The Origin of Epithelium with Low-Grade Atypia in Early Gastric Cancer.

INTRODUCTION: Helicobacter pylori (HP) infection causes chronic inflammation and atrophy of the gastric mucosa and thus a high risk of gastric cancer (GC). With the increasing success of HP infection treatment, a larger number of GCs that develop after eradication can be assessed. Several studies have shown that epithelium with low-grade atypia (ELA) is a frequent characteristic of these GCs, but the origin of this condition is unknown. In this study, we compared the mucin phenotype, cellular proliferation, and p53 staining in ELA and cancerous tissues obtained from patients with GC with and without HP eradication. METHODS: The study population consisted of 23 patients with GC that developed after successful HP eradication therapy (eradicated group) and 24 patients with GC and HP infection (infected group). The prevalence of ELA was determined by hematoxylin and eosin staining. Tumor tissue and ELA samples were further analyzed by immunohistochemical staining for Muc5AC, Muc2, p53, and Ki-67. RESULTS: The ELA coverage rate was significantly higher in the eradicated group than in the infected group. Gastric-type mucin was frequently expressed by the ELA, and the mucin phenotypes of ELA and cancerous areas differed in 75% of cases. The Ki-67 labeling index was consistently lower in ELA than in the cancerous mucosa. Fourteen of 21 (66.7%) cancerous lesions, but only 3 ELA samples, were p53-positive. CONCLUSION: In most cases, ELA on the surfaces of GCs seems to have originated from normal gastric cells, not from cancer cells.

Quantitative monitoring of circulating tumor DNA in patients with advanced pancreatic cancer undergoing chemotherapy.

According to cancer genome sequences, more than 90% of cases of pancreatic ductal adenocarcinoma (PDAC) harbor active KRAS mutations. Digital PCR (dPCR) enables accurate detection and quantification of rare mutations. We assessed the dynamics of circulating tumor DNA (ct-DNA) in patients with advanced PDAC undergoing chemotherapy using dPCR. KRAS G12/13 mutation was assayed by dPCR in 47 paired tissue- and ct-DNA samples. The 21 patients were subjected to quantitative ct-DNA monitoring at 4 to 8-week intervals during chemotherapy. KRAS mutation was detected in 45 of those 47 patients using tissue DNA. In the KRAS mutation-negative cases, next-generation sequencing revealed KRAS Q61K and NRAS Q61R mutations. KRAS mutation was detected in 23/45 cases using ct-DNA (liver or lung metastasis, 18/19; mutation allele frequency [MAF], 0.1%-31.7%; peritoneal metastasis, 3/9 [0.1%], locally advanced, 2/17 [0.1%-0.2%]). In the ct-DNA monitoring, the MAF value changed in concordance with the disease state. In the 6 locally advanced cases, KRAS mutation appeared concurrently with liver metastasis. Among the 6 cases with liver metastasis, KRAS mutation disappeared during the duration of stable disease or a partial response, and reappeared at the time of progressive disease. The median progression-free survival was longer in cases in which KRAS mutation disappeared after an initial course of chemotherapy than in those in which it was continuously detected (248.5 vs 50 days, P < .001). Therefore, ct-DNA monitoring enables continuous assessment of disease state and could have prognostic utility during chemotherapy.

Use of intra-procedural fusion imaging combining contrast-enhanced ultrasound using a perflubutane-based contrast agent and auto sweep three-dimensional ultrasound for guiding radiofrequency ablation and evaluating its efficacy in patients with hepatocellular carcinoma.

Purpose: This study evaluated the usefulness of intraprocedural contrast-enhanced ultrasound (CEUS)/ultrasound (US) fusion imaging using a perflubutane-based contrast agent combined with preprocedural auto sweep three-dimensional US to obtain volume data for guidance and evaluation of the therapeutic efficacy of radiofrequency ablation (RFA).Methods: This uncontrolled clinical trial included 50 hepatocellular carcinomas (HCCs) with a mean diameter of 15.3 mm that had been treated by RFA. The efficacy of RFA was evaluated by CEUS/US fusion imaging during the procedure. If the ablation was deemed to be inadequate, further ablation was performed until adequate ablation was achieved. Contrast-enhanced computed tomography (CECT) or contrast-enhanced magnetic resonance imaging (CEMRI) was performed a month after RFA, and the images obtained using each modality were reviewed to evaluate the efficacy of RFA.Results: Thirty-three of the 50 lesions were evaluated by CEUS/US fusion imaging as having been adequately ablated after the first RFA procedure. The ablation was evaluated as inadequate in the remaining 17 lesions, for which additional ablation was performed. Ninety-eight (49/50) of all HCCs were evaluated as having been eventually adequately ablated on intraprocedural CEUS/US fusion imaging. The concordance rate for evaluations between intraprocedural CEUS/US fusion imaging and CECT/CEMRI performed 1 month after RFA was 88% (44/50). The kappa value for agreement between the two methods of evaluation was 0.792.Conclusion: Intraprocedural fusion imaging combining CEUS and auto sweep three-dimensional US appears to be a useful modality for RFA guidance and evaluation of therapeutic efficacy of RFA in patients with HCC.

Vonoprazan and high-dose amoxicillin dual therapy for Helicobacter pylori first-line eradication: A single-arm, interventional study.

Background: To date, no interventional trial has assessed the efficacy and safety of vonoprazan and high-dose (500 mg four times daily, 2000 mg/day) amoxicillin dual therapy in terms of Helicobacter pylori eradication. We explored whether this was an appropriate first-line treatment. Methods: This prospective, dual-center, single-arm interventional study was performed in Japan. Twenty H. pylori-positive patients lacking any eradication history were treated with vonoprazan 20 mg twice daily and amoxicillin 500 mg four times daily (qid) for 7 days. Eradication was evaluated using a stool H. pylori antigen test. We evaluated safety using patient questionnaires. This study was registered in the jRCT database (jRCT031200128). Results: The intention-to-treat and per-protocol eradication rates were 90% (95% confidence interval [CI] 68.3-98.8%, n = 20) and 94.4% (95% CI 72.7-99.9%, n = 18) respectively. No significant adverse event was recorded. Conclusion: Vonoprazan/high-dose amoxicillin dual therapy can be a safe standard first-line therapy. We are now undergoing a randomized controlled trial comparing dual therapy and vonoprazan-based triple therapy.

Hemoperitoneum due to a ruptured right gastroepiploic artery following non-interventional endoscopic ultrasonography: a case report.

Endoscopic ultrasonography has become a routine procedure in clinical practice and is widely accepted as a safe procedure. Previous studies have reported that severe bleeding rarely occurs even when performing fine-needle aspiration biopsy. Severe hemorrhage following non-interventional endoscopic ultrasonography has never been reported. We herein report a case of hemorrhagic shock due to hemoperitoneum caused by a ruptured right gastroepiploic artery consequent to a diagnostic endoscopic ultrasonography. The patient was administered two antithrombotic agents. An extensive diagnostic workup contributed to the correct diagnosis, which led to a successful treatment by transcatheter arterial embolization. Endoscopists should be aware of this rare, but potentially fatal, adverse event of endoscopic ultrasonography.

Biliary stent removal through a transgastric fistula created with endoscopic ultrasound-guided hepaticogastrostomy.

Therapeutic endoscopic ultrasound has become widespread as an effective procedure for biliary drainage; however, it is rarely used to remove foreign bodies such as a biliary stent. A 57-year-old man was referred to our hospital for a benign biliary stricture in the left hepatic duct after hepatectomy. Initially, a 7-Fr plastic stent was placed in the left hepatic duct with the distal end set above the papilla, and it was replaced with an 8.5-Fr stent as the stricture remained after 3 months. Endoscopic retrograde cholangiopancreatography was performed to retrieve the plastic stent 3 months later; however, the stent could not be moved because the proximal flap was caught in the stricture. Attempts using various devices failed to retrieve the stent; thus, endoscopic ultrasound-guided hepaticogastrostomy was performed to create a route for stent retrieval. Eventually, the plastic stent was successfully retrieved with biopsy forceps through a fully covered self-expandable metallic stent located in a transgastric fistula. We propose our new method involving endoscopic ultrasound-guided hepaticogastrostomy for endoscopic stent retrieval that fails via the transpapillary route.

Clinical outcome of a highly flexible duodenal stent for gastric outlet obstruction: A multicenter prospective study.

BACKGROUND AND AIM: Endoscopic duodenal stenting for patients with malignant gastric outlet obstruction (GOO) has been widespread; however, clinical trials evaluating the structures of duodenal stents are lacking. Thus, we aimed to investigate the clinical outcomes of a highly flexible duodenal stent for GOO patients. METHODS: A prospective study of duodenal stenting for GOO patients from five hospitals between August 2017 and August 2018 was performed. WallFlex Duodenal Soft were used in all procedures. The primary endpoint was clinical success, defined as an improvement in the GOO scoring system. RESULTS: The study enrolled 31 patients (12 women, 19 men) with GOO, with a median age of 70 (range 52-90) years. Primary diseases were pancreatic cancer, gastric cancer, biliary tract cancer, and others in 14, 10, 3, and 4 patients, respectively. The technical success rate was 97%, and the clinical success rate was 87%. Simultaneous biliary drainage was performed in 19% of patients. Adverse events occurred in three patients. Chemotherapy was given in 41% of clinically successful cases, and the median overall survival time after stent placement was 82 days (range, 30-341 days), and. Stent dysfunction occurred in 30% of clinically successful cases (stent ingrowth in seven and stent overgrowth in one patient). The median time to stent dysfunction was 157 days (range, 11-183 days). Six patients were treated with additional stent placement after dysfunction. CONCLUSION: Placement of a highly flexible duodenal stent is an effective and safe treatment for patients with GOO (UMIN-CTR 000028783).

Differential diagnosis of gallbladder polypoid lesions using contrast-enhanced ultrasound.

PURPOSE: The purpose of the study is to evaluate the utility of contrast-enhanced ultrasound (CEUS) for the differential diagnosis of gallbladder polypoid lesions (GPLs). METHODS: Thirty-six patients with GPLs (17 with gallbladder cancer, 19 with benign polyps) who underwent CEUS were enrolled in the study. The mean age of patients was 65.7 ± 12.6 years. Perflubutane-based contrast agent and high-mechanical index mode, which can eliminate the background B-mode and provide precise visualization of tumor vessels, were used for CEUS, and two blinded readers evaluated the images, retrospectively. RESULTS: Patient age and size of malignant GPLs (72.4 ± 9.4 years and 23.4 ± 7.5 mm) were significantly greater than those for benign lesions (59.6 ± 12.3 years and 12.4 ± 2.9 mm) (P < 0.01, respectively), and the receiver operating characteristic analysis showed the cut-off value as over 65 years and 16 mm. Univariate analysis showed that heterogeneity in B-mode (80% [12/15]), sessile shape (76% [13/17]), dilated vessel (71% [12/17]), irregular vessel (82% [14/17]), and heterogeneous enhancement (59% [10/17]) on CEUS were significantly correlated with malignant GPLs (P < 0.01, respectively). On CEUS, the diagnostic criterion for malignant GPLs was defined as having one or more of the above four features because of the highest accuracy. Sensitivity, specificity, and accuracy for malignant GBLs were 88%, 68%, and 78% for patient age; 76%, 89%, and 83% for size of GPLs; 80%, 68%, and 74% for B-mode; and 94%, 89%, and 92% for CEUS, respectively. CONCLUSIONS: CEUS is useful for the differential diagnosis of malignant and benign GPLs.

The Superiority of Vonoprazan-based First-line Triple Therapy with Clarithromycin: A Prospective Multi-center Cohort Study on Helicobacter pylori Eradication.

Objective We evaluated the safety and efficacy of vonoprazan-based amoxicillin and clarithromycin 7-day triple therapy (VAC) in comparison to proton pump inhibitor (PPI)-based (PAC) as a first-line treatment and vonoprazan-based amoxicillin and metronidazole 7-day triple therapy (VAM) in comparison to PPI-based (PAM) as a second-line treatment for the eradication of Helicobacter pylori in Japan. Methods We performed a non-randomized, multi-center, parallel-group study to compare first-line VAC to PAC and second-line VAM to PAM. A pre-planned subgroup analysis on CAM resistance was also performed. Safety was evaluated with an adverse effects questionnaire (AEQ), which was completed by patients during therapy. Results The first-line eradication rates (ER) in the intention-to-treat (ITT) and per protocol (PP) analyses were 84.9% (95% CI: 81.9-87.6%, n=623) and 86.4% (83.5-89.1%, n=612), respectively, for VAC and 78.8% (75.3-82.0%, n=608) and 79.4% (76.0-82.6%, n=603), respectively, for PAC. The ER of VAC was higher than that of PAC in the ITT (p=0.0061) and PP analyses (p=0.0013). The ERs for VAC in patients with CAM-resistant and CAM-susceptible bacteria were 73.2% (59.7-84.2%, n=56) and 88.9% (83.4-93.1%, n=180), respectively. PAC was associated with higher AEQ scores for diarrhea, nausea, headache, and general malaise. In the second-line ITT and PP analyses VAM achieved ERs of 80.5% (74.6-85.6%, n=216) and 82.4% (76.6-87.3%, n=211), respectively, while PAM achieved ERs of 81.5% (74.2-87.4%, n=146) and 82.1% (74.8-87.9%, n=145), respectively. No significant differences were observed in the ITT (p=0.89) or PP (p=1.0) analyses. Conclusion The ER of first-line VAC was higher than that of PAC, but still <90%. No difference was observed between second-line VAM and PAM. Vonoprazan-based triple therapy was safe and well tolerated.