A Report of Ulcerative Colitis With Relapse on the Rectal Side of the Loop Sigmoid Colostomy and Not on the Oral Side.

A patient who received a loop sigmoid colostomy was diagnosed with ulcerative colitis (pancolitis type) and treated with infliximab. Thereafter, he relapsed with intestinal inflammation only on the rectal side of the loop sigmoid colostomy and not on the oral side. Autologous fecal microbiota transplantation from the proximal intestine to the distal intestine was performed to treat the inflammation but was ineffective. He was treated with oral prednisolone and induced into remission. After analyzing fecal samples from the patient, we observed an alteration of the composition of the intestinal microbiota with intestinal inflammation, including a reduction of phylum Firmicutes in the inflamed distal intestine, whereas Firmicutes was conserved in the proximal non-inflamed intestine and recovered in the distal intestine after induction of remission. Thus, our results indicated that the inflammation was associated with an alteration of the intestinal microbiota.

Mediation of Ferroptosis Suppressor Protein 1 Expression via 4-Hydroxy-2-Nonenal Accumulation Contributes to Acquisition of Resistance to Apoptosis and Ferroptosis in Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. New therapeutic strategies are needed for the treatment of refractory DLBCL. 4-Hydroxy-2-nonenal (4-HNE) is a cytotoxic lipid peroxidation marker, which alters intracellular signaling and induces genetic mutations. Lipid peroxidation is associated with nonapoptotic cell death, called ferroptosis. However, the relationship between 4-HNE accumulation and feroptotic regulators in DLBCL has not been fully evaluated. Here, we aimed to evaluate the accumulation of lipid peroxide and the expression of ferroptosis suppressor protein 1 (FSP1) in DLBCL using immunohistochemistry. We found a significant increase in the expression of FSP1 in cases with nuclear 4-HNE accumulation (P = .021). Both nuclear and cytoplasmic 4-HNE accumulation and FSP1 positivity were independent predictors of worse prognosis. In vitro exposure to 4-HNE resulted in its concentration- and time-dependent intracellular accumulation and increased expression of FSP1. Furthermore, short-term (0.25 and 1.0 µM) or long-term (0.25 µM) exposure to 4-HNE induced resistance to not only apoptosis but also ferroptosis. Taken together, regulation of FSP1 through 4-HNE accumulation may attenuate resistance to cell death in treatment-resistant DLBCL and might help develop novel therapeutic strategies for refractory DLBCL.

Helicobacter pylori Eradication Does Not Adversely Affect the Clinical Course of Gastric Cancer: A Multicenter Study on Screening Endoscopic Examination in Japan.

BACKGROUND: Since gastric cancers (GCs) detected after Helicobacter pylori (HP) eradication present with different morphological characteristics from conventional HP-positive GCs, delayed detection of early-stage GCs may be observed. This study aimed to investigate the clinical impact of HP eradication on diagnosing GC during screening endoscopy. METHODS: Eleven health checkup institutions in Japan participated in the present study. All GC cases newly diagnosed by screening endoscopy between January 2016 and December 2020 were included. After propensity score matching, multivariable regression analysis was performed to estimate the effect of HP eradication on deep tumor invasion among HP-eradicated and HP-positive GC cases. RESULTS: A total of 231 patients with GCs (134 HP-eradicated and 97 HP-positive cases) were enrolled. After propensity score matching, there were 81 cases in each group. The distribution of the depth of tumor invasion (pT1a, pT1b1, pT1b2, and pT2) between the HP-eradicated group and HP-positive group was similar (p = 0.82). In the propensity analysis, with HP-positive as the reference value, HP eradication was not significantly associated with T1b-T4-GCs and T1b2-T4-GCs, with odds ratios (95% confidence intervals) of 1.16 (0.48-2.81) and 1.16 (0.42-3.19), respectively. CONCLUSIONS: HP eradication does not adversely affect the clinical course of GCs, supporting the recommendation of HP eradication in screening programs to reduce the total number of GC cases without delaying diagnosis.

Iron overload in patients with Crohn's disease with short bowel syndrome who received long-term parenteral nutrition with trace elements.

Crohn's disease patients often need regular home parenteral nutrition (HPN) for intestinal failure due to multiple intestinal resections. Trace elements are necessary for long-term HPN but the requirement volume of iron is undetermined. We describe three patients with Crohn's disease with short bowel syndrome (SBS) who had iron overload as a result of long-term HPN including iron. Serum ferritin level was significantly decreased through depleting intravenous iron administration in all cases. One patient needed regular insulin injection and phlebotomy for diabetes mellitus due to hemochromatosis, and intravenous iron administration had a significant impact on the patient's health. Long-term routine intravenous iron administration should be cautious in SBS patients to avoid the overload.

Disproportionate cancer worries in ultra-short-segment Barrett's esophagus in Japan.

Objectives: Although Barrett's esophagus (BE), especially ultra-short-segment BE (USSBE), is very frequently diagnosed in Japan, how subjects feel about receiving a diagnosis of BE is unclear. We therefore prospectively investigated cancer worry in subjects who received a BE diagnosis. Methods: Self-administered questionnaires were sent to subjects who were diagnosed with BE at three health checkup institutes in Akita Prefecture, Japan. The cancer worry scale (CWS) was used to quantitatively assess the fear of developing cancer. The BE subjects were classified into USSBE <1 cm and non-USSBE ≥1 cm groups. Factors associated with the CWS were investigated using logistic regression analyses. Results: A total of 325 (31%) subjects, comprising 229 USSBE and 96 non-USSBE patients were included in this study. Compared with the USSBE group, the non-USSBE group had a significantly higher frequency of a history of a BE diagnosis and perception of carcinogenesis. However, the CWS was similar between the USSBE and non-USSBE groups, with a median CWS of 12.5 (3.75) versus 12.7 (3.65). A multivariate logistic regression analysis revealed that while positive reflux symptoms were significantly associated with a positive CWS, the BE length was not significantly associated with it, with an odds ratio (95% confidence interval) of 1.3 (0.75-2.2). Conclusions: A BE diagnosis promotes a similar level of worry about cancer among subjects, irrespective of the length of BE. In Japan, since USSBE poses a much lower cancer risk than non-USSBE, the former may frequently be associated with a disproportionate cancer worry relative to the latter. (UMIN000044010).

[A case of severe inflammatory bowel disease triggered by vaccination with SARS-CoV-2 mRNA].

A 64-year-old woman received a third dose of SARS-CoV-2 mRNA vaccine. On the next day, she developed fever, diarrhea, and abdominal pain and had bloody stools. Total colonoscopy revealed deep ulceration on the whole colon. She was treated with corticosteroid and infliximab and her symptoms improved. She was diagnosed with severe enteritis resembling ulcerative colitis triggered by SARS-CoV-2 mRNA vaccination.

Nature and Clinical Outcomes of Acute Hemorrhagic Rectal Ulcer.

Acute hemorrhagic rectal ulcer (AHRU) is a relatively rare disease that can lead to massive hematochezia. Although AHRU is a potentially life-threatening disease, its characteristics and clinical course are not fully understood. In this study, the clinical features were compared between AHRU and lower gastrointestinal bleeding (LGIB) from other causes (non-AHRU). Then, risk factors for all-cause in-hospital mortality in patients with AHRU were identified. A total of 387 consecutive adult patients with LGIB who were managed at two tertiary academic hospitals in Akita prefecture in Japan were retrospectively enrolled. Subjects were divided into AHRU and non-AHRU groups according to the source of bleeding. Regression analyses were used to investigate significant associations, and the results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). AHRU was found as the bleeding source in 72 (18.6%) of the patients. In comparison to non-AHRU, having AHRU was significantly associated with in-hospital onset, age > 65 years, and systolic blood pressure < 90 mmHg. The AHRU group had a significantly higher in-hospital mortality rate in comparison to the non-AHRU group (18.0% vs. 8.3, p = 0.02), and hypoalbuminemia (<2.5 g/dL) was significantly associated with in-hospital mortality in the AHRU group (OR, 4.04; 95%CI, 1.11−14.9; p = 0.03). AHRU accounts for a substantial portion (18.6%) of LGIB in our area, where the aging rate is the highest in Japan. Since AHRU is a potentially life-threatening disease that requires urgent identification and management, further studies to identify robust risk factors associated with serious clinical outcomes are required.

Usefulness of the CHAMPS score for risk stratification in lower gastrointestinal bleeding.

We have recently developed a simple prediction score, the CHAMPS score, to predict in-hospital mortality in patients with upper gastrointestinal bleeding. In this study, the primary outcome of this study was the usefulness of the CHAMPS score for predicting in-hospital mortality with lower gastrointestinal bleeding (LGIB). Consecutive adult patients who were hospitalized with LGIB at two tertiary academic medical centers from 2015 to 2020 were retrospectively enrolled. The performance for predicting outcomes with CHAMPS score was assessed by a receiver operating characteristic curve analysis, and compared with four existing scores. In 387 patients enrolled in this study, 39 (10.1%) of whom died during the hospitalization. The CHAMPS score showed good performance in predicting in-hospital mortality in LGIB patients with an AUC (95% confidence interval) of 0.80 (0.73-0.87), which was significantly higher in comparison to the existing scores. The risk of in-hospital mortality as predicted by the CHAMPS score was shown: low risk (score ≤ 1), 1.8%; intermediate risk (score 2 or 3), 15.8%; and high risk (score ≥ 4), 37.1%. The CHAMPS score is useful for predicting in-hospital mortality in patients with LGIB.

Leucine-Rich Alpha-2 Glycoprotein in Monitoring Disease Activity and Intestinal Stenosis in Inflammatory Bowel Disease.

Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for monitoring disease activity in inflammatory bowel disease (IBD). The aim of this study was to evaluate its utility in monitoring disease activity. In this retrospective study based on case records between August 2020 and July 2021 at our two centers, we examined the correlation between serum levels of LRG and C-reactive protein (CRP) with disease activity in IBD patients. Background factors related to serum LRG levels were also analyzed. Overall, 47 Crohn's disease (CD) and 123 ulcerative colitis (UC) patients were evaluated. In patients with CD, LRG and CRP levels correlated with Harvey-Bradshaw Index (HBI) and Simple Endoscopic Score for CD (SES-CD) (LRG and HBI, r = 0.397; LRG and SES-CD, r = 0.637; CRP and HBI, r = 0.253; CRP and SES-CD, r = 0.332). In patients with UC, LRG and CRP significantly correlated with the partial Mayo score (PMS) and Mayo endoscopic subscore (MES) (LRG and PMS, r = 0.3; CRP and PMS, r = 0.282; LRG and MES, r = 0.424; CRP and MES, r = 0.459). In CD patients with normal CRP, serum LRG level was significantly higher in those with mucosal inflammation than in those with mucosal healing (16.4 vs. 10.7 µg/ mL). Stenosis was associated with serum LRG levels in CD group using multiple regression analysis. Therefore, LRG is a useful biomarker for monitoring disease activity and mucosal inflammation, and indicates the status of intestinal stenosis in IBD patients.

Stratification of lung squamous cell carcinoma based on ferroptosis regulators: Potential for new therapeutic strategies involving ferroptosis induction.

OBJECTIVES: Lung squamous cell carcinoma (LSCC) exhibits poor response to treatment compared with other lung cancer subtypes, resulting in worse prognosis. Therefore, new therapeutic strategies are required for advanced LSCC. Ferroptosis is a recently discovered nonapoptotic cell death caused by intracellular lipid peroxidation that can bring about effective cell death in cancer cells resistant to apoptosis. Hence, ferroptosis is a potential therapeutic strategy for refractory cancer. MATERIALS AND METHODS: In this study, we performed clinicopathological and molecular analyses on tumor specimens from 270 patients with squamous cell lung cancer, focusing on the expression of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1), which are known to be key regulators of ferroptosis, and the accumulation of 4-hydroxynoneral (4-HNE), a lipid peroxidation marker. RESULTS: Immunohistochemistry revealed that patients with low 4-HNE accumulation and low levels of GPX4 or FSP1 had significantly worse prognoses than other patients (P = 0.001). This stratification was an independent prognostic predictor (P = 0.003). A dramatic cell death synergistic effect was observed on LSCC-derived LK-2 and EBC1 cells treated with GPX4 and FSP1 inhibitors. This effect was completely inhibited by treatment with the ferroptosis inhibitor. Notably, this was not the case in LK-2 cells treated with the apoptosis inhibitor, and in these cells, ferroptosis was induced. CONCLUSION: Ferroptosis regulators GPX4 and FSP1 are associated with lung squamous cell cancer cancer's prognosis. We present the clinicopathological and molecular basis of novel therapeutic strategies for refractory LSCC.

Effects of anti-thrombotic drugs on all-cause mortality after upper gastrointestinal bleeding in Japan: A multicenter study with 2205 cases.

OBJECTS: Although anti-thrombotic use is recognized as a risk factor for upper gastrointestinal bleeding (UGIB), there has been no clear evidence that it worsens the outcomes after the bleeding. The aim of this study is to investigate the effects of anti-thrombotic agents on in-hospital mortality following UGIB. METHODS: Information on clinical parameters, including usage of anti-thrombotic agents, was retrospectively collected from consecutive patients with UGIB at 12 high-volume centers in Japan between 2011 and 2018. The all-cause in-hospital mortality rate was evaluated according to the usage of anti-thrombotic agents. RESULTS: Clinical data were collected from 2205 patients with endoscopically confirmed UGIB. Six hundred and forty-five (29.3%) patients used anti-thrombotic agents. The all-cause in-hospital mortality rate was 5.7% (125 deaths). After excluding 29 cases in which death occurred due to end-stage malignancy, 96 deaths (bleeding-related, n = 22 ; non-bleeding-related, n = 74) were considered "preventable." Overall, the "preventable" mortality rate in anti-thrombotic users was significantly higher than that in non-users (6.0% vs. 3.7%, P < 0.05). However, the "preventable" mortality of anti-thrombotic users showed a marked improvement over time; although the rate in users remained significantly higher than that in non-users until 2015 (7.3% vs. 4.2%, P < 0.05), after 2016, the difference was no longer statistically significant (4.8% vs. 3.5%). CONCLUSIONS: Although the usage of anti-thrombotic agents worsened the outcomes after UGIB, the situation has recently been improving. We speculate that the recent revision of the Japanese guidelines on the management of anti-thrombotic treatment after UGIB may have partly contributed to improving the survival of users of anti-thrombotic agents.

Nature and treatment outcomes of bleeding post-bulbar duodenal ulcers.

BACKGROUND: Although post-bulbar duodenal ulcers (PBDUs) could become a source of upper gastrointestinal bleeding, the whole picture of the disease is unknown. We compared the characteristic features and treatment outcomes after endoscopic hemostasis between PBDUs and bulbar duodenal ulcers (BDUs). METHODS: Data on duodenal ulcers with evidence of endoscopically-active bleeding were extracted from the data that were retrospectively collected from 12 institutes in Japan between 2011 and 2018. Rebleeding and in-hospital mortality were compared between patients with PBDUs and those with BDUs by logistic regression analyses. RESULTS: Among 468 consecutive patients with bleeding duodenal ulcers, 96 (20.5%) had endoscopically-confirmed PBDUs. PBDUs were more frequently observed in patients with a poor general condition in comparison to BDUs. The rates of rebleeding and in-hospital mortality in patients with PBDUs were approximately three times higher than those in patients with BDUs (PBDU vs. BDU: 29.2% vs. 10.2% [P < 0.0001] and 14.6% vs. 5.1% [P = 0.0029], respectively). Although the high in-hospital mortality in PBDUs could be explained, to a lesser extent, by the likelihood of rebleeding, and, to a greater extent, by the patients' poor general condition, the presence of a PBDU itself was largely responsible for the high rebleeding rates in PBDUs. CONCLUSION: This is the first study focusing on the nature and treatment outcomes of bleeding PBDUs. PBDUs were associated with much higher rebleeding and mortality rates in comparison to BDUs, and the likelihood of rebleeding may be derived from their unique anatomic location.

HADHB, a fatty acid beta-oxidation enzyme, is a potential prognostic predictor in malignant lymphoma.

In haematological malignancies, such as malignant lymphoma, reprogramming of fatty acid metabolism favours tumour cell survival and drug resistance. Hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA), an enzyme involved in fatty acid beta-oxidation (FAO), is overexpressed in high-grade lymphoma and is a predictor of poor prognosis in diffuse large B-cell lymphoma (DLBCL). HADHB forms a heterodimer with HADHA and functions as an FAO enzyme together with HADHA; however, the relevance of its expression in malignant lymphoma is unknown. In this study, we investigated the roles and antitumour effects of HADHB expression in malignant lymphoma. Immunohistochemical analysis showed that HADHB was frequently overexpressed in the high-grade lymphoma subtype. HADHB overexpression was observed in 68% (87/128) of DLBCL cases and was an independent predictor of poor prognosis (p=0.001). In vitro analysis demonstrated that HADHB knockdown suppressed cell proliferation in LCL-K and MD901 cells (p<0.05). Additionally, treatment with the FAO inhibitor, ranolazine, increased cell death in control cells compared with that in HADHB knockdown LCL-K and MD901 cells (p<0.01). Cell death was also suppressed by the ferroptosis inhibitor, ferrosatin-1, in LCL-K and MD901 cells (p<0.05). Collectively, these findings provide basic evidence for the development of new cell death-based therapies for refractory malignant lymphoma. We plan to perform prospective studies and preclinical studies using animal models to confirm these results.

Low risk of esophageal adenocarcinoma among patients with ultrashort-segment Barrett's esophagus in Japan.

OBJECTS: Ultrashort-segment Barrett's esophagus (USSBE; length of <1 cm) is very frequently diagnosed in Japan, but the cancer risk of USSBE is unknown. In this study, by retrieving endoscopic images, we retrospectively investigated the incidence of esophageal adenocarcinoma (EAC) by the grade of Barrett's esophagus (BE) and compared the findings with those of gastric cancer by the degree of endoscopic gastric atrophy in the same population. METHODS: Among consecutive participants who had undergone endoscopy for an annual health checkup in 2014, the 9121 who had received at least one follow-up endoscopy by December 2020 were enrolled in this study. Using the retrieved endoscopic images, we retrospectively evaluated BE and gastric atrophy. Information on the subsequent occurrence of EAC and gastric cancer as of December 2020 was also collected. The incidence of cancer by the extent of BE and gastric atrophy was calculated and expressed as the percentage per year. RESULTS: On reviewing the endoscopic image in 2014, 4190 (45.9%) were found to have been diagnosed with BE, of whom 3318 (36.4%) were judged to have USSBE. During an observation period of 54.1 (17.9) months, 89 gastric cancers and only two EACs were identified. The incidence of EAC in USSBE was 0.0068%/year, which was nearly as low as the incidence of gastric cancer in atrophy-free patients (0.0068% vs. 0.0059%/year). CONCLUSIONS: Although the prevalence of USSBE is quite high (36.4%), the incidence of EAC in USSBE is very low (0.0068%/year). Accordingly, USSBE can be excluded from targets for endoscopic surveillance in Japan.

Limited endoscopic mucosal inflammation on equivalent to Mayo endoscopic subscore of 0 unaffect clinical relapse of ulcerative colitis.

BACKGROUND AND AIM: Mayo endoscopic subscore is a simple and validated endoscopic score for ulcerative colitis but the range of inflammation was not considered for scoring. There were few reports analyzing the range of inflammation for clinical relapse using Mayo endoscopic subscore (MES). The aim of this study is to investigate the relapsing potential of limited mucosal inflammation on endoscopic remission equivalent to MES of 0. METHODS: For this retrospective observational study, ulcerative colitis patients underwent total colonoscopy were enrolled. Small mucosal lesion (SML) was defined as limited inflammation of range less than 3 cm. Clinical relapse was analyzed using the Kaplan-Meier curve with log-rank test, and factors associated with clinical relapse was analyzed using the cox proportional hazard regression model. RESULTS: A total of 102 periods with mucosal healing or modified MES of 0 with SML were analyzed. In 12-months observation periods, clinical relapse occurred more frequently in MES of 1 than in MES of 0 or modified MES of 0 with SML, but it was comparable between MES of 0 and modified MES of 0 with SML. When compared to patients with modified MES of 0 with SML, the hazard ratio in patients with MES of 1 (6.55; p = .028) was significantly high but similar in those with MES of 0 (2.59; p = .29). CONCLUSIONS: Small mucosal inflammation in UC does not affect the clinical relapse if most of the mucosa achieved a score similar to MES of 0.

A simple prediction score for in-hospital mortality in patients with nonvariceal upper gastrointestinal bleeding.

BACKGROUND: No prediction scores for the mortality of both inpatients and outpatients who developed nonvariceal upper gastrointestinal bleeding (UGIB) without endoscopic findings have been established. We aimed to derive and validate a novel prediction score for in-hospital mortality. METHODS: We conducted a three-stage, multicenter retrospective study. In the derivation stage, patients with nonvariceal UGIB at six institutions were enrolled to derive the prediction score by logistic regression analysis. External validation of the score was performed to analyze discrimination by patients at six other institutions. Then the performance of this score was compared with that of four existing scores. RESULTS: We enrolled 1380 and 825 patients in the derivation and validation cohorts, respectively. A prediction score (CHAMPS-R Score) comprising seven variables (Charlson Comorbidity Index ≥ 2, in-hospital onset, albumin < 2.5 g/dL, altered mental status, Eastern Cooperative Oncology Group performance status ≥ 2, steroids, and rebleeding) with equal-weight scores was established, with high discriminative ability in both derivation and validation cohorts (c statistic, 0.91 and 0.80, respectively). When rebeeding was excluded from the score (an onset model; CHAMPS Score), this score also achieved high discriminative ability (c statistic, 0.90 and 0.81, respectively). The prediction scores had significantly higher discriminative ability than the Glasgow Blatchford Score, AIMS65, ABC Score, and clinical Rockall Score in both cohorts (all, p < 0.05). CONCLUSIONS: We derived and externally validated prediction scores for in-hospital mortality in patients with nonvariceal UGIB. The CHAMPS Score might be optimal for managing such patients. Its mobile application is freely available ( https://apps.apple.com/app/id1565716902 for iOS and https://play.google.com/store/apps/details?id=hatta.CHAMPS for Android).

Potent Acid Suppression With Vonoprazan vs Proton Pump Inhibitors Does Not Have Higher Association With Clostridioides difficile Infection.

INTRODUCTION: Proton pump inhibitors (PPIs) are associated with the onset of Clostridioides difficile infection (CDI). Although a new potassium-competitive acid blocker, vonoprazan, consistently shows a more potent acid inhibitory effect in comparison to PPIs, the risk of CDI in vonoprazan-treated patients relative to those treated with PPIs is unknown. In this retrospective case-control study, using a nationwide hospital-based administrative database in Japan, we investigated the association of the onset of CDI in patients treated with vonoprazan. METHODS: A CDI case was defined as a case in which a patient was diagnosed and treated for CDI. For each CDI case, 3 non-CDI patients were extracted as controls. Information on the usage of acid suppressants in the 2 months before the onset of CDI and other confounding factors was collected. Relative associations of gastric acid suppressants with the onset of CDI were estimated. RESULTS: A total of 4,466 CDI cases and 13,220 of non-CDI controls were extracted. A multivariate conditional regression analysis revealed that PPI or vonoprazan use was modestly, but significantly associated with CDI (odds ratio [95% confidence interval]: PPI, 1.3 [1.2-1.4]; vonoprazan, 1.4 [1.2-1.7]). With PPI users as a reference, vonoprazan did not show a stronger association with CDI (odds ratio [95% confidence interval]: 1.07 [0.91-1.26]). DISCUSSION: We found a significant positive association between vonoprazan use and CDI; however, the magnitude of the association was not beyond that in PPI users. This is the first report on any potential adverse effects of vonoprazan.

Effect of acid-reducing agents on clinical relapse in ulcerative colitis with pH-dependent-released 5-aminosalicylic acid: a multicenter retrospective study in Japan.

BACKGROUND/AIMS: 5-Aminosalicylic acid (5-ASA) is a basic drug for inducing and maintaining remission for ulcerative colitis. One of its formulations has a coating with a pH-dependent degradation that ensures the release 5-ASA at the terminal ileum. No evidence has been shown concerning the effects of proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs) on the clinical course of ulcerative colitis patients in remission. The present study assessed the effect of PPIs or H2RAs on the relapse of ulcerative colitis patients in clinical remission maintained by pH-dependent released 5-ASA. METHODS: Ulcerative colitis patients who had been prescribed time- or pH-dependent-released 5-ASA between January 2015 and December 2018 were enrolled in this multicenter retrospective study. The period of remission until relapse occurred was analyzed among the patients taking time-dependent-released 5-ASA or pH-dependent-released 5-ASA with/without PPIs or H2RAs. RESULTS: One hundred and nineteen patients were analyzed in this study. In the primary endpoint, the relapse rate was higher in patients taking pH-dependent-released 5-ASA and PPIs or H2RAs than in those taking the pH-dependent-released 5-ASA without PPIs or H2RAs, while the relapse rate was similar in patients taking the time-dependent-released 5-ASA with or without PPIs or H2RAs concomitantly. Patients with a short duration of disease and middle-aged patients more frequently showed relapse with PPIs or H2RAs than the other patients. CONCLUSIONS: The coadministration of PPIs or H2RAs affects the clinical course of ulcerative colitis in remission maintained by pH-dependent-released 5-ASA.

Outcome of colorectal cancer in Diamond-Blackfan syndrome with a ribosomal protein S19 mutation.

Diamond-Blackfan anemia is an autosomal dominant syndrome, characterized by anemia and a predisposition for malignancies. Ribosomal proteins are responsible for this syndrome, and the incidence of colorectal cancer in patients with this syndrome is higher than the general population. This patient's Diamond-Blackfan anemia was caused by a novel ribosomal protein S19 gene mutation, and he received chemotherapy for colorectal cancer caused by it. In his cancer, ribosomal proteins S19 and TP53 were overexpressed. He received 5FU and cetuximab; however, his anemia made chemotherapy difficult, and he did not survive long. Patients with Diamond-Blackfan anemia should be screened earlier and more often for colorectal cancer than usual.