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Abstract The use of left ventricular assist device (LVAD) implantation has increased in recent years. Here, we report the first case of gastric endoscopic submucosal dissection (ESD) following LVAD implantation. A 69‐year‐old man who previously underwent LVAD implantation for severe heart failure underwent esophagogastroduodenoscopy, which revealed a 15‐mm flat‐elevated cancerous lesion at the greater curvature of the gastric angle. Before ESD, antithrombotic drugs were discontinued and replaced with 10,000 units of heparin. However, on the second day, the patient experienced dysarthria and right upper‐extremity movement disorder despite a prothrombin time/international normalized ratio (PT‐INR) of 2.01. On the fifth day, computed tomography revealed a low‐density area extending from the left corona radiata to the basal ganglia, leading to a diagnosis of acute cerebral infarction. Aspirin and warfarin were immediately restarted, while the heparin infusion was discontinued after confirming recovery of PT activity. Thereafter, the neurological abnormalities did not aggravate and a trend toward symptomatic improvement was observed. Two months later, ESD was performed under continuous warfarin administration (PT‐INR, 2.62) without heparin replacement, and the lesion was curatively resected without complications. The patient was discharged without adverse events. This case report provides useful information on the feasibility and perioperative management of ESD in patients with LVAD.

Abstract Background Autophagy plays an important role in carcinogenesis and tumor progression in many cancers, including gastric cancer. Cytotoxin-associated gene A (CagA) is a well-known virulent factor in Helicobacter pylori (H. pylori) infection that plays a critical role in gastric inflammation and gastric cancer development. However, its role in autophagy during these processes remains unclear. Therefore, we aimed to clarify the role of CagA in autophagy in CagA-related inflammation. Methods We evaluated the autophagic index of AGS cells infected with wild-type cagA-positive H. pylori (Hp-WT) and cagA-knockout H. pylori (Hp-ΔcagA) and rat gastric mucosal (RGM1) cells transfected with CagA genes. To identify the mechanisms underlying the down regulation of autophagy in AGS cells infected with H. pylori, we evaluated protein and mRNA expression levels of autophagy core proteins using western blotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR). To determine whether autophagy induced the expression of the pro-inflammatory mediator, cyclooxygenase-2 (COX-2), we evaluated COX-2 expression in AGS cells treated with an autophagy inducer and inhibitor and infected with H. pylori. In addition, we evaluated whether COX-2 protein expression in AGS cells influenced beclin-1 (BECN1) expression with si-RNA transfection when infected with H. pylori. Results Autophagic flux assay using chloroquine showed that autophagy in AGS cells was significantly suppressed after H. pylori infection. The autophagic index of AGS cells infected with Hp-WT was decreased significantly when compared with that in AGS cells infected with Hp-ΔcagA. The autophagic index of RGM1 cells transfected with CagA was lower, suggesting that CagA inhibits autophagy. In addition, BECN1 expression levels in AGS cells infected with Hp-WT were reduced compared to those in AGS cells infected with Hp-ΔcagA. Furthermore, COX-2 expression in AGS cells infected with H. pylori was controlled in an autophagy-dependent manner. When AGS cells were transfected with small interfering RNA specific for BECN1 and infected with Hp-WT and Hp-ΔcagA, COX-2 was upregulated significantly in cells infected with Hp-ΔcagA. Conclusions In conclusion, the H. pylori CagA protein negatively regulated autophagy by downregulating BECN1. CagA-induced autophagy inhibition may be a causative factor in promoting pro-inflammatory mediator production in human gastric epithelial cells.

Abstract Deficiency of p53 in cancer cells activates the transformation of normal tissue fibroblasts into carcinoma-associated fibroblasts; this promotes tumor progression through a variety of mechanisms in the tumor microenvironment. The role of autophagy in carcinoma-associated fibroblasts in tumor progression has not been elucidated. We aimed to clarify the significance of autophagy in fibroblasts, focusing on the TP53 status in co-cultured human colorectal cancer cell lines (TP53-wild-type colon cancer, HCT116; TP53-mutant colon cancer, HT29; fibroblast, CCD-18Co) in vitro. Autophagy in fibroblasts was significantly suppressed in association with ACTA2, CXCL12, TGFβ1, VEGFA, FGF2, and PDGFRA mRNA levels, when co-cultured with p53-deficient HCT116 sh p53 cells. Exosomes isolated from the culture media of HCT116 sh p53 cells significantly suppressed autophagy in fibroblasts via inhibition of ATG2B. Exosomes derived from TP53-mutant HT29 cells also suppressed autophagy in fibroblasts. miR-4534, extracted from the exosomes of HCT116 sh p53 cells, suppressed ATG2B in fibroblasts. In conclusion, a loss of p53 function in colon cancer cells promotes the activation of surrounding fibroblasts through the suppression of autophagy. Exosomal miRNAs derived from cancer cells may play a pivotal role in the suppression of autophagy.

Background and study aims Patients with esophageal squamous cell carcinoma (SCC) are at high risk of developing second primary SCCs in the hypopharynx. However, such second primary tumors are difficult to observe because of lumen closure. The Valsalva maneuver using a dedicated mouthpiece is a promising technique to visualize the hypopharynx during transoral endoscopy. In the current study, we investigated the utility of this method. Patients and methods The current study was a randomized, controlled, crossover trial. Patients with esophageal SCC were randomly assigned first to undergo pharyngeal observation using the dedicated mouthpiece followed by observation using a conventional mouthpiece, or vice versa. The primary endpoint was complete visualization of the hypopharynx, which was assessed blindly by three external evaluators. Results A total of 68 pharyngeal examinations were analyzed – 34 with the dedicated mouthpiece and 34 with a conventional mouthpiece. Complete visualization was achieved in 68 % of the examinations (23/34) using the dedicated mouthpiece, whereas none of the examinations using the conventional mouthpiece achieved complete visualization of the hypopharynx. Observation scores of the oropharynx were not significantly different between both types of examination (P = 0.50). No serious adverse events (AEs) occurred. Conclusions Endoscopic view of the hypopharynx was markedly improved by the Valsalva maneuver using the dedicated mouthpiece, with no serious AEs. This procedure should be included in the endoscopic examinations for the patients with esophageal SCCs.

Background and study aims: Sessile serrated adenoma/polyps (SSA/Ps) have a different potential than traditional adenomatous polyps for developing into malignant colorectal cancer. However, little is known about the coexistent cancer rate. Here, we evaluate the frequency of carcinoma in serrated polyps removed by endoscopic resection (ER). Patients and methods: This was a retrospective single-center cohort study of consecutive patients with colorectal polyps who underwent ER from March 2003 to October 2014. We determined the frequency of serrated polyps among all resected colorectal polyps and analyzed the clinicopathological findings as well as the frequency and characteristics of coexistent carcinoma in the serrated polyps resected by ER based on pathology reports. Results: A total of 21,048 polyps from 15,326 patients were identified, including 15,984 traditional adenomatous polyps (75.9 %), 621 SSA/Ps (3.0 %), 136 traditional serrated adenomas (TSAs) (0.6 %), 1,121 hyperplastic polyps (5.3 %), and 3,186 polyps of other types (15.1 %). The clinical and endoscopic findings of SSA/Ps revealed a male predominance (68.6 %), with 61.7 % of the polyps located in the proximal colon. Males accounted for 77.2 % of all patients with TSAs, and 77.2 % of these polyps were located in the distal colon. The mean sizes of the SSA/Ps and TSAs were 8.8 and 10.7 mm, respectively. Among the SSA/Ps, 8 (1.3 %) cases had coexistent carcinoma, and 1 (0.7 %) patient with TSA showed coexistent carcinoma. In the patients with SSA/Ps, female sex and a tumor size ≥ 10 mm were predictive factors for coexistent carcinoma. Conclusions: The frequency of SSA/Ps with carcinoma was lower than that for traditional adenoma. Female sex and tumor size ≥ 10 mm were significant predictive factors for coexistent carcinoma.

An 80-year-old man underwent colonoscopy for proctorrhagia. Conventional white-light imaging showed a superficially flat and elevated lesion that appeared to be a submucosal tumor of the sigmoid colon. Chromoendoscopy with Indigo Carmine showed that the margin of the tumor was covered with normal epithelium but that there was a slight depression on its surface. Magnification endoscopy with Crystal Violet staining revealed the amorphous surface structure of the depressed lesion, but the surrounding mucosa showed a normal pit pattern. Endoscopic ultrasonography demonstrated that a hypoechoic mass was located in the submucosal layer, and a biopsy specimen obtained from the surface of the lesion showed evidence of adenocarcinoma. We then performed sigmoidectomy on the patient. Immunohistochemically, the tumor cells were positive for two mismatch repair proteins (MLH1 and MSH2), but in situ hybridization revealed that the specimen was negative for the Epstein – Barr virus. We finally diagnosed the lesion as adenocarcinoma with a dome-like phenotype of the sigmoid colon.

Background and study aims: Endoscopic submucosal dissection (ESD) is technically difficult because of poor visualization and instability in the cutting area. Although mucosal flap formation improves visualization of the cutting area, it is difficult to achieve, especially in colorectal ESD. To facilitate mucosal flap formation, we developed the "clip-flap method" by substituting an endoclip for the mucosal flap until it is formed. Patients and methods: The clip-flap method was applied to 114 of 119 large superficial colorectal tumors being treated by ESD. Therapeutic efficacy and safety were assessed. Results: Mean tumor diameter, resected specimen diameter, and procedure time were 32.5 mm, 38.9 mm, and 82.0 minutes, respectively. The en bloc resection rate was 97.5 %. Intraoperative perforation occurred in one patient who was treated conservatively. A single endoclip was used for 92 lesions and improved visualization of the cutting area. A cross pattern of endoclips was used for 22 lesions and further stabilized the visual field, especially near the lateral side. Conclusions: The clip-flap method is a simple, safe, and effective option for ESD of large superficial colorectal tumors. [ABSTRACT FROM AUTHOR]