Severe induction of aberrant DNA methylation by nodular gastritis in adults.

BACKGROUND: Nodular gastritis (NG) is characterized by marked antral lymphoid follicle formation, and is a strong risk factor for diffuse-type gastric cancer in adults. However, it is unknown whether aberrant DNA methylation, which is induced by atrophic gastritis (AG) and is a risk for gastric cancer, is induced by NG. Here, we analyzed methylation induction by NG. METHODS: Gastric mucosal samples were obtained from non-cancerous antral tissues of 16 NG and 20 AG patients with gastric cancer and 5 NG and 6 AG patients without, all age- and gender-matched. Genome-wide methylation analysis and expression analysis were conducted by a BeadChip array and RNA-sequencing, respectively. RESULTS: Clustering analysis of non-cancerous antral tissues of NG and AG patients with gastric cancer was conducted using methylation levels of 585 promoter CpG islands (CGIs) of methylation-resistant genes, and a large fraction of NG samples formed a cluster with strong methylation induction. Promoter CGIs of CDH1 and DAPK1 tumor-suppressor genes were more methylated in NG than in AG. Notably, methylation levels of these genes were also higher in the antrum of NG patients without cancer. Genes related to lymphoid follicle formation, such as CXCL13/CXCR5 and CXCL12/CXCR4, had higher expression in NG, and genes involved in DNA demethylation TET2 and IDH1, had only half the expression in NG. CONCLUSIONS: Severe aberrant methylation, involving multiple tumor-suppressor genes, was induced in the gastric antrum and body of patients with NG, in accordance with their high gastric cancer risk.

Noninvasive rapid urinary trypsinogen-2 dipstick test for early exclusion of post-endoscopic retrograde cholangiopancreatography pancreatitis within hours after endoscopic retrograde cholangiopancreatography: Clinical diagnosis and considerations.

Objective: Few reports have explored the application of urinary trypsinogen-2 measurement in the early diagnosis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, and none have demonstrated the benefits of noninvasive testing. This study aimed to evaluate the clinical application of the rapid urinary trypsinogen-2 dipstick test (Nipro, Japan) compared with serum amylase and lipase levels for the early diagnosis of post-ERCP pancreatitis (PEP). Methods: A total of 100 consecutive patients (54 men and 46 women) who were admitted and underwent ERCP at Tokyo Medical University Hospital from August 2021 to December 2021 were recruited. All patients underwent rapid urinary trypsinogen-2 measurement using the dipstick test before and after ERCP. Measurements were taken 24 h before ERCP for pre-ERCP and 1-4 h after ERCP for post-ERCP. Additionally, serum amylase and lipase levels were measured at 8:00 a.m. of the day after ERCP (at least 8 h after ERCP), and their diagnostic abilities for PEP were compared and evaluated. Results: PEP occurred in 5/100 patients (5%). The sensitivity, specificity, positive predictive value, and negative predictive value of the dipstick test for diagnosing PEP were 100%, 83.2%, 23.8%, and 100%, respectively. These results were comparable to the diagnostic performance of serum amylase and lipase levels at 8:00 a.m. on the day after ERCP (at least 8 h after ERCP). However, false positives must be considered. Conclusion: The dipstick test may be useful in clinical practice as a noninvasive screening test for the early prediction of PEP.

Identifying predictors for comorbidities related mortality versus pancreatic cancer related mortality in patients with intraductal papillary mucinous neoplasm.

BACKGROUNDS: Few data are available for surveillance decisions focusing on factors related to mortality, as the primary outcome, in intraductal papillary mucinous neoplasm (IPMN) patients. AIMS: We aimed to identify imaging features and patient backgrounds associated with mortality risks by comparing pancreatic cancer (PC) and comorbidities. METHODS: We retrospectively conducted a multicenter long-term follow-up of 1864 IPMN patients. Competing risk analysis was performed for PC- and comorbidity-related mortality. RESULTS: During the median follow-up period of 5.5 years, 14.0% (261/1864) of patients died. Main pancreatic duct ≥5 mm and mural nodules were significantly related to all-cause and PC-related mortality, whereas cyst ≥30 mm did not relate. In 1730 patients without high-risk imaging features, 48 and 180 patients died of PC and comorbidity. In the derivation cohort, a prediction model for comorbidity-related mortality was created, comprising age, cancer history, diabetes mellitus complications, chronic heart failure, stroke, paralysis, peripheral artery disease, liver cirrhosis, and collagen disease in multivariate analysis. If a patient had a 5 score, 5- and 10-year comorbidity-related mortality is estimated at 18.9% and 50.2%, respectively, more than 7 times higher than PC-related mortality. The model score was also significantly associated with comorbidity-related mortality in a validation cohort. CONCLUSIONS: This study demonstrates main pancreatic duct dilation and mural nodules indicate risk of PC-related mortality, identifying patients who need periodic examination. A comorbidity-related mortality prediction model based on the patient's age and comorbidities can stratify patients who do not require regular tests, especially beyond 5 years, among IPMN patients without high-risk features. CLINICAL TRIAL REGISTRATION: T2022-0046.

Rebleeding Risk of Acute Hemorrhagic Rectal Ulcer: A Multicenter Retrospective Study.

Objective Acute hemorrhagic rectal ulcer (AHRU) is characterized by sudden, painless, and massive bleeding from rectal ulcers. To date, few studies have analyzed the risk factors for AHRU rebleeding. In this study, we clarified the risk factors of rebleeding after initial hemostasis of AHRU through a multicenter study. Methods A total of 149 patients diagnosed with AHRU between January 2015 and May 2020 at 3 medical centers were enrolled. We retrospectively investigated the following factors: age, sex, body mass index (BMI), performance status (PS), Charlson comorbidity index (CCI), comorbidities, medications, laboratory examinations, endoscopic findings, view of the entire rectum on endoscopy, hemostasis method, blood transfusion history, shock, instructions for posture change after initial hemostasis, and clinical course. Results Rebleeding was observed in 35 (23%) of 149 patients. A multivariate analysis showed that significant factors for rebleeding were PS 4 [odds ratio (OR), 5.23; 95% confidence interval (CI)], 1.97-13.9; p=0.001], a blood transfusion history (OR, 3.66; 95% CI, 1.41-9.51; p=0.008), low an estimated glomerular filtration rate (eGFR) levels (OR, 0.98; 95% CI, 0.97-0.99; p=0.001), poor view of the whole rectum on endoscopy (OR, 0.33; 95% CI, 0.12-0.90; p=0.030), and use of monopolar hemostatic forceps (OR, 4.89; 95% CI, 1.37-17.4; p=0.014). Conclusion Factors associated with rebleeding of AHRU were a poor PS (PS4), blood transfusion, a low eGFR, poor view of the whole rectum on endoscopy, and the use of monopolar hemostatic forceps.

Endoscopic ultrasound-guided biopsy using a three-prong asymmetry tip needle for pancreatic tumors and peridigestive tract lesions: Retrospective single-center study.

BACKGROUND: Endoscopic ultrasound-guided tissue acquisition is vital for diagnosing pancreatic and peridigestive tract lesions. A new three-prong asymmetry tip needle has been developed for this procedure. In this study, we retrospectively assessed the diagnostic ability, tissue collection volume, and procedural adverse events of the three-prong asymmetry tip needle for solid pancreatic, subepithelial, and other organ lesions. METHODS: We analyzed the data of 58 consecutive patients who underwent endoscopic ultrasound-guided tissue acquisition using a three-prong asymmetry tip needle between August 2022 and April 2023 at a single care center. RESULTS: The tissue collection rate was 91.4% with 89.7% accuracy, 89.3% sensitivity, 100% specificity, 100% positive predictive value, and 25% negative predictive value. No significant differences in collection rates or diagnostic performance were observed based on the target organ, puncture route, or lesion size. Using our original assessment method, the average histological core tissue score was 3.1 ± 0.8, whereas the blood contamination volume was 2.5 ± 0.8. Only one of 58 patients (1.7%) developed a pancreatic fistula of moderate severity as an adverse event. CONCLUSIONS: The three-prong asymmetry tip needle demonstrated good diagnostic capability and adequate sample volume with safety for pancreatic, subepithelial, and other organ lesions.

Early and late effects of endoscopic interventions in patients with malignant afferent loop syndrome: A single-center experience and literature review.

BACKGROUND/PURPOSE: Afferent loop syndrome (ALS) is a rare adverse event after gastrointestinal surgery requiring appropriate early decompression treatment. Several endoscopic interventions have been attempted for treatment, including endoscopic enteral metal stent placement (EMSP), endoscopic ultrasound (EUS)-guided entero-enterostomy (EUS-EE), and EUS-guided hepaticogastrostomy (EUS-HGS). However, there are limited data on outcomes, including duration of stent patency. In this study, we evaluated the usefulness of each endoscopic intervention for malignant ALS. METHODS: We retrospectively investigated nine patients with malignant ALS who underwent EMSP, EUS-EE, or EUS-HGS. Information on technical success, clinical efficacy, adverse events, stent dysfunction, and overall survival was collected and analyzed. RESULTS: The most common symptoms were abdominal pain and cholangitis. ALS was treated by EMSP in three patients, EUS-EE in three patients, and EUS-HGS in three patients. Stent placement was successful and clinically effective in all patients with no adverse events. During follow-up, stent dysfunction occurred in two patients treated by EUS-HGS. Eight patients died of primary disease during a median follow-up of 157 days. CONCLUSIONS: Each of the available endoscopic interventions for malignant ALS can be expected to produce similar outcomes, including duration of stent patency. The choice of endoscopic intervention should be made based on the characteristics of each treatment.

Endoscopic ultrasonography-guided gastroenterostomy versus uncovered duodenal metal stenting for unresectable malignant gastric outlet obstruction (DRA-GOO): a multicentre randomised controlled trial.

BACKGROUND: Endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) is a novel endoscopic method to palliate malignant gastric outlet obstruction. We aimed to assess whether the use of EUS-GE with a double balloon occluder for malignant gastric outlet obstruction could reduce the need for reintervention within 6 months compared with conventional duodenal stenting. METHODS: The was an international, multicentre, randomised, controlled trial conducted at seven sites in Hong Kong, Belgium, Brazil, India, Italy, and Spain. Consecutive patients (aged ≥18 years) with malignant gastric outlet obstruction due to unresectable primary gastroduodenal or pancreatobiliary malignancies, a gastric outlet obstruction score (GOOS) of 0 (indicating an inability in intake food or liquids orally), and an Eastern Cooperative Oncology Group performance status score of 3 or lower were included and randomly allocated (1:1) to receive either EUS-GE or duodenal stenting. The primary outcome was the 6-month reintervention rate, defined as the percentage of patients requiring additional endoscopic intervention due to stent dysfunction (ie, restenosis of the stent due to tumour ingrowth, tumour overgrowth, or food residue; stent migration; or stent fracture) within 6 months, analysed in the intention-to-treat population. Prespecified secondary outcomes were technical success (successful placement of a stent), clinical success (1-point improvement in gastric outlet obstruction score [GOOS] within 3 days), adverse events within 30 days, death within 30 days, duration of stent patency, GOOS at 1 month, and quality-of-life scores. This study is registered with ClinicalTrials.gov (NCT03823690) and is completed. FINDINGS: Between Dec 1, 2020, and Feb 28, 2022, 185 patients were screened and 97 (46 men and 51 women) were recruited and randomly allocated (48 to the EUS-GE group and 49 to the duodenal stent group). Mean age was 69·5 years (SD 12·6) in the EUS-GE group and 64·8 years (13·0) in the duodenal stent group. All randomly allocated patients completed follow-up and were analysed. Reintervention within 6 months was required in two (4%) patients in the EUS-GE group and 14 (29%) in the duodenal stent group [p=0·0020; risk ratio 0·15 [95% CI 0·04-0·61]). Stent patency was longer in the EUS-GE group (median not reached in either group; HR 0·13 [95% CI 0·08-0·22], log-rank p<0·0001). 1-month GOOS was significantly better in the EUS-GE group (mean 2·41 [SD 0·7]) than the duodenal stent group (1·91 [0·9], p=0·012). There were no statistically significant differences between the EUS-GE and duodenal stent groups in death within 30 days (ten [21%] vs six [12%] patients, respectively, p=0·286), technical success, clinical success, or quality-of-life scores at 1 month. Adverse events occurred 11 (23%) patients in the EUS-GE group and 12 (24%) in the duodenal stent group within 30 days (p=1·00); three cases of pneumonia (two in the EUS-GE group and one in the duodenal stent group) were considered to be procedure related. INTERPRETATION: In patients with malignant gastric outlet obstruction, EUS-GE can reduce the frequency of reintervention, improve stent patency, and result in better patient-reported eating habits compared with duodenal stenting, and the procedure should be used preferentially over duodenal stenting when expertise and required devices are available. FUNDING: Research Grants Council (Hong Kong Special Administrative Region, China) and Sociedad Española de Endoscopia Digestiva.

Deep learning approach for discrimination of liver lesions using nine time-phase images of contrast-enhanced ultrasound.

PURPOSE: Contrast-enhanced ultrasound (CEUS) shows different enhancement patterns depending on the time after administration of the contrast agent. The aim of this study was to evaluate the diagnostic performance of liver nodule characterization using our proposed deep learning model with input of nine CEUS images. METHODS: A total of 181 liver lesions (48 benign, 78 hepatocellular carcinoma (HCC), and 55 non-HCC malignant) were included in this prospective study. CEUS were performed using the contrast agent Sonazoid, and in addition to B-mode images before injection, image clips were stored every minute up to 10 min. A deep learning model was developed by arranging three ResNet50 transfer learning models in parallel. This proposed model allowed inputting up to nine datasets of different phases of CEUS and performing image augmentation of nine images synchronously. Using the results, the correct prediction rate, sensitivity, and specificity between "benign" and "malignant" cases were analyzed for each combination of the time phase. These accuracy values were also compared with the washout score judged by a human. RESULTS: The proposed model showed performance superior to the referential standard model when the dataset from B-mode to the 10-min images were used (sensitivity: 93.2%, specificity: 65.3%, average correct answer rate: 60.1%). It also maintained 90.2% sensitivity and 61.2% specificity even when the dataset was limited to 2 min after injection, and this accuracy was equivalent to or better than human scoring by experts. CONCLUSION: Our proposed model has the potential to identify tumor types earlier than the Kupffer phase, but at the same time, machine learning confirmed that Kupffer-phase Sonazoid images contain essential information for the classification of liver nodules.

Does Congenital Biliary Dilatation Todani Type II (Diverticular Type) Really Exist?

AIM OF THE STUDY: The aim of the study is to clarify the clinicopathological and biliary morphological characteristics in reported cases of diverticular congenital biliary dilatation (CBD). METHOD: Using PubMed and the Japan Medical Abstracts Society, articles on possible diverticular CBD were extracted and the clinical pictures examined. We also sought evidence for definitions of diverticular CBD and the associated condition of pancreaticobiliary maljunction (PBM) using the original articles by Alonso-Lej and Todani. The characteristic biliary morphologies of cases with images were also investigated. RESULTS: Analyses of 211 possible cases superficially demonstrated multiple diverticula in 12 (12%) and single diverticulum in 89 (88%), with diverticula located in the upper (n = 38, 38%), middle (n = 32, 32%), or lower (n = 26, 26%) biliary tract in and presence of intra-diverticular stones, PBM, and biliary carcinoma in 23% (n = 18), 39% (n = 25), and 11% (n = 14), respectively. However, evidence defining diverticular CBD or justifying the lack of associated PBM was not demonstrated even in the original articles. Scrutiny of the biliary anatomy in 59 cases with images showed incorrect inclusions of types I or IV-A with an irregular biliary duct wall or dilated cystic duct, periampullary choledochal diverticula, or even solitary biliary cysts. Authentic diverticular CBD, representing the diverticulum connected to the middle of the common bile duct via a thin, patent stalk was seen in only 6 cases. CONCLUSION: Real diverticular CBD appears extremely rare. The lack of an objective definition allows wide interpretations of clinical pictures, creating inconsistencies in the diagnosis and treatment of CBD and raising questions regarding the utility of conventional classifications. LEVEL OF EVIDENCE: Level III.

A multi-institutional study designed by members of Tokyo Guidelines (TG) Core Meeting to elucidate the clinical characteristics and pathogenesis of acute cholangitis after bilioenteric anastomosis and biliary stent insertion with a focus on biliary obstruction: Role of transient hepatic attenuation difference (THAD) and pneumobilia in improving TG diagnostic performance.

BACKGROUND/PURPOSE: The aim of this study was to clarify the clinical characteristics of acute cholangitis (AC) after bilioenteric anastomosis and stent-related AC in a multi-institutional retrospective study, and validate the TG18 diagnostic performance for various type of cholangitis. METHODS: We retrospectively reviewed 1079 AC patients during 2020, at 16 Tokyo Guidelines 18 (TG 18) Core Meeting institutions. Of these, the post-biliary reconstruction associated AC (PBR-AC), stent-associated AC (S-AC) and common AC (C-AC) were 228, 307, and 544, respectively. The characteristics of each AC were compared, and the TG18 diagnostic performance of each was evaluated. RESULTS: The PBR-AC group showed significantly milder biliary stasis compared to the C-AC group. Using TG18 criteria, definitive diagnosis rate in the PBR-AC group was significantly lower than that in the C-AC group (59.6% vs. 79.6%, p < .001) because of significantly lower prevalence of TG 18 imaging findings and milder bile stasis. In the S-AC group, the bile stasis was also milder, but definitive-diagnostic rate was significantly higher (95.1%) compared to the C-AC group. The incidence of transient hepatic attenuation difference (THAD) and pneumobilia were more frequent in PBR-AC than that in C-AC. The definitive-diagnostic rate of PBR-AC (59.6%-78.1%) and total cohort (79.6%-85.3%) were significantly improved when newly adding these items to TG18 diagnostic imaging findings. CONCLUSIONS: The diagnostic rate of PBR-AC using TG18 is low, but adding THAD and pneumobilia to TG imaging criteria may improve TG diagnostic performance.

ERCP using balloon-assisted endoscopes versus EUS-guided treatment for common bile duct stones in Roux-en-Y gastrectomy.

BACKGROUND AND AIMS: We compared ERCP using a balloon-assisted endoscope (BE-ERCP) with EUS-guided antegrade treatment (EUS-AG) for removal of common bile duct (CBD) stones in patients with Roux-en-Y (R-Y) gastrectomy. METHODS: Consecutive patients who had previous R-Y gastrectomy undergoing BE-ERCP or EUS-AG for CBD stones in 16 centers were retrospectively analyzed. RESULTS: BE-ERCP and EUS-AG were performed in 588 and 59 patients, respectively. Baseline characteristics were similar, except for CBD diameter and angle. The technical success rate was 83.7% versus 83.1% (P = .956), complete stone removal rate was 78.1% versus 67.8% (P = .102), and early adverse event rate was 10.2% versus 18.6% (P = .076) in BE-ERCP and EUS-AG, respectively. The mean number of endoscopic sessions was smaller in BE-ERCP (1.5 ± .8 vs 1.9 ± 1.0 sessions, P = .01), whereas the median total treatment time was longer (90 vs 61.5 minutes, P = .001). Among patients with biliary access, the complete stone removal rate was significantly higher in BE-ERCP (93.3% vs 81.6%, P = .009). Negative predictive factors were CBD diameter ≥15 mm (odds ratio [OR], .41) and an angle of CBD <90 degrees (OR, .39) in BE-ERCP and a stone size ≥10 mm (OR, .07) and an angle of CBD <90 degrees (OR, .07) in EUS-AG. The 1-year recurrence rate was 8.3% in both groups. CONCLUSIONS: Effectiveness and safety of BE-ERCP and EUS-AG were comparable in CBD stone removal for patients after R-Y gastrectomy, but complete stone removal after technical success was superior in BE-ERCP.

Long-term outcomes after EUS-guided antegrade intervention for benign bilioenteric anastomotic stricture.

BACKGROUND AND AIMS: Bilioenteric anastomotic stricture (BES) is a well-known adverse event after bilioenterostomy. Recently, EUS-guided antegrade intervention (EUS-AI) has been developed for cases that are difficult to treat by balloon enteroscopy-assisted ERCP. However, no data are available on the long-term outcomes after EUS-AI. The main goal of the present study was to clarify the long-term outcomes of EUS-AI in such patients. METHODS: Between November 2013 and November 2021, 34 patients who were followed for more than 1 year after EUS-AI for BES were identified. The primary endpoint was the rate of stricture resolution. Secondary endpoints were factors associated with stricture resolution, rate of BES recurrence, rate of conversion to surgery, and rate of hepatic fibrosis progression during follow-up. RESULTS: The median follow-up period was 56.7 months. Stricture resolution was achieved in 17 of 34 patients (50%). A multivariate analysis confirmed that the presence of bile duct stones (odds ratio, 9.473; 95% confidence interval, 1.66-53.98; P = .01) was significantly associated with stricture resolution. The stricture recurrence rate was 33%, and the median time from stent removal to recurrence was 31.2 months. Four patients underwent surgery because of recurrent cholangitis. During the median follow-up period of 56.7 months, 25% progressed to hepatic fibrosis based on the Fibrosis-4 index grade. Interestingly, patients without cholangitis during follow-up did not show progression of hepatic fibrosis. CONCLUSIONS: EUS-AI has achieved acceptable long-term clinical outcomes. EUS-AI can be a viable alternative treatment of choice before surgical treatment in patients who are difficult to treat by conventional approaches.