A Novel Hemostatic Peptide Solution for Common Acute Gastrointestinal Bleeding Diseases: First Case Series Study on the Treatment Results of Endoscopic Hemostasis by Nonexpert Endoscopists.

INTRODUCTION: We investigated the hemostatic effect and safety of a hemostatic peptide solution for the treatment of gastrointestinal bleeding requiring emergency endoscopy. METHODS: We retrospectively examined the patient backgrounds, hemostatic results, and procedural safety in patients who were treated with a hemostatic peptide solution for hemostasis during emergency endoscopies for gastrointestinal bleeding. All hemostatic procedures were performed by nonexpert physicians with less than 10 years of endoscopic experience. All of the cases were treated at a single institution over the months from January 2022 to January 2023. RESULTS: Twenty-six consecutive patients (17 males and 9 females) with a median age of 74 (45-95) years were included. Their conditions requiring emergency endoscopy were melena in 8 patients, hematochezia in 2, hematemesis in 8, anemia in 6, and bleeding during esophagogastroduodenoscopy in 2. The sites of bleeding were the esophagus in 3 patients, the stomach in 17, the duodenum in 3, the small intestine in 2, and the colon in 1. Hemostasis was obtained with another hemostasis device used in conjunction with the hemostatic peptide solution in 13 cases and with the hemostatic peptide solution alone in 13 cases. The hemostasis success rate was 100%, with no complications. Rebleeding occurred within 1 week in 4 cases. CONCLUSION: Hemostasis with the hemostatic peptide solution was safe and provided a temporary high hemostatic effect in emergency gastrointestinal endoscopy.

Multiple ulcerative colitis-associated aseptic abscesses successfully treated with infliximab: a case report.

Aseptic abscesses are rare extraintestinal manifestations of inflammatory bowel disease. Herein, we present the case of a 69-year-old female patient with ulcerative colitis in whom multiple aseptic abscesses were successfully treated with infliximab. Aseptic abscesses associated with ulcerative colitis are difficult to differentiate from infectious abscesses. In the present case, we reached a diagnosis of aseptic abscesses associated with ulcerative colitis as antibiotics were ineffective and repeated Gram stains and cultures of blood and abscess were negative. Aseptic abscesses are commonly found in the spleen, lymph nodes, liver, and skin; however, in the present case, the periosteum was the major site. Prednisolone is often effective for aseptic abscesses; however, the present patient was initially treated with a combination of 40 mg/day of prednisolone and granulocyte and monocyte adsorption apheresis, with inadequate effect. Infliximab was administered as the patient was steroid-resistant, with strong effect. Subsequently, infliximab treatment has been continued, with no recurrence after 2 years. However, as there have been reports of cases of recurrence even after remission with treatment, careful follow-up in the future is therefore necessary.

Neoangiogenesis of gastric submucosa-invasive adenocarcinoma.

Early gastric cancer may be defined as mucosal or submucosal invasive carcinoma, and exhibits a good prognosis: 90% of patients survive >10 years. Early gastric cancer infrequently exhibits lymph node metastasis, although submucosal invasion, the presence of vascular invasion and/or lymphatic permeation are independent risk factors for lymph node metastasis in early gastric cancer. The analysis of tumor lymphangiogenesis and angiogenesis are important to determine the extent of invasive progression and metastasis in patients. Previously, the presence of vessels expressing the D2-40 antibody and the factor-VIII protein has been identified immunohistochemically. The vessels that are immunoreactive for D2-40 and factor-VIII are morphologically similar to lymphatic vessels or small-size veins, also termed venules. In the present study, the association between tumor invasion and neoangiogenesis in early gastric cancer was examined. The D2-40/factor-VIII double-stained vessel (DSV) density was analyzed, in addition to lymphatic and blood vessel (vein and artery) density, using 46 submucosa-invasive and 50 mucosal carcinomas, and 20 non-neoplastic gastric tissues. The lymphatic density and DSV density of submucosa beneath the carcinoma and submucosa of the surrounding region in submucosa-invasive carcinoma were significantly increased (P<0.001) in comparison with those in mucosal carcinoma or non-neoplastic gastric tissue. No significant difference was observed in blood vessel density between non-neoplastic gastric, mucosal carcinoma and submucosa-invasive carcinoma tissues other than that of mucosa. The present study suggests the potential for the presence of D2-40/factor-VIII DSV and the importance of this vessel for neoangiogenesis in early gastric cancer.

Recognition accuracy of tumor extent using a prototype 3D endoscope for superficial gastric tumor: an ex vivo crossover study.

BACKGROUND AND STUDY AIMS: Many studies have shown the utility of rigid three-dimensional (3 D) endoscopes in surgery, but few have reported the utility of flexible 3 D endoscopes. This ex vivo study was intended to investigate whether a newly developed 3 D endoscope (GIF-Y0083; Olympus) improves diagnostic accuracy for superficial gastric tumor. METHODS: Twelve observers comprising experts, trainees, and novices (4 each) evaluated 2 D and 3 D images of 20 specimens resected by gastric ESD. Evaluation items were diagnostic accuracy of tumor extent and degree of confidence in assessing (a) tumor extent, (b) morphology, and (c) comprehensive recognition. The 2 D and 3 D endoscopy data were compared in a crossover analysis. RESULTS: Overall, diagnostic accuracy was significantly higher with 3 D images (88.1 %) than with 2 D images (84.2 %) ( P  < 0.01). Comparison by skill level showed that 3 D images significantly improved diagnostic accuracy among novices but not among experts or trainees. Comparison by morphology showed that diagnostic accuracy did not differ significantly for type IIa/IIb lesions but improved significantly for type IIc lesions among trainees and novices. Overall, 3 D images significantly increased the degree of confidence in the assessment of all three items (a - c). Comparison by skill level showed similar results, and comparison by morphology showed that regardless of skill level, the degree of confidence in assessing all items (a - c) increased significantly only when examining type IIc lesions. CONCLUSION: Compared with 2 D images, 3 D images significantly improved both diagnostic accuracy of tumor extent and degree of confidence for diagnosing superficial gastric tumor. The utility of the 3 D endoscope was apparent among trainees and novices and for the diagnosis of type IIc lesions.

Characterization of Helicobacter pylori-Naïve Early Gastric Cancers.

AIM: Helicobacter pylori-naïve gastric cancers(GCs) have not been well documented. We aimed to characterize early H. pylori-naïve GCs. SUBJECTS AND METHODS: Of 666 patients with GC resected by endoscopic submucosal dissection, H. pylori-naïve patients were extracted according to the definition: no H. pylori eradication history, negative for serum H. pylori-antibody and current H. pylori-infection tests, and no gastric atrophy by pepsinogen (PG) test, endoscopy, and histology. RESULTS: It was found that 16 GCs were H. pylori-naïve, and classified into undifferentiated and differentiated type adenocarcinoma. All 9 undifferentiated type GCs were pale, depressed, mucosal pure signet ring cell adenocarcinoma except one of them and 7 differentiated type GCs were classified into 3 fundic gland type GCs and 4 foveolar type GCs. All fundic gland type GCs positive for PG-1 were cardia small submucosal tumor (SMT)-like protrusions with dilated vessels on the surface. All 4 foveolar type GCs were composed of dysplastic clear cells resembling foveolar epithelium, negative for PG-1 but positive for mucin 6 (MUC6) and MUC5AC. Endoscopically, all were laterally spreading elevations with papillary or villous surface. CONCLUSIONS: H. pylori-naïve GCs were infrequent at 2.5%, and classified into 3 types: a small pale depression of signet ring cell adenocarcinoma, a small SMT-like protrusion of fundic gland type GC, and a large laterally spreading elevation of foveolar type GC.

Clinicopathological features of superficial non-ampurally duodenal epithelial tumor; gastric phenotype of histology correlates to higher malignant potency.

BACKGROUND: Superficial non-ampullary duodenal epithelial tumors (SNADETs) are relatively rare, but they are now being detected more frequently due to advances in endoscopic technology. Nevertheless, the pathological nature of SNADETs remains unclear and a management strategy for these tumors has not been established. METHODS: To elucidate the clinicopathological features, we conducted a retrospective analysis of 138 endoscopically resected SNADETs. Lesions were classified into two groups by histological grade according to the Vienna classification: category 3 (71 lesions, 51.4%) and category 4/5 (67 lesions, 48.6%). RESULTS: Compared with category 3 lesions, category 4/5 lesions were significantly more common in elderly patients (p < 0.001) and had a significantly larger tumor diameter (p = 0.001). Immunohistochemical analysis showed that category 4/5 lesions expressed MUC5AC (p = 0.002), MUC6 (p < 0.001), and p53 (p = 0.003) significantly more frequently and expressed CD10 (p = 0.002) and CDX2 (p = 0.029) significantly less frequently. Multivariate regression analysis showed that advanced age (p < 0.001), MUC6 expression (p = 0.001), and p53 expression (p = 0.004) were independent risk factors for a classification of category 4/5. In addition, advanced age (p = 0.010) and MUC5AC expression (p = 0.011) were identified as risk factors for lesions classified as category 4.2 (noninvasive carcinoma) or higher. All category 5 lesions expressed MUC5AC. CONCLUSIONS: The gastric phenotype of MUC5AC and MUC6 may be linked to the malignant potential of SNADETs.

Feasibility Study of the Three-Dimensional Flexible Endoscope in Endoscopic Submucosal Dissection: An ex vivo Animal Study.

BACKGROUND/AIM: Clinical application of 3-dimensional (3D) technology for flexible endoscopes has not been reported. We developed a 3D flexible endoscope and conducted a feasibility study of endoscopic submucosal dissection (ESD) in porcine stomach. METHODS: Four endoscopists used a 3D flexible endoscope to perform a total of 8 ESD procedures on resected porcine stomachs. We assessed the en bloc resection rate, perforation rate, and mechanical issues that arise during ESD. A visual analog scale (0, 2D superior; 100, 3D superior) was used to evaluate the depth perception, sense of security of the procedure, and eyestrain of 3D visualization. RESULTS: En bloc resection was achieved in all cases and there were no cases of perforation or mechanical issues. Depth perception and sense of security were rated 85.5 ± 12.4 and 70.7 ± 9.7 respectively (mean ± SDs). Eyestrain was rated high for 3D visualization (mean ± SDs, 12.6 ± 8.6). CONCLUSIONS: ESD using a 3D flexible endoscope was technically feasible. The endoscopists reported good depth perception and a high sense of security when using 3D visualization but also noted strong eyestrain.

Recognition Accuracy Using 3D Endoscopic Images for Superficial Gastrointestinal Cancer: A Crossover Study.

Aim. To determine whether 3D endoscopic images improved recognition accuracy for superficial gastrointestinal cancer compared with 2D images. Methods. We created an image catalog using 2D and 3D images of 20 specimens resected by endoscopic submucosal dissection. The twelve participants were allocated into two groups. Group 1 evaluated only 2D images at first, group 2 evaluated 3D images, and, after an interval of 2 weeks, group 1 next evaluated 3D and group 2 evaluated 2D images. The evaluation items were as follows: (1) diagnostic accuracy of the tumor extent and (2) confidence levels in assessing (a) tumor extent, (b) morphology, (c) microsurface structure, and (d) comprehensive recognition. Results. The use of 3D images resulted in an improvement in diagnostic accuracy in both group 1 (2D: 76.9%, 3D: 78.6%) and group 2 (2D: 79.9%, 3D: 83.6%), with no statistically significant difference. The confidence levels were higher for all items ((a) to (d)) when 3D images were used. With respect to experience, the degree of the improvement showed the following trend: novices > trainees > experts. Conclusions. By conversion into 3D images, there was a significant improvement in the diagnostic confidence level for superficial tumors, and the improvement was greater in individuals with lower endoscopic expertise.

Conventional White Light Endoscopic Features of Small Superficial Barrett's Esophageal Adenocarcinoma.

BACKGROUND: Superficial Barrett's esophageal adenocarcinoma (BEA) arising from short-segment Barrett's esophagus (SSBE) is visualized as a reddish lesion located on the right or anterior side wall of the esophagogastric mucosal junction (EGJ) and showing an elevated macroscopic appearance under conventional white light endoscopy (WLE). However, because the form and color are variable, misdiagnosis as reflux esophagitis or SSBE is frequent under WLE. The aim of this study is to clarify conventional WLE features of small superficial BEA. SUMMARY: We retrospectively analyzed 30 lesions ≤20 mm in diameter in 30 patients who underwent endoscopic mucosal resection or endoscopic submucosal dissection at Toranomon Hospital between 2002 and 2014. Mean age of patients with small superficial BEA arising from SSBE was 64.3 ± 11.2 years, and mean tumor size was 12.0 ± 4.8 mm. Small superficial BEA fell into the following 4 categories based on WLE features: EGJ polyp type, 43.3% (13 of 30 lesions); triangular SSBE type, 43.3% (13 of 30 lesions); cardiac erosion type, 10.0% (3 of 30 lesions); and unclassified or mixed type, 3.4% (1 of 30 lesions). EGJ polyp-type tumors were located on the right or anterior side wall of the EGJ, and no tumors showed invasion to the submucosal layer. On the other hand, triangular SSBE-type tumors were located anywhere in the EGJ, and 38.5% showed submucosal invasion (5 of 13 lesions). KEY MESSAGES: We consider this classification significantly contributes to the detection of small superficial BEA arising from SSBE under WLE.

Adenocarcinoma of the cervical esophagus arising from ectopic gastric mucosa: report of two cases and review of the literature.

Esophageal adenocarcinoma arising from ectopic gastric mucosa (EGM) is extremely rare. We describe here two Japanese patients with adenocarcinoma of the cervical esophagus arising from EGM. Case 1 is a 62-year-old man who had slightly red EGM in the cervical esophagus on upper gastrointestinal endoscopy (UGE). Because the biopsy showed atypical glands that were suspicious for adenocarcinoma, endoscopic submucosal dissection was performed. Histopathological examination revealed that the lesion was a well-differentiated adenocarcinoma (pT1a MM). Lymphovascular invasion was absent, and the margins were free from carcinoma. Case 2 is a 57-year-old man who had an elevated lesion with a bleeding tendency in an area of EGM in the cervical esophagus on UGE. Adenocarcinoma was diagnosed in the biopsy. Because of the presence of enlarged lymph nodes (#106recL), preoperative chemoradiotherapy was performed to reduce the size of the adenocarcinoma and lymph nodes prior to resection of the cervical esophagus and reconstruction with free jejunal grafts. Histopathological examination revealed moderately differentiated adenocarcinoma (0-I, pT2N1M0, pStage II). In both cases, adenocarcinoma was surrounded by EGM, which led to the diagnosis of EGM-derived esophageal adenocarcinoma. Here, we report its immunohistochemical characteristics in the present cases and discuss the histogenesis.

Phlegmonous gastritis secondary to superior mesenteric artery syndrome.

We herein report a case of phlegmonous gastritis secondary to superior mesenteric artery syndrome. An 80-year-old woman visited the hospital emergency department with the chief complaints of epigastric pain and vomiting. She was hospitalized urgently following the diagnosis of superior mesenteric artery syndrome based on abdominal computed tomography findings. Conservative therapy was not effective, and phlegmonous gastritis was diagnosed based on the findings of upper gastrointestinal endoscopy and biopsy performed on the 12th day of the disease. Undernutrition and reduced physical activity were observed on hospital admission, and proactive nutritional therapy with enteral nutrition was started. An upper gastrointestinal series, performed approximately 1 month later, confirmed the persistence of strictures and impaired gastric emptying. Because conservative therapy was unlikely to improve oral food intake, open total gastrectomy was performed on the 94th day of the disease. Examination of surgically resected specimens revealed marked inflammation and fibrosis, especially in the body of the stomach. Following a good postoperative recovery, the patient was able to commence oral intake and left our hospital on foot approximately 1 month after surgery.

Histological phenotype is correlated with the wall-invasion pattern of gallbladder adenocarcinoma.

Gallbladder carcinoma (GBC) is one of the most aggressive malignancies, and frequently shows vascular invasion and lymph node metastasis. Our previous study has classified the wall-invasion pattern of GBC into two groups, i.e., infiltrative growth type (IG type) and destructive growth type (DG type). The DG type was significantly associated with poor clinical outcome. In this study, we analyzed the relationship between the wall-invasion pattern and the histological phenotype of GBC, using 61 surgically-resected primary gallbladder adenocarcinomas. Histologically, the 61 cases were classified into the biliary (44 cases, 72.1%), gastric foveolar (13 cases, 21.3%), and intestinal (4 cases, 6.6%) types. Biliary type frequently exhibited MUC1, but less frequently showed MUC2, MUC5AC, and MUC6. The biliary type and MUC1 expression were significantly correlated with DG type wall-invasion pattern (P = 0.020 and P < 0.001, respectively). In conclusion, histological phenotype and mucin expression were thought to be indicators of aggressiveness of GBC.

Invasive micropapillary carcinoma of the extrahepatic bile duct and its malignant potential.

Invasive micropapillary carcinoma (IMPC) was originally described as a distinctive type of invasive carcinoma in the breast, but it has not been recognized as a histological type of the extrahepatic bile duct cancer. The present study demonstrated clinicopathological features and patient prognosis of IMPC. We examined histological reviews of 93 consecutive cases of the extrahepatic bile duct cancer and identified 13 cases which included IMPC component. The component of IMPC ranged from 5 to 60% of the primary tumor tissue, which was mainly detected at the invasive front of the tumor. Of the 13 cases, 12 (92.3%) carcinomas with IMPC showed lymph node metastasis more frequently compared to conventional adenocarcinoma (39.2%, P<0.001). Presence of IMPC component was significantly associated with poor overall survival (P=0.003). In conclusion, extrahepatic bile duct carcinoma with IMPC component showed significant lymphatic invasion, lymph node metastasis, and resulted in poor prognosis.