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OBJECTIVES: No protocol for esophagogastroduodenoscopic examination of the duodenum has been established. We examined the feasibility and ability to detect neoplasms of a novel duodenal examination protocol. METHODS: This was a two-facility, prospective, observational study. Our protocol, the Seven Pictures Rule (7PR), requires pictures of the following seven locations: anterior and posterior to the bulb, area of and contralateral to the superior duodenal angle, area of and contralateral to the ampulla, and the transverse duodenum. The primary outcome was rate of completion of 7PR. Secondary outcomes were overall rates of detecting neoplasms, rates of detecting neoplasms for each location, examination time, and completion rates for standard or ultrathin endoscopes. RESULTS: There were 1549 participants. The 7PR completion rate was 81.1% and the detection rates of overall neoplasms, adenomas, and carcinomas were 0.84%, 0.71%, and 0.06%, respectively. The area in which most neoplasms was detected was contralateral to the ampulla (69.2%), and the fewest the transverse duodenum (0%). Mean duration of duodenal examination was 53.1 s. Completion rates for standard vs. ultrathin were 84.4% (1077/1276) vs. 65.6% (179/273) (P < 0.01), respectively. CONCLUSIONS: Seven Pictures Rule is acceptable for duodenal examination and a potential quality indicator.

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Background and Aim: Nonalcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome. This study was performed to examine the association between NAFLD and each factor of metabolic syndrome and to identify the factors that are most strongly associated with NAFLD in participants undergoing health checkups. Methods: We studied 6538 participants who underwent a health checkup from 2017 to 2018 in our institution. Participants with alcohol intake exceeding 20 g/day or with other chronic liver diseases were excluded. Fatty liver was detected by ultrasonography. Results: In total, 4310 participants were enrolled, and 28.4% had fatty liver (NAFLD). The prevalence of NAFLD was highest in the diabetes mellitus (DM)-only group than in the dyslipidemia-only or hypertension-only group. The DM-only group was the only group whose prevalence of NAFLD was >50% in the overall study and in males. The prevalence of NAFLD was higher in males than in females in the DM-only, hypertension-only, and dyslipidemia-only groups. The prevalence of NAFLD was >70% in the dyslipidemia and DM combined group. Multivariate analysis showed that gender and HbA1c were the independent factors most strongly associated with NAFLD. The cutoff value for HbA1c by receiver operating characteristic curve analysis was 5.8% (sensitivity, 57.9%; specificity, 72.6%; area under the curve, 0.70). Conclusion: NAFLD was most strongly associated with DM, among the various components of metabolic syndrome. We strongly recommend abdominal ultrasonography to detect NAFLD in patients with an HbA1c of ≥5.8% in general practice and during health checkups.

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We analyzed the clinical features of 157 patients admitted to 11 institutions in the Kagawa Prefecture for volvulus of the sigmoid colon. The following were the background information of the patients:median age, 79.0 years;male-to-female ratio, 102:55;median body mass index, 20.0kg/m2;and the proportion of patients with performance status ≥3, 43.9%. Abdominal bloating and pain were the chief complaints. During hospitalization, endoscopy and endoscopic detorsion were performed 157 and 100 times, respectively. An accidental complication was observed in 3 cases, all of which were intestinal perforations. Surgery, which was indicated for ischemia, was performed in 62 of the 157 cases. Endoscopy is useful in the diagnosis of ischemia, which can be treated following an early diagnosis. Of the 157 patients, 19 died, whereas the rest were discharged. The risk factors for death were age ≥80 years and creatinine kinase level ≥200IU/L.

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We report a case of unresectable advanced esophagogastric junction carcinoma that was treated with nab-paclitaxel and ramucirumab, which resulted in complete response and salvage surgery. A 57-year-old male complained of upper abdominal discomfort. While attending a hospital for diabetes mellitus, upper gastrointestinal endoscopy was performed. A tumor protruding from the gastric cardia to the abdominal esophagus was found, and histological examination revealed well-differentiated adenocarcinoma. Multiple liver metastases and para-aortic lymph node metastases were found on abdominal contrast-enhanced CT. The patient was diagnosed with stage Ⅳ cancer, and chemotherapy was performed as unresectable advanced esophagogastric junction carcinoma. S-1 plus CDDP therapy was started as the first-line treatment. After 2 courses of S-1 plus CDDP therapy, tumor markers were elevated. Further, the cancer was judged to be highly toxic and refractory to treatment; therefore, we started nab-paclitaxel and ramucirumab as the secondary treatment. After 4 courses, normalization of tumor markers, disappearance of liver metastases, and marked reduction of enlarged lymph nodes were observed. However, PET-CT showed increased uptake, consistent with the primary lesion. Residual cancer could not be ruled-out; therefore, total gastrectomy was performed. Histopathological examination of the surgically resected specimen showed no residual tumors.

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Esophageal carcinoma is the eighth most common cancer worldwide and the sixth leading cause of cancer-related deaths, with one of the worst prognoses of any form of cancer. Treatment with the anti-diabetic drug metformin has been associated with reduced cancer incidence in patients with type 2 diabetes. This study therefore evaluated the effects of metformin on the proliferation, in vitro and in vivo, of human esophageal adenocarcinoma cells, as well as the microRNAs associated with the antitumor effects of metformin. Metformin inhibited the proliferation of the esophageal adenocarcinoma cell lines OE19, OE33, SK-GT4 and OACM 5.1C, blocking the G0 to G1 transition in the cell cycle. This was accompanied by strong reductions in G1 cyclins, especially cyclin D1, cyclin-dependent kinase (Cdk)4, and Cdk6, and decreases in retinoblastoma protein phosphorylation. In addition, metformin reduced the phosphorylation of epidermal growth factor receptor and insulin-like growth factor and insulin-like growth factor-1 receptor, as well as angiogenesis-related proteins, such as vascular endothelial growth factor, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2. Metformin also markedly altered microRNA expression. Treatment with metformin of athymic nude mice bearing xenograft tumors reduced tumor proliferation. These findings suggest that metformin may have clinical use in the treatment of esophageal adenocarcinoma.

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We address the pathological complete response and long-term survival of elderly patients after neoadjuvant chemotherapy in locally advanced, unresectable gastric cancer. An 83-year-old man was hospitalized for upper abdominal pain. Gastrointestinal endoscopy showed a large tumor spanning from the gastric angle to the antrum, and extending to the duodenum. Histological analysis of the biopsy specimen revealed a poorly differentiated adenocarcinoma. Computed tomography images showed thickening of the gastric wall and invasion of the body and head of the pancreas, but did not show distant metastases. The patient was diagnosed with unresectable gastric cancer, and was treated with neoadjuvant chemotherapy using S-1 (80 mg/m(2)) and paclitaxel (60 mg/m(2)). After the third course of chemotherapy, gastrointestinal endoscopy and abdominal computed tomography revealed a remarkable reduction in tumor size. This reduction allowed distal gastrectomy to be conducted. Histological examination of the specimen revealed no cancer cells in the primary lesion or lymph nodes. The patient was treated with adjuvant chemotherapy of oral tegafur-uracil (300 mg/day) for one year after surgery. He lived for five years after surgery without recurrence. Neoadjuvant chemotherapy using S-1 and paclitaxel is a potent strategy for improving survival in very elderly patients with unresectable gastric cancer.

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Recent studies suggest that small non­coding microRNAs (miRNAs or miRs) play an important role in the regulation of genes involved in various cellular and developmental processes. However, the expression of miRNAs during the aging process remains largely unknown. The aim of the present study was to analyze miRNA expression profiles in rat livers during the aging process. The livers of male Wistar rats at different stages of development (fetal, aged 3 days, and 1, 2, 4, 8 and 36 weeks of age) were used. Total RNA was extracted from the livers. We analyzed the expression levels of 679 rat miRNA probes. In addition, immunohistochemical staining for proliferating cell nuclear antigen (PCNA) was performed. Several up- and downregulated miRNAs were identified in the rat livers at 7 different fetal developmental stages and at 36 weeks of age. We observed the upregulation of miR­29a, miR­29c, miR­195 and miR­497, whereas miR­301a, miR­148b-3p, miR­7a, miR­93, miR­106b, miR­185, miR­450a, miR­539 and miR­301b were downregulated in the aging rat livers. The number of PCNA-positive hepatocytes was decreased with age. In conclusion, our findings suggest that these up- and downregulated miRNAs play an important role in aging by regulating cell cycles that are involved in liver senescence. Further investigation is required to reveal additional target genes of the miRNAs expressed in the liver and the roles of miRNAs in the developmental process of aging in the liver.

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Metformin is a commonly used oral anti-hyperglycemic agent of the biguanide family. Recent studies suggest that metformin may reduce cancer risk and improve prognosis. However, the antitumor mechanism of metformin in several types of cancers, including hepatocellular carcinoma (HCC), has not been elucidated. The goal of the present study was to evaluate the effects of metformin on HCC cell proliferation in vitro and in vivo, and to study microRNAs (miRNAs) associated with the antitumor effect of metformin in vitro. We used the cell lines Alex, HLE and Huh7, and normal hepatocytes to study the effects of metformin on human HCC cells. In an in vivo study, athymic nude mice bearing xenograft tumors were treated with metformin or left untreated. Tumor growth was recorded after 4 weeks, and the expression of cell cycle-related proteins was determined. Metformin inhibited the proliferation of Alex, HLE and Huh7 cells in vitro and in vivo. Metformin blocked the cell cycle in G0/G1 in vitro and in vivo. This blockade was accompanied by a strong decrease of G1 cyclins, especially cyclin D1, cyclin E and cyclin-dependent kinase 4 (Cdk4). In addition, microRNA (miRNA) expression was markedly altered by the treatment with metformin in vitro and in vivo. In addition, various miRNAs induced by metformin also may contribute to the suppression of tumor growth. Our results demonstrate that metformin inhibits the growth of HCC, possibly by inducing G1 cell cycle arrest through the alteration of microRNAs.

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AIM: To retrospectively review the results of over-the-scope clip (OTSC) use in our hospital and to examine the feasibility of using the OTSC to treat perforations after endoscopic submucosal dissection (ESD). METHODS: We enrolled 23 patients who presented with gastrointestinal (GI) bleeding, fistulae and perforations and were treated with OTSCs (Ovesco Endoscopy GmbH, Tuebingen, Germany) between November 2011 and September 2012. Maximum lesion size was defined as lesion diameter. The number of OTSCs to be used per patient was not decided until the lesion was completely closed. We used a twin grasper (Ovesco Endoscopy GmbH, Tuebingen, Germany) as a grasping device for all the patients. A 9 mm OTSC was chosen for use in the esophagus and colon, and a 10 mm device was used for the stomach, duodenum and rectum. The overall success rate and complications were evaluated, with a particular emphasis on patients who had undergone ESD due to adenocarcinoma. In technical successful cases we included not only complete closing by using OTSCs, but also partial closing where complete closure with OTSCs is almost difficult. In overall clinical successful cases we included only complete closing by using only OTSCs perfectly. All the OTSCs were placed by 2 experienced endoscopists. The sites closed after ESD included not only the perforation site but also all defective ulcers sites. RESULTS: A total of 23 patients [mean age 77 years (range 64-98 years)] underwent OTSC placement during the study period. The indications for OTSC placement were GI bleeding (n = 9), perforation (n = 10), fistula (n = 4) and the prevention of post-ESD duodenal artificial ulcer perforation (n = 1). One patient had a perforation caused by a glycerin enema, after which a fistula formed. Lesion closure using the OTSC alone was successful in 19 out of 23 patients, and overall success rate was 82.6%. A large lesion size (greater than 20 mm) and a delayed diagnosis (more than 1 wk) were the major contributing factors for the overall unsuccessful clinical cases. The location of the unsuccessful lesion was in the stomach. The median operation time in the successful cases was 18 min, and the average observation time was 67 d. During the observation period, none of the patients experienced any complications associated with OTSC placement. In addition, we successfully used the OTSC to close the perforation site after ESD in 6 patients. This was a single-center, retrospective study with a small sample size. CONCLUSION: The OTSC is effective for treating GI bleeding, fistulae as well as perforations, and the OTSC technique proofed effective treatment for perforation after ESD.

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Endoscopic submucosal dissection (ESD) is not a common treatment for colorectal neoplasms because of its technical difficulties and has a higher incidence of complication. In particular, perforation is one of the severe complications and these patients require surgical intervention. However, whether prophylactic closure after colorectal ESD prevents perforation and other complications is not known. In the present study, we assessed the efficacy and safety of prophylactic closure for a large mucosal defect after colorectal ESD using a conventional clip and over-the-scope clip (OTSC) system. From April 2010 to December 2012, 68 patients with colorectal tumors were treated with ESD. The prohylactic closure was indicated for patients with excessive coagulation in the muscularis propria or larger resection size. The closure group reduced the peritoneal inflammatory reaction and abdominal symptoms without increasing complications. The closure group also had a significantly lower WBC count (post operative day 1), CRP (post operative day 4) and abdominal pain after colorectal ESD compared to the non-closure group. Perforation occurred in 1 case, and postoperative bleeding in 2 cases, with only 1 bleeding case needing an emergency endoscopy in the non-closure group. One perforation case needed emergency surgery because the endoscopic treatment was ineffective. Without increasing adverse effects, the prophylactic closure efficiently reduced the inflammatory reaction and abdominal symptoms of colorectal ESD in patients with large superficial colorectal neoplasms.

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In Europe and the United States, the incidence of esophageal adenocarcinoma has increased 6-fold in the last 25 years and currently accounts for more than 50% of all esophageal cancers. Barrett's esophagus is the source of Barrett's adenocarcinoma and is characterized by the replacement of squamous epithelium with columnar epithelium in the lower esophagus due to chronic gastroesophageal reflux disease (GERD). Even though the prevalence of GERD has recently been increasing in Japan as well as in Europe and the United States, the clinical situation of Barrett's esophagus and Barrett's adenocarcinoma differs from that in Western countries. In this paper, we focus on specific differences in the background factors and pathophysiology of these lesions.

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AIM: To investigate the influence of percutaneous local therapy on gastric myoelectrical activity in patients with hepatocellular carcinomas. METHODS: Forty-four patients with hepatocellular carcinoma (HCC) [27 males and 17 females, ranging in age from 49 to 81 years old (69.7 ± 8.01 years)] who were admitted for percutaneous local therapy were enrolled in this study. We examined clinical abdominal symptoms using the Gastrointestinal Symptom Rating Scale (GSRS) before and 3 d after percutaneous local therapy. We also measured cutaneous fasting and postprandial electrogastrography (EGG) recordings before and 3 d after percutaneous local therapy. RESULTS: We found that the percentage of normogastria in the fasting period was lower in the Child B group than in the Child A group (66.8% ± 8.6% vs 84.0% ± 3.8%). After percutaneous local therapy for HCC, the percentages of normogastria in the fasting period were significantly decreased (81.6% ± 3.5% vs 75.2% ± 4.5%). None of the postprandial EGG parameters changed significantly after percutaneous local therapy for HCC. Percutaneous local therapy for HCC reduced the power ratio (PR). In particular, the PR of tachygastria was significantly decreased after therapy (P < 0.01). However, no significant differences were found in the postprandial EGG parameters. Likewise, no significant differences were found in the calculated GSRS scores obtained from the questionnaire before and after therapy. CONCLUSION: Gastric slow-wave dysrhythmias were induced by percutaneous local therapy in HCC patients, even though the GSRS scores obtained from the questionnaire did not change significantly.

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Closure of post-endoscopic submucosal dissection (ESD) duodenal artificial ulcer is not common in the clinical setting. We consider that post-ESD ulcer closure by an over-the-scope-clip (OTSC) method is one of the most effective ways to prevent delayed perforation. We report here two cases of mucosal duodenal cancer in a 65-year-old woman and in a 78-year-old man. Pathological examinations of the resected specimens revealed well-differentiated adenocarcinomas. In these two clinical cases, we successfully carried out complete closures of post-ESD duodenal ulcer using OTSC without any complications.

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A 74-year-old man was transferred to our hospital due to melena and syncope. He had a history of an abdominal aortic aneurysm treated with aortobifemoral grafting 15 years previously. One month before admission, he reported several episodes of melena for which he underwent repeated gastrointestinal endoscopic examinations. None of these examinations revealed the site of gastrointestinal bleeding. Aortoenteric fistulae can therefore be missed if they are not considered in the differential diagnosis of gastrointestinal bleeding due to their rarity. As a result, secondary aortoenteric fistulae should therefore be considered in any patient presenting with gastrointestinal bleeding and a history of aortic surgery.

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Metformin is a commonly used oral anti-hyperglycemic agent of the biguanide family. Recent studies suggest that metformin may reduce cancer risk and improve prognosis. However, the antitumor mechanism of metformin in several types of cancers, including hepatocellular carcinoma (HCC), has not been elucidated. The goal of the present study was to evaluate the effects of metformin on HCC cell proliferation in vitro and in vivo, and to study microRNAs (miRNAs) associated with the antitumor effect of metformin in vitro. We used the cell lines Alex, HLE and Huh7, and normal hepatocytes to study the effects of metformin on human HCC cells. In an in vivo study, athymic nude mice bearing xenograft tumors were treated with metformin or left untreated. Tumor growth was recorded after 4 weeks, and the expression of cell cycle­related proteins was determined. Metformin inhibited the proliferation of Alex, HLE and Huh7 cells in vitro and in vivo. Metformin blocked the cell cycle in G0/G1 in vitro and in vivo. This blockade was accompanied by a strong decrease of G1 cyclins, especially cyclin D1, cyclin E and cyclin-dependent kinase 4 (Cdk4). In addition, microRNA (miRNA) expression was markedly altered by the treatment with metformin in vitro and in vivo. In addition, various miRNAs induced by metformin also may contribute to the suppression of tumor growth. Our results demonstrate that metformin inhibits the growth of HCC, possibly by inducing G1 cell cycle arrest through the alteration of microRNAs.

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Recent studies suggest that metformin, which is a member of the biguanide family and commonly used as an oral anti-hyperglycemic agent, may reduce cancer risk and improve prognosis of numerous types of cancer. However, the mechanisms underlying the antitumor effect of metformin on esophageal cancer remain unknown. The goal of the present study was to evaluate the effects of metformin on the proliferation of human ESCC in vitro, and to study changes in the expression profile of microRNAs (miRNAs), since miRNAs have previously been associated with the antitumor effects of metformin in other human cancers. The human ESCC cell lines T.T, KYSE30 and KYSE70 were used to study the effects of metformin on human ESCC in vitro. In addition, we used miRNA array tips to explore the differences between miRNAs in KYSE30 cells with and without metformin treatment. Metformin inhibited the proliferation of T.T, KYSE30 and KYSE70 cells in vitro. Metformin blocked the cell cycle in G0/G1 in vitro. This blockade was accompanied by a strong decrease of G1 cyclins, especially cyclin D1, as well as decreases in cyclin-dependent kinase (Cdk)4, Cdk6 and phosphorylated retinoblastoma protein (Rb). In addition, the expression of miRNAs was markedly altered with the treatment of metformin in vitro. Metformin inhibited the growth of three ESCC cell lines, and this inhibition may have involved reductions in cyclin D1, Cdk4 and Cdk6.

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INTRODUCTION: Although duodenal diverticula are common, periampullary duodenal diverticula are rare. Periampullary duodenal diverticula are usually asymptomatic and may be difficult to diagnose and treat. However, they may present with massive bleeding, requiring prompt diagnosis. CASE PRESENTATION: We report the case of a 71-year-old Asian woman with bleeding from a periampullary duodenal diverticulum. She presented with severe anemia and tarry stools. Two examinations using a forward-viewing endoscope did not identify the source of the bleeding. However, examination using a side-viewing endoscope found an exposed bleeding vessel overlying the bile duct within a periampullary diverticulum of the descending part of the duodenum. The bleeding was successfully controlled by using hemostatic forceps. CONCLUSIONS: Bleeding periampullary duodenal diverticula are rare, and a bleeding point in the mucosa overlying the bile duct within a large periampullary duodenal diverticulum is very rare. Identification of a bleeding point within a duodenal diverticulum often requires repeated examination and may require the use of a side-viewing endoscope. Use of hemostatic forceps to control bleeding from a periampullary duodenal diverticulum is very rare but, for bleeding lesions overlying the bile duct within a periampullary duodenal diverticulum, is the best way to prevent obstructive jaundice.

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INTRODUCTION: Endoscopic hemostasis for severe upper gastrointestinal bleeding due to tumors, such as gastrointestinal stromal tumors and malignant lymphoma, is temporarily effective. However, permanent hemostasis is difficult in many cases because of diffuse bleeding. CASE PRESENTATION: A 60-year-old Japanese woman was admitted to our hospital with hematemesis. Endoscopy revealed multiple gastric polyps and fresh blood in her stomach. One of the gastric polyps, which was associated with oozing bleeding, was found near the anterior wall of the lower gastric body. We initially applied hemostatic forceps and argon plasma coagulation over the tumor surface, but the bleeding persisted. After endoscopic mucosal resection, exposed vessels were seen at the base of the mucosal resection site with oozing bleeding. Coagulation of the bleeding vessels using hemostatic forceps allowed successful completion of the hemostatic procedure. Our patient also had eight synchronous gastric cancer lesions. Histological examination of the resected specimens showed various types of cancer. CONCLUSION: This is a case report of gastric cancer associated with eight gastric cancer lesions, confirmed by histology, in which hemostasis was achieved through endoscopy.

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Rectal perforations due to glycerin enemas (GE) typically occur when the patient is in a seated or lordotic standing position. Once the perforation occurs and peritonitis results, death is usually inevitable. We describe two cases of rectal perforation and fistula caused by a GE. An 88-year-old woman presented with a large rectal perforation and a fistula just after receiving a GE. Her case was further complicated by an abscess in the right rectal wall. The second patient was a 78-year-old woman who suffered from a rectovesical fistula after a GE. In both cases, we performed direct endoscopic abscess lavage with a saline solution and closed the fistula using an over-the-scope-clip (OTSC) procedure. These procedures resulted in dramatic improvement in both patients. Direct endoscopic lavage and OTSC closure are very useful for pararectal abscess lavage and fistula closure, respectively, in elderly patients who are in poor general condition. Our two cases are the first reports of the successful endoscopic closure of fistulae using double OTSCs after endoscopic lavage of the debris and an abscess of the rectum secondary to a GE.

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