modality, and CIE1976 (L*a*b*) color space was used to measure the color values. The primary endpoint was color differences (ΔE) between GIM and surrounding mucosa in each modality. RESULTS: For surrounding mucosa, the mean a* value with Mint-LCI was significantly higher than the mean values with WLI and LCI (P < 0.01). The mean b* value of GIM with LCI was significantly lower than that of surrounding mucosa, and spraying l-menthol decreased the b* values of GIM with a change to a deeper lavender color (LCI: 10.0 ± 5.8, Mint-LCI: 3.7 ± 6.1, P < 0.01). However, there was no significant difference in mean ΔE values between LCI and Mint LCI (LCI: 21.1 ± 6.6, Mint-LCI: 22.7 ± 5.4, NS). After spraying l-menthol, the microstructure of GIM changed to translucent and microvessels were obscured. CONCLUSIONS: As shown by LCI, spraying l-menthol optically enhances the color of GIM in the antrum.