Advanced diagnostic endoscopy in the upper gastrointestinal tract: Review of the Japan Gastroenterological Endoscopic Society core sessions.

The Japan Gastroenterological Endoscopy Society (JGES) held four serial symposia between 2021 and 2022 on state-of-the-art issues related to advanced diagnostic endoscopy of the upper gastrointestinal tract. This review summarizes the four core sessions and presents them as a conference report. Eleven studies were discussed in the 101st JGES Core Session, which addressed the challenges and prospects of upper gastroenterological endoscopy. Ten studies were also explored in the 102nd JGES Core Session on advanced upper gastrointestinal endoscopic diagnosis for decision-making regarding therapeutic strategies. Moreover, eight studies were presented during the 103rd JGES Core Session on the development and evaluation of endoscopic artificial intelligence in the field of upper gastrointestinal endoscopy. Twelve studies were also discussed in the 104th JGES Core Session, which focused on the evidence and new developments related to the upper gastrointestinal tract. The endoscopic diagnosis of upper gastrointestinal diseases using image-enhanced endoscopy and AI is one of the most recent topics and has received considerable attention. These four core sessions enabled us to grasp the current state-of-the-art in upper gastrointestinal endoscopic diagnostics and identify future challenges. Based on these studies, we hope that an endoscopic diagnostic system useful in clinical practice is established for each field of upper gastrointestinal endoscopy.

Multicenter study of invasive gastric cancer detected after 10 years of Helicobacter pylori eradication in Japan: Clinical, endoscopic, and histopathologic characteristics.

Objectives: Gastric cancer can be diagnosed even in patients long after Helicobacter pylori eradication. Most cases involve intramucosal lesions; however, some are invasive and require surgery. To clarify appropriate long-term surveillance methods, this study compared invasive gastric cancer diagnosed ≥10 and <10 years after eradication. Methods: This retrospective multicenter study included 14 institutions. We included 377 patients with gastric cancer with submucosal or deep invasion after surgical or endoscopic resection. Ordered logistic regression analysis was used to explore the factors contributing to the pathological stage and histological type. Results: Invasive gastric cancer was detected in 84 patients (Group L) and 293 patients (Group S) ≥10 and <10 years after H. pylori eradication, respectively. Endoscopic mucosal atrophy at the time of cancer detection was similar in both groups; 50% of the patients had severe atrophy. Annual endoscopy correlated with early pathological stage (odds ratio [OR] 0.28, 95% confidence interval [CI] 0.14-0.54, p < 0.001). Group L exhibited an independent correlation with the advanced pathological stage (OR 2.27, 95% CI 1.06-4.88, p = 0.035) and the undifferentiated type (OR 2.12, 95% CI 1.16-3.90, p = 0.015). The pure differentiated type and early pathological stage significantly (p = 0.001) correlated with severe mucosal atrophy in Group S but not in Group L. Conclusions: Invasive cancers diagnosed ≥10 years after H. pylori eradication were likely to be more malignant in histological type and pathological stage. Gastric cancer surveillance should continue regardless of endoscopic atrophy, particularly ≥10 years after eradication.

A simpler diagnostic algorithm of the Japan Esophageal Society classification for Barrett's esophagus-related superficial neoplasia.

BACKGROUND: We previously developed a Japan Esophageal Society Barrett's Esophagus (JES-BE) magnifying endoscopic classification for superficial BE-related neoplasms (BERN) and validated it in a nationwide multicenter study that followed a diagnostic flow chart based on mucosal and vascular patterns (MP, VP) with nine diagnostic criteria. Our present post hoc analysis aims to further simplify the diagnostic criteria for superficial BERN. METHODS: We used data from our previous study, including 10 reviewers' assessments for 156 images of high-magnifying narrow-band imaging (HM-NBI) (67 dysplastic and 89 non-dysplastic histology). We statistically analyzed the diagnostic performance of each diagnostic criterion of MP (form, size, arrangement, density, and white zone), VP (form, caliber change, location, and greenish thick vessels [GTV]), and all their combinations to achieve a simpler diagnostic algorithm to detect superficial BERN. RESULTS: Diagnostic accuracy values based on the MP of each single criterion or combined criteria showed a marked trend of being higher than those based on VP. In reviewers' assessments of visible MPs, the combination of irregularity for form, size, or white zone had the highest diagnostic performance, with a sensitivity of 87% and a specificity of 91% for dysplastic histology; in the assessments of invisible MPs, GTV had the highest diagnostic performance among the VP of each single criterion and all combinations of two or more criteria (sensitivity, 93%; specificity, 92%). CONCLUSION: The present post hoc analysis suggests the feasibility of further simplifying the diagnostic algorithm of the JES-BE classification. Further studies in a practical setting are required to validate these results.

Case report: New subtype of gastric adenocarcinoma arising from an H. pylori infection-negative stomach: Foveolar epithelium and mucous neck cell-mixed type adenocarcinoma.

The characteristics of Helicobacter pylori (H. pylori) infection-negative gastric cancer have not been well documented because of its rarity, despite several types of H. pylori infection-negative gastric cancers being reported. In this report, we describe a case of early gastric cancer that developed without H. pylori infection with characteristic magnifying narrow-band imaging and novel histological findings. The difficulty in making an accurate diagnosis and differential diagnosis is highlighted, with the goal of providing more clinical experience for the diagnosis of H. pylori infection-negative gastric cancer.

Gravity assistance enables liver stiffness measurements to detect liver fibrosis under congestive circumstances.

BACKGROUND: As survival has been prolonged owing to surgical and medical improvements, liver failure has become a prognostic determinant in patients with congestive heart diseases. Congestive hepatopathy, an abnormal state of the liver as a result of congestion, insidiously proceed toward end-stage liver disease without effective biomarkers evaluating pathological progression. Regular measurements of shear wave elastography cannot qualify liver fibrosis, which is a prognosticator in any type of chronic liver disease, in cases of congestion because congestion makes the liver stiff without fibrosis. We hypothesized that the effects of congestion and fibrosis on liver stiffness can be dissociated by inducing architectural deformation of the liver to expose structural rigidity. AIM: To establish a strategy measuring liver stiffness as a reflection of architectural rigidity under congestion. METHODS: Two-dimensional shear wave elastography (2dSWE) was measured in the supine (Sp) and left decubitus (Ld) positions in 298 consecutive cases as they were subjected to an ultrasound study for various liver diseases. Regions of interest were placed at twelve sites, and the median and robust coefficient of variation were calculated. Numerical data were compared using the Mann-Whitney U or Kruskal-Wallis test followed by Dunn's post-hoc multiple comparisons. The inferior vena cava (IVC) diameters at different body positions were compared using the Wilcoxon matched pairs signed rank test. The number of cases with cardiothoracic ratios greater than or not greater than 50% was compared using Fisher's exact test. A correlation of 2dSWE between different body positions was evaluated by calculating Spearman correlation coefficients. RESULTS: The IVC diameter was significantly reduced in Ld in subjects with higher 2dSWE values in Ld (LdSWE) than in Sp (SpSWE) (P = 0.007, (average ± SD) 13.9 ± 3.6 vs 13.1 ± 3.4 mm) but not in those with lower LdSWE values (P = 0.32, 13.3 ± 3.5 vs 13.0 ± 3.5 mm). In 81 subjects, SpSWE was increased or decreased in Ld beyond the magnitude of robust coefficient of variation, which suggests that body postural changes induced an alteration of liver stiffness significantly larger than the technical dispersion. Among these subjects, all 37 with normal SpSWE had a higher LdSWE than SpSWE (Normal-to-Hard, SpSWE - LdSWE (∆2dSWE): (minimum-maximum) -0.74 - -0.08 m/sec), whereas in 44 residual subjects with abnormal SpSWE, LdSWE was higher in 27 subjects (Hard-to-Hard, -0.74 - -0.05 m/sec) and lower in 17 subjects (Hard-to-Soft, 0.04 - 0.52 m/sec) than SpSWE. SpSWE was significantly correlated with ∆2dSWE only in Hard-to-Soft (P < 0.0001). ∆2dSWE was larger in each lobe than in the entire liver. When Hard-to-Hard and Hard-to-Soft values were examined for each lobe, fibrosis-4 or platelet counts were significantly higher or lower only for Hard-to-Soft vs Normal-to-Hard cases. CONCLUSION: Gravity alters the hepatic architecture during body postural changes, causing outflow blockage in hepatic veins. A rigid liver is resistant to structural deformation. Stiff-liver softening in the Ld position suggests a fibrous liver.

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.

Diagnostic utility of a novel magnifying endoscopic classification system for superficial Barrett's esophagus-related neoplasms: a nationwide multicenter study.

BACKGROUND: Currently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett's esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society-Barrett's esophagus working group (JES-BE) for superficial Barrett's esophagus-related neoplasms. METHODS: The JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter. RESULTS: The sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found. CONCLUSION: The JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician's experience level.

Endoscopic retrieval of multiple sewing needles by using the tip of a magnetic tube.

Video 1Multiple sewing needles are retrieved from the stomach endoscopically using the tip of a magnet tube.

A Superinfection of Salmonella typhi and Hepatitis E Virus Causes Biphasic Acute Hepatitis.

A 47-year-old Japanese man was referred to our hospital because of a sustained high fever with diarrhea 12 days after a flight from India. Liver enzymes were elevated with rose spots, hepatosplenomegaly, relative bradycardia, and acute cholecystitis. A liver biopsy depicted the dense infiltration of lymphocytes and Kupffer cells in sinusoids and the granulomatous formation in the parenchyma. The liver damage was initially resolved with the administration of ceftriaxone for 16 days but flared up 1 week later. Laboratory tests yielded positive reactions for Salmonella typhi and hepatitis E virus RNA. The pathophysiological presentations of concurrent typhoid and type E hepatitis are discussed.

Conversion of percutaneous transhepatic biliary drainage to endoscopic ultrasound-guided biliary drainage.

Introduction: Percutaneous transhepatic biliary drainage (PTBD) is a useful alternative treatment for malignant biliary obstruction (MBO) when patients have difficulty with endoscopic transpapillary drainage. We examined the feasibility of conversion of PTBD to endoscopic ultrasound-guided biliary drainage (EUS-BD) in patients with MBO unsuited for endoscopic transpapillary biliary drainage. Methods: This retrospective study included patients who underwent conversion of PTBD to EUS-BD between March 2017 and December 2019. Eligible patients had unresectable MBO, required palliative biliary drainage, and were not suited for endoscopic transpapillary drainage. Initial PTBD had been performed for acute cholangitis or obstructive jaundice in all patients. EUS-BD was performed following improvements in cholangitis. Sixteen patients underwent conversion of PTBD to EUS-BD. We evaluated technical success, procedure time, clinical success (defined as subsequent external catheter removal), adverse events (AEs), time to recurrent biliary obstruction (TRBO), and re-intervention rates. Results: Technical success was achieved in all patients (100%). The median procedure time was 45.0 minutes (interquartile range [IQR] 30.0-50.0 minutes). Clinical success was achieved in all patients (100%). There were mild early AEs in two patients (12.5%) (acute cholangitis: 1, bile peritonitis: 1), which improved with antibiotic administration alone. Recurrent biliary obstruction (RBO) occurred in six patients (37.5%). Kaplan-Meier analysis revealed a 50% TRBO of 95 days (IQR 41-246 days). Endoscopic treatment was possible in all RBO cases, and repeat PTBD was not required. Conclusions: Conversion of PTBD to EUS-BD for the management of MBO is both feasible and safe. This approach is expected to be widely practiced at centers with little experience in EUS-BD.

Transcatheter Arterial Embolization Using Microspheres for Palliating Pain from Bone Metastasis in a Patient with Cholangiocellular Carcinoma.

A 72-year-old man with intractable left shoulder pain due to bone metastasis from cholangiocellular carcinoma was admitted to our hospital. Computed tomography showed an osteoblastic metastatic lesion of the left scapula. Since the pain persisted even after the administration of opioids and external irradiation, microspheres were injected through a catheter; the catheter tip was placed at the arteries feeding the metastatic lesion. After the intervention, the shoulder pain was alleviated without any procedure-related complications, leading to a reduction in the opioid dose. This case suggests the efficacy of transcatheter arterial embolization using microspheres for palliating pain from bone metastasis.

Stent Placement for Malignant Inferior Vena Cava Syndrome in a Patient with Recurrent Colon Cancer.

A 70-year-old man was admitted to our hospital with gait disturbance due to marked edema of the lower limbs for more than 6 months. He had been receiving systemic chemotherapy over two years for multiple recurrence after sigmoid colon cancer resection. Contrast-enhanced computed tomography demonstrated severe inferior vena cava (IVC) stenosis due to compression by lymph node metastases, i.e. IVC syndrome. As increased doses of diuretic agents failed to improve the edema, IVC stent placement was performed. This led to significant improvement of the edema and complete gait normalization. This case demonstrates the efficacy of IVC stent placement for IVC syndrome.

Synchronous Double Bile Duct Cancers with Distinct Genetic Features.

A 69-year-old man was referred to our hospital because of appetite loss. Imaging showed a nodular tumor in the perihilar bile duct and a second flat lesion in the distal bile duct. Right hepatopancreaticoduodenectomy was performed, and the histopathological findings demonstrated that the perihilar and distal lesions were moderately and poorly differentiated adenocarcinoma, respectively, and anatomically separated. Furthermore, the resected specimens showed no pancreaticobiliary maljunction. Histological and TP53 gene analyses in a rare case of synchronous double bile duct cancers suggest that there are various genetic pathways through which bile duct cancer develops, highlighting the complexity of its pathogenesis.

Non-insulin-dependent Diabetes Mellitus Induced by Immune Checkpoint Inhibitor Therapy in an Insulinoma-associated Antigen-2 Autoantibody-positive Patient with Advanced Gastric Cancer.

A 70-year-old man with insulinoma-associated antigen-2 autoantibodies developed diabetes mellitus (DM) without ketoacidosis after starting nivolumab to treat advanced gastric cancer. He subsequently exhibited preserved insulin-secretion capacity for over one year. Immune checkpoint inhibitors (ICIs) infrequently cause type 1 DM associated with the rapid loss of insulin secretion and ketoacidosis as an immune-related adverse event. ICIs may also cause non-insulin-dependent DM by inducing insulin resistance if there is islet autoantibody-related latent beta-cell dysfunction. The present case highlights the importance of testing blood glucose levels regularly to diagnose DM in patients treated with ICIs, even if they do not have diabetic ketoacidosis.

Rational arrangement of measuring shear wave speed in the liver.

BACKGROUND: Shear wave speed has been widely applied to quantify a degree of liver fibrosis. However, there is no standardized procedure, which makes it difficult to utilize the speed universally. AIM: To provide procedural standardization of shear wave speed measurement. METHODS: Point shear wave elastography (pSWE) was measured in 781 patients, and two-dimensional shear wave elastography (2dSWE) was measured on the same day in 18 cases. Regions-of-interest were placed at 12 sites, and the median and robust coefficient-of-variation (CVR) were calculated. A residual sum-of-square (Σdi 2) was computed for bootstrap values of 1000 iterations in 18 cases with each assumption of 1 to 12 measurements. The proportion of the Σdi 2 (%Σdi 2) was calculated as the ratio of Σdi 2 to pSWE after converting it based on the correlation between pSWE and 2dSWE. RESULTS: The CVR showed a significantly broader distribution in the left lobe (P < 0.0001), and the smallest CVR in the right anterior segment that covered 95% cases was 40.4%. pSWE was significantly higher in the left lobe than in the right lobe (1.63 ± 0.78 m/s vs 1.61 ± 0.78 m/s, P = 0.0004), and the difference between the lobes became further discrete when the subjects were limited to the cases with a CVR less than 40.4% in any segment (1.76 ± 0.80 m/s vs 1.70 ± 0.82 m/s, P < 0.0001). The highest values of the CVR in every 0.1 m/s interval were plotted in convex upward along pSWE and peaked at 1.93 m/s. pSWE and 2dSWE were significantly correlated (P < 0.0001, r = 0.95). In 216000 resamples from 18 cases, the %Σdi 2 of 12 sites was 8.0% and gradually increased as the acquisition sites decreased to reach a significant difference with a %Σdi 2 of 7 sites (P = 0.027). CONCLUSION: These data suggest that shear wave speed should be measured at 8 or more sites of spreading in both lobes.

A cut-off value of shear wave speed to distinguish nonalcoholic steatohepatitis candidates.

To distinguish and characterize nonalcoholic steatohepatitis (NASH) candidates from among medical checkup visitor diagnosed with nonalcoholic fatty liver diseases (mcNAFLDs).A cut-off value has not been established to differentiate NASH at the earliest stage in NAFLD.Shear wave speed (SWS) was measured in the livers of 480 mcNAFLDs. NASH candidates were screened out by adopting a statistically defined cut-off value of SWS and were characterized in terms of food preference.SWS ranged between 1.11 and 2.18 m/s and fit a Gaussian distribution (r = 0.98) with an average and SD of 1.324 and 0.0847 m/s, respectively, in 320/160 males/females 64.4 (interquartile range 57.3-69.4) years old. The average plus SD (1.41 m/s) screened out 82 (17.1%) NASH candidates, who were significantly older (66.8 vs. 64.1 years old, P = 0.001) and had higher fibrosis 4 index values (1.58 vs. 1.33, P < 0.0001) than the remaining mcNAFLDs. The number of patients with a BMI greater than 25 kg/m was 118 (29.6%) mcNAFLDs and 34 (41.5%) NASH candidates, with a significantly higher frequency in NASH candidates (P = 0.05). Obese patients preferentially ate fatty acids in general, while NASH candidates preferred to consume several long-chain unsaturated fatty acids irrespective of their BMI.These results suggest that NASH candidates who have a longer disease duration and pathological progression can be distinguished from mcNAFLDs by a statistically defined cut-off value of SWS. The defined value indicates that there are different food habitats associated with obesity and NAFLD progression.