Ryota Hokari

• Head of Department at National Defense Medical College

Irritable bowel syndrome (IBS) have major economic effects on healthcare systems and adversely affect quality of life. However, usefulness of routine tests to identify IBS is very low. Thus, algorithms are useful to diagnose IBS patients efficiently. Diagnostic algorithms are used for patients with chronic abdominal pain or discomfort and/or abnorm...

Despite accumulating evidence and recommendations for management of colonic diverticular bleeding (CDB), the changes in its clinical management and outcomes remain unknown. We performed a retrospective tendency analysis on a biennial basis, a propensity score-matched cohort study between the first and latter half groups, and mediation analyses to c...

Background The involvement of Mediterranean fever (MEFV) gene mutations in patients with inflammatory bowel disease unclassified (IBDU) remains unclear. This study aimed to determine the clinical characteristics and responsiveness to colchicine in Japanese patients with IBDU carrying MEFV mutations. Methods In this retrospective cohort study, we e...

The Japan Gastroenterological Association (JGA) published the first version of clinical guidelines for chronic diarrhea 2023. These guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic diarrhea, and provide flowcharts for the diagnosis and treatm...

In July 2023 the Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. Th...

Background Paneth cells play multiple roles in maintaining intestinal homeostasis. However, the clinical role of Paneth cell metaplasia (PCM) in ulcerative colitis (UC) remains unclear. We aimed to investigate the relationship between PCM and relapse in patients with UC and compare the usefulness of PCM with other histological indexes, including mu...

The gut–skin axis has recently been widely recognized, and both the gut and skin have been found to affect each other through a bidirectional connection; however, the precise mechanisms remain to be elucidated. Therefore, we aimed to investigate the effects of chronic skin damage (CSD) on mouse intestines. Following the CSD model, 4% sodium dodecyl...

Background Although the involvement of intestinal microbiota in innate immunity has been reported recently, the pathogenicity of autoimmune pancreatitis (AIP) remains unclear. This study aimed to investigate whether probiotics ameliorate inflammation in AIP through interactions with innate immunity. Methods The AIP mouse model was generated by int...

Introduction: We examined the associations among disease-related symptoms, health-related quality of life (HRQOL), and sense of coherence (SOC) in Japanese patients with ulcerative colitis (UC). Methods: This cross-sectional survey involved patients and physicians at 23 hospitals specializing in UC treatment in Japan (December 2019-December 2020...

The prevalence of elderly-onset ulcerative colitis (UC) is increasing worldwide. Elderly onset-UC presents a more severe disease course, a wider disease distribution and a higher incidence of hospitalization and surgery. Patients with multiple comorbidities are more often observed in elderly UC than younger UC. Management of elderly UC requires est...

Idiopathic peptic ulcer poses a clinical challenge since it is more frequently associated with underlying disease, especially atherosclerosis and liver cirrhosis with portal hypertension, is more refractory, with a higher recurrence rate than simple Helicobacter pylori-positive ulcers. This large-scale study investigated the trends in idiopathic pe...

This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC). In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-r...

Background and Aims Japan has experienced 8 waves of the coronavirus disease 2019 (COVID-19) outbreak over the past 3 years, resulting in an increasing number of deaths and incidence of severe infections. This study aimed to analyze the data from the Japanese inflammatory bowel disease (IBD) patients with COVID-19 registry (J-COSMOS) up to the eigh...

Background Mild blast‐induced traumatic brain injury (bTBI) induces various gut symptoms resembling human irritable bowel syndrome (IBS) as one of mental and behavioral disorders. However, the underlying mechanisms remain unclear. We investigated whether the extremely localized brain impact extracranially induced by laser‐induced shock wave (LISW)...

Little is known about iatrogenic splenic injury (SI) as an adverse event after colonoscopy. SI is sometimes fatal because of hemorrhaging. We herein report a man who developed SI after colonoscopy. He recovered conservatively. His history of left hydronephrosis and insertion with a maximally stiffened scope were suspected as possible risk factors....

Background/aims: Recent studies indicate that probiotics, which have attracted attention as a treatment for irritable bowel syndrome, affect intestinal homeostasis. In this study, we investigated whether Zygosaccharomyces sapae (strain I-6), a probiotic yeast isolated from miso (a traditional Japanese fermented food), could improve irritable bowel...

Objective: Bleeding occurs after liver biopsy in up to 10.9% cases, and patients with impaired hemostasis or ascites are considered to have absolute or relative contraindications. N-butyl cyanoacrylate enables immediate hemostasis, even in lethal situations. Therefore, percutaneous liver biopsy combined with tract embolization using N-butyl cyanoa...

Luminal antigens, nutrients, metabolites from commensal bacteria, bile acids, or neuropeptides influence the function and trafficking of immune cells in the intestine. Among the immune cells in the gut, innate lymphoid cells, including macrophages, neutrophils, dendritic cells, mast cells, and innate lymphoid cells, play an important role for the m...

Background Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy, the mechanism of which is involved in oxidative stress, can be lethal due to hemorrhage. Thus, we aimed to investigate the effect of hydrogen-rich water (HRW), in terms of oxidative stress, on intestinal mucosal damage as well as changes in the gut microbiome and the short-...

Background: The specific etiopathogenesis of inflammatory bowel disease (IBD) is still unknown. Although the conventional anti-inflammatory or immunomodulatory drugs relatively nonspecific to pathogenesis have been quite useful in many cases, elucidating the pathogenesis has gradually facilitated developments of disease-specific therapies for refr...

Background and aim: The study of the impact of environmental factors during pregnancy on fetal development has so far been focused primarily on the those negatively affecting human health; however, little is known about the effects of probiotic treatment during pregnancy on inflammatory bowel diseases (IBD). In this study, we investigated whether...

Background The interleukin (IL)-23/Th17 pathway plays a critical role in ulcerative colitis (UC). The IL-12p40 subunit, which is shared by IL-23 and IL-12, is encoded by the IL12B gene. The current case-control study investigated the association between IL12B SNP rs6887695 and the UC risk. Methods There were 384 cases within 4 years of UC diagnosi...

Introduction: The functions of basophils have not been elucidated until recently because of their rarity. However, with recent developments in basophil-specific antibodies and basophil-deficient animals, the roles of basophils in various diseases related to chronic inflammation have been clarified. In this study, we aimed to investigate the roles...

Cronkhite–Canada Syndrome (CCS) is a non-hereditary disorder characterized by multiple non-neoplastic polyps in the gastrointestinal tract. CCS is considered to be a rare disease worldwide, but the majority of reported cases are from Japan. Polyps are frequently detected particularly in the stomach and colon, and in more than half of cases, polyps...

Endoscopic images and clinical description of CCS cases with coincident esophageal legions or coincident tumor are shown in this chapter (16 cases).

Endoscopic images and clinical description of CCS cases treated with other than corticosteroids are shown in this chapter (4 cases).

Endoscopic images and clinical description of CCS cases with atypical clinical symptoms or possible cases are shown in this chapter (17 cases).

CCS might be easily suspected based on the findings of white light observation. However, a combination of small bowel endoscopy and image-enhanced endoscopy with high magnification can provide a more detailed picture of the disease. Representative endoscopic images of CCS observed by these newly developed endoscopy are shown in this chapter.

Endoscopic images and clinical description of relapse-remitting cases and chronic continuous cases are shown in this chapter (17cases).

Coincident carcinoma and adenoma are not rare in CCS. Thus, it is very important to pick up them from multiple polyps. NBI and BLI are both techniques that allow detailed observation of glandular and microvascular structures. Case reports using NBI have shown that many inflammatory hyperplastic polyps do not have abnormal microvasculature on their...

In this chapter, comparison of pathological and endoscopic images of polyps or mucosal changes is shown. Polyps observed in CCS are classified as non-neoplastic. The glandular ducts are unequally sized, irregularly branched, and dilated, and may show the appearance of serrated changes. In cases with endoscopically white mucus adhered appearance, th...

Endoscopic images and clinical description of steroid-resistant / refractory / intolerant CCS cases are shown in this chapter (11 cases).

Endoscopic images and clinical description of CCS cases suffering from first attack are shown in this chapter (23 cases).

In CCS, multiple polyps are found in the gastrointestinal tract mainly in the stomach and colon. Representative endoscopic images of polyps and mucosal change are shown in this chapter. Typical gastric polyps are described as “red cavir like,” which is characterized by findings of dense distribution of small hemispheric, edematous, and erythematous...

Hepatic portal venous gas (HPVG) is considered to be a sign of poor prognosis in abdominal diseases and a potentially fatal condition. However, HPVG after colonic endoscopic submucosal dissection (ESD), is an even rarer complication that there is just one report of it at the moment. In this report, we present a case of HPVG and bacteremia that happ...

Background AJM300 is an oral, small-molecule α4-integrin antagonist. We assessed the efficacy and safety of AJM300 in patients with moderately active ulcerative colitis. Methods This multicentre, randomised, double-blind, placebo-controlled, phase 3 study consisted of two phases: a treatment phase and an open-label re-treatment phase. The study wa...

Background The spread of coronavirus disease 2019 (COVID-19) had a major impact on the health of people worldwide. The clinical background and clinical course of inflammatory bowel disease (IBD) among Japanese patients with COVID-19 remains unclear. Methods This study is an observational cohort of Japanese IBD patients diagnosed with COVID-19. Dat...

A 78-year-old man presented to our hospital with a history of 10kg weight loss within 6 months previously, and general fatigue and fever for 2 and 1 months, respectively. On hospitalization, the patient was diagnosed with polyarteritis nodosa after multiple microaneurysms were observed in the liver, kidney, pancreas, and mesenteries. He achieved re...

The lymphatic vasculature returns filtered interstitial arterial fluid and tissue metabolites to the blood circulation. It also plays a major role in lipid absorption and immune cell trafficking. Lymphatic vascular defects have been revealed in inflammatory diseases, Crohn’s disease, obesity, cardiovascular disease, hypertension, atherosclerosis, a...

Background and Aim Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking a...

Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a systemic condition associated with fibroinflammatory lesions and is characterized by elevated serum IgG4 levels and IgG4-positive cell infiltration into the affected tissues. It has been reported that IgG4-RD affects a variety of organs but uncommonly affects the gastrointestinal tract. In partic...

Takayasu arteritis (TA) sometimes presents with colitis, which may be diagnosed as inflammatory bowel disease unclassified (IBDU) because of atypical or mixed findings of ulcerative colitis (UC) and Crohn's disease. We herein report an 18-year-old girl presenting with colitis with an occasional high fever eventually diagnosed as TA with IBDU. Colon...

Background and Aims The artificial sweetener acesulfame potassium (ACK) is officially approved as safe for intake and has been used in processed foods. However, ACKs have been reported to induce metabolic syndrome, along with alteration of the gut microbiota in mice. In recent years, studies have suggested that this artificial sweetener promotes my...

Background: Yeasts are a type of fungi thought to have probiotic functions. In this study, we isolated a novel probiotic yeast (Zygosaccharomyces sapae strain I-6) from Miso (a traditional Japanese fermented food). We examined its effects on phenotypic changes in intestinal dendritic cells (DCs), and evaluated its anti-inflammatory effects in dext...

A man in his 40s with a history of hospitalization for acute exacerbation of chronic pancreatitis presented with dyspnea. Chest radiography revealed left pleural effusion, and he was hospitalized for further evaluation and treatment. Thoracentesis was performed, and we suspected pancreatic pleural effusion based on high pancreatic enzyme levels in...

Objective: Oxidative stress is considered to be one of the etiologic factors involved in ulcerative colitis (UC), yet there is limited epidemiological information regarding the relationship between antioxidant intake and the risk of UC. The aim of the present case–control study in Japan was to examine the association between intake of green and yel...

Background Anti-tumour necrosis factor (TNF) agents are the mainstay of long-term treatment for refractory ulcerative colitis. However, long-term use of anti-TNF therapy might lead to an increased risk of malignancy or infection. To date, no randomised controlled trial has evaluated whether anti-TNF agents can be safely discontinued in patients wit...

Background The small intestine plays a central role in gut immunity, and enhanced lymphocyte migration is involved in the pathophysiology of various enteropathy. Bile acid (BA) is closely related to lipid metabolism and gut microbiota, and essential for gut homeostasis. However, the effects of BA on gut immunity have not been studied in detail, esp...

Introduction Innate lymphoid cells (ILCs) are abundant in the intestinal mucosa, forming boundaries externally. Herein, ILCs were directly obtained from intestinal lymph using a lymph fistula rat model and analyzed under physiological and pathological conditions. Methods Thoracic duct (TD) lymphocytes were collected by cannulation with/without pre...

Background Uric acid (UA) has anti- and pro-inflammatory properties. We previously revealed that elevated serum UA levels provide protection against murine small intestinal injury probably via luminal UA secreted in the small intestine. Luminal UA may act as an antioxidant, preventing microbiota vulnerability to oxidative stress. However, whether l...

Managing irritable bowel syndrome (IBS) has attracted international attention because single-agent therapy rarely relieves bothersome symptoms for all patients. The Japanese Society of Gastroenterology (JSGE) published the first edition of evidence-based clinical practice guidelines for IBS in 2015. Much more evidence has accumulated since then, an...

Background Adherence to medications is important to maintain disease under control and to prevent complications in pregnant patients with ulcerative colitis (UC). To evaluate the incidence of non-adherence during pregnancy and its effect on relapse and pregnancy outcomes, we conducted a multicenter prospective study using a patient self-reporting s...

Background Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called “mesalamine allergy,” which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the gen...

Purpose Assessment of liver fibrosis is essential for the management of liver disease. Although liver biopsy is the gold-standard modality for the diagnosis of liver fibrosis, it has some limitations. Thus, other methods are required to overcome the disadvantages of a liver biopsy. T1ρ magnetic resonance imaging (MRI) values are potential biomarker...

A 70-year-old asymptomatic man presented with a growing submucosal tumor in the duodenal bulb; and despite two EUS-FNA procedures, a diagnosis could not be confirmed. Since the mass was stalked and enlarged to 40 mm in size, the patient underwent endoscopic resection with grasping scissor forceps, while traction was applied for diagnostic treatment...

Aim We recently reported that lipoprotein lipase (LPL)‐mediated free cholesterol (FC) accumulation in hepatic stellate cells (HSCs) augmented liver fibrosis in nonalcoholic steatohepatitis (NASH). The aim of the present study was to explore the role of angiopoietin‐like protein 4 (Angptl4), an LPL inhibitor, in the pathogenesis of liver fibrosis in...

Introduction Worldwide increasing aging societies have many elderlies with intractable diseases including ulcerative colitis (UC). Reportedly, each patients’ frailty as well as chronological age is a clinical risk factor of elderly‐onset UC (EOUC). Since malnutrition is one of the major manifestations of frailty, we aimed to investigate the effect...

Background and Aim Very early‐onset inflammatory bowel disease is defined as inflammatory bowel disease diagnosed before 6 years of age. Very early‐onset inflammatory bowel disease has various differential diagnoses, including primary immunodeficiency disorders, and is known to be resistant to conventional treatment. Therefore, global attention is...

The nuclear receptor peroxisome proliferator-activated receptor (PPAR)γ has been implicated in the pathogenesis of various human diseases including fatty liver. Although nuclear translocation of PPARγ plays an important role in PPARγ signaling, details of the translocation mechanisms have not been elucidated. Here we demonstrate that PPARγ2 translo...

A 69-year-old man had been intermittently experiencing abdominal pain from his 30s and was diagnosed with colonic diverticulitis. He further experienced right lower abdominal pain and received treatment. However, his condition did not improve, and he was referred to the National Defense Medical College Hospital. His abdominal pain episodes continue...

Background The genetic variants of NUDT15 have been verified to induce adverse events (AEs) of thiopurines. Codon 139 variants are frequently observed in Asians, while multiple variants are seen in codon 18 which also cause AEs including the European ancestry. The purpose of this study is to establish a technique capable of the simple genotyping of...

Management of elderly ulcerative colitis in Japan

Background & aims: We compared the diagnostic accuracy of the fecal calprotectin (FCP) test vs the fecal immunochemical blood test (FIT) in determining the endoscopic severity and predicting outcomes of patients with ulcerative colitis (UC). Methods: We performed a nationwide study of 879 patients with UC, enrolled at medical centers across Japa...

Objective: Dietary emulsifiers are widely used in processed foods and officially approved as safe for intake. However, recent studies have demonstrated that some emulsifiers alter the colonic microbiota, leading to colonic low-grade inflammation, in mice. The effect of dietary emulsifiers on small-intestinal microbiota, which is important for gut...