Published papers

© 2018 Togasaki et al. Standard treatment options for patients with advanced gastric cancer (GC) offer limited efficacy and are associated with some toxicity, which necessitates the development of more effective therapies for improving the treatment outcomes for this disease. Immunotherapy involving immune checkpoint inhibitors (ICIs) which inhibit the programmed death 1 (PD-1)/ programmed death ligand 1 interaction has emerged as a new treatment option. Nivolumab, a human IgG4 monoclonal antibody inhibitor of PD-1, has demonstrated promising clinical activity and induced durable responses in patients with advanced GC. Nivolumab has recently been approved for treating patients with pretreated advanced GC in Japan. In the present review, we summarized current evidence of the clinical efficacy of ICIs in a variety of solid tumors and reported our experience in patients with GC who were treated with nivolumab and the interesting features that were observed in these cases. Certain ICI-specific clinical features such as pseudo-and hyper-progression of tumor and hyper-response to subsequent chemotherapy have been reported in several cancer types. Lastly, we discussed the present scenario regarding research on biomarkers for assessing the clinical benefits of ICI therapies.

© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd Background and Aim: A significant percentage of patients with colonic diverticular bleeding (CDB) experience bleeding that is severe enough to necessitate prolonged hospitalization. Prolonged hospitalization causes deterioration in patients' quality of life, as well as difficulties with cost-effective utilization of medical resources, and is a financial burden to the society. Therefore, we investigated the factors associated with the length of hospitalization for the optimal management of patients hospitalized with CDB. Methods: This study included patients who were hospitalized for the treatment of CDB and underwent colonoscopy between July 2008 and February 2016. Logistic regression analysis was performed to investigate the association between the length of hospitalization and the patients' baseline characteristics, in-hospital procedures performed, and the clinical outcomes. Results: The study included 223 patients. Diabetes mellitus (odds ratio [OR] 3.4, P = 0.014) and blood transfusion (OR 3.1, P = 0.0006) were identified as risk factors for prolonged hospitalization (≥ 8 days). Urgent colonoscopy (OR 0.41, P = 0.0072) predicted a shorter length of hospitalization (≤ 7 days). The study also indicated that endoscopic treatment showed a stronger association with urgent colonoscopy (OR 7.8, P < 0.0001) than with elective colonoscopy and that urgent colonoscopy was not associated with an increased rate of adverse events or re-bleeding. Conclusions: Compared with elective colonoscopy, urgent colonoscopy shortens the length of hospitalization in patients with CDB. Moreover, it is not associated with an increased rate of adverse events. Urgent colonoscopy may be impracticable in a few cases; however, if possible, aggressive urgent colonoscopy should be considered for the efficient management of the patient's hospital stay.

Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com. BACKGROUND: Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn's disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. METHODS: In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. RESULTS: There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher's exact test, p <0.001]. Kaplan-Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. CONCLUSIONS: Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

The small intestine is the main organ for nutrient absorption, and its extensive resection leads to malabsorption and wasting conditions referred to as short bowel syndrome (SBS). Organoid technology enables an efficient expansion of intestinal epithelium tissue in vitro1, but reconstruction of the whole small intestine, including the complex lymphovascular system, has remained challenging2. Here we generate a functional small intestinalized colon (SIC) by replacing the native colonic epithelium with ileum-derived organoids. We first find that xenotransplanted human ileum organoids maintain their regional identity and form nascent villus structures in the mouse colon. In vitro culture of an organoid monolayer further reveals an essential role for luminal mechanistic flow in the formation of villi. We then develop a rat SIC model by repositioning the SIC at the ileocaecal junction, where the epithelium is exposed to a constant luminal stream of intestinal juice. This anatomical relocation provides the SIC with organ structures of the small intestine, including intact vasculature and innervation, villous structures, and the lacteal (a fat-absorbing lymphatic structure specific to the small intestine). The SIC has absorptive functions and markedly ameliorates intestinal failure in a rat model of SBS, whereas transplantation of colon organoids instead of ileum organoids invariably leads to mortality. These data provide a proof of principle for the use of intestinal organoids for regenerative purposes, and offer a feasible strategy for SBS treatment.

The aim of this study was to determine the risk factors for immune-related adverse events (irAEs) induced by immune checkpoint inhibitors. The authors conducted a retrospective study in which patients with malignant melanoma, non-small-cell lung cancer, gastric cancer or renal cell carcinoma who received anti-PD-1/PD-L1 antibodies were included. Of 247 patients, 118 developed a total of 182 irAEs. In the multivariate Fine-Gray regression analysis, serum albumin level ≥3.6 g/dl (hazard ratio: 1.62; 95% CI: 1.10-2.39; p = 0.015) and history of Type I hypersensitivity reactions (hazard ratio: 1.48; 95% CI: 1.02-2.14; p = 0.037) were significantly associated with the development of irAEs. High serum albumin levels and history of Type I hypersensitivity reactions are risk factors for irAEs.

Background/Aims: PF-00547659 is a monoclonal antibody against human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) that prevents the binding of α4β7+ lymphocytes to MAdCAM-expressing sites in the gastrointestinal tract with high affinity and selectivity, and is being developed for the treatment of Crohn's disease (CD). Methods: OPERA is a randomized, multicenter, double-blind, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of PF-00547659 following subcutaneous administration in subjects with active CD, a history of failure or intolerance to anti-tumor necrosis factor and/or immunosuppressants, high-sensitivity C-reactive protein >3.0 mg/L, and ulcers on colonoscopy. The primary endpoint was Crohn's Disease Activity Index-70 response at week 8 or 12. Subpopulation analyses for Asian subjects were performed as some differences are observed in genetics and clinical phenotypes in Asian CD patients compared with Western patients. Results: In this study, 265 CD subjects were randomized, with a subpopulation of 21 subjects (8 Japanese and 13 Korean) defined as the Asian population. In the overall and Asian populations; PF-00547659 was pharmacologically active as evidenced by soluble MAdCAM and circulating β7+ central memory CD4+ T-lymphocytes, although no clear evidence of efficacy was observed in any clinical endpoints; pharmacokinetics of PF-00547659 in the Asian subpopulation was generally comparable to the overall population; and the safety profile of PF-00547659 appeared acceptable up to 12 weeks of treatment. Conclusions: In the overall and Asian populations, efficacy of PF-00547659 could not be demonstrated using any clinical endpoints compared with placebo. Pharmacokinetics and safety of PF-00547659 were generally comparable. Further studies with larger numbers of patients are required to confirm our results.

Aims/hypothesis: Accumulation of adipose tissue macrophages is considered pivotal in the development of obesity-associated inflammation and insulin resistance. In addition, recent studies suggest an involvement of the intestine as the primary organ in inducing hyperglycaemia and insulin resistance. We have reported that the C-C motif chemokine receptor (CCR) CCR9 is associated with intestinal immunity and has a pathogenic role in various liver diseases. However, its contribution to type 2 diabetes is unknown. In the current study, we aimed to clarify the involvement of CCR9 in the pathology of type 2 diabetes and the potential underlying mechanisms. Methods: To elucidate how CCR9 affects the development of metabolic phenotypes, we examined the impact of CCR9 deficiency on the pathogenesis of type 2 diabetes using male C57BL/6J (wild-type [WT]) and CCR9-deficient (CCR9 knockout [KO]) mice fed a 60% high-fat diet (HFD) for 12 weeks. Results: WT and Ccr9KO mice fed an HFD exhibited a comparable weight gain; however, glucose tolerance and insulin resistance were significantly improved in Ccr9KO mice. Moreover, visceral adipose tissue (VAT) and the liver of Ccr9KO mice presented with less inflammation and increased expression of glucose metabolism-related genes than WT mice. Ccr9 and Ccl25 expression were specifically higher in the small intestine but was not altered by HFD feeding and type 2 diabetes development. Accumulation of IFN-γ-producing CD4+ T lymphocytes and increased intestinal permeability in the small intestine was observed in WT mice following HFD feeding, but these changes were suppressed in HFD-fed Ccr9KO mice. Adoptive transfer of gut-tropic CCR9-expressing T lymphocytes partially reversed the favourable glucose tolerance found in Ccr9KO mice via exacerbated inflammation in the small intestine and VAT. Conclusions/interpretation: CCR9 plays a central role in the pathogenesis of type 2 diabetes by inducing an inflammatory shift in the small intestine. Our findings support CCR9 as a new therapeutic target for type 2 diabetes via the gut–VAT–liver axis. Graphical abstract: [Figure not available: see fulltext.]

Background: Ulcerative colitis (UC) is characterized by chronic intestinal epithelial damage, and previous studies have evaluated the epithelial structure of patients with active UC using electron microscopy. Aims: This study aimed to assess the intestinal epithelial structure using scanning electron microscopy (SEM) and the features of patients with UC who are in remission. Methods: In total, eight healthy controls and 20 patients with UC were enrolled, and colonic tissue samples from the cecum and rectum were collected. Then, we compared the epithelial surface structure on SEM between patients with UC who are in clinical remission and healthy controls. Results: In healthy controls, the colonic surface comprises small lobes (termed units), with one crypt located in the middle of each unit. In patients with UC, we found irregular unit and crypt mouth size, double crypt sign (> 1 crypt per unit), and lower number of small vesicles in the intestinal epithelial cells. Compared with healthy controls, patients with UC often presented with irregular unit size, double crypt sign, and irregular crypt mouth size in the rectum. The small vesicles were observed less frequently in patients with UC than in healthy controls. Conclusions: SEM revealed a unique epithelial structure in patients with UC who are in remission.

Background & Aims: Traditional serrated adenomas (TSAs) are rare colorectal polyps with unique histologic features. Fusions in R-spondin genes have been found in TSAs, but it is not clear whether these are sufficient for TSA development, due to the lack of a chromosome engineering platform for human tissues. We studied the effects of fusions in R-spondin genes and other genetic alterations found in TSA using CRISPR-Cas9–mediated chromosome and genetic modification of human colonic organoids. Methods: We introduced chromosome rearrangements that involve R-spondin genes into human colonic organoids, with or without disruption of TP53, using CRISPR-Cas9 (chromosome-engineered organoids). We then knocked a mutation into BRAF encoding the V600E substitution and overexpressed the GREM1 transgene; the organoids were transplanted into colons of NOG mice and growth of xenograft tumors was measured. Colon tissues were collected and analyzed by immunohistochemistry or in situ hybridization. We also established 2 patient-derived TSA organoid lines and characterized their genetic features and phenotypes. We inserted a bicistronic cassette expressing a dimerizer-inducible suicide gene and fluorescent marker downstream of the LGR5 gene in the chromosome-engineered organoids; addition of the dimerizer eradicates LGR5+ cells. Some tumor-bearing mice were given intraperitoneal injections of the dimerizer to remove LGR5-expressing cells. Results: Chromosome engineering of organoids required disruption of TP53 or culture in medium containing IGF1 and FGF2. In colons of mice, organoids that expressed BRAFV600E and fusions in R-spondin genes formed flat serrated lesions. Patient-derived TSA organoids grew independent of exogenous R-spondin, and 1 line grew independent of Noggin. Organoids that overexpressed GREM1, in addition to BRAFV600E and fusions in R-spondin genes, formed polypoid tumors in mice that had histologic features similar to TSAs. Xenograft tumors persisted after loss of LGR5-expressing cells. Conclusions: We demonstrated efficient chromosomal engineering of human normal colon organoids. We introduced genetic and chromosome alterations into human colon organoids found in human TSAs; tumors grown from these organoids in mice had histopathology features of TSAs. This model might be used to study progression of human colorectal tumors with RSPO fusion gene and GREM1 overexpression.

Pyogenic granuloma (PG) generally appears in the skin or oral cavity, but rarely occurs in the small intestine, where it can cause bleeding. To date, only 35 cases of small intestinal PG have been reported in the English literature. We retrospectively collected information from the clinical records of seven cases of small intestinal PG that were managed in our hospital and summarized the characteristics. Further information on the clinical characteristics was obtained from the literature. Capsule endoscopy, useful for identifying the source of hemorrhage in obscure gastrointestinal bleeding, can detect PGs. Treatment can often be accomplished with endoscopic mucosal resection.

Background: We have previously reported that Helicobacter pylori (H. pylori)-associated nodular gastritis could occur in both the antrum and the cardia. Cardiac nodularity-like appearance (hereafter, called as cardiac nodularity) had a high predictive accuracy for the diagnosis of H. pylori infection. In the previous study, we included only the patients who were evaluated for H. pylori infection for the first time, and excluded patients with a history of eradication. Therefore, the prevalence and clinical features of cardiac nodularity remains unknown. Aim: To perform this cross-sectional study to explore the characteristics of cardiac nodularity. Methods: Consecutive patients who underwent esophagogastroduodenoscopy between May, 2017 and August, 2019 in the Toyoshima Endoscopy Clinic were enrolled in this study. We included H. pylori-negative, H. pylori-positive, and H. pylorieradicated patients, and excluded patients with unclear H. pylori status and eradication failure. H. pylori infection was diagnosed according to serum anti-H. pylori antibody and the urea breath test or histology. Cardiac nodularity was defined as a miliary nodular appearance or the presence of scattered whitish circular small colorations within 2 cm of the esophagogastric junction. Nodularity was visualized as whitish in the narrow-band imaging mode. We collected data on the patients' baseline characteristics. Results: A total of 1078 patients were finally included. Among H. pylori-negative patients, cardiac nodularity and antral nodularity were recognized in 0.14% each. Among H. pylori-positive patients, cardiac nodularity and antral nodularity were recognized in 54.5% and 29.5%, respectively. Among H. pylori-eradicated patients, cardiac nodularity and antral nodularity were recognized in 4.5% and 0.6%, respectively. The frequency of cardiac nodularity was significantly higher than that of antral nodularity in H. pylori-positive and -eradicated patients. The frequencies of cardiac nodularity and antral nodularity in H. pylori-eradicated patients were significantly lower than those in H. pylori-positive patients (P < 0.001). The patients with cardiac nodularity were significantly younger than those without cardiac nodularity (P = 0.0013). Intestinal metaplasia score of the patients with cardiac nodularity were significantly lower than those without cardiac nodularity (P = 0.0216). Among H. pylori-eradicated patients, the patients with cardiac nodularity underwent eradication significantly more recently compared with those without cardiac nodularity (P < 0.0001). Conclusion: This report outlines the prevalence and clinical features of cardiac nodularity, and confirm its close association with active H. pylori infection.

Background: Prognostic value or clinical implications of fluid status monitoring in liver cirrhosis are not fully elucidated. Tolvaptan, an orally available, selective vasopressin V2-receptor antagonist approved for hyponatremia in the United States and European Union. It is also used for cirrhotic ascites at a relatively low dose (3.75 mg to 7.5 mg) in Japan, exerts its diuretic function by excreting electrolyte-free water. We hypothesized that bioimpedance-defined dynamic changes in fluid status allow prediction of response of V2 antagonism and survival in cirrhotic patients. Methods: In this prospective observational study, 30 patients with decompensated liver cirrhosis who were unresponsive to conventional diuretics were enrolled. Detailed serial changes of body composition that were assessed by using non-invasive bioimpedance analysis (BIA) devices, along with biochemical studies, were monitored at 5 time points. Results: Sixteen patients were classified as short-term responders (53%). Rapid and early decrease of BIA-defined intracellular water, as soon as 6 h after the first dose (ΔICWBIA%-6 h), significantly discriminated responders from non-responders (AUC = 0.97, P < 0.0001). ΔICWBIA%-6 h was highly correlated with the change of BIA-derived phase angle of trunk, e.g. reduced body reactance operated at 50 kHz after 24 h of the first dose of tolvaptan. Lower baseline blood urea nitrogen and lower serum aldosterone were predictive of a rapid and early decrease of ICWBIA. A rapid and early decrease of ICWBIA in response to tolvaptan was also predictive of a better transplant-free survival. Conclusions: BIA-defined water compartment monitoring may help predict short-term efficacy and survival in decompensated cirrhotic patients treated with tolvaptan.

© 2018, Author(s) 2018. Background: The need for a blood transfusion, defined as hemoglobin < 70 g/L, is the measure for assessing the risk levels in patients with upper gastrointestinal bleeding (UGIB). However, not all patients with a low hemoglobin level have a poor prognosis. Objective: We assessed the clinical predictive factors associated with poor short-term prognosis in patients with a low hemoglobin level. Methods: In this prospective cohort study, all consecutive patients with suspected acute UGIB at Tokyo Metropolitan Tama Medical Center were enrolled between 2008 and 2015. Then, we extracted those who needed a blood transfusion (hemoglobin < 70 g/L) and explored the variables associated with all-cause mortality within 28 days after presentation. Results: Among 1307 patients, 311 needed a blood transfusion and 13 (4.2%) died from all causes. The presence of high-risk stigmata requiring endoscopic treatment (peptic ulcers; Forrest scores Ia, Ib and IIa; varices with current bleeding or signs of recent bleeding; and spurting or gushing bleeding or visible vessel in other diseases), diagnosed by emergency endoscopy, was a unique factor affecting mortality (odds ratio: 8.47, 95% confidence interval: 1.45–160, P = 0.01). Patients without high-risk stigmata neither died from UGIB nor had rebleeding, irrespective of the hemoglobin levels. Conclusions: Patients without high-risk stigmata showed a good prognosis even if they needed a blood transfusion. This result could facilitate triage of patients with suspected acute UGIB who only need a blood transfusion.

© 2017, © Author(s) 2017. Background and aim: Although sitafloxacin (STFX)-containing regimens are effective rescue treatments for Helicobacter pylori infection, prevalence of fluoroquinolone resistance in H. pylori has increased rapidly worldwide. The change in resistance levels and gyrA mutations, a major cause of fluoroquinolone resistance, after unsuccessful STFX-containing treatment has not been investigated. Methods: We conducted a retrospective, non-randomized study to compare the minimum inhibitory concentrations (MICs) of STFX and the location of gyrA mutations in H. pylori before and after unsuccessful eradication with STFX-containing regimens at Keio University Hospital between December 2011 and March 2015. Results: A total of 266 patients treated with STFX-containing regimens for third-line H. pylori eradication were evaluated. Double mutations in gyrA were acquired by 20.8% of strains that exhibited seven-fold increased STFX MICs, compared to pre-treatment MICs. The STFX MICs did not increase, however, when the location of the gyrA mutations did not change after treatment. Double mutations in gyrA developed in 60.0% of the strains in which eradication failed, which exhibited a baseline mutation at position D91, and in 11.1% of strains with baseline mutations at position N87. Conclusion: Acquisition of double mutations in gyrA evoked high-level resistance to STFX in H. pylori after unsuccessful eradication with STFX-containing regimens.

© 2018. Korean Association for the Study of Intestinal Diseases. Ulcerative colitis (UC) is one of the major clinical phenotypes of inflammatory bowel diseases. Although 5-aminosalicylic acid (5-ASA) is widely used for UC and its efficacy and safety have been demonstrated, a few patients paradoxically develop a severe exacerbation of colitis by 5-ASA administration. It is crucial to know clinical features including endoscopic findings in this condition for making a correct diagnosis and a prompt decision to withdraw the medication. Here, we report case series with UC exacerbated by 5-ASA. Medical records of 8 UC patients experiencing an exacerbation of colitis after induction of 5-ASA that was improved by the withdrawal of 5-ASA but also re-aggravated by dose increase or re-administration of 5-ASA were reviewed. The patients were newly diagnosed with UC, started 5-ASA and developed an exacerbation in approximately 2 to 3 weeks. They did not appear to have systemic allergic reactions. Seven of the 8 patients had a high fever. Three of 5 patients who undertook total colonoscopy showed right-side-dominant colitis. These findings suggest clinical characteristics in this condition. Further assessment of clinical and endoscopic features in more cases is necessary for establishing diagnostic criteria and understanding underlying mechanisms in those cases where 5-ASA aggravates the colitis.

© 2019, Japanese Society of Gastroenterology. Background: Although indigo naturalis (IN) is effective for patients with active ulcerative colitis (UC), IN was associated with adverse events (AEs), including pulmonary arterial hypertension (PAH). Our aim was to evaluate the occurrence of IN-associated AEs and to evaluate any IN dose–effect on AEs. Methods: A nationwide survey, using questionnaires, was conducted by conducted by the research group funded by the Ministry of Health, Labour and Welfare of Japan, between June 2017 and September 2018. A first questionnaire determined the occurrence of AEs associated with the therapeutic use of IN or herbal medicines containing IN in patients with UC. A second survey identified the clinical characteristics of patients who developed IN-associated critical AEs, namely, liver dysfunction, PAH, and intussusception. Results: Across 337 participating institutions, 49,320 patients with UC were identified, with IN used in 877 (1.8%). AEs were reported in 91 patients (107 events), including liver dysfunction (n = 40), gastrointestinal symptoms (n = 21), headache (n = 13), and PAH (n = 11). No dose–effect relationship between IN and AEs was identified. Liver dysfunction tended to be mild and reversible. Ten cases of intussusception were reported, with 40% of these patients requiring surgical resection. IN-induced PAH was recovered in patients who discontinued to use IN. No IN-associated deaths were reported. Conclusions: IN-associated AEs were identified among patients with UC, with liver dysfunction often being reversible, while surgical resection was required in a high proportion of patients who developed intussusception. Both healthcare workers and patients should adequately recognize the potential for AEs with the use of IN.

© 2019 S. Karger AG, Basel. All rights reserved. Background/Aims: Sitafloxacin (STFX)-containing regimens were shown to be useful options for third-line Helicobacter pylori eradication therapy. It is reported that resistance to quinolone is also increasing globally. Therefore, we conducted an analysis of the current efficacy of a 10-day-STFX-containing third-line rescue therapy and the changes of antibiotic resistance to H. pylori compared to 2 historical controls. Methods: Patients in whom eradication treatment using both first-and second-line triple therapies failed were enrolled from 2014 to 2015. The minimum inhibitory concentrations of STFX, clarithromycin (CLR), amoxicillin (AMX), metronidazole (MTZ) and the gyrA mutation status of the H. pylori strains were determined before treatment. After that, the patients received a 10-day triple therapy containing esomeprazole (20 mg, b.i.d.), AMX (500 mg, q.i.d.) and STFX (100 mg, b.i.d.; 10-day EAS). The eradication rate and the rate of antibiotic resistance to H. pylori were compared with 2 previous reports about STFX-containing third-line rescue therapies in 2009-2011 and 2012-2013. To explore the association between the eradication rates of regimens containing STFX, AMX and proton pump inhibitors and the location of gyrA mutation or AMX resistance, a meta-analysis was attempted. Results: The overall eradication rates, the eradication rate for gyrA mutation negative-and positive-strains were 81.6% (31/38), 94.7% (18/19) and 68.4% (13/19) respectively. These rates were not significantly different from 2 previous reports. The resistant rates to STFX, CLR, AMX, MTZ and the rate of presence of mutation in gyrA were 50.0, 81.6, 36.8, 78.9 and 50.0%, respectively, which was also not significantly different from 2 previous reports. A meta-analysis showed that the relative risk of the eradication failure is significantly lower in gyrA mutation negative strains compared to gyrA mutation positive strains, and that the relative risk of the eradication failure is significantly lower in gyrA mutation at D91 compared to gyrA mutation at N87 (p < 0.001 and p = 0.022, respectively). Moreover, a meta-analysis showed that the relative risk of the eradication failure is significantly lower in AMX-sensitive strains compared to AMX-resistant ones. Conclusion: Changes in the rate of antibiotic resistance to H. pylori were not observed from 2009 to 2015. The status of gyrA mutation is a superior marker for predicting successful eradication in STFX/AMX-containing triple regimen as a third-line rescue therapy.

Background/Aims: 5-Aminosalicylic acid (ASA) causes intolerance reactions in some patients. This study was performed to examine the prognosis of patients with ulcerative colitis (UC) and 5-ASA intolerance, and to evaluate the potential interaction between 5-ASA intolerance and the intestinal microbiota. Methods: We performed a retrospective cohort study of patients with UC who visited participating hospitals. The primary endpoint was to compare the incidence of hospitalization within 12 months between the 5-ASA intolerance group and the 5-ASA tolerance group. The secondary endpoint was to compare the risk of adverse clinical outcomes after the start of biologics between the 2 groups. We also assessed the correlation between 5-ASA intolerance and microbial change in an independently recruited cohort of patients with UC. Results: Of 793 patients, 59 (7.4%) were assigned to the 5-ASA intolerance group and 734 (92.5%) were assigned to the 5-ASA tolerance group. The admission rate and incidence of corticosteroid use were significantly higher in the intolerance than tolerance group (P<0.001). In 108 patients undergoing treatment with anti-tumor necrosis factor biologics, 5-ASA intolerance increased the incidence of additional induction therapy after starting biologics (P<0.001). The 5-ASA intolerance group had a greater abundance of bacteria in the genera Faecalibacterium, Streptococcus, and Clostridium than the 5-ASA tolerance group (P<0.05). Conclusions: In patients with UC, 5-ASA intolerance is associated with a risk of adverse clinical outcomes and dysbiosis. Bacterial therapeutic optimization of 5-ASA administration may be important for improving the prognosis of patients with UC.

An 87-year-old man with an enlarged hepatic tumor was referred to our institute by a medical examination center. He had been diagnosed with a malignant liver tumor through several contrast imaging studies. Because of the patient’s age, the underlying disease, and the absence of bile duct invasion on imaging, radiofrequency ablation (RFA) was selected as a treatment option. A histological examination during the RFA procedure revealed the tumor to be a cholangiocellular carcinoma. In addition, the deposition of Thorotrast, a contrast agent used in the 1930s to 1950s, was suspected in the background liver collected simultaneously. Radiofrequency ablation was performed twice for recurrent lesions, and the tumor was controlled for roughly 3 years following the initial treatment. A case of intrahepatic cholangiocellular carcinoma due to Thorotrast deposition was observed and successfully controlled by RFA. Since intrahepatic cholangiocellular carcinoma from Thorotrast deposition occurs multicentrically and intrahepatically, RFA and other local therapies may present effective options for older patients with cholangiocarcinoma who are at a higher risk of surgical resection intolerance.