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.

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.

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.

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.

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.

Endoscopic analysis of colorectal serrated lesions with cancer.

Serrated lesions, including hyperplastic polyps (HPs), traditional serrated adenomas (TSAs) and sessile serrated adenomas/polyps (SSA/Ps), are important contributors to colorectal carcinogenesis. The aim of the present study was to analyze the potential of conventional endoscopy and advanced endoscopic imaging techniques to delineate the characteristic features of serrated lesions with cancer. The present study was a retrospective analysis of the data of 168 patients who had undergone colonoscopy, and a total of 228 serrated lesions (77 HPs, 58 TSAs, 84 SSA/Ps, 9 SSA/P plus TSAs) have been identified in these patients. A cancer component was identified in 2.6% of HPs, 13.8% of TSAs and 10.7% of SSA/Ps, but none of SSA/P plus TSAs. Compared with the lesions without cancer, the lesions with cancer exhibited a larger size (HP, TSA and SSA/P), a reddish appearance (SSA/P), a two-tier raised appearance (HP and SSA/P), a central depression (HP, TSA and SSA/P), the type V pit pattern (HP, TSA and SSA/P), and/or the type III capillary pattern (TSA and SSA/P). Deep invasion was identified in 50.0% of HPs, 12.5% of TSAs and 55.6% of SSA/Ps with cancer. The Ki-67 proliferative zone was distributed diffusely within the area of the cancer, but partially within the non-cancer area of HPs, TSAs and SSA/Ps. The lesion types were also analyzed on the basis of mucin phenotype. The present study suggested that a detailed endoscopic analysis of serrated lesions with cancer is useful for delineating characteristic features, and the analysis aids treatment selection.

Diagnostic and clinical role of serum proteinase 3 antineutrophil cytoplasmic antibodies in inflammatory bowel disease.

BACKGROUND AND AIM: Proteinase 3 antineutrophil cytoplasmic antibodies (PR3-ANCAs) are well-known serological markers for granulomatosis with polyangiitis, but their role as serological markers for inflammatory bowel disease remains uncertain. The present study aimed to evaluate the diagnostic and clinical role of PR3-ANCAs as markers for inflammatory bowel disease. METHODS: Using a new methodology with chemiluminescence enzyme immunoassay, serum PR3-ANCA titers were assessed in 102 patients with ulcerative colitis (UC), 67 patients with Crohn's disease (CD), 44 controls with other intestinal diseases, and 66 healthy controls. Associations with clinical data were investigated. The diagnostic role of PR3-ANCAs was evaluated by receiver operating characteristic analysis. RESULTS: Proteinase 3 antineutrophil cytoplasmic antibody titers were significantly higher in patients with UC than in those with CD patients, patients with intestinal diseases (intestinal controls), and healthy controls (all P < 0.001). Receiver operating characteristic analysis demonstrated an area under the curve of 0.85 (95% confidence interval: 0.83-0.87) and showed that the manufacturer's cutoff value (3.5 U/mL) had a sensitivity of 39.2% and specificity of 96.6% for UC. There was a significant difference between PR3-ANCA-positive and PR3-ANCA-negative patients with regard to disease duration (P < 0.05) and disease severity (P < 0.01). CONCLUSIONS: Proteinase 3 antineutrophil cytoplasmic antibodies were significantly more prevalent in patients with UC than in those with CD and controls. Our results suggested the role of PR3-ANCAs as serological markers for aiding in diagnosing UC and evaluating disease severity. Further prospective studies are needed across multiple populations of patients and ethnic groups.

Detection of calprotectin in inflammatory bowel disease: Fecal and serum levels and immunohistochemical localization.

The aim of the present study was to quantify calprotectin levels using an enzyme-linked immunosorbent assay (ELISA) and a point-of-care test (POCT) in patients with inflammatory bowel disease. Overall, 113 patients with ulcerative colitis (UC; 51 men and 62 women) and 42 patients with Crohn's disease (CD; 29 men and 13 women), who were scheduled to undergo a colonoscopy, were prospectively enrolled and scored endoscopically and clinically. An additional 96 healthy, age-matched subjects served as the normal controls. Feces and blood samples from the patients with UC and CD, and the normal controls were analyzed. These patients had received adequate medical treatment. The tissue distribution of calprotectin was investigated using immunohistochemistry. The fecal calprotectin levels, as measured using an ELISA, were correlated with the endoscopic and clinical disease activities and laboratory parameters, including serum levels of hemoglobin (Hb), albumin and C-reactive protein, and erythrocyte sedimentation rate, particularly among the patients with UC. The fecal Hb level was close to that of the fecal calprotectin level (r=0.57; P<0.0001). The fecal calprotectin level measured using an ELISA was well-correlated with the fecal calprotectin level measured using the POCT (r=0.81; P<0.0001), but was not correlated with the serum calprotectin level (r=0.1013; P=0.47). An immunohistochemical investigation revealed that patients with both UC and CD had higher neutrophil and monocyte/macrophage calprotectin-positive cell expression levels, compared with those in the normal controls. Fecal calprotectin was considered a reliable marker for disease activity, and the assessment of fecal calprotectin via POCT showed potential as a rapid and simple measurement in clinical settings.

Stereomicroscopic features of colitis-associated tumors in mice: Evaluation of pit pattern.

Patients with longstanding ulcerative colitis have an increased risk of colorectal cancer. Mouse models for colitis-associated tumors are indispensable for the development of novel strategies for prevention and intervention, as well as an improved understanding of the mechanisms underlying tumor formation. The present study examined whether stereomicroscopic observations with dye-application were able to detect and discriminate tumors in a colitis-associated tumor model in mice. Colonic tumors were induced in C57BL/6 mice by 15 cycles of treatment with dextran sulfate sodium (DSS) in drinking water. The mice were then divided into 4 groups: normal mice fed a control diet, normal mice fed an iron-supplemented diet, 0.7% DSS mice fed an iron diet and 1.5% DSS mice fed an iron diet. The entire colons were characterized with respect to both morphology and histology. The pit pattern architecture was analyzed using stereomicroscopy with dye agents (0.2% indigo carmine or 0.06% crystal violet). The tumor histology was graded as negative, indefinite or positive for dysplasia. The positive category was divided into two subcategories: low-grade dysplasia (LGD) and high-grade dysplasia (HGD). The tumor incidences and multiplicity were significantly higher in mice fed an iron diet and 1.5% DSS compared with in mice fed an iron diet and 0.7% DSS. Compared with LGD, HGD was predominantly located in the distal colon, was larger in size and had a higher incidence of elevated lesions (Is and IIa) and a lower incidence of flat lesions (IIb). In regards to the pit pattern, HGD had a high incidence of VI pits and a low incidence of IV, IIIL and II pits. In conclusion, evaluation of the pit pattern using stereomicroscopy with dye-application is useful for detecting and discriminating neoplastic changes in DSS mice and may further our understanding of the mechanisms that induce tumor formation in patients with ulcerative colitis and the characterization of pharmaceutical responses.

Study to determine guidelines for pediatric colonoscopy.

AIM: To investigated characteristics, diagnosis, bowel-cleansing preparation, sedation, and colonoscope length and diameter in Japanese pediatric patients receiving total colonoscopy. METHODS: The present study evaluated consecutive patients aged ≤ 15 years who had undergone their first colonoscopy in Kurume University between January 2007 and February 2015. Data were retrospectively analyzed. We identified 110 pediatric patients who had undergone colonoscopy that had reached the cecum, allowing the observation of the total colon. RESULTS: Hematochezia, abdominal pain, and diarrhea were the most common symptoms. For bowel-cleansing preparation, pediatric patients aged ≤ 12 years were treated with magnesium citrate, and patients aged 13-15 years were treated with polyethylene glycol 4000. For sedation, thiamylal with pentazocine, which has an analgesic effect, was used in patients aged ≤ 6 years, and midazolam with pentazocine was used in patients aged ≥ 7 years. Regarding the choice of endoscope, short and thin endoscopes were selected for younger patients, particularly patients aged ≤ 3 years. Positive diagnoses were made in 78 patients (70.9%). Inflammatory bowel disease (n = 49, 44.5%), including ulcerative colitis (n = 37, 33.6%) and Crohn's disease (n = 12, 10.9%), was the most common diagnosis. CONCLUSION: Colonoscopy offers a high diagnostic capability for pediatric patients with gastrointestinal symptoms. The selection of appropriate management the performance of colonoscopy is important in pediatric patients.

Increased levels of circulating adrenomedullin following treatment with TU­100 in patients with Crohn's disease.

Daikenchuto (TU­100) is a traditional Japanese medicine that is widely used to treat intestinal symptoms. The mechanisms underlying it effects on the circulating levels of adrenomedullin (ADM) are of interest. In addition, the effect of TU­100 in the treatment of Crohn's disease (CD) in humans remains to be elucidated. The primary objective of the present study was to evaluate the effect of TU­100 on the circulating ADM levels in patients with active CD. An additional objective was to assess the effect of the drug on the disease activity and its potential side effects. In an open­label study, 10 patients with active CD received 15 g TU­100 per day for 8 consecutive weeks, and baseline anti­inflammatory therapy was continued. The pre­ and post­treatment blood plasma levels of total ADM (t­ADM) and mature­ADM (m­ADM) were determined using enzyme­linked immunosorbent assays. The response of patients to the treatment was evaluated clinically using the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) score. The plasma levels of t­ADM (16.4±1.1 vs. 20.2±1.7 fmol/ml, P=0.0218) and m­ADM (1.7±0.1 vs. 2.2±0.1 fmol/ml, P=0.0284) increased following 8 weeks of TU­100 treatment, compared with control. The IOIBD score of patients also improved, with a significant decrease in the score from 3.9±0.5 at 0 weeks to 2.4±0.4 at 8 weeks (P=0.0284). Out of the 10 components of the IOIBD scoring system, the scores for abdominal pain and tenderness, decreased significantly (P=0.014 and P=0.046). Therefore, TU­100 was safe and well­tolerated by the patients that participated in the current study. The present study determined that the pharmacologic action of TU­100 is associated with changes in the circulating ADM levels and that treatment with TU­100 may aid in the management of CD. These promising findings warrant further investigation in larger, multicenter studies.

Antibody markers in the diagnosis of inflammatory bowel disease.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic intestinal inflammation of unknown etiology. The diagnosis of IBD is based on endoscopic, radiologic and histopathologic criteria. Recently, the search for a noninvasive marker that could augment or replace part of this diagnostic process has become a focus of IBD research. In this review, antibody markers, including microbial antibodies, autoantibodies and peptide antibodies, will be described, focusing on their common features. At present, no single marker with qualities that are satisfactory for the diagnosis and treatment of IBD has been identified, although panels of some antibodies are being evaluated with keen interest. The discovery of novel IBD-specific and sensitive markers is anticipated. Such markers could minimize the use of endoscopic and radiologic examinations and could enable clinicians to implement individualized treatment plans designed to improve the long-term prognosis of patients with IBD.

Advanced endoscopic features of ulcerative colitis-associated neoplasias: Quantification of autofluorescence imaging.

Ulcerative colitis (UC) patients are well known to carry a higher risk of developing colorectal dysplasia/cancer. However, it is hard to detect the lesion in the early phase during colonoscopy. This pilot study was conducted to analyze the endoscopic characteristics of neoplastic lesions associated with UC using advanced imaging techniques. This is a retrospective analysis of 15 colorectal neoplastic lesion obtained from 11 UC patients during remission who underwent white-light- and advanced endoscopic imaging techniques, including chromoendoscopy, narrow-band imaging and autofluorescence imaging (AFI), and were treated with surgery. These lesions were analyzed for histology, location, size, shape, color and endoscopic features. The green/red ratio was also assessed to quantify the AFI intensity. All 11 patients had extensive colitis with the median disease duration of 14.0 years. A total of 15 lesions, consisting of 8 high-grade dysplasia and 7 cancer, was mostly located in the distal colon (86.7%, 13/15) with the mean size of 8.6 mm. The shape was protruding in 46.7% (7/15), flat elevated in 40.0% (6/15) and flat in 13.3% (2/15) and the color was red in 60.0% (9/15), same colored in 33.3% (5/15) and discolored in 6.7% (1/15). The lesion predominantly showed Kudo's neoplastic pit pattern in 86.7% (13/15; 5 type IIIL, 7 type IV and 1 type VI) on chromoendoscopy and Sano's neoplastic capillary pattern (type IIIa) in 63.6% (7/11) on narrow-band imaging, but were colored purple as neoplastic lesions in only 37.5% (3/8) on AFI. Of note, the AFI green/red ratio was significantly lower in the neoplastic lesions than UC-involved areas (p=0.00014) and UC-uninvolved areas (p=0.00651) irrespective of the lesion's size and histological type. In conclusion, endoscopic analysis based on advanced imaging, in particular AFI quantitation, may be helpful to detect early stage neoplastic lesions in long standing UC. Large-scale, prospective studies are needed.