Efficacy and safety of filgotinib for ulcerative colitis: A real-world multicenter retrospective study in Japan.

BACKGROUND AND AIMS: While filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, is approved for moderately to severely active ulcerative colitis (UC), real-world studies assessing its short- and long-term efficacy and safety are limited. METHODS: This is a multicenter, retrospective study of UC patients who started filgotinib between March 2022 and September 2023. The primary outcome was clinical remission, defined as a partial Mayo score ≤1 with a rectal bleeding score of 0, or Simple Clinical Colitis Activity Index (SCCAI) ≤2 with a blood-in-stool score of 0. Secondary outcomes included clinical response, corticosteroid-free remission, and endoscopic improvement. Outcomes were assessed at 10, 26, and 58 weeks based on patients with available follow-up. Adverse events were evaluated. RESULTS: We identified 238 UC patients and 54% had prior exposure to biologics/JAK inhibitors. The median baseline partial Mayo score and SCCAI were 5 (IQR 3-6) and 4 (IQR 2-7). Clinical remission rates based on per-protocol analysis at 10, 26, and 58 weeks were 47% (70/149), 55.8% (48/86), and 64.6% (31/48), respectively. At a median follow-up of 28 weeks (IQR 10-54) with a discontinuation rate of 39%, the rates of clinical remission, clinical response, corticosteroid-free remission, and endoscopic improvement were 39.9% (81/203), 54.7% (111/203), and 36.5% (74/203), and 43.5% (10/23), respectively. These rates were comparable between biologic/JAK inhibitor-naïve and -experienced patients. While three patients (1.3%) developed herpes zoster infection, no cases of thrombosis or death were reported. CONCLUSIONS: Real-world data demonstrate favourable clinical and safety outcomes of filgotinib for UC.

Medical treatment selection and outcomes for hospitalized patients with severe ulcerative colitis as defined by the Japanese criteria.

BACKGROUND: Hospitalization for ulcerative colitis (UC) is potentially life-threatening. Severe disease in the Japanese criteria which modifies the Truelove-Witts' criteria might encompass more fulminant cases than the definition for acute severe UC. However, few studies have investigated the predictive factors for clinical remission (CR) after medical treatments for severe hospitalized patients by Japanese criteria. METHODS: Medical treatment selection, CR rates, and factors contributing to CR on day 14 were assessed in severe patients by Japanese criteria. We also investigated whether the reduction rate in patient-reported outcome 2 (PRO2) on day 3 could predict short-term prognosis. RESULTS: Eighty-five severe hospitalized patients were selected. Corticosteroids, tacrolimus, and infliximab were mainly selected as first-line treatments (76/85; 89.4%). The CR rates on day 14 were 26.8%, 21.4%, and 33.3% in patients receiving corticosteroids, tacrolimus, and infliximab, respectively. Extensive disease (odds ratio [OR] 0.022; 95% confidence interval [CI] 0.002-0.198), higher PRO2 (OR 0.306; 95% CI 0.144-0.821), and higher reduction rate in PRO2 on day 3 (OR 1.047; 95% CI 1.019-1.075) were independent factors predicting CR on day 14. If the cutoff value for the reduction rate in PRO2 on day 3 was 18.3%, sensitivity was 0.714 and specificity was 0.731 to predict CR on day 14. A higher reduction rate in PRO2 on day 3 (OR 0.922; 95% CI 0.853-0.995) was a negative factor to predict surgery within 28 days. CONCLUSIONS: Tacrolimus and infliximab in addition to corticosteroids were used as first-line treatment in severe hospitalized patients. PRO2 on day 3 is a useful marker for switching to second-line therapy or colectomy.

Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis.

BACKGROUND: This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC). METHODS: In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-reported outcome score < 2 with no blood in the stool) rate on Day 7 and 14 in hospitalized patients who received corticosteroids (CS) and AT. RESULTS: Among patients with ASUC, 120 and 101 patients received CS or any AT as first-line treatment, respectively. The CR rates on Day 7 and 14 were 22.5% and 35.0%, respectively, in hospitalized patients who received CS as first-line treatment. Most patients who used ATs had CS-dependent or frequent recurrences. Eight different ATs (apheresis, tacrolimus, infliximab, golimumab, tofacitinib, vedolizumab, ustekinumab, and cyclosporine) were used as first-line treatment in patients with ASUC, and the CR rates on Day 7 and 14 were 16.8% and 29.7%, respectively. Twenty-five patients received the second ATs after hospitalizations, and the CR rates on Day 7 and 14 were 0% and 12%, respectively. The CR rates on Day 14 were significantly higher in patients who changed to AT than in those whose dose of CS increased (34.0% vs 10.7%, p = 0.020) among patients who had already used CS before hospitalization. CONCLUSION: Most first-use ATs were effective for patients with ASUC, while second-use ATs might have had limited benefits in inducing CR. These findings may contribute to considerations for the management of hospitalized patients.

Symptoms Contributing to the Diagnosis of Small Bowel Tumors.

INTRODUCTION: Small bowel tumors (SBTs) are difficult to diagnose because of limited opportunities and technical difficulties in evaluating the small bowel. Asymptomatic conditions or nonspecific symptoms make SBT diagnosis more challenging. In Asia, SBTs are reported to be more frequently malignant lymphoma (ML), adenocarcinoma, and gastrointestinal stromal tumor (GIST). In this study, we examined 66 patients diagnosed with SBTs and determined their clinical characteristics. METHODS: This retrospective study was conducted from January 2013 to July 2020 at Kurume University Hospital. The modalities used to detect SBTs were computed tomography (CT), positron emission tomography, magnetic resonance imaging, and ultrasonography. Endoscopy was also performed in some cases to confirm SBT diagnosis. The study included 66 patients. The medical data collected included presenting symptoms, tumor location, underlying condition, diagnostic modalities, pathologic diagnosis, and treatment. RESULTS: ML and adenocarcinoma were the most common tumors (22.7%), followed by GIST (21.2%) and metastatic SBT (18.2%). Symptoms that led to SBT detection were abdominal pain (44.5%), asymptomatic conditions (28.8%), hematochezia (12.1%), and anemia (10.6%). CT was the most used modality to detect SBTs. Nineteen patients were asymptomatic, and SBTs were incidentally detected in them. GISTs and benign tumors were more often asymptomatic than other malignant tumors. CONCLUSION: Abdominal pain was the main symptom for SBTs in particular adenocarcinoma, ML, and metastatic SBT. In addition, GIST, which was highly prevalent in Asia, had fewer symptoms. An understanding of these characteristics may be helpful in the clinical practice of SBTs.

Utility of Diagnostic Colonoscopy in Pediatric Intestinal Disease.

BACKGROUND: The roles and methods of diagnostic colonoscopy in pediatric patients were previously demonstrated. With advances in medical equipment and the increasing need for pediatric endoscopic diagnosis, we compared recent results with those previously reported. METHODS: A retrospective analysis was conducted on pediatric patients aged ≤15 years, comparing those who underwent their first diagnostic colonoscopy between 1 January 2007 and 28 February 2015 with those who did so between 1 March 2015 and 28 February 2022 at Kurume University Hospital. RESULTS: A total of 274 patients were included, including 110 in the previous study and 164 in the present study. The main indications were hematochezia in the previous study (63/110, 57.3%) and abdominal pain in the present study (64/164, 39.0%). Ulcerative colitis (74/274, 27.0%) was the most common diagnosis in both studies. The major difference from the previous study was an increase in the number of Crohn's disease and eosinophilic gastrointestinal disorder cases. Bowel preparation with magnesium citrate was significantly increased across all ages in the present study (142/164, 86.6%). Midazolam + pentazocine was used for sedation in most cases (137/164, 83.5%). An ultrathin upper endoscope was mainly used in patients aged ≤6 years, while ultrathin colonoscopes were applied in patients aged 7-12 years. CONCLUSION: In the present study, appropriate changes were found in the roles and methods of diagnostic colonoscopy in pediatric patients compared to the previous study. The increasing trend of patients presenting with inflammatory bowel disease and eosinophilic gastrointestinal disorder worldwide indicates the importance of colonoscopy in infants and children.

Role of Serum Proteinase 3 Antineutrophil Cytoplasmic Antibodies in the Diagnosis, Evaluation of Disease Severity, and Clinical Course of Ulcerative Colitis.

BACKGROUND/AIMS: Proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) is a serologic marker for granulomatosis with polyangiitis. However, recent studies have also shown their role as diagnostic markers for ulcerative colitis (UC). This study was performed to investigate the clinical roles of PR3-ANCAs in the disease severity, disease extension, and clinical course of UC. METHODS: Serum PR3-ANCAs were measured in 173 UC patients including 77 patients with new-onset patients UC diagnosed within 1 month, 110 patients with Crohn's disease, 48 patients with other intestinal diseases, and 71 healthy controls. Associations between the PR3-ANCA titer and clinical data, such as disease severity, disease extension, and clinical course, were assessed. The clinical utility of PR3-ANCA measurement was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: PR3-ANCA ≥3.5 U/mL demonstrated 44.5% sensitivity and 95.6% specificity for the diagnosis of UC in all patients. PR3-ANCA positivity was more prevalent in the 77 new-onset UC patients (58.4%). In this group, the disease severity and extension were more severe in PR3-ANCA positive patients than in PR3-ANCA negative group (p<0.001). After treatment, the partial Mayo scores were significantly decreased with the PR3-ANCA titers. The proportion of patients who required steroids for induction therapy was significantly higher among PR3-ANCA positive than negative group. ROC analysis revealed that PR3-ANCA ≥3.5 U/mL had 75% sensitivity and 69.0% specificity for steroid requirement in new-onset UC patients. CONCLUSIONS: Our results indicate that PR3-ANCA measurement is useful not only for diagnosing UC but also for evaluating disease severity and extension and predicting the clinical course.

Evaluation of Serum Calprotectin Levels in Patients with Inflammatory Bowel Disease.

BACKGROUND: Fecal calprotectin has been proposed as a useful biomarker of disease activity in inflammatory bowel disease (IBD). However, the role of calprotectin in systemic circulation is not well established. Thus, this study aimed to quantify serum calprotectin levels to identify a potential inflammatory marker for IBD. METHODS: Ninety-eight patients with ulcerative colitis (UC) and 105 patients with Crohn's disease (CD) were prospectively enrolled and clinically scored. Ninety-two healthy, age-matched subjects served as controls. Blood samples from UC and CD patients and controls were analyzed for serum calprotectin levels and routine laboratory parameters. Disease activity was assessed by partial Mayo score and Harvey-Bradshaw index for UC and CD, respectively. RESULTS: Serum calprotectin levels were higher in CD and UC patients than in controls and were higher during active disease than during inactive disease in CD but not in UC. In UC, serum calprotectin levels were correlated with C-reactive protein (CRP) but not with other laboratory parameters or disease activity. In CD, serum calprotectin levels were positively correlated with disease activity, serum CRP, and platelet count. In UC and CD, serum calprotectin and CRP levels increased during the acute phase and decreased towards remission. CONCLUSIONS: Serum calprotectin is an inflammatory marker in IBD but might be more effective in evaluating patients with CD than those with UC. Further studies are needed to confirm these findings and to better determine the specific uses of serum calprotectin in routine practice.

Evaluation of Serum Leucine-Rich Alpha-2 Glycoprotein as a New Inflammatory Biomarker of Inflammatory Bowel Disease.

Studies on serum leucine-rich alpha-2 glycoprotein (LRG) in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are scarce; the methods for estimating disease activity are less established, particularly for CD. This study is aimed at evaluating the utility of serum LRG as a potential inflammatory marker for IBD and to investigate the LRG gene expression in peripheral blood mononuclear cells (PBMCs) as a possible source of serum LRG. Overall, 98 patients with UC and 96 patients with CD were prospectively enrolled and clinically evaluated; 92 age-matched individuals served as the healthy controls. The blood samples were analyzed for serum LRG levels and routine laboratory parameters. Disease activity was assessed clinically and endoscopically. Finally, LRG gene expression in the PBMCs from a different cohort (41 patients with UC, 34 patients with CD, and 30 healthy controls) was examined. The serum LRG levels were higher during active disease than during inactive disease; additionally, serum LRG levels were positively correlated with clinical disease activity, C-reactive protein (CRP) levels, and other laboratory parameters in patients with UC and CD and with endoscopic disease activity in UC. UC and CD showed comparable areas under the curve (AUC) values for determining clinical remission and differentiating between endoscopic remission associated with LRG and CRP. The levels of LRG mRNA were also increased in PBMCs from patients with UC and CD and reflected disease activity. These data suggest that serum LRG, originated partially from PBMCs, is an inflammatory marker in UC and CD. A large-scale well-designed study should be conducted in the future to more accurately reveal the clinical significance of LRG in patients with IBD.

Therapeutic Potential of a Self-Assembling Peptide Hydrogel to Treat Colonic Injuries Associated with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: The Self-assembling Peptide Hydrogel [SAPH, PuraMatrix], a fully synthetic peptide solution designed to replace collagen, has recently been used to promote mucosal regeneration in iatrogenic ulcers following endoscopic submucosal dissection. Herein, we evaluated its utility in ulcer repair using a rat model of topical trinitrobenzene sulphonic acid [TNBS]-induced colonic injuries. METHODS: Colonic injuries were generated in 7-week-old rats by injecting an ethanol solution [35%, 0.2 mL] containing 0.15 M TNBS into the colonic lumen. At 2 and 4 days post-injury, the rats were subjected to endoscopy, and SAPH [or vehicle] was topically applied to the ulcerative lesion. Time-of-flight secondary ion mass spectrometry [TOF-SIMS] was used to detect SAPH. Colonic expression of cytokines and wound healing-related factors were assessed using real-time polymerase chain reaction or immunohistochemistry. RESULTS: SAPH treatment significantly reduced ulcer length [p = 0.0014] and area [p = 0.045], while decreasing colonic weight [p = 0.0375] and histological score [p = 0.0005] 7 days after injury. SAPH treatment also decreased colonic expression of interleukin [IL]-1α [p = 0.0233] and IL-6[p = 0.0343] and increased that of claudin-1 [p = 0.0486] and villin [p = 0.0183], and ß-catenin staining [p = 0.0237]. TOF-SIMS revealed lesional retention of SAPH on day 7 post-injury. Furthermore, SAPH significantly promoted healing in in vivo mechanical intestinal wound models. CONCLUSIONS: SAPH application effectively suppressed colonic injury, downregulated inflammatory cytokine expression, and upregulated wound healing-related factor expression in the rat model; thus, it may represent a promising therapeutic strategy for IBD-related colonic ulcers.

Clinical Features and Pathogenic Mechanisms of Gastrointestinal Injury in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the global coronavirus disease 2019 (COVID-19) outbreak. Along with the respiratory tract, the gastrointestinal (GI) tract is one of the main extra-pulmonary targets of SARS-CoV-2 with respect to symptom occurrence and is a potential route for virus transmission, most likely due to the presence of angiotensin-converting enzyme 2. Therefore, understanding the mechanisms of GI injury is crucial for a harmonized therapeutic strategy against COVID-19. This review summarizes the current evidence for the clinical features of and possible pathogenic mechanisms leading to GI injury in COVID-19.

Altered serum profile of the interleukin-22 system in inflammatory bowel disease.

BACKGROUND AND AIM: Interleukin-22 (IL-22), plays a vital role in the mucosal repair of inflammatory bowel disease (IBD). Serum levels of IL-22 and IL-22 binding protein (IL-22BP), a soluble inhibitory IL-22 receptor, were measured in patients with IBD to investigate the profile of IL-22 in the systemic circulation. METHODS: Blood samples from 92 healthy subjects, 98 patients with ulcerative colitis (UC), and 105 patients with Crohn's disease (CD) were analyzed for serum levels of IL-22, IL-22BP, human ß-defensin 2 (hBD-2), and serum inflammatory parameters. Disease activity was assessed by the partial Mayo score and Harvey-Bradshaw index for UC and CD, respectively. RESULTS: Serum IL-22 level was lower in UC (P < 0.001) and CD (P < 0.001) vs control and its decrease was more pronounced in CD than in UC (P = 0.019). Serum IL-22BP level was lower in UC (P < 0.001) and CD (P < 0.001) vs control and correlated with inflammatory parameters (albumin and C-reactive protein (CRP) in UC; hemoglobin, albumin, and CRP in CD). Serum IL-22/IL-22BP ratios were higher in UC (P = 0.009) vs control and correlated with inflammatory parameters (albumin and CRP). Serum hBD-2 level was higher only in CD (P = 0.015) but did not correlate with serum IL-22 levels, IL-22BP levels, IL-22/IL-22BP ratios, or inflammatory parameters. CONCLUSIONS: Dysregulation of the IL-22 system in the blood may play a role in the pathogenesis of IBD. Further studies are needed to understand the pathogenic and clinical significance of the blood IL-22 system in IBD.

Gene Expression of Transient Receptor Potential Channels in Peripheral Blood Mononuclear Cells of Inflammatory Bowel Disease Patients.

We examined the expression profile of transient receptor potential (TRP) channels in peripheral blood mononuclear cells (PBMCs) from patients with inflammatory bowel disease (IBD). PBMCs were obtained from 41 ulcerative colitis (UC) patients, 34 Crohn's disease (CD) patients, and 30 normal subjects. mRNA levels of TRP channels were measured using the quantitative real-time polymerase chain reaction, and correlation tests with disease ranking, as well as laboratory parameters, were performed. Compared with controls, TRPV2 and TRPC1 mRNA expression was lower, while that of TRPM2, was higher in PBMCs of UC and CD patients. Moreover, TRPV3 mRNA expression was lower, while that of TRPV4 was higher in CD patients. TRPC6 mRNA expression was higher in patients with CD than in patients with UC. There was also a tendency for the expression of TRPV2 mRNA to be negatively correlated with disease activity in patients with UC and CD, while that of TRPM4 mRNA was negatively correlated with disease activity only in patients with UC. PBMCs from patients with IBD exhibited varying mRNA expression levels of TRP channel members, which may play an important role in the progression of IBD.

Safety and efficacy of single-needle leukocyte apheresis for treatment of ulcerative colitis.

Leukocyte apheresis (LCAP) is a safe and effective treatment for active ulcerative colitis (UC) in Japan. Nevertheless, a limitation of LCAP is its requirement for two puncture sites (double-needle [DN] apheresis), sometimes leading to problems with needle puncture. Single-needle (SN) apheresis is useful in hemodialysis and reduces needle puncture pain. If SN apheresis were found to be useful in LCAP for UC, it may reduce patient burden. The aim of this study was to compare the safety and efficacy of SN apheresis with that of DN apheresis. Twenty-four patients with active UC were retrospectively enrolled. They underwent either SN apheresis (n = 12) or conventional double-needle (DN) apheresis (n = 12) at the Kurume University Hospital from February 2014 to March 2018. At each session, we recorded access problems defined by the time required to initiate apheresis and the frequency of puncture-related problems, as well as blood circuit clotting, defined as clotting necessitating interruption of apheresis and changing of the circuit. Efficacy was assessed using partial Mayo scores. The number of apheresis sessions was comparable between SN and DN apheresis (9.0 ± 2.0 times vs 9.6 ± 1.4 times, mean ± SEM). SN significantly reduced the time required to start apheresis (10.0 ± 5.4 minutes vs 19.4 ± 11.9 minutes, P < .05) as well as needle puncture troubles (0.9% vs 11.5%, P < .05). SN had comparable frequency of blood clotting episodes (5.6% vs 8.7%). SN apheresis had similar clinical efficacy (P < .001 in SN and P < .01 in DN). The improvement and remission rates were comparable between groups. SN apheresis may be safe and effective and may reduce patient burden during UC treatment. Nevertheless, further comparative studies are needed.

Single Needle Granulocyte and Monocyte Apheresis for Ulcerative Colitis: A Retrospective Safety Analysis.

INTRODUCTION: Granulocyte and monocyte apheresis (GMA) is an effective treatment strategy for active ulcerative colitis (UC) in Japan. Single needle (SN) apheresis reduces needle puncture pain in patients because it requires only one puncture site. We evaluated whether single-needle apheresis could be a safe and effective means of reducing patient burden. METHOD: We performed a retrospective study of active UC patients who were treated with either SN apheresis or conventional double-needle (DN) apheresis at the Kurume university hospital from April 2014 to March 2018. All the patients treated with GMA after September 2016 underwent SN apheresis. Thus, the two groups predominantly belonged to different time periods. We assessed the safety of SN apheresis. RESULT: Six patients underwent SN apheresis, and 6 underwent DN apheresis. The average time to the start of apheresis was significantly reduced from 23.1 minutes in the case of DN apheresis to 12.6 minutes for SN apheresis. In addition, the number of difficult punctures was significantly reduced with SN apheresis. There were no differences in adverse events between SN and DN apheresis. Treatment benefits, remission rate and disease activity were similar between SN and DN apheresis. CONCLUSION: SN apheresis reduced both the time to treatment initiation and pain during puncture, and there was no difference in the number of blood clotting episodes as compared with DN. Although further comparative studies are needed, SN apheresis may be a safe alternative for patients to reduce the strain of treatment.

Leukocyte Apheresis Using a Fiber Filter Suppresses Colonic Injury Through Calcitonin Gene-Related Peptide Induction.

BACKGROUND: The aim of this study was to address whether the therapeutic effect of leukocytapheresis (LCAP) depends on calcitonin gene- related peptide (CGRP) induction. METHODS: An HLA-B27 transgenic rat model was treated with an LCAP column. The effects of LCAP on clinical, endoscopic, and histologic disease activity, the colony-forming ability of colony-forming unit (CFU)-granulocyte macrophages (GMs), colonic blood flow, and tissue expression of tumor necrosis factor (TNF)-α and CGRP were examined. Changes in the effects of LCAP after pretreatment with the CGRP antagonist CGRP8-37 were also observed. A dextran sulfate sodium-induced colitis rat model included treatment with CGRP, and the effect was assessed based on clinical, endoscopic, and histologic disease activity, colonic blood flow, the colony-forming ability of CFU-GMs, and tissue expression of inflammatory cytokines and CGRP receptor families. RESULTS: LCAP improved disease activity, enhanced colonic blood flow, and induced the bone marrow colony-forming ability of CFU-GMs with an increase in CGRP mRNA levels. These effects were abolished by pretreatment with CGRP8-37. The administration of CGRP suppressed colitis, promoting colonic blood flow, inducing bone marrow-derived cells, downregulating inflammatory cytokines, and upregulating receptor activity-modifying protein-1. The mRNA and protein levels of inflammatory cytokines in lipopolysaccharide-stimulated mononuclear cells were also decreased after CGRP treatment. CONCLUSIONS: The therapeutic effects of LCAP depend on CGRP induction. CGRP can effectively suppress colitis through the downregulation of inflammatory events and upregulation of protective events.

Questionnaire Survey from the 1st Kurume University Inflammatory Bowel Disease Center Educational Lecture.

INTRODUCTION: The number of inflammatory bowel disease (IBD) patients is increasing steadily in Japan, and it is expected that patient groups and patient education will improve the quality of life of patients and IBD care. The 1st Kurume University IBD Center educational lecture was held and a questionnaire survey was administered at this lecture. METHODS: We asked 78 participants to answer a questionnaire survey on the occasion of the 1st Kurume University IBD Center educational lecture. RESULTS: We obtained responses from 56 (71.8%) participants; 31 (55.4%) had IBD [21 (37.4%) had ulcerative colitis (UC) and 10 (17.9%) had Crohn's disease (CD)]. Most participants were female (37, 66%). The age range with the highest number of participants was 40 to 69 (27, 48.2%). Most had heard about this educational lecture through "notification by the patient's doctor" 23 (41.1%). A total of 30 (53.6%) of participants answered "good" about the lecture content, while 50 (89.7%) of participants answered "very good" and "good" about the impression of this lecture. Meanwhile, 10 (32.3%) of patients were interested in patient groups. The percentage of patients who were interested in patient groups was higher in patients with CD 4 (66.7%) than those with UC 2 (33.3%). CONCLUSION: We held the 1st Kurume University IBD center educational lecture. Further studies are needed to assess whether educational lectures and/or patient groups can improve patients' quality of life (QOL) and IBD care in our hospital.

Infantile-onset inflammatory bowel disease in a patient with Hermansky-Pudlak syndrome: a case report.

BACKGROUND: Hermansky-Pudlak syndrome (HPS) is a rare, genetically heterogeneous disorder that manifests oculocutaneous albinism together with bleeding diatheses that reflect a platelet storage pool deficiency. Ten genetic subtypes of this autosomal recessive condition have been described to date. Some patients with Hermansky-Pudlak syndrome type 1, 4, or 6 develop Crohn's-like inflammatory bowel disease at any age including early childhood, but most often in adolescence or young adulthood. Here we report infantile-onset of inflammatory bowel disease in a patient with Hermansky-Pudlak syndrome type 1 who responded to infliximab. CASE PRESENTATION: A Japanese boy, the second child of non-consanguineous healthy parents, was born with chalky white skin, silvery-white hair, and gray eyes, representing oculocutaneous albinism. He developed frequent diarrhea and fever accompanied by weight loss at 6 months, and was diagnosed with Crohn's-like inflammatory bowel disease based on the endoscopic finding of longitudinal ulcerations in the colon and the histopathologic finding of nonspecific chronic inflammation without granulomas at the age of 11 months. Treatment with an elemental diet, salazosulfapyridine, and corticosteroids failed to improve clinical or laboratory abnormalities, and the diarrhea became bloody. At 13 months he began treatment with infliximab, which produced marked improvement followed by clinical remission. Endoscopy at 20 months demonstrated healing of the colonic mucosa. At 22 months he is in sustained clinical remission receiving only infliximab. Because albinism with inflammatory bowel disease suggested Hermansky-Pudlak syndrome, we performed genetic screening using next-generation sequencing in a targeted gene panel analysis for primary immunodeficiency disease and/or inflammatory bowel disease. The patient proved to have a compound heterozygous mutation of the HPS1 gene resulting in Hermansky-Pudlak syndrome type 1. CONCLUSIONS: We consider this report to be the first account of type 1 Hermansky-Pudlak syndrome with infantile-onset of inflammatory bowel disease. Early administration of infliximab was effective. We recommend next-generation sequencing for patients with very early-onset inflammatory bowel disease suspected to be monogenic.

Prediction of colorectal tumor grade and invasion depth through narrow-band imaging scoring.

AIM: To determine the usefulness of assigning narrow-band imaging (NBI) scores for predicting tumor grade and invasion depth in colorectal tumors. METHODS: A total of 161 colorectal lesions were analyzed from 138 patients who underwent endoscopic or surgical resection after conventional colonoscopy and magnifying endoscopy with NBI. The relationships between the surface and vascular patterns of the lesions, as visualized with NBI, and the tumor grade and depth of submucosa (SM) invasion were determined histopathologically. Scores were assigned to distinct features of the surface microstructures of tubular and papillary-type lesions. Using a multivariate analysis, a model was developed for predicting the tumor grade and depth of invasion based on NBI-finding scores. RESULTS: NBI findings that correlated with a high tumor grade were associated with the "regular/irregular" (P < 0.0001) surface patterns and the "avascular area" pattern (P = 0.0600). The vascular patterns of "disrupted vessels" (P = 0.0714) and "thick vessels" (P = 0.0133) but none of the surface patterns were associated with a depth of invasion of ≥ 1000 µm. In our model, a total NBI-finding score ≥ 1 was indicative of a high tumor grade (sensitivity: 0.97; specificity: 0.24), and a total NBI-finding score ≥ 9 (sensitivity: 0.56; specificity: 1.0) was predictive of a SM invasion depth ≥ 1000 µm. Scores less than these cutoff values signified adenomas and a SM invasion depth < 1000 µm, respectively. Associations were also noted between selected NBI findings and tumor tissue architecture and histopathology. CONCLUSION: Our multivariate statistical model for predicting tumor grades and invasion depths from NBI-finding scores may help standardize the diagnosis of colorectal lesions and inform therapeutic strategies.

The characteristics of nivolumab-induced colitis: an evaluation of three cases and a literature review.

BACKGROUND: The use of immune-checkpoint inhibitors in cancer treatment has become increasingly common, resulting in an increase in the incidence of related side effects. Diarrhoea and colitis have been previously documented as gastrointestinal tract-related side effects of immune-checkpoint inhibitors. Although PD-1/PD-L1 inhibitors produce fewer side effects than CTLA-4 inhibitors, diarrhoea and colitis continue to be reported. However, little is known about the endoscopic features associated with PD-1/PD-L1 inhibitors. In this report, we describe three cases of colitis induced by a PD-1 inhibitor nivolumab. These cases showed endoscopic findings characteristic of ulcerative colitis (UC). Treatment was in accordance with UC therapy, which resulted in beneficial outcomes. CASE PRESENTATION: Three patients with lung cancer treated with nivolumab presented with diarrhoea with (case 2) or without haematochezia (cases 1 and 3). Treatment with nivolumab was ceased and colonoscopy was performed, revealing endoscopic features similar to those of UC. These patients were diagnosed with nivolumab-induced colitis. Case 1 was treated with mesalazine, whereas cases 2 and 3 were treated with corticosteroids. Subsequently, their symptoms improved. CONCLUSIONS: Nivolumab-induced colitis exhibited similar characteristics to UC. Treatment was similar to that for UC and was successful.