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Background: The management of delayed bleeding after gastric endoscopic submucosal dissection (ESD) is currently an important issue because of recent increases in the number of patients on antithrombotic therapy. Artificial ulcer closure has been shown to prevent delayed complications in the duodenum and colon. However, its effectiveness in cases involving the stomach remains unclear. In this study, we aimed to determine whether endoscopic closure reduces post-ESD bleeding in patients undergoing antithrombotic therapy., Methods: We retrospectively analyzed 114 patients who had undergone gastric ESD while on antithrombotic therapy. The patients were allocated to one of 2 groups: a closure group (n=44) and a non-closure group (n=70). Endoscopic closure had been performed using multiple hemoclips or using the endoscopic ligation with O-ring closure method after coagulation of exposed vessels on the artificial floor. Propensity score matching resulted in 32 pairs of patients (closure vs. non-closure 32:32). The primary outcome was post-ESD bleeding., Results: The post-ESD bleeding rate was significantly lower in the closure group (0%) than in the non-closure group (15.6%) (P=0.0264). There were no significant differences between the 2 groups regarding white blood cell count, C-reactive protein, maximum body temperature, or scores on a verbal rating scale that assesses the degree of abdominal pain., Conclusion: Endoscopic closure may contribute to decreasing the incidence of post-ESD gastric bleeding in patients undergoing antithrombotic therapy., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Competing Interests: Conflict of Interest: None

Competing Interests: Conflict of Interest: None

Aim: To demonstrate the clinical outcomes of a multicenter experience and to suggest guidelines for choosing a suction method., Methods: This retrospective study at 5 medical centers involved 58 consecutive patients undergoing over-the-scope clips (OTSCs) placement. The overall rates of technical success (TSR), clinical success (CSR), complications, and procedure time were analyzed as major outcomes. Subsequently, 56 patients, excluding two cases that used the Anchor device, were divided into two groups: 14 cases of simple suction (SS-group) and 42 cases using the Twin Grasper (TG-group). Secondary evaluation was performed to clarify the predictors of OTSC success., Results: The TSR, CSR, complication rate, and median procedure time were 89.7%, 84.5%, 1.8%, and 8 (range 1-36) min, respectively, demonstrating good outcomes. However, significant differences were observed between the two groups in terms of the mean procedure time (5.9 min vs 14.1 min). The CSR of the SS- and TG-groups among cases with a maximum defect size ≤ 10 mm and immediate or acute refractory bleeding was 100%, which suggests that SS is a better method than TG in terms of time efficacy. The CSR in the SS-group (78.6%), despite the technical success of the SS method (TSR, 100%), tended to decrease due to delayed leakage compared to that in the TG-group (TSR, CSR; 88.1%), indicating that TG may be desirable for leaks and fistulae with defects of the entire layer., Conclusion: OTSC system is a safe and effective therapeutic option for gastrointestinal defects. Individualized selection of the suction method based on particular clinical conditions may contribute to the improvement of OTSC success., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to report.

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.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. Diabetes mellitus, a risk factor for cancer, is also globally endemic. The clinical link between these two diseases has been the subject of investigation for a century, and diabetes mellitus has been established as a risk factor for HCC. Accordingly, metformin, a first-line oral anti-diabetic, was first proposed as a candidate anti-cancer agent in 2005 in a cohort study in Scotland. Several subsequent large cohort studies and randomized controlled trials have not demonstrated significant efficacy for metformin in suppressing HCC incidence and mortality in diabetic patients; however, two recent randomized controlled trials have reported positive data for the tumor-preventive potential of metformin in non-diabetic subjects. The search for biological links between cancer and diabetes has revealed intracellular pathways that are shared by cancer and diabetes. The signal transduction mechanisms by which metformin suppresses carcinogenesis in cell lines or xenograft tissues and improves chemoresistance in cancer stem cells have also been elucidated. This review addresses the clinical and biological links between HCC and diabetes mellitus and the anti-cancer activity of metformin in clinical studies and basic experiments.

Aim: To apply the laparoscopic and endoscopic cooperative surgery concept, we investigated whether endoscopic cholecystectomy could be performed more safely and rapidly via only 1 port or not., Methods: Two dogs (11 and 13-mo-old female Beagle) were used in this study. Only 1 blunt port was created, and a flexible endoscope with a tip attachment was inserted between the fundus of gallbladder and liver. After local injection of saline to the gallbladder bed, resection of the gallbladder bed from the liver was performed. After complete resection of the gallbladder bed, the gallbladder was pulled up to resect its neck using the Ring-shaped thread technique. The neck of the gallbladder was cut using scissor forceps. Resected gallbladder was retrieved using endoscopic net forceps via a port., Results: The operation times from general anesthetizing with sevoflurane to finishing the closure of the blunt port site were about 50 min and 60 min respectively. The resection times of gallbladder bed were about 15 min and 13 min respectively without liver injury and bleeding at all. Feed were given just after next day of operation, and they had a good appetite. Two dogs are in good health now and no complications for 1 mo after endoscopic cholecystectomy using only a flexible endoscope via one port., Conclusion: We are sure of great feasibility of endoscopic cholecystectomy via single port for human.

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.

Aim: To investigate the effects of gastric lavage with 2000 mL of saline in laparoscopic and endoscopic cooperative surgery., Methods: Twenty two patients who were diagnosed with a gastric gastrointestinal stromal tumor were enrolled. In former term, irrigations of the stomach were conducted whenever it was necessary, not systematically (Non systemic lavage group). In latter term, the stomach was thoroughly cleaned with 2000 mL of saline using an endoscope with a water jet, and Duodenal balloon occlusion was conducted to prevent refluxed bile and pancreatic juice (Systemic lavage+balloon occlusion group). The gastric wall was sprayed with 20 mL of distilled water, and 20 mL of gastric juice was collected in a sterile tube and submitted for culture. 20 mL of ascites was also collected from the laparoscopic ports and submitted for culture. We compared WBC, CRP, BT between two groups, and verify the reduction effect of bacterial counts in Systemic lavage+balloon occlusion group., Results: WBC count before, 1 d after, and 3 d after laparoscopic and endoscopic cooperative surgery (LECS) were 5060 (95%CI: 4250-9640), 12140 (6050-14110), and 6910 (5320-12520) in Non systemic lavage group, 4400 (3660-7620), 8910 (6480-10980), and 5950 (4840-7860) in Systemic lavage+balloon occlusion group. Significant differences between two groups at the day after LECS (P = 0.029) and the 3 d after LECS (P = 0.042). CRP levels in Non systemic lavage group and in Systemic lavage+balloon occlusion group were significantly different at the day after LECS (P = 0.005) and the 3 d after LECS (P = 0.028). BTs (°C) in Non systemic lavage group and in Systemic lavage+balloon occlusion group were also significantly different at the day after LECS (P = 0.004) and the 3 d after LECS (P = 0.006). In a logarithmic comparison, bacterial load before gastric lavage, after lavage, and ascites culture were 6.08 (95%CI: 4.04-6.97), 0.48 (0-0.85), and 0.21 (0-0.56). The bacterial counts before and after gastric lavage were significantly suppressed (P = 0.007), but no significant difference between gastric juice culture after lavage and ascites (P = 0.154)., Conclusion: Pre-LECS lavage with 2000 mL of saline exhibited a bacteria-reducing effect equivalent to disinfectants and obtained favorable results in terms of clinical symptoms and data.

Endoscopic submucosal dissection (ESD) of large gastric lesions often leads to severe gastric strictures, especially in cases of large ESD in the antrum of the stomach. It has recently been reported that balloon dilation, mucosal incision, and local steroid injections can successfully treat gastric strictures. However, there are some complications with existing methods and decreasing the quality of life. We have developed a novel method to prevent severe gastric strictures that does not involve balloon dilation, mucosal incision, or steroid injections after circumferential ESD. Our original method involves the submucosal injection of a mixed solution composed of triamcinolone acetonide and a general solution of glycerol, hyaluronic acid, and a small amount of indigo carmine and epinephrine during the ESD procedure; this mixture is called a mixed solution of triamcinolone (MST). According to standard ESD procedures, several milliliters of MST are injected into the submucosal layer for the purpose of elevating the submucosa during ESD resulting in prevention of severe strictures. Our method using MST take several advantages such as MST method suppress inflammation in ulcer from initial phase, prevention of stricture without obstructive symptoms, and does not require several ballooning. Therefore, MST method is safe and gentle, shorten the hospitalization duration. Here, we described two cases in which we prevented severe strictures of the gastric antrum after completing a circumferential ESD using MST without any complications.

Gastric hamartomatous inverted polyps (GHIP) are difficult to diagnose accurately because of inversion into the submucosal layer. GHIP are diagnosed using the pathological characteristics of the tumor, including the fibroblast cells, smooth muscle, nerve components, glandular hyperplasia, and cystic gland dilatation. Although Peutz-Jeghers syndrome, juvenile polyposis, and Cowden disease are hereditary, it is rare to encounter 2 cases of monostotic and asymptomatic gastric hamartomas. The pathogeneses of hamartomatous inverted polyps and inverted hyperplastic polyps remain controversial because of the paucity of reported cases. There are 3 hypotheses regarding the pathogenesis of complete gastric inverted polyps. Based on our experience with 2 successive, rare GHIP cases, we affirm the hypothesis that after a hamartomatous change occurs in the submucosal layer, some of these components are exposed to the gastric mucosa and, consequently, form a hypertrophic lesion. In Case 1, our hypothesis explains why a tiny hypertrophic change was first detected on the top of the submucosal tumor using a detailed narrow band imaging-magnified endoscopy. There was no confirmation that the milky white mucous and calcification structures were exuding directly from the biopsy site like Case 1, and in Case 2 the presence of this mucous was indirectly confirmed during an endoscopic submucosal dissection (ESD). Regarding the pathogenesis of GHIP, a submucosal hamartomatous change may occur prior to the growth of hypertrophic portions. An en bloc resection using ESD is recommended for treatment.

Molecularly targeted therapeutic agents are constantly being developed and have been shown to be effective in various clinical trials. One group of representative targeted oncogenic kinases, the receptor tyrosine kinases (RTKs), has been associated with gastric cancer development. Trastuzumab, an inhibitor of ERBB2, has been approved for the treatment of gastric cancer, although other receptor tyrosine kinases, such as epidermal growth factor receptor, vascular endothelial growth factor, platelet-derived growth factor receptor, c-Met, IGF-1R and fibroblast growth factor receptor 2, are also activated in gastric cancer. The promising results of the trastuzumab clinical trial for gastric cancer resulted in the approval of trastuzumab-based therapy as a first-line treatment for human epidermal growth factor receptor 2-positive patients. On the other hand, the trial examining bevacizumab in combination with conventional chemotherapy did not meet its primary goal of increasing the overall survival time of gastric cancer patients; however, a significantly higher response rate and a longer progression-free survival were observed in the bevacizumab arm of the trial. Other clinical trials, especially phase III trials that have tested drugs targeting RTKs, such as cetuximab, panitumumab, gefitinib, erlotinib, figitumumab, sorafenib, sunitinib and lapatinib, have shown that these drugs have modest effects against gastric cancer. This review summarizes the recent results from the clinical trials of molecularly targeted drugs and suggests that further improvements in the treatment of advanced gastric cancer can be achieved through the combination of conventional drugs with the new molecularly targeted therapies.

Previously, we reported the efficacy of a newly developed inverted overtube in shortening the hemostatic time and obtaining a clear endoscopic view in emergency endoscopic hemostasis. This device also helped us to perform gastric endoscopic submucosal dissection (ESD) more safely by changing the direction of gravity in the right lateral position. To perform a safe ESD, it is important to make an appropriate angle and distance between the electric knife and the gastric mucosa. In this position, the distance to gastric mucosa is reduced, and the angle of the electric knife changes from vertical to somewhat oblique, facilitating safer cutting.

There are many case reports on colon diverticula that cause irritable bowel syndrome, constipation, bleeding, diverticulitis, stricture due to multiple recurrences of diverticulitis, and perforation. However, few articles have examined neoplasms that arise from a diverticulum, such as adenoma and adenocarcinoma, and there have been no reports of granulation polyps that arise from a colon diverticulum after recurrent diverticulitis. We observed a rare granulation polyp that arose from a diverticulum as a result of repeated episodes of local diverticulitis. Narrow band imaging magnified colonoscopy was very useful to diagnose the polyp as a granulation polyp because of the absence of a pit pattern on the surface of the polyp. We successfully resected the polyp using endoscopic mucosal resection. We inverted the diverticulum, and the resected stalk of the polyp was used to close the diverticulum with an over-the-scope clip. If a granulomatous polyp could arise from a diverticulum, differential diagnosis between a colon neoplasm and a granulomatous polyp would not only be difficult but also necessary for suitable endoscopic treatment.

Plasmablastic lymphoma (PBL) is a very rare B-cell lymphoproliferative disorder was with an aggressive clinical behavior that recently characterized by the World Health Organization. Although PBL is most commonly observed in the oral cavity of human immunodeficiency virus (HIV)-positive patients, it can also be observed at extra-oral sites in HIV-negative patients. Epstein-Barr virus (EBV) may be closely related the pathogenesis of PBL. PBL shows different clinicopathological characteristics between HIV-positive and -negative patients. Here, we report a case of PBL of the liver in a 79-year-old HIV-negative male. The patient died approximately 1.5 mo after examination and autopsy showed that the main lesion was a very large liver mass. Histopathological examination of the excised lesion showed large-cell lymphoma with plasmacytic differentiation diffusely infiltrating the liver and involving the surrounding organs. The neoplastic cells were diffusely positive for CD30, EBV, Bob-1, and CD38. The autopsy findings suggested a diagnosis of PBL. To our knowledge, the present case appears to be the first report of PBL with initial presentation of the liver in a patient without HIV infection.

Castleman disease often develops in the neck, mediastinum and pulmonary hilum. Its onset in the peritoneal cavity is very rare. The patient, a woman in her 70s, was referred to our department for a detailed examination of an abdominal mass. On abdominal ultrasonography, computed tomography scan, magnetic resonance imaging and positron emission tomography, a mass approximately 15 mm in diameter was noted in the hepatic S6. We attempted radical treatment and conducted a laparoscope-assisted right lobectomy. On the basis of histopathological findings, the patient was diagnosed as having hyaline type Castleman disease in the liver, a very rare condition.