Analysis of Genetic Relatedness between Gastric and Oral Helicobacter pylori in Patients with Early Gastric Cancer Using Multilocus Sequence Typing.

The oral cavity is the second most colonized site of Helicobacter pylori after the stomach. This study aimed to compare the genetic relatedness between gastric and oral H. pylori in Japanese patients with early gastric cancer through multilocus sequence typing (MLST) analysis using eight housekeeping genes. Gastric biopsy specimens and oral samples were collected from 21 patients with a fecal antigen test positive for H. pylori. The number of H. pylori allelic profiles ranged from zero to eight since the yield of DNA was small even when the nested PCR was performed. MLST analysis revealed that only one patient had a matching oral and gastric H. pylori genotype, suggesting that different genotypes of H. pylori inhabit the oral cavity and gastric mucosa. The phylogenetic analysis showed that oral H. pylori in six patients was similar to gastric H. pylori, implying that the two strains are related but not of the same origin, and those strains may be infected on separate occasions. It is necessary to establish a culture method for oral H. pylori to elucidate whether the oral cavity acts as the source of gastric infection, as our analysis was based on a limited number of allele sequences.

Visceral Adipose Tissue Index and Hepatocellular Carcinoma Are Independent Predictors of Outcome in Patients with Cirrhosis Having Endoscopic Treatment for Esophageal Varices.

BACKGROUND: The relationship between the amount of adipose tissue and advanced-stage liver cirrhosis with esophageal varices (EV) is unknown. We aimed to reveal the prognostic significance of adipose tissues in patients with liver cirrhosis. METHODS: We enrolled 87 patients with EV who received initial endoscopic treatment and underwent scheduled treatments in our hospital. Computed tomography (CT) images were obtained of a 5-mm slice at the umbilical level. We evaluated the effect of mortality based on the visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue ratio (VSR). RESULTS: Cox hazard multivariate analysis showed that the presence of hepatocellular carcinoma (HCC; hazard ratio [HR]: 4.650, 95% confidence interval [CI]: 1.750-12.353, p = 0.002), γ-GTP (HR: 1.003, 95% CI: 1.001-1.006, p = 0.026), and VATI (HR: 1.057, 95% CI: 1.030-1.085, p < 0.001) significantly affected mortality. Cox hazard multivariate analysis for liver-related death was also significantly affected by HCC (HR: 1.057, 95% CI: 1.030-1.085, p < 0.001) and VATI (HR: 1.052, 95% CI: 1.019-1.086, p = 0.002). The difference between the Child-Pugh scores 12 months after treatment and that during initial treatment were significantly positively correlated with VATI (r = 0.326, p = 0.027). Patients with high VATI had a significantly higher frequency of HCC after EV treatment by Kaplan-Meier analysis (p = 0.044). CONCLUSION: Our findings suggest that VATI measured by CT could significantly predict mortality in cirrhosis patients through decreasing liver function and increasing HCC frequency, and appropriately controlling VATI could improve their prognosis.

Esophageal High-Resolution Manometry for Diagnosing the Severity of the Chronic Intestinal Pseudo-Obstruction: A Case Series.

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a severe and refractory intestinal motility disorder. However, due to its rarity and difficult histological investigation, its pathophysiology has not been characterized. AIM: Therefore, in this study, we aimed to determine the role of esophageal high-resolution manometry (HRM) in CIPO and the histological and clinical characteristics of the disease. METHODS: Patients with CIPO were analyzed for clinical characteristics; histological findings; and clinical courses after therapeutic intervention. In addition, HRM was performed to determine the esophageal involvement. RESULTS: Eleven patients were diagnosed with CIPO, and five required the long period of parenteral nutrition showing impaired esophageal motility including achalasia and absent contractility diagnosed with HRM. The four of these five cases showed acute onset of the CIPO following the triggering events of pregnancy, appendicitis, and surgery. In contrast, other six patients with normal or Jackhammer esophagus on HRM had moderate severity of CIPO with gradual onset. The histological analyses revealed that the loss of the intestinal neural ganglion cells and layers by inflammation, destruction, and atrophy are related to the severity of the clinical course of the disease and esophageal HRM findings of achalasia and absent contractility. CONCLUSIONS: HRM may be useful to diagnose the severity of the clinical course and to determine the therapeutic options for CIPO.

Molecular Mechanisms and Treatment of Sarcopenia in Liver Disease: A Review of Current Knowledge.

Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength that occurs with aging or in association with various diseases. The condition is prevalent worldwide and occurs more frequently in patients with chronic diseases owing to the intrinsic relationship of muscles with glucose, lipid, and protein metabolism. Liver cirrhosis is characterized by the progression of necro-inflammatory liver diseases, which leads to fibrosis, portal hypertension, and a catabolic state, which causes loss of muscle tissue. Sarcopenia is of significant concern in the state of liver cirrhosis because sarcopenia has been associated with higher mortality, increased hospital admissions, worse post-liver transplant outcomes, decreased quality of life, and increased risk for other complications associated with cirrhosis. Therefore, sarcopenia is also an important feature of liver cirrhosis, representing a negative prognostic factor and influencing mortality. An increased understanding of sarcopenia could lead to the development of novel therapeutic approaches that could help improve the cognitive impairment of cirrhotic patients; therefore, we present a review of the mechanisms and diagnosis of sarcopenia in liver disease and existing therapeutic approaches.

Change in body composition in patients with achalasia before and after peroral endoscopic myotomy.

BACKGROUND AND AIM: Patients with achalasia experience weight loss because of dysphagia caused by impaired relaxation of the lower esophageal sphincter. This study aimed to use dual bioelectrical impedance analysis (BIA) to determine the change in bodyweight and body composition in patients with achalasia before and after peroral endoscopic myotomy (POEM). METHODS: Patients with achalasia who underwent POEM from 2013 to 2018 (n = 72) were retrospectively analyzed for change in bodyweight before and after 3 months. Additionally, change in body composition was prospectively investigated in the final 10 of 72 patients using non-radiation dual BIA. RESULTS: Twenty patients (27.8%) were underweight (body mass index < 18.5) before undergoing POEM. No clinical parameters were identified to be associated with the underweight condition before POEM and be predictive of an increase in bodyweight after POEM. Low visceral fat volume observed on dual BIA correlated closely with the result obtained using computed tomography (Pearson correlation coefficient: r = 0.850, P < 0.01). Patients with achalasia had a statistically significant increase in visceral (P < 0.01) and subcutaneous fat volumes (P < 0.01) after POEM. Skeletal muscle mass index slightly increased (P = 0.02), although the value after POEM was still low. No blood biomarkers were indicators for low bodyweight or low visceral fat volume. CONCLUSIONS: Dual BIA is an effective non-invasive tool to evaluate the change in body composition of underweight patients with achalasia. Skeletal muscle volume was not enough after POEM, although a rapid increase in the intra-abdominal fat volume was observed. Additional studies are warranted to understand the pathological implications.

Early injection of human adipose tissue-derived mesenchymal stem cell after inflammation ameliorates dextran sulfate sodium-induced colitis in mice through the induction of M2 macrophages and regulatory T cells.

Inflammatory bowel diseases (IBDs) are sometimes refractory to current therapy or associated with severe adverse events during immunosuppressive therapy; thus, new therapies are urgently needed. Recently, mesenchymal stem cells (MSCs) have attracted attention based on their multitude of functions including anti-inflammatory effects. However, proper timing of MSC therapy and the mechanisms underlying the therapeutic effects of MSCs on colitis are not fully elucidated. Human adipose tissue-derived mesenchymal stem cells (hAdMSCs; 1 × 106) were administrated via the tail vein on day 3 (early) or 11 (delayed) using a 7-day dextran sulfate sodium (DSS)-induced mouse model of colitis. The effects were evaluated based on colon length, disease activity index (DAI) and histological score. Cytokine-encoding mRNA levels T cells and macrophages were evaluated by real-time PCR and flow cytometry. Regarding the timing of administration, early (day 3) injection significantly ameliorated DSS-induced colitis in terms of both DAI and histological score, compared to those parameters with delayed (day 11) injection. With early cell injection, the tissue mRNA levels of anti-inflammatory cytokine genes (Il10, Tgfb) increased, whereas those of inflammatory cytokine genes (Il6, Tnfa and Il17a) decreased significantly. Regarding the associated mechanism, hAdMSCs suppressed T cell proliferation and activation in vitro, increased the number of regulatory T cells in vivo and changed the polarity of macrophages (into the anti-inflammatory M2 phenotype) in vitro. Timing of injection is critical for the effective therapeutic effects of hAdMSCs. Furthermore, part of the associated mechanism includes T cell activation and expansion and altered macrophage polarization.

Novel Magnified Single-Balloon Enteroscopy Enables Observation of Jejunal White Spots Associated with Lymphangiectasia.

A 59-year-old woman was diagnosed with primary intestinal lymphangiectasia (PIL), with characteristic findings on capsule enteroscopy and confirmation by histopathological examination of biopsy specimens. We viewed the abnormal jejunal mucosa using a newly developed magnifying single-balloon enteroscope (SIF-Y0007). Conventional observation showed leakage of chyle. However, using this new scope, we could see scattered white villi, representing dilated lymphatic vessels within the intestinal villi protruding from the dilated submucosal lymphoid vessels (D2-40 positive) within an edematous jejunal lesion. This report is the first to describe the white villi in a patient with PIL observed clearly using a newly developed magnifying enteroscope. Technological advancements and the accumulation of reported pathological data would further improve our understanding of the pathophysiological aspects of this disease entity, even in the jejunum.

Overlap in disease concept of functional esophageal disorders and minor esophageal motility disorders.

BACKGROUND AND AIM: Functional gastrointestinal disorders are the most common disorders in gastroenterology and are currently considered as gut-brain interaction disorders with multiple related factors including motility disturbance. However, high-resolution manometry (HRM) had revealed a new disease concept known as minor esophageal motility disorders. This study aimed to investigate the correlation between functional esophageal disorders (FEDs) and minor esophageal motility disorders. METHODS: Functional esophageal disorders were diagnosed using upper endoscopy, pH monitoring, and HRM, to exclude achalasia, esophago-gastric junction outflow obstruction, and other major esophageal motility disorders. FEDs with or without minor esophageal motility disorders were compared using the Chicago classification. RESULTS: Twelve healthy volunteers also subjected to HRM showed no minor esophageal motility disorders. Of the 40 patients with FEDs, 15 (37.5%) were diagnosed with minor esophageal motility disorders. Characteristics were not different between patients with and without minor esophageal motility disorders (sex: P = 0.609, age: P = 0.054, body mass index: P = 0.137, and presence of psychiatric disorders: P = 0.404). The type and location of symptoms were not related to the comorbidity rate of minor esophageal motility disorders (P = 0.744 and 0.094). No patients with FEDs developed major esophageal motility disorders. CONCLUSIONS: Minor esophageal motility disorders were frequently observed in FEDs, but the causal relationship between esophageal symptoms remains unclear. The disease concepts of FEDs and minor esophageal motility disorders are considered to overlap and are both independent of major esophageal motility disorders.

Management decision based on lymphovascular involvement leads to favorable outcomes after endoscopic treatment of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosae (MM) and submucosa up to 200 µm (SM1) has a risk of metastasis. The aims of this study were to investigate the long-term outcome of endoscopic submucosal dissection (ESD) for MM/SM1 ESCC and to assess the management after ESD in our hospital. METHODS: This was a retrospective cohort study conducted at a single institution. Patients with MM or SM1 ESCC who were treated with ESD were included. Additional prophylactic therapy was added if lymphovascular involvement (LVI) was noted in the ESD specimens. RESULTS: A total of 102 patients were analyzed. The median length of follow-up was 71.5 months (range 9 - 144 months) and the median number of CTs was 6 (range 0 - 24). LVI was found in 21 patients (20.6 %), and 12 patients underwent additional prophylactic therapy. The 5-year overall survival, disease-specific survival, and tumor-free survival rates were 84.1 %, 97.5 %, and 82.1 %, respectively. A total of 26 patients died, but only 2 of them died from ESCC. The cumulative metastasis rate was 11.8 %, and LVI was a significant predictor of metastasis (hazard ratio 5.42, 95 % confidence interval 1.39 - 21.18; P = 0.02). There were no differences between patients with MM ESCC and those with SM1 ESCC. CONCLUSIONS: The long-term outcome after ESD for MM/SM1 ESCC was favorable with additional prophylactic therapy and strict adherence to follow-up. These results indicate that our management decision based on LVI is a valid approach and that ESD can be offered as a therapeutic option to MM/SM1 ESCCs.

Long-term outcomes of colorectal endoscopic submucosal dissection in elderly patients.

BACKGROUND AND AIMS: The safety and efficacy of endoscopic submucosal dissection (ESD) in elderly patients remain unclear. The aim of this study is to clarify the short- and long-term outcomes of colorectal ESD in elderly patients. PATIENTS AND METHODS: A total of 482 consecutive patients with 501 colorectal lesions treated with ESD from February 2005 to December 2013 were retrospectively reviewed. Patients were divided into two groups: an elderly group (≥ 75 years of age) and a non-elderly group (< 75 years of age). Short-term outcomes of interest were procedure time, complication rate, hospital stay, en bloc resection rate, and non-curative resection rate. Long-term outcomes of interest were disease-specific survival, and overall survival rates in the elderly group (51 patients) and non-elderly group (92 patients) were also analyzed. RESULTS: No significant differences were observed between the groups with respect to short-term outcomes. Two patients in each group required emergency surgery. Of the patients who underwent non-curative resection, 7/12 (58%) in the elderly group and 15/23 (65%) in the non-elderly group underwent additional surgery. The 5-year disease-specific survival rates in the elderly and non-elderly groups were both 100%, and the corresponding 5-year overall survival rates were 86.3 and 93.5%, respectively (p = 0.026). CONCLUSIONS: Short-term outcomes after colorectal ESD were equivalent in both groups, and all patients showed favorable long-term outcomes. Considering the benign prognosis of lesions resected with ESD, preoperative screening of comorbidities is essential to improve overall survival.

The relationship between iron deficiency in patients with Helicobacter pylori-infected nodular gastritis and the serum prohepcidin level.

BACKGROUND AND AIMS: Helicobacter pylori (H. pylori) is recognized as a causative agent for unexplained iron-deficiency anemia (IDA). We evaluated many background factors influencing an iron-deficiency state in adult patients with various H. pylori-infected upper gastrointestinal tract diseases. METHOD: Study 1: H. pylori-infected 121 patients (nodular gastritis (NG) (n = 19), duodenal ulcer (DU) (n = 30), or gastric ulcer (GU) (n = 47), or gastric hyperplastic polyp (GHP) (n = 25)) were enrolled. The RBC count and hemoglobin, iron, ferritin, pepsinogen (PG) I, PG II, gastrin, and anti-H. pylori antibody (Ab) levels in the serum were measured. Study 2: H. pylori-infected 105 patients (NG, n = 19; DU, n = 43; GU, n = 32; GHP, n = 11) and non-H. pylori-infected individuals (n = 35) were examined for the levels of prohepcidin, ferritin, and iron in the serum. In addition, we measured the data before and after the H. pylori eradication. RESULTS: In the patients with GHP and NG, hypoferritinemia was observed in comparison with the GU and DU patients. In the GHP patients, low levels of PG I, a decreased PG I/II ratio, and hypergastrinemia were observed. The levels of serum prohepcidin in the patients with H. pylori-associated disease were higher than those in the uninfected adults. In the patients with NG, the serum prohepcidin levels were higher than those in the other H. pylori-infected patient groups and decreased after the eradication. CONCLUSION: H. pylori-related iron-deficiency state might be associated with several factors, such as hypochlorhydria and hepcidin, in patients with GHP or NG.

Comparison of Local Recurrence Between LEN-TACE and TACE for Hepatocellular Carcinoma According to Lipiodol Accumulation.

Background/Aim: Transarterial chemoembolization (TACE) is the standard treatment for patients with hepatocellular carcinoma in the intermediate stage; however, with advances in systemic therapy, the indications for TACE have gained significance. While lenvatinib (LEN)-TACE offers the potential for good outcomes, local recurrence has not yet been adequately investigated. Therefore, this study investigated local recurrence factors for each type of TACE, focusing on the lipiodol (Lip) value in LEN-TACE and conventional TACE. Patients and Methods: Fifty patients (50 nodes) with hepatocellular carcinoma and a tumor size <7 cm who underwent LEN-TACE or TACE between January 2022 and June 2023 were included in this study to investigate local recurrence and its influencing factors. Results: The local recurrence rate after LEN-TACE was 5.6% at 6 months and 11.5% at 12 months, whereas those after TACE were 6.4% at 6 months and 13.2% at 12 months (p=0.028). There were no significant differences in local recurrence rates according to background liver factors, alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP) values, sex, age, and albumin-bilirubin (ALBI) score. Lipiodol (Lip) values immediately after LEN-TACE were significantly higher than those after TACE alone (p=0.021). Multivariate analysis showed that LEN-TACE had a recurrence hazard ratio of 0.184. Conclusion: LEN-TACE provided good local tumor control. Local recurrence factors included LEN pretreatment, and Lip CT values were higher immediately after LEN-TACE. Thus, LEN-TACE after upfront LEN administration may increase the effectiveness of TACE.

Determinants of Survival of Ablation Treatment for Portal Vein Tumor Thrombus in Patients With Hepatocellular Carcinoma.

BACKGROUND/AIM: The prognosis of hepatocellular carcinoma (HCC) complicated with portal vein tumor thrombus (PVTT) is extremely poor. This study investigated whether local ablation-a curative treatment similar to resection-could improve the prognosis of patients with Child-Pugh B/C PVTT. PATIENTS AND METHODS: Between January 2020 and December 2023, 25 patients with Child-Pugh B/C PVTT HCC were enrolled, and their overall survival with radiofrequency ablation treatment and the associated drivers were investigated. RESULTS: Overall survival (median 282 days) differed between the group treated with transarterial chemoembolization (TACE, 285 days) and the group without it (159 days, p=0.0151). The median survival in the esophagogastric variceal exacerbation group (120.5 days) was shorter than that in the non-exacerbation group (284.0 days, p=0.00964). In multivariate analysis, concomitant TACE had a hazard ratio (HR) of 0.121 (p=0.0097), and the exacerbation of esophagogastric varices had a HR of 6.761 (p=0.01). CONCLUSION: Local ablation for PVTT may promote patient survival specifically by inhibiting the exacerbation of portal hypertension in patients with hepatocellular carcinoma.

Clinical Efficacy and Body Composition Changes with Sodium Glucose Cotransporter 2 Inhibitor/Glucagon-like Peptide-1 Antagonist Combination Therapy in Patients with Type 2 Diabetes Mellitus-associated Nonalcoholic Fatty Liver Disease.

Objective Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) treatment guidelines recommend sodium glucose cotransporter 2 inhibitor (SGLT2I) and glucagon-like peptide-1 agonist (GLP-1A) therapy in patients with type 2 diabetes mellitus (T2DM). SGLT2I improves the pathological condition of NAFLD/NASH in T2DM patients. However, cases of rebound during long-term SGLT2I treatment have been reported. This study investigated the efficacy of SGLT2I and GLP-1A combination therapy in diabetic patients with NAFLD by examining changes in computed tomography (CT)-based body composition and clinical outcomes. Methods Fifteen patients (5 men/10 women) with T2DM-associated NAFLD who had not responded to SGLT2I treatment and were being treated with GLP-1A combination therapy were included. Changes in the liver function, visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were compared using CT to evaluate the body composition. Results SGLT2I significantly improved alanine aminotransferase (28.0 to 13.0 IU/L), alkaline phosphatase (250.0 to 77.0 IU/L), and gamma glutamyl transpeptidase (23.0 to 12.0 IU/L) levels. The body mass index (BMI) decreased from 25.7 to 25.2 kg/m2. A CT-based analysis showed a significant improvement in SATI (80.9 to 66.1, p=0.002), with no significant change in VATI (53.2 to 51.5). GLP-1A addition improved the BMI (25.2 to 23.5 kg/m2) and hemoglobin A1c (6.5% to 6.2%, p=0.001). A further analysis revealed additional improvement in SATI (66.1 to 56.6, p=0.007) and a significant decrease in VATI (51.5 to 48.3, p=0.001). Conclusion SGLT2I and GLP-1A combination therapy improved the liver function, body composition, and glycemic control in diabetic patients with NAFLD/NASH, as well as SATI and VATI. The optimal timing of combination therapy remains to be determined.

Diagnosis and resolution of olmesartan-associated sprue-like enteropathy confirmed by capsule endoscopy: a case report and literature review.

Herein, we describe a case of olmesartan-associated sprue-like enteropathy, in which improvement in villous atrophy was confirmed using small bowel capsule endoscopy. The patient was a 69-year-old woman who had persistent watery diarrhea (20 bowel movements/day) for 1 year and experienced a weight loss of 10 kg in the same period. Abdominal computed tomography revealed no abnormalities, and blood test results revealed no inflammatory reactions. Upper endoscopy and colonoscopy revealed villous atrophy in the duodenum and terminal ileum. As the patient was administered olmesartan for a long time and capsule endoscopy showed villous atrophy throughout the small bowel, she was diagnosed with olmesartan-associated sprue-like disease. Following the discontinuation of the medication, symptoms of diarrhea soon improved, and repeat capsule endoscopy indicated improvement in small intestinal villous atrophy. Olmesartan-associated sprue-like enteropathy should be considered a differential diagnosis in patients with severe chronic watery diarrhea. Our report is the first in which capsule endoscopy was performed multiple times over a long period for follow-up observation of improvements in the small intestine. In addition, our literature review regarding capsule endoscopy for olmesartan-associated enteritis might aid clinicians in the early diagnosis of the condition and the assessment of treatment efficacy.

Efficacy of Adding Locoregional Therapy in Non-Complete Remission Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab: A Preliminary Study.

BACKGROUND/AIM: Atezolizumab plus bevacizumab (Atez/Bev) therapy is extremely effective and has a high response rate in hepatocellular carcinoma (HCC) treatment. This study investigated the efficacy of adding locoregional therapy with Atez/Bev for non-complete response (CR) HCC cases. PATIENTS AND METHODS: Twenty-eight HCC patients without CR during Atez/Bev therapy received locoregional therapy, and treatment efficacy was evaluated based on the modified RECIST criteria. RESULTS: The study included 23 male and five female participants with a mean age of 73.5 years. In the Atez/Bev and locoregional combination therapy effective group, both transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) were combined in all patients. A significant reduction in neutrophil-to-lymphocyte ratio (NLR) was observed after adding locoregional therapy (p=0.039). Moreover, a combination of TACE and RFA was performed in all patients of the CR group. When assessing the add-on effect of the combination of TACE and RFA in the progressive disease (PD) group, seven patients were found to achieve non-PD. For patients who did not achieve PD, a significant NLR reduction was noted after the addition of locoregional therapy. CONCLUSION: Adding locoregional therapy such as TACE/RFA was found to exert an effect even in non-CR patients who had received Atez/Bev therapy. A reduction in NLR after locoregional therapy was noted. Even when a response is not obtained during Atez/Bev therapy, it is important to avail the option to add locoregional therapy, as it may contribute to improved prognosis via immune modulation with tolerable adverse reactions.

Add-on multiple submucosal injections of the RNA oligonucleotide GUT-1 to anti-TNF antibody treatment in patients with moderate-to-severe ulcerative colitis: an open-label, proof-of concept study.

BACKGROUND: Carbohydrate sulfotransferase 15 (CHST15) is an enzyme biosynthesizing matrix glycosaminoglycan that modulates tissue remodeling. We evaluated the efficacy of add-on submucosal injections of GUT-1, the RNA oligonucleotide inhibitor of CHST15, to ongoing anti-tumor necrosis factor (TNF) antibody treatment in patients with moderate-to-severe ulcerative colitis (UC). METHODS: This was an open-label study of 250 nM of GUT-1 by endoscopic submucosal injections at weeks 0, 2, 4 in five UC patients who lost response during maintenance treatment to anti-TNF antibodies. The primary endpoint was the rate of endoscopic improvement at week 6 and secondary endpoints included the rates of clinical remission by modified Mayo Score (mMS). Patients received follow-up observation with continuous maintenance treatment by the same anti-TNF antibody till the time of clinical recurrence or for overall 52 weeks. RESULTS: At week 6, rates of endoscopic improvement and clinical remission were 80% (n = 4/5) and 60% (n = 3/5), respectively. The mean Endoscopy Subscore was reduced from 2.4 (95%CI: 1.7 to 3.1) at baseline, to 1.0 (95%CI: 0.1 to 1.9) at week 6. The mean mMS was reduced from 7.8 (95%CI: 6.2 to 9.4) to 1.3 (95%CI: 2.9 to 4.3). GUT-1 was well tolerated. Three patients did not show clinical recurrence for 52 weeks. All three corticosteroid-dependent patients showed no corticosteroid exposure for at least 24 weeks after achieving clinical remission. Multiple dosing was also well tolerated. CONCLUSIONS: Add-on multiple injections of GUT-1 to ongoing anti-TNF antibody was able to induce rapid and durable clinical responses in UC patients who lost response to anti-TNF therapy. TRIAL REGISTRATION: Clinical trial Registration Number (Japan): UMIN000020900.