Beige mucosa observable under narrow-band imaging indicates the active sites of eosinophilic esophagitis.

BACKGROUND AND AIM: The majority of patients with eosinophilic esophagitis (EoE) are likely to have observable features under narrow-band imaging, namely beige mucosa. However, the histological features and clinical implications of beige mucosa have not been investigated. The aim of this study was to determine whether beige mucosa could serve as an endoscopic marker for predicting active inflammatory sites of EoE. METHODS: We retrospectively analyzed both the narrow-band images and biopsied specimens of 77 esophageal lesions from 35 consecutive patients with EoE. We divided these specimens into two groups: target biopsied specimens from beige mucosa (beige group) and specimens biopsied from non-beige mucosa (non-beige group). The number of eosinophils per high-powered field, thickness of the superficial differentiated cell layer, and depth of the hemoglobin component from the surface layer were compared between the two groups. RESULTS: Forty-four out of the 45 specimens were diagnosed as histological active lesions in the beige group. The sensitivity, specificity, and overall accuracy of beige mucosa in predicting EoE activity were 97.8%, 96.9%, and 97.8%, respectively. Compared with the non-beige group, specimens in the beige group had a significantly thinner superficial differentiated cell layer. CONCLUSIONS: Beige mucosa is associated with thinning of the normal superficial differentiated cell layer, and these histological changes in the active inflammatory sites of EoE could be recognized endoscopically as color differences. Beige mucosa may serve as an endoscopic indicator for predicting the histological activity of EoE.

Endoscopic and Upper Gastrointestinal Barium X-ray Radiography Images of Early-stage Autoimmune Gastritis: A Report of Two Cases.

We herein report two patients with early-stage autoimmune gastritis who did not exhibit complete atrophy. Endoscopic examinations showed no manifestations of severe atrophic gastritis, but revealed a mosaic pattern with slight swelling of the areae gastricae restricted to the corpus in both patients. In the patient in case 2, upper gastrointestinal barium X-ray radiography revealed a slightly protruded irregular areae gastricae throughout the gastric body, except for in the antrum. Our findings emphasize the need for clinicians to recognize that autoimmune gastritis might be present in the absence of severe atrophic gastritis; this can aid in the identification of the early stages of autoimmune gastritis.

Comparison of submucosal tunneling biopsy versus EUS-guided FNA for gastric subepithelial lesions: a prospective study with crossover design.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided fine needle aspiration (FNA) for gastrointestinal subepithelial lesions (SELs) has limited diagnostic accuracy due to technical problems and small lesion size. We previously reported a novel submucosal tunneling biopsy (STB) technique for sampling SELs. This study aimed to evaluate the diagnostic ability and safety of STB compared to that of FNA for SELs. PATIENTS AND METHODS: The study was a non-randomized, prospective comparative study with crossover design in patients with endoluminal gastric SELs. Forty-three patients, including 29 cases with lesions < 2 cm were enrolled. A crossover design with 2 intervention stages (Group A: FNA followed by STB for 23 SELs, Group B: STB followed by FNA for 20 SELs) was implemented. The primary outcome was the diagnostic yield (DY). Secondary outcomes were technical success rate, procedure time, complication rate, and sample quality. RESULTS: The DY of STB was significantly higher than that of FNA (100 % vs. 34.8 %; P  < 0.0001) in group A, including 100 % in overall STB. The technical success rate of STB was significantly higher than that of FNA (100 % vs. 56.5 %; P  = 0.0006), whereas the median procedure time of STB was significantly longer than that of FNA (37 minutes vs. 18 minutes; P  < 0.0001). The median specimen area of STB samples was markedly larger than that of FNA samples (5.54 mm 2 vs. 0.69 mm 2 ; P  < 0.001). No complications occurred in either method. CONCLUSIONS: STB had significantly superior diagnostic ability and a more adequate sample quality than FNA for endoluminal gastric SELs, indicating the suitability of STB for small SELs. CLINICAL TRIAL REGISTRATION: UMIN 000006754.

Flexible magnifying endoscopy with narrow band imaging for the diagnosis of uterine cervical tumors: A cooperative study among gastrointestinal endoscopists and gynecologists to explore a novel microvascular classification system.

Narrow band imaging with magnifying endoscopy (NBI-ME), which is useful for the assessment of micro-vessels, has excellent diagnostic potential for early gastrointestinal epithelial neoplasia. Conventional diagnostic tools for uterine cervical epithelial tumors are still unsatisfactory. An accurate diagnostic tool for uterine cervical epithelial tumors is required to preserve the reproductive ability of young women with uterine cervical tumors. Flexible NBI-ME was performed in patients with cervical squamous cell lesions that required further examinations based on their Pap smear results (cytology ≥ low-grade squamous intraepithelial lesion) at Kagawa University Hospital between April 2014 and April 2015. NBI-ME results concordant with the punch biopsy sites were compared with the histological results. A retrospective review of the NBI-ME images identified abnormal NBI-ME results regarding micro-vascular patterns. All images were categorized as having abnormal features. NBI-ME revealed the following vascular pattern differences of different stage tumors: Dot-like vessels without irregular arrangements and high density in cervical intraepithelial neoplasia (CIN) CIN1-CIN2; dot-like vessels with irregular arrangements and high density in CIN3-carcinoma in situ; crawling vessels in minimum invasive cancer; and willow branch vessels and new tumor vessels in invasive cancer. NBI-ME may be an effective diagnostic tool for uterine cervical epithelial tumors, which may lead to the establishment of a novel classification system.

Therapeutic potential of the antidiabetic drug metformin in small bowel adenocarcinoma.

Small bowel adenocarcinoma (SBAC) accounts for 3% of all gastrointestinal tract tumors and approximately 0.5% of all cancer cases. Recent studies have indicated that the use of metformin, one of the most commonly prescribed antidiabetic drugs, is associated with a better prognosis for certain malignant diseases. However, there have been no reports on the effect of metformin in SBAC. In the present study, we evaluated the effect of metformin on human SBAC cell proliferation in vitro and in vivo and identified the microRNAs (miRNAs) associated with its antitumor effects. Metformin inhibited the proliferation of HuTu80 cells in a time- and dose-dependent manner. Importantly, metformin reduced the expression of cyclin D1, cyclin E, cyclin-dependent kinase 4, and phosphorylated retinoblastoma protein, which resulted in cell cycle arrest at the G0/G1 phase. This arrest was accompanied by activation of AMPKα and inhibition of mammalian target of rapamycin and p70s6k. Additionally, metformin reduced the levels of phosphorylated epidermal growth factor receptor and ROR2 as well as markedly altered miRNA expression in HuTu80 cells. Metformin also inhibited tumor growth in vivo in a xenograft mouse model. Our data suggest that metformin might have therapeutic potential in SBAC.

Current Status of Exposed Endoscopic Full-Thickness Resection and Further Development of Non-Exposed Endoscopic Full-Thickness Resection.

Endoscopic full-thickness resection (EFTR) is a procedure that makes it possible to access the lesions that are on the wall of the digestive tract via the shortest distance through the mouth. Because of the ultra-minimal invasive nature of the treatment, pure EFTR is a highly promising surgical procedure that allows the radical excision of full-thickness layers of digestive tract tumors using only a flexible endoscope. There are 2 types of EFTR methods: exposed and non-exposed. Considering the risks of contracting infection and intraperitoneal dissemination of tumor cells, non-exposed EFTR is an ideal method. However, a number of issues remain unresolved, including the method for performing a full-thickness suture under endoscopic view and the challenge of securing the operating field in the case of gastrointestinal tract collapse. Moreover, advances in the development of equipment such as full-thickness suturing devices would be helpful to make this therapeutic procedure the most minimally invasive endoscopic surgery ever.

Novel effective and repeatedly available ring-thread counter traction for safer colorectal endoscopic submucosal dissection.

BACKGROUND: Although several methods to create an effective counter traction for safer endoscopic submucosal dissection (ESD) have been reported, these methods do not overcome problems regarding delivery and ease of use. This randomized prospective study assessed the usefulness of ring-shaped thread counter traction, which not only allowed the safer colorectal ESD but also the easiest and lower cost counter traction without any special devices. METHODS: Forty-five patients diagnosed with colorectal lateral spreading tumors over 20 mm were allocated to the conventional ESD group (CE) (n = 22) and the ring-shaped thread counter traction ESD group (RE) (n = 21). The ring-shaped thread was hooked and lifted up to the contralateral mucosa with a hemoclip. The primary outcome was the dissected area per minute during ESD (cm2/min) (UMIN000020160). RESULTS: There were significant differences in the dissection time (min), with 130.0 (56.0-240.0) versus 80 (35.0-130.0) min for the CE and RE groups, respectively (P = 0.001). For the dissected areas per minute (cm2/min), there was a significant difference, with 0.125 (0.1-0.18) versus 0.235 (0.16-0.36) min (P = 0.003) for the CE and RE groups, respectively. There were 1 cases of perforation during ESD in the CE compared to 0 for the RE, and this was no significantly different (P = 0.31). The procedure time of producing and setting the ring-shaped thread counter traction was approximately 1.80 (0.80-3.30) min only. CONCLUSIONS: The ring-shaped thread counter traction is simple, effective, lower cost and does not require special devices to obtain repeated counter traction.

Management of a large mucosal defect after duodenal endoscopic resection.

Duodenal endoscopic resection is the most difficult type of endoscopic treatment in the gastrointestinal tract (GI) and is technically challenging because of anatomical specificities. In addition to these technical difficulties, this procedure is associated with a significantly higher rate of complication than endoscopic treatment in other parts of the GI tract. Postoperative delayed perforation and bleeding are hazardous complications, and emergency surgical intervention is sometimes required. Therefore, it is urgently necessary to establish a management protocol for preventing serious complications. For instance, the prophylactic closure of large mucosal defects after endoscopic resection may reduce the risk of hazardous complications. However, the size of mucosal defects after endoscopic submucosal dissection (ESD) is relatively large compared with the size after endoscopic mucosal resection, making it impossible to achieve complete closure using only conventional clips. The over-the-scope clip and polyglycolic acid sheets with fibrin gel make it possible to close large mucosal defects after duodenal ESD. In addition to the combination of laparoscopic surgery and endoscopic resection, endoscopic full-thickness resection holds therapeutic potential for difficult duodenal lesions and may overcome the disadvantages of endoscopic resection in the near future. This review aims to summarize the complications and closure techniques of large mucosal defects and to highlight some directions for management after duodenal endoscopic treatment.

Successful mucosal incision-assisted biopsy for the histological diagnosis of duodenal lymphoma: A case report.

Tissue sampling of primary duodenal lymphoma is essential for its histological diagnosis. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which is frequently used for submucosal tumor (SMT)-like duodenal tumors, is adequate for cytological diagnosis, but not for histological diagnosis. Therefore, in the present study, a mucosal incision-assisted biopsy (MIAB) was performed in an 81-year-old woman for the diagnosis of an SMT-like duodenal mass, as tissue sampling for histological analysis using a regular endoscopic biopsy had failed to establish a definite diagnosis of malignant lymphoma. EUS-FNA had also led to poor tissue sampling due to the difficult location of the duodenal tumor. The pathological examination of biopsy samples using MIAB revealed the presence of a diffuse proliferation of atypical lymphocytes, and the expression of cluster of differentiation (CD)20 and CD79a, but no expression of CD3 in the tumor specimens. The patient was diagnosed with diffuse large B-cell lymphoma. To the best of knowledge, this is first report of a case using MIAB as a sampling method for the histological diagnosis of SMT-like primary duodenal lymphoma. This case suggests that MIAB may be an essential method for obtaining tissue samples from SMT-like duodenal tumors.

Differences in miRNA expression profiles between GIST and leiomyoma in human samples acquired by submucosal tunneling biopsy.

BACKGROUND AND STUDY AIMS: Small gastrointestinal stromal tumors (GISTs) rarely have malignant potential with poor prognosis. Using conventional imaging to differentiate between small GISTs and leiomyoma, which often have similar characteristics, is difficult but essential in daily practice. Although some studies have reported on the utility of serum c-kit as a biomarker for non-small GIST and specific miRNA, clinical aspects of such testing are controversial. The aim of this study was to identify differences between small GIST and leiomyoma through the investigation of miRNA expression patterns in human cases. PATIENTS AND METHODS: MiRNA expression was examined in nine GIST (less than low risk, mean 18 mm in size) samples and seven leiomyoma samples acquired by a novel sampling method, submucosal tunneling biopsy (STB), which produces tumor specimens of submucosal tumor (SMT) without contamination of sufficient size to be examined under direct vision. Total RNA was extracted from these tissues and analyzed for miRNA expression patterns by microarray. Subsequently, real-time quantitative polymerase chain reaction (qPCR) were used to confirm specific miRNA overexpression, comparing GISTs with leiomyomas. RESULTS: Microarray analysis revealed upregulation of the miR-140 family up to 20 times higher in GISTs than in leiomyomas. Real-time qPCR revealed that the expression level of miR-140-5 p in GISTs was 27.86 times higher than in leiomyomas; miR-140-3 p was 12.24 times higher as well. CONCLUSIONS: The STB method provided suitable SMT samples for miRNA analysis. MiR-140 family members may serve as specific biomarkers to distinguish GIST from leiomyoma.

Seatbelt syndrome with gastric mucosal breaks and intra-gastric wall air leakage.

As numerous reports were published regarding the so-called seatbelt syndrome involved in car crashes, most of them were mentioned about small intestine, duodenum and colon perforations and solid organ bleeding. No reports have been published regarding multiple gastric mucosal tears with intra-gastric wall air leakage with massive bleeding. A 65-year-old woman was admitted after a motor vehicle crash. She vomited massive fresh blood. Gastric mucosal breaks, approximately 5 cm in length, were observed. Computed tomography imaging revealed multiple gastric mucosal breaks. We report a rare case wherein a traffic accident caused a serious condition associated with massive digestive bleeding.

Usefulness of magnifying endoscopy with narrow-band imaging for identification of early gastric cancer around an ulcer scar

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Comparison of Retroflexed and Forward Views for Colorectal Endoscopic Submucosal Dissection.

BACKGROUND: The use of a retroflexed view exposes the entire tumor surface, which is obscured in the forward view, and contributes to complete tumor resection when combined with forward views. However, the efficacy and safety of using the retroflexed view for colorectal endoscopic submucosal dissection (ESD) are poorly understood. METHODS: In this study, we assessed the efficacy and safety of the retroflexed view in colorectal ESD. From April 2009 to December 2013, 130 colorectal tumors were examined in 128 patients treated with ESD. A total of 119 patients with a mean tumor size of 27.2 mm were enrolled in the study, and these patients were assigned to undergo colorectal ESD with or without a retroflexed view. RESULTS: The use of retroflexion was successful in 84.2% of patients. There were no perforations in the study and no complications related to the use of retroflexed views. The mean procedure time was 103.6 ± 55.8 min in the retroflexed group, as compared with 108.0 ± 66.5 min in the forward view group. The mean procedure time for resecting tumors >40 mm was significantly shorter in the retroflexed group relative to the forward group. Additionally, the mean dissection speed per unit area was significantly faster in the retroflexed group, as compared with the forward group. CONCLUSIONS: Retroflexed views can be used to remove lesions >40 mm and shorten procedure times. Retroflexion may also contribute to an improved en bloc resection rate.

Suitable closure for post-duodenal endoscopic resection taking medical costs into consideration.

AIM: To compare closure methods, closure times and medical costs between two groups of patients who had post-endoscopic resection (ER) artificial ulcer floor closures. METHODS: Nineteen patients with duodenal adenoma, early duodenal cancer, and subepithelial tumors that received ER between September 2009 and September 2014 at Kagawa University Hospital and Ehime Rosai Hospital, an affiliated hospital of Kagawa University, were included in the study. We retrospectively compared two groups of patients who received post-ER artificial ulcer floor closure: the conventional clip group vs the over-the-scope clip (OTSC) group. Delayed bleeding, procedure time of closure, delayed perforation, total number of conventional clips and OTSCs and medical costs were analyzed. RESULTS: Although we observed delayed bleeding in three patients in the conventional clip group, we observed no delayed bleeding in the OTSC group (P = 0.049). We did not observe perforation in either group. The mean procedure times for ulcer closure were 33.26 ± 12.57 min and 9.71 ± 2.92 min, respectively (P = 0.0001). The resection diameters were 18.8 ± 1.30 mm and 22.9 ± 1.21 mm for the conventional clip group and the OTSC group, respectively, with significant difference (P = 0.039). As for medical costs, the costs of all conventional clips were USD $1257 and the costs of OTSCs were $7850 (P = 0.005). If the post-ER ulcer is under 20 mm in diameter, a conventional clip closure may be more suitable with regard to the prevention of delayed perforation and to medical costs. CONCLUSION: If the post-ER ulcer is over 20 mm, the OTSC closure should be selected with regard to safety and reliable closure even if there are high medical costs.

Establishment of the hybrid endoscopic full-thickness resection of gastric gastrointestinal stromal tumors.

A prospective observational study was conducted to establish the procedure of hybrid endoscopic full-thickness resection (EFTR) using an existing flexible endoscope. The present study included 16 patients who underwent hybrid EFTR between September 2009 and February 2013 for gastric gastrointestinal stromal tumor (GIST). The patients were selected using the following inclusion criteria for histological findings: Mitotic counts <5/high-power field and immunohistochemical stains positive for KIT or cluster of differentiation 34 (CD34). The mean patient age was 68.2 years (range, 44-81 years); the male-to-female ratio was 6:10; lesion sites at upper (U), middle (M) and lower regions (L) of the stomach were 9/6/1; and the average tumor diameter was 28.3 mm. The mean surgical time was 271 min and the surgical time became progressively faster with each successive surgery. There were 12 and four patients with mitotic counts of <5 and 5-10, respectively, which was significantly different (P=0.01). Immunohistochemical stains showed that tumors from 13 and 10 patients (81.2 and 62.5%, respectively) were positive for KIT and CD34, respectively (P=0.328). All resected surgical margins were negative. According to Fletcher's risk classification, there were five, eight and three patients at an 'extremely low', 'low', and 'intermediate' risk (31.2, 50 and 18.8%, respectively) (P=0.003). The mean postoperative hospital duration was 12.3 days (range, 10-15 days). In conclusion, an ultra-minimally invasive surgery-hybrid EFTR is a safe and established surgical endoscopy procedure.

Novel method for the management of stenosis after gastric endoscopic submucosal dissection: mucosal incision with steroid injection contralateral to the severely contracted scar.

The aim of the present report was to investigate the efficacy of local steroid injection and oral administration contralateral to a severe contracted scar of large endoscopic submucosal dissection (ESD) for gastric cancer. Among 254 cases that underwent gastric ESD, seven patients underwent resection of more than three-quarters of the circumference of the stomach. Two patients were excluded because they did not meet curative resection criteria of Japan Gastroenterological Endoscopy Society. Therefore, in five patients, circumferentiality, symptom appearance period, and weight loss period were examined. Effect of a contralateral normal mucosa incision for releasing the stenosis followed by local injection and oral steroids were also examined. Abdominal bloating, vomiting, and loss of appetite appeared 42 days on average after gastric ESD, whereas weight loss >5 kg was observed an average of 52.6 days after gastric ESD. Average contralateral mucosal incision length was 51 mm, whereas the average mucosal incision width was 31 mm. All patients underwent a mucosal incision and were given a local injection of 100 mg triamcinolone acetonide. Two patients received an additional 20 mg oral steroid. In cases combined with oral steroid, there was no re-stenosis after the mucosal incision, but two to three balloon dilatations were necessary in three cases in which oral steroids were not given. This method is considered useful for stenosis after large ESD for gastric cancer.