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Endoscopic submucosal dissection (ESD) enables en bloc complete resection of superficial gastrointestinal neoplasms regardless of the size and location of the lesions. Although a high level of skill is required, oesophageal and gastric ESD are recognized as established therapeutic procedures in Japan, and colorectal ESD is also becoming popular. With the development of suitable devices for improvement of techniques, ESD should become an established procedure in many other countries as well. More than 10 years have passed since endoscopic submucosal dissection (ESD) was first developed in Japan. ESD enables en bloc complete resection of superficial gastrointestinal neoplasms regardless of the size and location of the lesions. With improvements in techniques and devices, excellent therapeutic results have been achieved despite the inherent technical difficulties of this procedure. ESD aiming for curative treatment can be performed for gastrointestinal neoplasms without risk of lymph node metastasis. Accurate histopathologic examination of the resected specimen is required to determine the risk of lymph node metastasis, for which en bloc resection is beneficial. Owing to the high success rate of en bloc complete resection and accurate histopathologic examination, tumour recurrence rates after ESD are reported to be very low in Japan. Excellent results of ESD in a large number of cases have also been reported from other Asian countries such as South Korea, Taiwan and China. Although scepticism exists among Western clinicians regarding the application of ESD, it is developing slowly and reports indicate promising results in some European countries. With further development of technologies, such as endoscopic robotics, ESD could become the worldwide treatment of choice for early gastrointestinal neoplasms. Key Points Endoscopic submucosal dissection (ESD) was developed in Japan to enable en bloc complete resection of superficial gastrointestinal neoplasms regardless of the size and location of the lesions High levels of endoscopic and histopathologic diagnosis are required to determine the indication and curativeness of ESD Oesophageal and gastric ESD are recognized as established therapeutic procedures in Japan Colorectal ESD (which is technically more difficult than oesophageal and gastric ESD) is also becoming popular in Japan, with satisfactory therapeutic results ESD is developing slowly in European countries, which suggests that ESD is a promising method for treating large superficial gastrointestinal tumours in worldwide settings

The purpose of this review was to examine a remarkable technical advance regarding the indications for and the technique of endoscopic resection of early gastric cancer. Endoscopic mucosal resection (EMR) of early gastric cancer with no risk of lymph node metastasis has been a standard technique in Japan, probably owing to the high incidence of gastric cancer in Japan and the fact that more than half of Japanese gastric cancer cases are diagnosed at an early stage. Very recently, several EMR techniques have become increasingly accepted and regularly used in Western countries. Although these minimally invasive techniques are safe, convenient, and efficacious, they are unsuitable for large lesions in particular. Difficulty in correctly assessing the depth of tumor invasion and an increase in local recurrence when standard EMR procedures are used have been reported in cases of large lesions, because such lesions are often resected piecemeal owing to the technical limitations of standard EMR. A new development in therapeutic endoscopy, called endoscopic submucosal dissection (ESD), allows the direct dissection of the submucosa, and large lesions can be resected en bloc. ESD is not limited by resection size and is expected to replace surgical resection. However, it is still associated with a higher incidence of complications than standard EMR procedures and requires a high level of endoscopic skill. The endoscopic indications, techniques, and management of complications of ESD for early gastric cancer for properly carrying out established therapeutic endoscopy are described.

BackgroundLinked color imaging (LCI) increases the visibility of early gastric cancers, which may be associated with characteristic findings including background purple mucosae. These lesions are found in areas of chronic gastritis and surrounding mucosa. The aim of this study is to objectively characterize these lesions by color differences and color component values using LCI.MethodsFifty-two patients with early gastric cancer were enrolled. Color differences were calculated prospectively in malignant lesions and adjacent mucosa and compared with histological findings in resected specimens. Color component values of L*, a*, and b* were compared between purple and non-purple mucosae in areas of chronic gastritis. Based on histological findings, the accuracy of identifying gastric intestinal metaplasia was calculated.ResultsCancers and surrounding mucosa in 74% of lesions had similar colors using white light imaging (WLI), whereas purple mucosa surrounded part or all of cancers appearing orange–red, orange or orange–white using LCI. Greater color differences were seen using LCI compared to WLI, including flat-type cancers, leading to higher contrast. The surrounding purple mucosa corresponded histologically to intestinal metaplasia, facilitating the identification of malignant lesions. Forty lesions (83%) with purple mucosa and eight lesions (17%) with non-purple mucosa in areas of chronic gastritis were diagnosed as intestinal metaplasia by biopsy (83% accuracy). Color component values of purple mucosa differ significantly from those of non-purple mucosae.ConclusionsLCI images have higher color contrast between early gastric cancers and surrounding mucosa compared to WLI. A characteristic purple color around gastric cancers using LCI represents intestinal metaplasia.

Nonalcoholic steatohepatitis (NASH) is a common cause of liver cirrhosis and hepatocellular carcinoma (HCC). However, effective therapeutic strategies for preventing and treating NASH‐mediated liver cirrhosis and HCC are lacking. Cholesterol is closely associated with vascular endothelial growth factor (VEGF), a key factor that promotes HCC. Recent reports have demonstrated that statins could prevent HCC development. In contrast, we have little information on ezetimibe, an inhibitor of cholesterol absorption, in regards to the prevention of NASH‐related liver cirrhosis and HCC. In the present study, a steatohepatitis‐related HCC model, hepatocyte‐specific phosphatase and tensin homolog (Pten)‐deficient (PtenΔhep) mice were fed a high‐fat (HF) diet with/without ezetimibe. In the standard‐diet group, ezetimibe did not reduce the development of liver tumors in PtenΔhep mice, in which the increase of serum cholesterol levels was mild. Feeding of a HF diet increased serum cholesterol levels markedly and subsequently increased serum levels of VEGF, a crucial component of angiogenesis. The HF diet increased the number of VEGF‐positive cells and vascular endothelial cells in the tumors of PtenΔhep mice. Kupffer cells, macrophages in the liver, increased VEGF expression in response to fat overload. Ezetimibe treatment lowered cholesterol levels and these angiogenetic processes. As a result, ezetimibe also suppressed inflammation, liver fibrosis and tumor growth in PtenΔhep mice on the HF diet. Tumor cells were highly proliferative with HF‐diet feeding, which was inhibited by ezetimibe. In conclusion, ezetimibe suppressed development of liver tumors by inhibiting angiogenesis in PtenΔhep mice with hypercholesterolemia. Ezetimibe, an inhibitor of cholesterol absorption, suppressed hepatocellular carcinoma by inhibiting angiogenesis in mice.

Before the development of double-balloon enteroscopy (DBE), the standard management of small-bowel polyposis was surgical resection. This is an invasive procedure that could lead to short bowel syndrome. In the 21st century, several new enteroscopy techniques were distributed worldwide, including DBE, single-balloon enteroscopy, spiral enteroscopy, and motorized spiral enteroscopy. These devices enable the diagnoses and endoscopic interventions in the entire small bowel, even in patients with a history of laparotomy. In patients with Peutz–Jeghers syndrome (PJS), endoscopic ischemic polypectomy with clips or a detachable snare is the preferred method for managing pedunculated polyps because it is less likely to cause adverse events than conventional polypectomy. Although polyps in patients with PJS always recur, repeat endoscopic resection can reduce the total number and mean size of polyps in the long-term clinical course. Endoscopic reduction of small-bowel intussusception caused by PJS polyps can be successfully performed using DBE without surgery. A transparent hood is useful for securing a visual field during the treatment of small-bowel polyps, and minimal water exchange method is recommended to facilitate deep insertion. Familial adenomatous polyposis (FAP) is a genetic disorder that increases the risk of developing colorectal cancer. Because jejunal and ileal polyps in patients with FAP have the potential to develop into cancer via the adenoma–carcinoma sequence, periodical surveillance, and endoscopic resection are needed for them, not only polyps in the duodenum. In cases of multiple small-bowel polyps in patients with FAP, cold snare polypectomy without retrieval is an acceptable treatment option for polyps that are 10 mm or smaller in size. Additional good pieces of evidence are necessary to confirm these findings because this narrative review mostly includes retrospective observational studies from single center, case reports, and expert reviews.

Background: A novel potassium-competitive acid blocker, vonoprazan (VPZ), improves first-line Helicobacter pylori eradication success. The aim of this systematic review is to clarify the effectiveness and safety of second-line H. pylori eradication therapy comparing VPZ and proton pump inhibitor (PPI)-based regimens. Methods: Medline (PubMed), EMBASE, Web of Science, Cochrane Library, and the Japan Medical Abstract Society Database were searched. Results: We selected 16 studies for quantitative review. Forest plot analysis showed significant superiority of VPZ over PPI-based regimens in overall second-line H. pylori eradication success (OR 1.51, 95% CI 1.27–1.81, p < 0.001). Forest plots from 2 studies with propensity score matched analysis showed significant superiority of VPZ over PPI-based regimens (OR 3.09, 95% CI 1.71–5.58, p < 0.001). The remaining 14 studies with per-protocol analysis and the full analysis set also showed significant superiority (OR 1.40, 95% CI 1.16–1.69, p < 0.001). Regarding adverse events, Forest plot analysis did not show a significant difference between the 2 regimens (OR 0.88, 95% CI 0.58–1.32, p = 0.53). Conclusions: A VPZ-based regimen has significant superiority over a PPI-based regimen for second-line H. pylori eradication therapy. A VPZ-based second-line H. pylori eradication regimen can be the first choice.

In routine upper and lower gastrointestinal endoscopy, overlooking neoplastic lesions is inevitable even for well-trained endoscopists. Various methods have been reported to improve the detection of gastrointestinal neoplasms including chromoendoscopy, special endoscopes, and processor and image enhanced technologies. Equipment-based image enhanced endoscopy (e-IEE) using narrow band imaging (NBI) and blue laser imaging (BLI) is useful to characterize known lesions with magnification at a close-up view. However, they are not useful for the early detection of superficial, pale neoplasms, or both because of the weak image at a distant view in a wide lumen such as the stomach or colon. Linked color imaging (LCI) is a novel pre- and post-processing technology developed by Fujifilm Corporation that has sufficient brightness to illuminate a wide lumen. LCI delineates early gastric cancers as orange–red and intestinal metaplasia as purple. LCI improves the adenoma detection rate in the colon and decreases the polyp miss rate. LCI contributes to the detection of superficial lesions throughout the gastrointestinal tract by enhancing the color contrast between the neoplasm and the surrounding mucosa. LCI can distinguish them by their specific color allocation based mainly on the distribution of capillaries. The authors believe that moving forward, LCI should be used in routine upper and lower gastrointestinal endoscopy.

Nonalcoholic fatty liver disease (NAFLD), a hepatic characteristic of metabolic syndrome, received significant attention in clinical settings. The multiple-hit theory is one of the proposed mechanisms of NAFLD, and gut dysbiosis is considered a hit. Thus, controlling gut microbiota is a potential target in the management of NAFLD, and probiotics can be used as a treatment agent for NAFLD. The current study aimed to investigate the efficacy of probiotics against nonalcoholic steatohepatitis in a hepatocyte-specific PTEN knockout mouse model that mimics the characteristics of human NAFLD. Probiotics were administered to male knockout mice for 8 or 40 weeks. Next, we assessed hepatic inflammation, fibrosis, carcinogenesis, and oxidative stress. Probiotics were found to reduce serum transaminase levels, NAFLD activity score, and the gene expression of pro-inflammatory cytokines. In addition, they decreased liver fibrosis grade, which was examined via Sirius red staining, gene expression of fibrotic markers, and hydroxyproline. Furthermore, probiotics suppressed the number of liver tumors, particular in HCC. Probiotics reduced oxidative stresses, including glutathione levels, and anti-oxidative stress marker, which may be an underlying mechanism for their beneficial effects. In conclusion, probiotics treatment had beneficial effects against NAFLD and carcinogenesis in hepatocyte-specific PTEN knockout mice.

BackgroundSerrated polyposis syndrome (SPS), a type of colorectal polyposis characterized by multiple serrated polyps, is associated with a high risk of colorectal carcinoma (CRC). This study aimed to clarify the clinicopathological characteristics of SPS in Japan.MethodsWe investigated the clinicopathological characteristics of patients with SPS from the “Multicenter Study on Clinicopathological Characteristics of SPS (UMIN 000032138)” by the Colorectal Serrated Polyposis Syndrome (SPS) Study Group. In this study, patients were diagnosed with SPS based on the 2019 World Health Organization (WHO) SPS diagnostic criteria.ResultsNinety-four patients were diagnosed with SPS in 10 institutions between January 2001 and December 2017. The mean number (± standard deviation [SD]) of resected lesions per patient was 11.3 ± 13.8. The mean age at diagnosis of SPS was 63.3 ± 11.6 years, and 58 patients (61.7%) were male. Eighty-seven (92.6%) and 16 (17.0%) patients satisfied WHO diagnostic criteria I and II, respectively. Nine patients (9.6%) satisfied both criteria I and II. Carcinoma (T1–T4) were observed in 21 patients (22.3%) and 24 lesions. Of the 21 patients with CRC, 19 (90.4%) satisfied diagnostic criterion I, 1 (4.8%) satisfied diagnostic criterion II, and 1 (4.8%) satisfied diagnostic criteria I and II. There was no notable difference in the prevalence of CRC among patients who met diagnostic criterion I, II, and both I and II.ConclusionsPatients with SPS have a high risk of CRC and should undergo regular surveillance colonoscopy. Raising awareness of this syndrome is crucial.

Double-balloon endoscopy (DBE) was developed as a new technique for visualization of and intervention in the entire small intestine. In DBE, the intestinal walls are held apart by a balloon attached to the distal end of a soft overtube. DBE has been reported worldwide to be very useful for not only diagnosis but also endoscopic therapy. Biopsy samples of small intestinal tumors can be obtained using DBE, and the appropriate treatment can be selected before a surgical procedure. For inflammatory diseases, DBE can reveal the localization of ulcers in the lumen (on the mesenteric or antimesenteric side), which is important for differential diagnosis. Some endoscopic therapies such as hemostatic procedures, polypectomy, and dilation therapy for benign strictures can be performed in the same manner as in the large intestine. DBE may also be suitable for colonoscopy for difficult insertion cases and therapeutic procedures such as endoscopic submucosal dissection. Furthermore, a double-balloon endoscope can be selectively inserted into the afferent loop to perform endoscopic retrograde cholangiopancreatography in patients with Roux-en-Y anastomosis, allowing various kinds of endoscopic treatments for biliary diseases to be successfully performed. Endoscopic therapy in the small intestine, whose wall is very thin, should be performed with special care to avoid complications such as bleeding and perforation. In the future, improvement is expected in terms of maneuverability, therapeutic capability, and imaging technology such as the addition of a magnifying function and flexible spectral imaging color enhancement. We anticipate that DBE will contribute to the establishment of medical science of the small intestine and to research elucidating the mechanisms of small intestinal diseases.