Yasumi Katayama

Helicobacter pylori causes runx3 gene methylation and its loss of expression in gastric epithelial cells, which is mediated by nitric oxide produced by macrophages

Previous reports have indicated that Helicobacter pylori (H. pylori) causes epigenetic changes of certain genes such as cancer suppression genes, which may be associated with carcinogenesis. However, the mechanism by which it causes epigenetic changes in certain genes and not in others is unclear. Presently, we focused on a cancer suppression gene, runx3, and demonstrated the following: (1) H. pylori induces nitric oxide (NO) production in macrophages. (2) NO causes methylation of runx3 in epithelial cells. (3) H. pylori induces the methylation of epithelial cells in the presence of macrophages, which is reversed by an NO-specific inhibitor. These results indicate that H. pylori-induced methylation is mediated by NO, and suggest that NO may be a key to the mechanism of how H. pylori causes epigenetic changes in certain genes. Additionally, we demonstrated that lipopolysaccharide, as well as H. pylori, induces NO-mediated methylation, indicating that other inflammation inducers beside H. pylori might induce aberrant methylation of runx3.

Shear wave elastography in hepatitis C patients before and after antiviral therapy

AIM To investigate shear wave (SW) propagation velocity in patients with untreated hepatitis C and patients with sustained virological response (SVR). METHODS A total of 136 hepatitis C patients [85 patients who had not received antiviral therapy (naïve group) and 51 patients who had received antiviral therapy and subsequently achieved SVR of at least 24 wk (SVR group)] and 58 healthy volunteers and outpatients without liver disease (control group) underwent evaluation of liver stiffness by SW elastography (SWE). Various parameters were evaluated in the chronic hepatitis C patients at the time of SWE. RESULTS SW propagation velocity (Vs) was 1.23 ± 0.14 m/s in the control group, 1.56 ± 0.32 m/s in the SVR group, and 1.69 ± 0.31 m/s in the naïve group. Significant differences were seen between the control group and the SVR group (P = 0.0000) and between the SVR group and the naïve group (P = 0.01417). All four fibrosis markers were higher in the naïve group than in the SVR group. In the naïve group, Vs was positively correlated with alanine aminotransferase (ALT) (r = 0.5372), α feto protein (AFP) (r = 0.4389), type IV collagen (r = 0.5883), procollagen III peptide (P-III-P) (r = 0.4140), hyaluronic acid (r = 0.4551), and Mac-2 binding protein glycosylation isomer (M2BPGi) (r = 0.6092) and negatively correlated with albumin (r = -0.4289), platelets (r = -0.5372), and prothrombin activity (r = -0.5235). On multiple regression analysis, Vs was the most strongly correlated with ALT (standard partial regression std β = 0.4039, P = 0.00000). In the SVR group, Vs was positively correlated with AFP (r = 0.6977), type IV collagen (r = 0.5228), P-III-P (r = 0.5812), hyaluronic acid (r = 0.5189), and M2BPGi (r = 0.6251) and negatively correlated with albumin (r = -0.4283), platelets (r = -0.4842), and prothrombin activity (r = -0.4771). On multiple regression analysis, Vs was strongly correlated with AFP (standard partial regression std β = 0.5953, P = 0.00000) and M2BPGi (standard partial regression std β= 0.2969, P = 0.03363). CONCLUSION In hepatitis C patients, liver stiffness is higher in treatment-naïve patients than in those showing SVR. SWE may be a predictor of hepatocarcinogenesis in SVR patients.

Study of pruritus in chronic hepatitis C patients

AIM To investigate the occurrence and severity of pruritus in chronic hepatitis C patients treated with or without interferon (IFN) therapy. METHODS A total of 89 patients with chronic hepatitis C and 55 control (non-hepatitis) patients were asked to rate their experience of diurnal and nocturnal pruritus in the preceding week using a visual analogue scale (VAS) and a five-point scale, respectively. Blood samples were taken and serum thymus and activation-regulated chemokine (TARC) levels were measured by enzyme-linked immunosorbent assay. RESULTS A significantly greater proportion of chronic hepatitis C patients experienced nocturnal pruritus compared with control (58.4% vs 5.5%, P < 0.0001). Chronic hepatitis C patients also had more severe pruritus compared with control patients, indicated by the higher mean VAS scores in both the IFN-treated and non-IFN-treated groups. In particular, patients who received combined peginterferon alfa-2b and ribavirin had significantly higher mean VAS scores than those receiving peginterferon alfa-2a or no IFN treatment. Serum TARC levels did not correlate with pruritus scores, and no significant differences in TARC levels were observed between the IFN-treated and non-IFN-treated groups. CONCLUSION Patients with chronic hepatitis C experience pruritus more than those without. Serum TARC levels do not correlate with pruritus severity in chronic hepatitis C patients.

Reversal of the tolerance phenomenon by the intermittent administration of a histamine H2-receptor antagonist.

Background and Aim:  The attenuated antisecretory activity of H2‐receptor antagonists (H2RA) during continuous administration is referred to as the tolerance phenomenon. A previous study indicated that Helicobacter pylori (H. pylori) infection prevents the occurrence of tolerance to H2RA. In the present study, we investigated whether intermittent (every other day) administration prevents the tolerance phenomenon in H. pylori‐negative patients.

3479 Non-invasive gastrointestinal anastomosis with magnet rings.

Patients with inoperable GI cancers and strictures or stenoses often require intestinal bypass. These patients usually have advanced disease and are poor surgical candidates. In addition, surgical intervention often result in substantial mortality and morbidity as well as hospitalization and recovery time. Non-invasive methods of performing GI anastomosis may help improve their outcome and quality of life. We present cases to illustrate the use of magnet compression anastomosis. METHODS: Discshaped magnets of 1.5 cm in diameter and 0.7 cm thick are used. Two magnets are placed within the GI tract, one magnet each in the respective portion of the GI tract to be anastomosed. The magnets are placed orally, rectally, or endoscopically and are then maneuvered into the desired locations either endoscopically or percutaneously with an external magnet. Once the magnets are in place, the magnetic force attracting the two magnets then serve to compress the walls of the two respective gastrointestinal tracts together. Over the course of one to four weeks, an anastomosis is formed between the two adjoining segments of the gastrointestinal tract. CASES: Both cases 1 and 2 are patients with advanced antral gastric cancer with multiple metastases, who were not surgical candidates but who were unable to eat because of marked gastric outlet obstruction. One magnet was placed in the stomach and the other magnet was placed in the third portion of the duodenum. Promptly after magnet placement, the two magnets could be seen fluoroscopically compressing the stomach wall and the duodenal wall between them. After two weeks, the anastomoses were formed and the magnet pair passed spontaneously in the stool.Well-functioning anastomoses were confirmed by X ray. Case 3: This is a patient with sigmoid colon cancer with colon stricture. An anastomosis between ascending colon and distal sigmoid would provide bypass of the stricture. The 2 magnets were placed orally and endoscopically at ascending and distal colon. Ten days after, the anastomosis was completed and the two magnets passed spontaneously in the stool. The anastomosis functioned very well and the patient has had no obstructive symptoms for 6 months. CONCLUSION: Magnet compression anastomosis does not require surgical intervention or anesthesia, and still forms a well functioning anastomosis for bypassing neoplastic strictures and stenoses. It may become an additional clinical tool for providing palliative relief of gastrointestinal strictures and stenoses in patients with irreversible end-stage disease.

Efficacy of vonoprazan-based second-line Helicobacter pylori eradication therapy in patients for whom vonoprazan-based first-line treatment failed

We read with great interest the article by Murakami et al ,1 who performed a randomised, double-blinded study of vonoprazan-based Helicobacter pylori ( H. pylori ) eradication therapy. They showed high success rates for vonoprazan-based first-line and second-line H. pylori treatments, with eradication rates of 92.6% and 98%, respectively. However, the study populations of second-line therapy included patients for whom both lansoprazole-based and vonoprazan-based first-line treatments failed, and those for whom vonoprazan-based first-line therapy failed numbered only 14. In terms of second-line therapy, we think that the eradication rate in patients for whom vonoprazan-based first-line therapy failed is more important. We conducted …

A Case of Gastric Ulcer With Mucosal Bridge

Endoscopic images of the mucosal bridge with gastric ulcer are unusual. The mucosal bridge is presumed to have changed to a special form based on repeated development of gastric ulcer. The clinical course of mucosal bridge is unclear.

Two cases of immunoglobulin G4-related sclerosing cholangitis in which transabdominal ultrasonography was useful in diagnosis and follow-up observation.

Immunoglobulin G4-related disease (IgG4-RD) represents a group of disorders that share features of inflammation, plasma cell infiltrates, and fibrosis. Sclerosing cholangitis is a disorder involving inflammation, scarring, and destruction of the bile ducts. IgG4-related sclerosing cholangitis (IgG4-SC) has been proposed as a bile duct lesion associated with IgG4-RD. This disease entity can be distinguished from other types of sclerosing cholangitis and classified into four types based upon the region of strictures revealed by cholangiography. Here, we present two cases in which the finding of bile duct wall thickening visualized with transabdominal ultrasonography was useful in the diagnosis of patients with IgG4-SC. At present, transabdominal ultrasonography is not included in the diagnostic algorithm for IgG4-SC. We are certain that detailed observation of the bile duct wall with transabdominal ultrasonography can make a significant contribution to the diagnosis of IgG4-SC. Furthermore, we propose that transabdominal ultrasonography may be useful in following clinical improvement in cases where a steroid trial is the best option for treatment. Both cases emphasize the practicality of transabdominal ultrasonography in the diagnosis and follow-up observation of IgG4-SC.

Pocket Creation Method of Endoscopic Submucosal Dissection to Ensure Curative Resection of Rectal Neuroendocrine Tumors

Purpose: Pancreatic/gastrointestinal tract neuroendocrine neoplasm (NEN) is divided into neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC) according to the grade of malignancy, and differences are seen in clinical prognosis. NET, and rectal NET in particular, is often treated endoscopically. Endoscopic mucosal resection (EMR) was previously the main intervention for rectal NET, but EMR with a ligation device (EMR-L) and endoscopic submucosal dissection (ESD) are now also used. However, complete resection with these therapies is not always achieved. The pocket creation method (PCM) is a safe ESD method for colon tumors that offers a high en bloc resection rate compared with conventional colonic ESD. We performed ESD using the PCM for rectal NET and evaluated the complete resection rate. Methods: We performed ESD using the PCM in 4 patients. This procedure was technically feasible in all patients. Results: Endoscopically, all cases were resected en bloc, and pathological complete resection was achieved in all cases. No complications such as perforation or delayed postoperative bleeding were encountered. Conclusions: PCM should be considered when treating NET of appropriate size.

Post-colonoscopy colorectal cancer rate in the era of high-definition colonoscopy

AIM To investigate the post-colonoscopy colorectal cancer (PCCRC) rate for high-definition (HD) colonoscopy compared with that for standard-definition colonoscopy reported previously. METHODS Using medical records at Sano Hospital (SH) and Dokkyo Medical University Koshigaya Hospital (DMUKH), we retrospectively obtained data on consecutive patients diagnosed as having CRC between January 2010 and December 2015. The definition of PCCRC was diagnosis of CRC between 7 and 36 mo after initial high-definition colonoscopy that had detected no cancer, and patients were divided into a PCCRC group and a non-PCCRC group. The primary outcome was the rate of PCCRC for HD colonoscopy. The secondary outcomes were factors associated with PCCRC and possible reason for occurrence of early and advanced PCCRC. RESULTS Among 892 CRC patients, 11 were diagnosed as having PCCRC and 881 had non-PCCRC. The PCCRC rate was 1.7% (8/471) at SH and 0.7% (3/421) at DMUKH. In comparison with the non-PCCRC group, the PCCRC group had a significantly higher preponderance of smaller tumors (39 mm vs 19 mm, P = 0.002), a shallower invasion depth (T1 rate, 25.4% vs 63.6%, P = 0.01), a non-polypoid macroscopic appearance (39.0% vs 85.7%, P = 0.02) and an earlier stage (59.7% vs 90.9%, P = 0.03). Possible reasons for PCCRC were “missed or new” in 9 patients (82%), “incomplete resection” in 1 (9%), and “inadequate examination’” in 1 (9%). Among 9 “missed or new” PCCRC, the leading cause was non-polypoid shape for early PCCRC and blinded location for advanced PCCRC. CONCLUSION The PCCRC rate for HD colonoscopy was 0.7%-1.7%, being lower than that for standard-definition colonoscopy (1.8%-9.0%) reported previously employing the same methodology.