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Abstract Background: Mucosal healing (MH) was proposed to be an ideal treatment goal for patients with inflammatory bowel disease (IBD). Instead of endoscopy to confirm MH, biomarkers are frequently used and have become an indispensable modality for the clinical examination of patients with IBD. Summary: Common biomarkers of IBD include C-reactive protein (CRP), erythrocyte sedimentation rate, antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies, leucine-rich α2 glycoprotein, fecal calprotectin (FCP), and the fecal immunochemical test. Biomarkers play five major roles in the management of IBD: (1) diagnosing and distinguishing between IBD and non-IBD or ulcerative colitis and Crohn’s disease; (2) predicting treatment response, especially before administrating biologics; (3) monitoring and grasping endoscopic or histological disease activity; (4) replacing endoscopy for diagnosing MH, including endoscopic and histological remission; and (5) predicting recurrence before disease activity appears through symptoms. Many reports have demonstrated the usefulness of CRP and FCP for those five roles; however, they have limitations for diagnosing MH or predicting treatment response. In general, FCP has better ability in those positions than CRP; additionally, leucine-rich α2 glycoprotein can diagnose endoscopic disease activity better than CRP. The novel biomarker, prostaglandin E-major urinary metabolite, and anti-αvβ6 antibody are expected to be noninvasive and reliable biomarkers; however, more evidence is required for future studies. Oncostatin M and microRNA are also prospects, in addition to other familiar and novel biomarkers. Key Messages: Each biomarker has a useful feature; therefore, we should consider their features and use appropriate biomarkers for the five roles to enable noninvasive and smooth management of IBD.

BackgroundNear-infrared photoimmunotherapy (NIR-PIT) constitutes a new class of molecular-targeted theranostics utilizing monoclonal antibody (mAb)-photosensitizer conjugates and NIR light. In this study, we developed a new type of NIR-PIT targeting vascular endothelial growth factor receptor 2 (VEGFR-2) expressed on vascular endothelium in an experimental gastric cancer model and evaluated the feasibility by comparing conventional NIR-PIT targeting cancer cell membrane in vitro and in vivo.MethodsHER2-positive human gastric cancer cells, NCI-N87, were used for the experiments. Anti-HER2 mAb, trastuzumab and anti-VEGFR-2 mAb, DC101 were conjugated to photosensitizer, IR700. Phototoxicity in response to NIR-PIT were investigated in vitro and in vivo. Microvessel densities, as an indicator of angiogenesis, were counted in harvested xenografts after NIR-PIT to elucidate the mechanism.ResultsDC101-IR700 did not induce phototoxic effect in vitro because of the absence of expression of VEGFR-2 in NCI-N87 cancer cells. However, it induced an antitumor effect in NCI-N87 xenograft tumors accompanied with damage in tumor neovasculature as determined by decreasing tumor microvessel density, which represents a different mechanism than that of conventional NIR-PIT targeting antigens expressed on the tumor cell membrane.ConclusionWe demonstrated a new approach of NIR-PIT utilizing a target on vascular endothelium, such as VEGFR-2, and this treatment might lead to the development of a new therapeutic strategy for human gastric cancer.

Inflammatory bowel disease (IBD) is a general term for chronic or remitting/relapsing inflammatory diseases of the intestinal tract and generally refers to ulcerative colitis (UC) and Crohn’s disease (CD). Since 1950, the number of patients with IBD in Japan has been increasing. The etiology of IBD remains unclear; however, recent research data indicate that the pathophysiology of IBD involves abnormalities in disease susceptibility genes, environmental factors and intestinal bacteria. The elucidation of the mechanism of IBD has facilitated therapeutic development. UC and CD display heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management depends on the understanding and tailoring of evidence-based interventions by physicians. In 2020, seventeen IBD experts of the Japanese Society of Gastroenterology revised the previous guidelines for IBD management published in 2016. This English version was produced and modified based on the existing updated guidelines in Japanese. The Clinical Questions (CQs) of the previous guidelines were completely revised and categorized as follows: Background Questions (BQs), CQs, and Future Research Questions (FRQs). The guideline was composed of a total of 69 questions: 39 BQs, 15 CQs, and 15 FRQs. The overall quality of the evidence for each CQ was determined by assessing it with reference to the Grading of Recommendations Assessment, Development and Evaluation approach, and the strength of the recommendation was determined by the Delphi consensus process. Comprehensive up-to-date guidance for on-site physicians is provided regarding indications for proceeding with the diagnosis and treatment.

Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn’s disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.

BackgroundColorectal endoscopic submucosal dissection (ESD) requires advanced endoscopic skill. For safer and more reliable ESD implementation, various traction devices have been developed in recent years. The purpose of this research was to evaluate whether an ESD training program using a traction device (TD) would contribute to the improvement of trainees’ skill acquisition.MethodsThe differences in treatment outcomes and learning curves by the training program were compared before and after the introduction of TD (control group: January 2014 to March 2016; TD group: April 2016 to June 2018).ResultsA total of 316 patients were included in the analysis (TD group: 202 cases; control group: 114 cases). The number of cases required to achieve proficiency in ESD techniques was 10 in the TD group and 21 in the control group. Compared to the control group, the TD group had a significant advantage in ESD self-completion rate (73.8% vs. 58.8%), dissection speed (19.5 mm2/min vs. 15.9 mm2/min), en bloc resection rate (100% vs. 90%), and R0 resection rate (96% vs. 83%).ConclusionsThe rate of colorectal ESD self-completion by trainees improved immediately after the start of the training program using a traction device compared to the conventional method, and the dissection speed tended to increase linearly with ESD experience. We believe that ESD training using a traction device will help ESD techniques to be performed safely and reliably among trainees.

The progression from compensated to decompensated cirrhosis markedly worsens prognosis. This study investigated the clinical utility of serum autotaxin (ATX) levels as a predictive biomarker for decompensation and mortality, particularly in patients with compensated cirrhosis. A total of 210 patients with cirrhosis (165 with compensated cirrhosis) were retrospectively analyzed and classified into three groups based on baseline serum ATX levels: low-, intermediate-, and high-ATX groups. Over a median follow-up of 51.6 months, 43 patients (20.5%) died of liver-related events, and 26 patients (15.8%) with compensated cirrhosis at baseline progressed to decompensation. In both the overall cohort and the compensated cirrhosis subgroup, the high-ATX group had significantly lower cumulative survival rates than the intermediate- and low-ATX groups (p < 0.001 for both). Multivariate analysis identified high serum ATX levels as an independent predictor of mortality (overall cohort: hazard ratio [HR], 1.661; p = 0.039; compensated cirrhosis subgroup: HR, 7.488; p < 0.001). Furthermore, the cumulative incidence of decompensation was highest in the high-ATX group (p < 0.001), and high serum ATX levels were independently associated with an increased risk of decompensation (HR, 5.502; p < 0.001). ATX represents a promising non-invasive biomarker for predicting decompensation and poor prognosis in patients with compensated cirrhosis.

Patients with cirrhosis are at high risk for sarcopenia and malnutrition, which are associated with reduced quality of life and increased mortality. We investigated the relationship between the Geriatric Nutritional Risk Index (GNRI) and sarcopenia/gait speed and assessed the usefulness of the GNRI for predicting sarcopenia in patients with cirrhosis. We evaluated 202 patients with cirrhosis and divided them into three groups based on baseline GNRI values: low (L)-GNRI (< 94.0, n = 49), intermediate (I)-GNRI (between 94.0 and 109.5, n = 103), and high (H)-GNRI groups (> 109.5, n = 50). Sarcopenia was diagnosed according to the criteria of the Japan Society of Hepatology. The prevalence of sarcopenia and slow gait speed was the lowest in the H-GNRI group (8.0% and 26.0%, respectively) and the highest in the L-GNRI group (49.0% and 44.9%, respectively). They increased stepwise with a decline in the GNRI group ( p  < 0.001 and p  = 0.05, respectively). The GNRI values were significantly and positively correlated with handgrip strength, skeletal muscle mass index, and gait speed. Multivariate analysis identified lower GNRI as an independent risk factor for sarcopenia. The optimal cutoff value of the GNRI for predicting sarcopenia was 102.1 (sensitivity/specificity, 0.768/0.630). The GNRI was significantly associated with sarcopenia and physical performance and could be a helpful screening tool for predicting sarcopenia in patients with cirrhosis.

Increasing number of patients with ulcerative colitis (UC) have received biologic treatment during the last decade. The association between endoscopic healing (EH) and biologic treatment failure remains understudied. Medical information of UC patients who started biologic treatment was retrospectively collected. EH was defined as Mayo endoscopic subscore of 0 or 1. Loss of response (LOR)-free drug continuation rate was compared between patients who achieved EH and those who did not using Kaplan–Meier estimator. Fifty-two patients received 53 biologic treatments and underwent follow-up colonoscopies within 2 years. Thirty-three patients achieved EH, all of which remained on the same treatment without LOR during the observational period. Twenty patients did not achieve EH, 8 of which ultimately discontinued the treatment due to LOR to biologic agents. Kaplan–Meier estimator found a significantly lower drug continuation rate in patients without EH ( p  < 0.001; log-rank test). A Cox regression analysis identified EH as an independent factor associated with a reduced risk of LOR-related biologic treatment failure irrespective of the types of biologic agents (Hazard Ratio = 0.0324, p  < 0.001). EH within 2 years is associated with a reduced risk of LOR-related biologic treatment failure in patients with UC.