Exploratory investigation of virtual lesions in gastrointestinal endoscopy using a novel phase-shift method for three-dimensional shape measurement.

Accurate measurement of the size of lesions or distances between any two points during endoscopic examination of the gastrointestinal tract is difficult owing to the fisheye lens used in endoscopy. To overcome this issue, we developed a phase-shift method to measure three-dimensional (3D) data on a curved surface, which we present herein. Our system allows the creation of 3D shapes on a curved surface by the phase-shift method using a stripe pattern projected from a small projecting device to an object. For evaluation, 88 measurement points were inserted in porcine stomach tissue, attached to a half-pipe jig, with an inner radius of 21 mm. The accuracy and precision of the measurement data for our shape measurement system were compared with the data obtained using an Olympus STM6 measurement microscope. The accuracy of the path length of a simulated protruded lesion was evaluated using a plaster model of the curved stomach and graph paper. The difference in height measures between the measurement microscope and measurement system data was 0.24 mm for the 88 measurement points on the curved surface of the porcine stomach. The error in the path length measurement for a lesion on an underlying curved surface was <1% for a 10-mm lesion. The software was developed for the automated calculation of the major and minor diameters of each lesion. The accuracy of our measurement system could improve the accuracy of determining the size of lesions, whether protruded or depressed, regardless of the curvature of the underlying surface.

Cancer risk by length of Barrett's esophagus in Japanese population: a nationwide multicenter retrospective cohort study.

BACKGROUND: The cancer risk for each length of Barrett's esophagus (BE) in Japanese is unknown. This nationwide, multi-institutional study aims to clarify the cancer risk by length of BE in the general Japanese population. METHODS: Consecutive subjects who underwent upper endoscopic screening at 17 centers between 2013 and 2017 and had at least one follow-up endoscopy by December 2022 were included. The presence/absence of BE and, if present, its length were retrospectively assessed using the retrieved endoscopic images recorded at baseline. Information on the subsequent occurrence of esophageal adenocarcinoma and other upper gastrointestinal cancers was also collected. Cancer incidence was calculated and expressed as %/year. RESULTS: A total of 33,478 subjects were enrolled, and 17,884 (53.4%), 10,641 (31.8%), 4889 (14.6%), and 64 (0.2%) were diagnosed as absent BE, BE < 1 cm, 1-3 cm, and ≥ 3 cm, respectively. During a median follow-up of 80 months, 11 cases of esophageal adenocarcinoma developed. The annual incidence of esophageal adenocarcinoma is 0%/year for absent BE, 0.0032 (0.00066-0.013)%/year for BE < 1 cm, 0.026 (0.011-0.054)%/year for 1-3 cm, and 0.58 (0.042-2.11)%/year for ≥ 3 cm, respectively. Meanwhile, the incidence of esophageal squamous cell carcinoma and gastric cancer were 0.039 (0.031-0.049)%/year and 0.16 (0.14-0.18)%/year, respectively. CONCLUSIONS: By enrolling a large number of subjects with long-term follow-up, this study demonstrated that the risk of cancer increased steadily with increasing length of BE in the Japanese population. Therefore, it is important to consider the length of BE when determining the management strategy for BE.

Serum immunoglobulin A levels: Diagnostic utility in alcoholic liver disease and association with liver fibrosis in steatotic liver disease.

The relationship between immunoglobulin A (IgA) levels and chronic liver disease remains poorly understood. The present study evaluated the clinical significance of IgA in 478 new patients who visited the Outpatient Clinic of Nagasaki Harbor Medical Center (Nagasaki, Japan). Serum IgA levels in comparison to liver stiffness (LS), as measured using a FibroScan® device, were evaluated in 358 patients. Furthermore, in 270 patients, the associations between serum IgA levels and body composition were analyzed using computed tomography. The IgA levels of patients in the groups with Child-Pugh classification B and C (CPGBC), alcoholic liver disease (ALD), steatotic liver disease (SLD) or diabetes were higher than the IgA levels of patients in the groups with CPGA, non-ALD, non-SLD or no diabetes, respectively. Logistic regression analysis showed that CPGBC, ALD, high IgG (>1,700 mg/dl), high macrophage galactose-specific lectin-2 binding protein glycosylation isomer (M2BPGi) (>1 cut-off index) and diabetes were contributing factors for high serum IgA level (>410 mg/dl). The ratio of IgA level divided by IgG level was highest in patients with ALD, followed by those with metabolic dysfunction-associated SLD (MASLD) and non-SLD. In SLD, IgA level was associated more with LS than M2BPGi and fibrosis-4 (FIB-4) in multiple regression analysis. In the receiver operating characteristic analysis, IgA level, M2BPG, and FIB-4 had similar area under the curve values for discriminating high LS (>8 kPa) from low LS (≤8 kPa) in SLD. IgA levels were also associated with visceral fat, and this association was only found in women. In conclusion, elevated IgA is an indicator of liver fibrosis that also reflects the presence of diabetes and an increased visceral fat level. Therefore, IgA is considered a useful marker of liver disease severity in the current era of increased SLD.

Development of a novel multipoint traction device for gastric and colorectal endoscopic submucosal dissection and evaluation of its efficacy and safety.

BACKGROUND: Proper traction allows safer and easier endoscopic submucosal dissection; however, single-point traction may not be sufficient. In this study we assessed the safety, efficacy, and feasibility of our newly developed multipoint traction device. METHODS: During an ex vivo study using a Konjac training model, two experts and two trainees resected 80 mock lesions of 20-mm diameter by performing endoscopic submucosal dissection with and without multipoint traction. The primary outcome was the success rate of the procedure involving traction. The secondary outcomes were the submucosal dissection time, dissection speed, and perforation during endoscopic submucosal dissection. During the in vivo study, to clarify the initial clinical outcomes, we used data from the electronic medical record of patients at our institution who underwent gastric and colorectal endoscopic submucosal dissection, which was performed by experts with our newly developed multipoint traction device, from March to December 2022. RESULTS: The ex vivo study indicated that all traction procedures were successful. Higher resection speeds were observed with endoscopic submucosal dissection with traction than without traction (P < 0.001). Perforations were not observed. During the first in vivo clinical study, traction was feasible during 20 gastric and colorectal endoscopic submucosal dissection procedures. No adverse events occurred. CONCLUSIONS: Our multitraction device can increase the submucosal dissection speed and simplify endoscopic submucosal dissection techniques, thus safely reducing technical challenges. The application of this device for endoscopic submucosal dissection could lead to safer and more efficient procedures. Clinical registration UMIN Clinical Trials Registry, Japan (registration number UMIN000053384).

Diagnosis by combination of endoscopic findings helps differentiate non-Helicobacter pylori Helicobacter-infected gastritis from Helicobacter pylori-infected gastritis.

BACKGROUND: The characteristic endoscopic findings of non-Helicobacter pylori Helicobacter (NHPH) gastritis, including white marbled appearance and crack-like mucosa, have been reported. However, these findings can also manifest in H. pylori (HP)-infected gastritis. This study compared NHPH gastritis and mild atrophic HP gastritis to identify features that may enhance NHPH diagnosis. MATERIALS AND METHODS: A total of 2087 patients underwent upper gastrointestinal endoscopy and were histologically evaluated by multiple gastric mucosal biopsies according to the updated Sydney System (USS) at Shinshu University Hospital between 2005 and 2023. Among them, nine patients were classified into the NHPH group and 134 patients with HP infection and mild atrophy were classified into the HP group for retrospective comparisons of endoscopic findings and clinicopathological characteristics. RESULTS: All nine patients in the NHPH group (eight males [89%], median ± standard deviation [SD] age: 49 ± 13.0 years) were infected with H. suis. The 134 patients in the HP group contained 70 men (52%) and had a median ± SD age of 35 ± 19.9 years. Endoscopic findings were statistically comparable for white marbled appearance (three patients [33%] in the NHPH group and 37 patients [31%] in the HP group) and crack-like mucosa (three patients [33%] and 27 patients [20%], respectively). Diffuse redness was significantly less frequent in the NHPH group (one patient [14%] vs. 97 patients [72%], p < 0.001). White marbled appearance or crack-like mucosa without diffuse redness was significantly more common in the NHPH group (56% vs. 13%, p = 0.004), with a sensitivity and specificity of 56% and 87%, respectively. Mean USS neutrophil infiltration and Helicobacter density scores were significantly higher in the HP group (both p < 0.01), which might have influenced the endoscopic findings of diffuse redness. CONCLUSIONS: When endoscopic findings of white marbled appearance or cracked-like mucosa are present, evaluation for diffuse redness may contribute to a more accurate diagnosis of NHPH gastritis.

Relationship between Helicobacter pylori Eradication and Barrett's Esophagus Elongation.

INTRODUCTION: Helicobacter pylori eradication therapy may worsen gastroesophageal reflux disease that is a significant risk factor for Barrett's esophagus. However, the relationship between eradication therapy and Barrett's esophagus remains controversial. This study evaluated the impact of Helicobacter pylori eradication on the lengthening of Barrett's esophagus. MATERIALS AND METHODS: We conducted a retrospective analysis of consecutive patients who successfully underwent Helicobacter pylori eradication between 2004 and 2017. Endoscopic images obtained before and after eradication therapy were compared for Barrett's esophagus length according to the Prague C&M criteria and the presence of reflux esophagitis based on the Los Angeles classification. RESULTS: A total of 340 patients were analyzed (mean age: 66.9 ± 12.9 years) for a median follow-up of 55 months (interquartile range: 29.8-89.3). At the initial endoscopic assessment, 187 patients (55%) had a hiatal hernia, and all patients had gastric atrophy (C-0 to I: 2%, C-II to III: 47%, O-I to III: 51%). Reflux esophagitis was detected in 7 patients (2%) before eradication and in 21 patients (6%) afterward, which was a significant increase (p = 0.007). Barrett's esophagus was identified in 69 patients (20%) before eradication, with a median length of C0M1. Elongation after treatment was observed in only 2 patients (0.6%). We observed no significant increase in either the prevalence (p = 0.85) or the median length (p = 0.5) of Barrett's esophagus. CONCLUSIONS: Only 0.6% of patients exhibited Barrett's esophagus lengthening after Helicobacter pylori eradication therapy, suggesting no significant impact of the treatment on the development or elongation of Barrett's esophagus.

PIVKA­II is associated with liver function, bone metabolism, and muscle function in patients with liver disease.

Protein induced by vitamin K (VK) absence-II (PIVKA-II) is a sensitive marker for diagnosing hepatoma but is occasionally detected in patients without hepatoma Here, the clinical significance of serum PIVKA-II levels in patients who were not administered warfarin and did not have hepatoma or liver disease were evaluated. As VK is related to muscle and bone metabolism, PIVKA-II and clinical factors related to bone and muscle were compared. A total of 441 patients with various liver diseases were evaluated. Of these, 236 patients were female. Clinical factors and anthropometric measurements were obtained for each participant during outpatient visits. Among the clinical factors, type I procollagen N-propeptide (P1NP), a low titer of undercarboxylated osteocalcin (ucOC), and 25(OH) vitamin D (VD) were used as bone metabolic markers, and SARC-F and grip strength were used as muscle-related markers. Serum PIVKA-II levels above the upper limit were associated with Child B/C (Child-Pugh score), high titers of total P1NP, and low titers of ucOC in females, and alcohol-related liver disease and low VD in males. The titer of PIVKA-II were associated with immunoglobulin (Ig) A and prothrombin time (PT)-international normalized ratio (INR) in females, and fibrosis-4-4, IgG, total bilirubin, PT-INR, and SARC-F in males. Elevated PIVKA-II levels were associated with abnormal bone physiology in females, weak muscles in males, and severe liver disease in both sexes. Assessing PIVKA-II may assist in evaluating the clinical and bone-muscle metabolic stages in liver disease. Nutrition and supplementation with fat-soluble vitamins, including VK and VD may thus serve as a potential method to alleviate or prevent bone-muscle pathophysiology in patients with liver disease.

Predictive Insights Into Exocrine Pancreatic Insufficiency in Chronic Pancreatitis and Autoimmune Pancreatitis: A Decision Tree Approach.

OBJECTIVE: Exocrine pancreatic insufficiency (EPI) is a common manifestation of chronic pancreatitis (CP) and autoimmune pancreatitis (AIP). This study aimed to estimate the presence of EPI in patients with CP or AIP using alternative clinical markers. MATERIALS AND METHODS: A machine learning analysis employing a decision tree model was conducted on a retrospective training cohort comprising 57 patients with CP or AIP to identify EPI, defined as fecal elastase-1 levels less than 200 µg/g. The outcomes were then confirmed in a validation cohort of 26 patients. RESULTS: Thirty-nine patients (68%) exhibited EPI in the training cohort. The decision tree algorithm revealed body mass index (≤21.378 kg/m 2 ) and total protein level (≤7.15 g/dL) as key variables for identifying EPI. The algorithm's performance was assessed using 5-fold cross-validation, yielding area under the receiver operating characteristic curve values of 0.890, 0.875, 0.750, 0.625, and 0.771, respectively. The results from the validation cohort closely replicated those in the training cohort. CONCLUSIONS: Decision tree analysis revealed that EPI in patients with CP or AIP can be identified based on body mass index and total protein. These findings may help guide the implementation of appropriate treatments for EPI.

Association between endoscopic evidence of bile reflux and Barrett's esophagus: A large-scale case-control study.

BACKGROUND: Although bile reflux plays an important role in the development of Barrett's esophagus, the relationship between endoscopic findings of bile reflux and Barrett's esophagus remains unclear. OBJECTIVE: This study evaluated whether endoscopic evidence of bile reflux was associated with the presence of Barrett's esophagus. METHODS: A retrospective analysis of a prospectively maintained database comprising consecutive patients who underwent screening esophagogastroduodenoscopy was conducted. Endoscopic evidence of bile reflux was defined as the presence of bile-stained fluid in the gastric fundus. We performed multivariate analysis to identify predictive factors that differed significantly between patients with and without Barrett's esophagus. RESULTS: Of 4021 patients, 922 (23%) had Barrett's esophagus, and 1000 (25%) showed endoscopic findings of bile reflux. Multivariate analysis revealed endoscopic evidence of bile reflux as the strongest independent factor associated with the presence of Barrett's esophagus (odds ratio [OR] 5.65, 95% confidence interval [CI] 4.71-6.76) in relation to the presence of hiatal hernia (OR 3.30, 95% CI 2.70-4.04) and male gender (OR 1.54, 95% CI 1.24-1.91). CONCLUSIONS: Endoscopic evidence of bile reflux was independently associated with the presence of Barrett's esophagus. This finding might help identify patients at future risk of Barrett's esophagus who could benefit from increased endoscopy surveillance.

Association of probiotic use with nivolumab effectiveness against various cancers: A multicenter retrospective cohort study.

BACKGROUND: Previous studies have revealed an association between probiotic use and effectiveness of immune checkpoint inhibitors in renal and lung cancers. However, little is known regarding other cancers, including gastrointestinal cancer. METHODS: To address this issue, we conducted a multicenter retrospective cohort study and the duration of nivolumab treatment for various cancers was compared between probiotic users and non-users. RESULTS AND CONCLUSIONS: In total, 488 patients who received nivolumab therapy were included. In all cancers, no significant differences in treatment duration of nivolumab were observed between probiotic users and non-users (median 62.0 vs. 56.0, hazard ratio = 1.02, p = 0.825), whereas probiotic use, compared with non-use, in patients with gastric cancer was significantly associated with a longer duration of nivolumab treatment (55.0 vs. 31.0 days, hazard ratio = 0.69, p = 0.039). In conclusion, probiotics may improve the response to nivolumab and potentially prolong progression-free survival in patients with gastric cancer.

CD8+ Lymphocyte Infiltration Is a Specific Feature of Colitis Induced by Immune Checkpoint Inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICPIs) have revolutionized cancer therapy, although immune-related adverse events (irAEs) remain a serious issue. The clinical characteristics of colitis induced by ICPIs are very similar to inflammatory bowel disease. Recently, cluster of differentiation 8 positive (CD8+) lymphocyte infiltration into organs has been associated with the onset of irAEs. The present study compared the histological infiltration of CD8+ lymphocytes in irAE colitis with that in other colitis. METHODS: Newly diagnosed and untreated patients were retrospectively enrolled. Biopsy specimens were obtained from endoscopic areas of high inflammation for immunohistochemical analysis of the number of cluster of differentiation 4 positive (CD4+) and CD8+ lymphocytes in the high-powered microscopic field with the most inflammation. RESULTS: A total of 102 patients [12 with irAE colitis, 37 with ulcerative colitis (UC), 22 with Crohn's disease (CD), and 31 with ischemic colitis (IC)] were analyzed. In irAE colitis, CD8+ lymphocyte infiltration was significantly greater than that of CD4+ lymphocytes (p < 0.01). The amount of CD8+ lymphocyte infiltration was significantly higher in irAE colitis than in UC (p < 0.05), CD (p < 0.05), and IC (p < 0.01). The CD8+/CD4+ ratio was also significantly higher in irAE colitis (p < 0.01 versus UC, CD, and IC, respectively). The optimal cutoff CD8+/CD4+ ratio for diagnosing irAE colitis was 1.17 (sensitivity 83%, specificity 84%). The optimal cutoff number of CD8+ lymphocytes for diagnosing irAE colitis was 102 cells per high-power field (sensitivity 75%, specificity 81%). CONCLUSIONS: Greater CD8+ lymphocyte infiltration and a higher CD8+/CD4+ ratio may be simple and useful biomarkers to distinguish irAE colitis from other forms of colitis.

Direct­acting antiviral treatment decreases serum undercarboxylated osteocalcin in male patients with chronic hepatitis C.

Hepatic osteodystrophy (HOD) is a common complication of chronic liver disease, including viral hepatitis. Hepatitis C virus (HCV) infection is associated with an increased risk of osteoporosis and bone mineral density (BMD) loss. Direct-acting antiviral (DAA) treatment is used to treat HCV infections; however, its effects on bone metabolism have not been reported. We compared the clinical data and bone metabolic markers at the start of DAA treatment and 1 year later in 78 patients. There were 41 female and 37 male patients. HCV was successfully treated with DAA in all patients. Bone metabolic markers included undercarboxylated osteocalcin (ucOC), 25(OH) vitamin D (VD), total type I procollagen N-propeptide (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and BMD. BMD was measured in the lumbar spine (mean, L2-L4) and femoral neck using dual-energy X-ray absorptiometry. ucOC in males decreased at 1 year after treatment initiation but not in females. In males, ucOC changes were related to alterations in proteins induced by vitamin K absence-II (PIVKA-II), hemoglobin A1c, and TRACP-5b, which contributed to P1NP and lumbar BMD at the start of DAA. Changes in ucOC among women contributed to the changes in grip strength and TRACP-5b levels. DAA treatment improved ucOC, a useful bone metabolic marker, in HCV-infected male patients. Changes in ucOC contributed to changes in PIVKA-II that likely ameliorated the vitamin K deficiency. DAA treatment has been reported to improve various extrahepatic disorders and abnormal bone metabolism, especially in HOD.

Histopathologically defined intestinal metaplasia in lesser curvature of corpus prior to Helicobacter pylori eradication is a risk factor for gastric cancer development.

BACKGROUND AND AIM: Helicobacter pylori eradication has been shown to reduce the risk of gastric cancer (GC), with the number of eradication therapy cases on the rise. However, GC can still occur after successful treatment, and the histological differences prior to eradication in patients with and without GC are unclear. This study investigated the pre-treatment histological risk factors for GC development following eradication therapy. METHODS: We retrospectively enrolled consecutive adult patients diagnosed as having H. pylori infection between April 2004 and December 2018. Atrophy and intestinal metaplasia (IM) were histologically assessed according to the updated Sydney System. The operative link on gastritis assessment and the operative link on gastric intestinal metaplasia (OLGIM) were evaluated as well. RESULTS: Of the 247 patients analyzed in this study, 11 (4.5%) experienced GC after eradication therapy. Histological IM scores in the GC group were significantly higher at all gastric biopsy sites (p < .05), and the proportion of OLGIM III/IV stage was significantly greater in GC patients (81.8% vs. 31.8%, p < .01). For GC prediction, the area under the receiver operating characteristic curve for IM score at the lesser curvature of the corpus was the highest among all biopsy sites and not inferior to OLGIM results. CONCLUSIONS: Patients with histological IM prior to H. pylori eradication, especially at the lesser curvature of the corpus, may be at elevated risk for GC development after eradication therapy and require close surveillance.

Gastric adenocarcinoma arising from hamartomatous inverted polyp during 8-year follow-up.

Gastric hamartomatous inverted polyp (GHIP) is rare, with few reports of carcinogenesis from GHIP during long-term follow-up. A 51-year-old woman was diagnosed as having a submucosal tumor (SMT) during esophagogastroduodenoscopy (EGD) in 2008. In 2016, although the size and height of the lesion had not changed, she was referred to our hospital for further investigation of the lesion. EGD depicted a gastric SMT of 20 mm in diameter in the greater curvature of the upper gastric body, and a biopsy specimen showed a well to poorly differentiated adenocarcinoma. Following successful laparoscopic total gastrectomy, histopathological examination revealed an intramucosal adenocarcinoma arising in GHIP.

Vascular E-selectin Expression Detected in Formalin-fixed, Paraffin-embedded Sections With an E-selectin Monoclonal Antibody Correlates With Ulcerative Colitis Activity.

It is widely accepted that E-selectin, an inducible endothelial cell adhesion molecule, plays a critical role in the initial step of neutrophil recruitment to sites of acute inflammation. However, immunohistological analysis of E-selectin has been hampered by lack of E-selectin-specific monoclonal antibodies that can stain formalin-fixed, paraffin-embedded (FFPE) tissue sections. Here, we employed E-selectin•IgM (a soluble form of E-selectin) as immunogen, and then, after negative selection with L-selectin•IgM and P-selectin•IgM and screening of FFPE sections of both COS-1 cells overexpressing E-selectin and acute appendicitis tissues, we successfully generated an E-selectin-specific monoclonal antibody capable of staining FFPE tissue sections. We used this antibody, designated U12-12, to perform quantitative immunohistological analysis of 390 colonic mucosal biopsy specimens representing ulcerative colitis. We found that the higher the histological disease activity, the greater the number of vessels expressing E-selectin, an observation consistent with previous analyses of frozen tissue sections. Furthermore, in active ulcerative colitis, E-selectin-expressing vessels contained neutrophils attached to endothelial cells, presumably in the process of extravasation, which eventually could cause epithelial damage. These results overall indicate that U12-12 is effective for E-selectin immunohistochemistry in archived FFPE samples representing various human diseases.