Superiority of mucosal incision-assisted biopsy over ultrasound-guided fine needle aspiration biopsy in diagnosing small gastric subepithelial lesions: a propensity score matching analysis.

BACKGROUND: Gastric subepithelial lesions, including gastrointestinal stromal tumors, are often found during routine gastroscopy. While endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) has been the gold standard for diagnosing gastric subepithelial lesions, alternative open biopsy procedures, such as mucosal incision-assisted biopsy (MIAB) has been reported useful. The aim of this study is to evaluate the efficacy of MIAB for the diagnosis of gastric SELs compared with EUS-FNAB. METHODS: We retrospectively analyzed medical records of 177 consecutive patients with gastric SELs who underwent either MIAB or EUS-FNAB at five hospitals in Japan between January 2010 and January 2018. Diagnostic yield, procedural time, and adverse event rates for the two procedures were evaluated before and after propensity-score matching. RESULTS: No major procedure-related adverse events were observed in either group. Both procedures yielded highly-accurate diagnoses once large enough samples were obtained; however, such successful sampling was more often accomplished by MIAB than by EUS-FNAB, especially for small SELs. As a result, MIAB provided better diagnostic yields for SELs smaller than 20-mm diameter. The diagnostic yields of both procedures were comparable for SELs larger than 20-mm diameter; however, MIAB required significantly longer procedural time (approximately 13 min) compared with EUS-FNAB. CONCLUSIONS: Although MIAB required longer procedural time, it outperformed EUS-FNAB when diagnosing gastric SELs smaller than 20-mm diameter.

[A case of swallow syncope with transient congestive liver caused by esophageal dilatation associated with huge hiatal hernia].

A 76-year-old woman suffered from repeated postprandial syncope of unknown cause. Computed tomography scanning revealed an enlarged hiatal hernia sac with food residues that compressed both the left atrium and inferior vena cava. As soon as the hernia cavity expanded during an upper gastrointestinal X-ray examination, she experienced a deterioration of her level of consciousness. Therefore, we diagnosed her of a swallow syncope due to left atrium compression by the huge hernia sac. The sac also compressed the inferior vena cava, and she experienced a transient elevation of her hepatobiliary enzyme level probably due to the influence of the congestive liver. Thus, clinicians should always keep this condition in mind when encountering patients with post-meal syncope.

The Altered Mucosal Barrier Function in the Duodenum Plays a Role in the Pathogenesis of Functional Dyspepsia.

BACKGROUND: An altered gastrointestinal barrier function is reportedly associated with the pathogenesis of functional dyspepsia (FD); however, the pathogenesis of FD has not yet been fully elucidated. AIMS: The objective of the present study was to determine whether the mucosal barrier function is impaired in patients with FD and to investigate the mechanisms underlying FD. METHODS: The present study included patients with FD (FD group, n = 24), non-FD patients with abdominal symptoms (symptomatic control group, n = 14), and patients with no abdominal symptoms (asymptomatic control group, n = 20). The groups were compared regarding the mucosal electrical impedance (MI) values of the stomach and duodenum, which were measured using a tissue conductance meter during esophagogastroduodenoscopy. RESULTS: There were no significant differences between the three groups in the MI of the stomach. In contrast, the duodenal MI of the FD group (17.8 ± 4.3 Ω) was significantly lower than those of the symptomatic control group (27.2 ± 6.4 Ω, p < 0.0001) and asymptomatic control group (23.0 ± 7.4 Ω, p = 0.016). The expression of zonula occludens-1 (ZO-1) was significantly lower in the FD group than in the symptomatic control group (p = 0.011), where ZO-1 was positively correlated with the duodenal MI (ß = 0.513, p = 0.017). The interleukin (IL)-1ß expression was significantly higher in the FD group than in the symptomatic control group (p = 0.041), where IL-1ß was inversely correlated with the duodenal MI (ß = - 0.600, p = 0.004). CONCLUSIONS: The mucosal barrier function of the duodenum was altered in patients with FD. Both a decreased ZO-1 and increased IL-1ß may play a role in the pathogenesis of FD.

Objective validity of the Japan Narrow-Band Imaging Expert Team classification system for the differential diagnosis of colorectal polyps.

BACKGROUND AND AIM: The Japan Narrow-Band Imaging (NBI) Expert Team (JNET) classification is a recently proposed NBI magnifying endoscopy-based classification system for colorectal tumors. Although the usefulness of this system has been reported by JNET experts, its objective validity remains unclear. We tested its validity and usefulness for the diagnosis of colorectal polyps by including colonoscopy experts and non-experts as test participants. METHODS: Forty NBI images of polyps of various JNET types were shown to 22 doctors (11 experts and 11 non-gastrointestinal [GI] trainees) who had not examined the patients. The doctors diagnosed the polyps based solely on the surface and vessel patterns in the magnified images and the JNET classification system. Concordance rates of their diagnoses with the pathological findings of the polyps were determined, and the results for experts and non-GI trainees were compared. RESULTS: Both for colonoscopy experts and non-GI trainees, the JNET classification system was particularly useful for classifying polyps as benign or malignant. Although the accuracy rates for classifying polyps into each JNET type varied among colonoscopy experts, those who were familiar with the JNET classification system were able to diagnose polyps with approximately 90% accuracy. Common mistakes were attributable to misunderstandings of the wording in the JNET classification chart and lack of proper training. CONCLUSION: The JNET classification system is a practical approach for the diagnosis of colorectal polyps. Training is required even for experienced colonoscopists to adopt the system properly. Common pitfalls must be shared among colonoscopists to improve the accuracy of the diagnosis.

Mucosal incision-assisted biopsy versus endoscopic ultrasound-guided fine-needle aspiration with a rapid on-site evaluation for gastric subepithelial lesions: A randomized cross-over study.

OBJECTIVES: This study aimed to compare the diagnostic yield of mucosal incision-assisted biopsy (MIAB) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with a rapid on-site evaluation (ROSE) for gastric subepithelial lesions (SEL) suspected of being gastrointestinal stromal tumors (GIST) with an intraluminal growth pattern. METHODS: This was a prospective randomized, cross-over multicenter study. The primary outcome was the diagnostic yield of EUS-FNA and MIAB. The secondary outcomes were the technical success rate, complication rate, procedure time and biopsy frequency. RESULTS: A total of 47 patients were randomized to the MIAB group (n = 23) and EUS-FNA group (n = 24). There was no significant difference in the diagnostic yield of MIAB and EUS-FNA (91.3% vs 70.8%, P = 0.0746). The complication rates of MIAB and EUS-FNA did not differ to a statistically significant extent. The mean procedure time in the MIAB group was significantly longer than that in the EUS-FNA group (34 vs 26 min, P = 0.0011). CONCLUSIONS: The diagnostic yield of MIAB was satisfactorily as high as EUS-FNA with ROSE for gastric SEL with an intraluminal growth pattern.

Endoscopic Submucosal Dissection is Feasible for Very Elderly Patients with Early Gastric Cancer : Comparison of Short-Term and Long-Term Outcomes in Very Elderly and Non-Elderly Patients.

Background/Aims: Endoscopic submucosal dissection (ESD) has become a standard procedure for the resection of early gastric cancer (EGC). However, the feasibility of ESD for very elderly patients, aged ≥ 80 years, has not been determined. Methodology: The study population included 67 non-elderly (NE) patients aged ≤ 65 years (80 lesions) and 22 very elderly (VE) patients ≥ 80 years (26 lesions) with EGC who underwent ESD and met the criteria for absolute or expanded indications. Eighteen patients (18 lesions) who underwent ESD but did not meet the criteria for absolute and expanded indications were defined as the outside the indications (OI) group. Results: En bloc and complete resection rates were excellent in both the VE and NE groups, without differing significantly. Although the rates of ischemic heart disease and antithrombotic agent use were higher in the VE than in the NE group, procedure-related complication rates did not differ significantly. Of the seven very elderly patients in the OI group, two underwent additional gastrectomy, and the other five were followed-up without surgery. No patient in any group experienced local recurrence, metastasis or disease-specific death. Conclusions: Short- and long-term outcomes of ESD for VE patients with EGC were favorable and did not differ significantly from outcomes in NE patients. ESD may therefore be a good therapeutic option for both VE and NE patients with EGC.

Suitability of the expanded indication criteria for the treatment of early gastric cancer by endoscopic submucosal dissection: Japanese multicenter large-scale retrospective analysis of short- and long-term outcomes.

OBJECTIVE: The criteria for endoscopic resection for early gastric cancer include absolute and expanded indications. Consensus already exists for the absolute indications. However, the suitability of the expanded indications must be validated by long-term outcome analyses since such lesions have only recently become resectable with the development of endoscopic submucosal dissection. The aim of this study is to clarify the suitability of the expanded indications for the treatment of early gastric cancer with endoscopic submucosal dissection. MATERIALS AND METHODS: The medical records of 1161 patients with early gastric cancers (1332 lesions) treated by endoscopic submucosal dissection and meeting the criteria for absolute or expanded indications without additional treatment with gastrectomy were divided into absolute indication group or expanded indication group. RESULTS: Complete resection rates were 96.4% and 93.4% in absolute and expanded indication groups, respectively, with no significant differences between the groups. Delayed bleeding rates were significantly higher in the expanded indication group, whereas all cases were successfully managed conservatively. The 5-year overall survival and recurrence-free rates were 93.7%/99.77% and 90.49%/98.90% in the absolute and the expanded indication groups, respectively, with no significant differences between the groups for either measure. Multivariate analyses revealed that affected horizontal margin and tumor location were independent predictive factors for recurrence. CONCLUSION: The expanded indication group showed excellent post-endoscopic submucosal dissection short-term and long-term outcomes compared with the absolute indications group, demonstrating that expanded indications are suitable for endoscopic submucosal dissection for early gastric cancer.

Endoscopic submucosal dissection using the "Clutch Cutter" for early esophageal squamous cell carcinoma.

BACKGROUND AND STUDY AIMS: To reduce the risk of complications related to the use of knives in endoscopic submucosal dissection (ESD), we developed the Clutch Cutter which can grasp and incise targeted tissue using electrosurgical current, similarly to a biopsy technique. The study aim was to evaluate the efficacy and safety of ESD using the Clutch Cutter for early esophageal squamous cell carcinoma. PATIENTS AND METHODS: ESD using the Clutch Cutter was performed on 32 consecutive patients with early esophageal squamous cell carcinoma. Therapeutic efficacy and safety were assessed. RESULTS: All lesions were treated easily and safely without unintended incision. En bloc resection was obtained in all patients. Histologically negative margins were obtained in 26/32 patients (81%). Endoscopic perforation due to the hood in one patient (3%), mediastinitis without endoscopic perforation in one patient (3%), and post-ESD stricture in 5 patients (16%) were observed. All were successfully managed conservatively. CONCLUSIONS: ESD using the Clutch Cutter appears to be a safe, easy, and technically efficient method for resecting early esophageal squamous cell carcinomas.

A new approach: endoscopic submucosal dissection using the Clutch Cutter® for early stage digestive tract tumors.

Endoscopic submucosal dissection (ESD) is accepted as minimally invasive therapy for early stage digestive tract tumors. It has allowed the achievement of histologically curative en-bloc resection of early stage digestive tract tumors regardless of size, including the resection of previously non-resectable tumors. Although numerous electrosurgical knives have been developed for ESD, technical difficulties and high complication rates (bleeding and perforation) have limited their use worldwide. Furthermore, conventional ESD usually needs several devices for each session. We developed the Clutch Cutter® (CC), which can grasp and incise the targeted tissue using electrosurgical current, to resolve such ESD-related problems. The ESD procedure using the CC is as follows: after marking using the CC and the injection of a solution into the submucosa, the lesion is separated from the surrounding normal mucosa by complete incision around the lesion using the CC. A piece of submucosal tissue is grasped and cut with the CC using electrosurgical current to achieve submucosal exfoliation. Intraoperative bleeding is also treated by the CC. Reported clinical studies showed that ESD using the CC is a safe, simple, easy-to-learn, technically efficient (en-bloc resection rate 100%), and a single-device method for the dissection of early stage digestive tract tumors. This new approach is promising to become the worldwide method of choice for early stage digestive tract tumors because it is technically simple and safe to perform.

A case of fulminant type 1 diabetes mellitus accompanied by myocarditis.

This report presents the case of a 47-year-old female patient with fulminant type 1 diabetes mellitus and myocarditis. Following a high fever, nausea, vomiting and diarrhea, diabetic ketoacidosis occurred and she was transferred to the hospital. The plasma glucose level was 63.6 mmol/L and HbA1c was 7.0%. C-peptide was undetectable in her plasma. Blood gas analysis showed a pH of 6.99. Antibodies to glutamic acid decarboxylase nor insulinoma associated antigen-2 were not detected. She was diagnosed to have fulminant type 1 diabetes mellitus. Her electrocardiogram showed diffuse ST-segment elevations on the second day of admission, along with a positive troponin test. However coronary angiography revealed neither occlusion nor stenosis of the cardiac arteries. An endomyocardial biopsy revealed hypertrophic cardiomyocytes with a disarrangement of myofibers and the focal accumulation of mononuclear cells in the stroma, thus suggesting myocarditis or mild myocarditic change. Viruses are an important cause of myocarditis and the preceding flu-like symptoms indicate the association of viral infection with myocarditis in this case. The mechanisms by which fulminant type 1 diabetes mellitus occurs is still uncertain, but the presence of islet injury accompanied by myocardial inflammation in the current case suggested that a viral infection accounted for the onset of this type of diabetes.

[A case of rectal implantation cyst diagnosed by EUS and EUS-guided FNA].

A 73-year-old woman was referred to our hospital complaining of bloody stool. She had undergone high anterior resection with the double stapling technique for a sigmoid colon cancer 2 years prior to this admission. Colonoscopy revealed a soft submucosal tumor, 4cm in size, on the anal side of the previous anastomosis in the rectum. EUS revealed a cystic lesion located in the third and fourth layers of the rectal wall. EUS-FNA was performed, and the content of the cystic lesion was transparent mucinous liquid. Histologically, the specimen revealed PAS and Alcian blue-positive mucinous material and a small number of inflammatory cells such as foamy macrophages. Therefore, this cystic lesion was diagnosed as a rectal implantation cyst.

Metabolic analysis of mouse bone-marrow-derived dendritic cells using an extracellular flux analyzer.

Dendritic cell (DC) maturation induced by Toll-like receptor (TLR) agonists requires the activation of downstream metabolic changes. Here, we provide a detailed protocol to measure glycolysis, mitochondrial respiration, and fatty acid oxidation in mouse bone-marrow-derived DCs with the Seahorse XF24 extracellular flux (XF) analyzer. XF analysis with the Seahorse bioanalyzer has become a standard method to measure bioenergetic functions in cells, and this protocol can be adapted to other immune cells. For complete information on using this protocol, please refer to Gotoh et al. (2018).

Advances in endoscopic therapy using grasping-type scissors forceps (with video).

Endoscopic submucosal dissection (ESD) is a globally accepted minimally invasive therapy for early-stage gastrointestinal tract tumors. Although numerous electrosurgical knives have been developed for ESD, technical difficulties and high complication rates (bleeding and perforation) have limited their use worldwide. The grasping-type scissors forceps [clutch cutter (CC)] is the first forceps-type resection device developed with reference to hemostatic forceps. The aim was to allow easy and safe ESD throughout the gastrointestinal tract, as a biopsy technique, using one device. The CC can grasp the target tissue accurately and pull it away from the underlying muscle layer prior to energizing the tissue, for safe and effective incision and hemostasis during ESD. Reported clinical studies showed that ESD using the CC (ESD-CC) is a safe (perforation rate: 0%-3.6%; delayed bleeding rate: 0%-4.2%), technically efficient (en-bloc resection rate: 88.9%-100%), and single-device method for dissecting early-stage gastrointestinal tract tumors. The ESD-CC technique is simple and easy to learn because it can be completed simply by repeating the grasp, pull, and coagulate and/or incise actions using an electrosurgical current. The reported self-completion rate by non-experts was significantly better with the CC than with conventional knives (61.7% vs 24.5%, respectively; P < 0.001). Furthermore, the CC is used for other endoscopic therapies, such as endoscopic polypectomy for large pedunculated polyps, endoscopic myotomy for Zenker's diverticulum, endoscopic treatment of buried bumper syndrome, and endoscopic necrosectomy for wall-off pancreatic necrosis. The initial reports using CC for these therapies have shown favorable results. In this review, we describe the structural features of the CC, how to use the instrument, efficacies of ESD-CC, and other unique endoscopic therapies using the CC.

Efficacy of endoscopic ultrasound with artificial intelligence for the diagnosis of gastrointestinal stromal tumors.

BACKGROUND: Although endoscopic ultrasound (EUS) is reported to be suitable for determining the layer from which subepithelial lesions (SELs) originate, it is difficult to distinguish gastrointestinal stromal tumor (GIST) from non-GIST using only EUS images. If artificial intelligence (AI) can be used for the diagnosis of SELs, it should provide several benefits, including objectivity, simplicity, and quickness. In this pilot study, we propose an AI diagnostic system for SELs and evaluate its efficacy. METHODS: Thirty sets each of EUS images with SELs ≥ 20 mm or < 20 mm were prepared for diagnosis by an EUS diagnostic system with AI (EUS-AI) and three EUS experts. The EUS-AI and EUS experts diagnosed the SELs using solely the EUS images. The concordance rates of the EUS-AI and EUS experts' diagnoses were compared with the pathological findings of the SELs. RESULTS: The accuracy, sensitivity, and specificity for SELs < 20 mm were 86.3, 86.3, and 62.5%, respectively for the EUS-AI, and 73.3, 68.2, and 87.5%, respectively, for the EUS experts. In contrast, accuracy, sensitivity, and specificity for SELs ≥ 20 mm were 90.0, 91.7, and 83.3%, respectively, for the EUS-AI, and 53.3, 50.0, and 83.3%, respectively, for the EUS experts. The area under the curve for the diagnostic yield of the EUS-AI for SELs ≥ 20 mm (0.965) was significantly higher than that (0.684) of the EUS experts (P = 0.007). CONCLUSION: EUS-AI had a good diagnostic yield for SELs ≥ 20 mm. EUS-AI has potential as a good option for the diagnosis of SELs.

The Efficacy and Safety of a Promising Single-Channel Endoscopic Closure Technique for Endoscopic Treatment-Related Artificial Ulcers: A Pilot Study.

BACKGROUND/AIMS: It is important to appropriately manage patients with procedure-related artificial mucosal ulcers or procedure-related complications. Many endoscopic closure techniques have been reported; however, they often require the use of special devices. We developed a single-channel endoscopic closure technique (SCCT) that can be performed with conventional devices. In the present study, we describe the technique and evaluate its efficacy. METHODS: Twenty-five consecutive patients who underwent endoscopic treatment and whose artificial ulcer was closed using the SCCT were enrolled in this study. The technical success rate, number of clips for closure, procedure time, complication rate on the day of the procedure, clinical success rates on days 1 and 5, and incidence of severe stenosis of the gastrointestinal (GI) tract at 2 months after the procedure were evaluated. RESULTS: The median ulcer diameter was 20 mm. The tumor locations were the stomach (n = 19), jejunum (n = 1), and colon (n = 5). The technical success rate was 100% (25/25), and the rate of incomplete closure was 0% (0/25). Eight clips were needed on average. The median procedure time was 18 min (range 5-49 min). The complication rate was 0% (25/25). The clinical success rates on days 1 and 5 were 100% (19/19) and 100% (9/9), respectively. No patients presented stenosis as a late complication at 2 months after the procedure (0/25). CONCLUSION: The SCCT could be applied in the treatment of artificial ulcers in several parts of the GI tract with a high clinical success rate and no complications. The SCCT appears to be a good option for closing artificial mucosal ulcers.

Prognostic factors associated with mortality in patients with gastric fundal variceal bleeding.

AIM: To determine the prognostic factors associated with mortality in patients with gastric fundal variceal (GFV) bleeding. METHODS: In total, 42 patients were endoscopically diagnosed with GFV bleeding from January 2000 to March 2014. We retrospectively reviewed the patients' medical records and assessed their history, etiology of liver cirrhosis, disease conditions, treatment options for GFV bleeding, medications administered before and after onset of GFV bleeding, blood test results (hemoglobin, albumin, and bilirubin concentrations), and imaging results (including computed tomography and abdominal ultrasonography). We also assessed the prognostic factors associated with short-term mortality (up to 90 d) and long-term mortality in all patients. RESULTS: Multivariate analysis showed that prophylactic administration of antibiotics was an independent prognostic factor associated with decreases in short-term mortality (OR = 0.08, 95%CI: 0.01-0.52) and long-term mortality (OR = 0.27, 95%CI: 0.08-0.91) in patients with GFV bleeding. In contrast, concurrent hepatocellular carcinoma (HCC) and regular use of proton pump inhibitors (PPI) were independent prognostic factors associated with increases in short-term mortality (HCC: OR = 15.4, 95%CI: 2.08-114.75; PPI: OR = 12.76, 95%CI: 2.13-76.52) and long-term mortality (HCC: OR = 7.89, 95%CI: 1.98-31.58; PPI: OR = 10.91, 95%CI: 2.86-41.65) in patients with GFV bleeding. The long-term overall survival rate was significantly lower in patients who regularly used PPI than in those who did not use PPI (P = 0.0074). CONCLUSION: Administration of antibiotics is associated with decreased short- and long-term mortality, while concurrent HCC and regular PPI administration are associated with increased short- and long-term mortality.

Endoscopic submucosal dissection for rectal carcinoid tumour using the Clutch Cutter.

BACKGROUND: To reduce the risk of complications related to endoscopic submucosal dissection (ESD) using knives, we developed the Clutch Cutter (CC), which can grasp and incise the target tissue similarly to biopsy techniques using an electrosurgical current. The aim of this study was to evaluate the efficacy and safety of ESD using the CC for removal of rectal carcinoid tumours. METHODS: Between December 2009 and December 2011, we prospectively enrolled seven patients (seven lesions) on 7 different days. Patients were endoscopically diagnosed with rectal subepithelial lesions (upper rectum, n = 3; lower rectum, n = 4) within the level 3 layer and without lymph node involvement, with the diagnosis confirmed by preliminary endoscopy, endoscopic ultrasound and endoscopic biopsies. ESD using the CC was performed in all cases, and the therapeutic efficacy, safety and tumour recurrence were assessed. RESULTS: All lesions were treated easily and safely, and there were no inadvertent incisions. En bloc resection was obtained in all cases, and histologic tumour-free lateral/basal margins were obtained in six of the seven patients. No delayed haemorrhage, perforation or tumour recurrence occurred. CONCLUSION: ESD using the CC appears to be an easy, safe and technically efficient method for resecting rectal carcinoid tumour.