The effect of granulocyte and monocyte adsorptive apheresis on serum cytokine levels in patients with ulcerative colitis.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) with an Adacolumn has been reported to be effective as induction therapy in ulcerative colitis (UC). However, the effects of GMA on serial changes in cytokine levels have not been well characterized. We therefore, investigated cytokine levels in UC patients before and after treatment with GMA. A total of 16 patients with active UC, 10 men, and six women, mean age, 42.6 years were included. Fourteen patients had total colitis and two patients had left-sided colitis. The study included nine patients with a chronic intermittent course, six with a chronic continuous course and one with a single episode. The duration of each GMA session was 60 min at a flow rate of 30 mL/min as per study protocol. Serum levels of 17 cytokines were determined simultaneously using a Bio-Plex suspension array system before and after treatment with GMA. Serum interleukin (IL)-10 and macrophage inflammatory protein-1ß levels were increased significantly in UC patients after GMA treatment compared to pre-treatment levels (P < 0.05). In particular, GMA treatment caused a significant increase in serum IL-10 levels compared to pre-treatment in patients with total colitis or with a chronic intermittent UC course. In conclusion, this investigation showed that GMA was associated with a marked increase in serum level of the anti-inflammatory cytokine, IL-10. The rise in circulating IL-10 is interesting, and potentially a significant factor in the efficacy of GMA in patients with inflammatory bowel diseases.

Serial changes in cytokine expression in irritable bowel syndrome patients following treatment with calcium polycarbophil.

BACKGROUND/AIMS: Calcium polycarbophil improves abdominal symptoms in patients with irritable bowel syndrome (IBS). We examined cytokine expression in IBS patients before and after administration of calcium polycarbophil. METHODOLOGY: A total of 24 IBS patients (13 diarrhea type, 11 constipation type; median age, 55 years) were enrolled. Serum levels of high sensitive C-reactive protein (CRP) and 17 cytokines (interleukin [IL]-1ß, -2, -4, 5, -6, -7, -8, -10, -12, -13 and -17; tumor necrosis factor-a [TNF-a]; interferon [IFN]-?; granulocyte colony-stimulating factor [G-CSF]; granulocyte macrophage colony-stimulating factor [GM-CSF]; macrophage inflammatory protein [MIP]-1ß; and macrophage chemo-attractant protein [MCP-1]) were simultaneously determined using a Bio-Plex suspension array system before and 12 weeks after administration of calcium polycarbophil 1,500-3,000mg/day. RESULTS: Serum MCP-1 levels in diarrhea type IBS patients were significantly higher than those in constipation type patients (p<0.05). In IBS patients, no significant changes in serum cytokine levels were observed following calcium polycarbophil administration. In constipation type patients, serum high sensitive CRP levels were significantly lower after treatment than before treatment. CONCLUSIONS: Decreases in serum high sensitive CRP levels following calcium polycarbophil treatment may be involved in the relief of abdominal symptoms in IBS patients; diarrhea type IBS is characterized by increased MCP-1 expression.

Microvascular density under magnifying narrow-band imaging endoscopy in colorectal epithelial neoplasms.

BACKGROUND/AIMS: Magnifying endoscopic classification systems, such as the Japan narrow-band imaging (NBI) Expert Team (JNET) classification, have been widely used for predicting the histologic diagnosis and invasion depth of colorectal epithelial tumors. However, disagreement exists among observers regarding magnifying endoscopic diagnosis, because these classification systems are subjective. We herein investigated the utility of endoscopic microvascular density (eMVD) calculated from magnifying NBI endoscopic images in colorectal tumors. METHODS: We reviewed magnifying NBI endoscopic images from 169 colorectal epithelial tumors (97 adenomas, 72 carcinomas/high-grade dysplasias) resected endoscopically or surgically. The eMVD on magnifying NBI endoscopic images was evaluated using image-editing software, and relationships between eMVD and clinical, endoscopic, and pathological findings were retrospectively analyzed. RESULTS: The eMVD in carcinomas (0.152 ± 0.079) was significantly higher than that in adenomas (0.119 ± 0.059, P< 0.05). The best cutoff value for distinguishing carcinoma from adenoma was 0.133. Sensitivity, specificity, and accuracy were 56.9%, 67.0%, and 62.7%, respectively. In addition, JNET type 2B tumors showed significantly higher eMVD (0.162 ± 0.079) compared to type 2A tumors (0.111 ± 0.050, P< 0.05). CONCLUSIONS: The eMVD as determined by magnifying NBI endoscopy is considered to be a possible objective indicator for differentiating colorectal carcinomas from adenomas.

Serial changes of cytokines in active ulcerative colitis: effects of antibiotic combination therapy.

BACKGROUND/AIMS: Although cytokines have an important role on the pathogenesis of ulcerative colitis (UC), the serial changes of cytokines have not been well characterized. It was examined cytokine levels in UC patients before and after administration of antibiotic combination therapy. METHODS: Protocol 1: A total of 26 patients with active UC (13 treatment group, 13 control group) with a median age of 40.5 years were enrolled. Patients were randomly assigned to receive amoxicillin, tetracycline, and metronidazole per os for 2 wks (treatment group) or placebo (control group). Lichtiger's symptom score was determined before, 1 month after, and 3 months after treatment, and Matts endoscopic score was determined before and 3 months after treatment. Protocol 2: A total of 23 patients with active UC were enrolled (13 men, 10 women; mean age, 34.8 years). Serum levels of 17 cytokines were simultaneously determined using a Bio-Plex suspension array system (Bio-Rad Laboratories, Inc.) before, 1 month after, and 3 months after treatment. RESULTS: Protocol 1: The incidence of clinical symptoms in the treatment group was significantly lower at 3 months after treatment compared to that before treatment and that in the control group (p < 0.05). The rate of change in endoscopic scores in the treatment group at 3 months after treatment was significantly decreased compared to that before treatment. Serum CRP in the treatment group at 1 month and 3 months after treatment was significantly decreased compared to before treatment. Protocol 2: There were no significant differences in the serum levels of the 17 cytokines before versus 1 month or 3 months after treatment. However, IL-6 and MCP-1 levels tended to be lower 1 month after treatment compared to before treatment. Additionally, there was a significant correlation between the symptom score severity and serum IL-8 and MIP-1beta levels. CONCLUSION: The present study results suggest that changes in IL-8 and MIP-1beta levels in UC treated with the antibiotic combination therapy may be associated with symptom relief.

Efficacy of Indigo Naturalis Therapy for Ulcerative Colitis: A Case Series.

Objective Indigo naturalis (IN) is a traditional Chinese medicine that has recently been reported to be effective for ulcerative colitis (UC). The aim of this study was to evaluate the efficacy and safety of IN. Methods We performed a retrospective observational study for 14 patients with UC treated with IN from October 2015 to December 2016. Results After 8 weeks of oral administration of IN, the partial Mayo score decreased from 4 (2-5) to 1.5 (0-4) [median, interquartile range (IQR), p=0.015]. Among 10 active UC patients, 5 (50%) showed a clinical response, and 4 (40%) achieved clinical remission. Serial changes of endoscopic activity were evaluated in nine patients using the Mayo endoscopic subscore (MES), Rachmilewitz endoscopic index (REI), and UC endoscopy index of severity (UCEIS). The MES decreased from 2 (2-3) to 1 (1-2) [median (IQR), p=0.005], the REI decreased from 7 (5.5-11) to 3 (1-7) [median (IQR), p=0.008], and the UCEIS decreased from 3 (3-4.5) to 1 (0.5-3.5) [median (IQR), p=0.039]. One patient developed acute right-sided colitis with wall thickening and edematous change, and the remaining 13 showed no adverse events. Conclusion We conclude that IN is effective for patients with UC as a therapy for inducing remission.

Gastrointestinal involvement in patients with vasculitis: IgA vasculitis and eosinophilic granulomatosis with polyangiitis.

Background and study aims Among vasculitides, IgA vasculitis (IgAV) and eosinophilic granulomatosis with polyangiitis (EGPA) frequently damage the gastrointestinal tract. However, only a few studies have investigated the entire gastrointestinal tract in patients with IgAV or EGPA by endoscopy. The aim of this study was to clarify endoscopic characteristics of patients with IgAV and those with EGPA. Patients and methods Clinicopathological and endoscopic findings were retrospectively compared between 33 patients with IgAV and 19 patients with EGPA. Results Gastrointestinal involvement was observed in 33 patients with IgAV (100 %) and in 8 patients with EPGA (42 %; P  = 0.0001). Duodenal involvement was more frequent in patients with IgAV (75.8 %) than in those with EGPA (21.1 %, P  = 0.0002). Jejunoileal involvement was frequent in both groups (IgAV 94.4 %; EGPA 77.8 %). Gastric mucosal erythema was more frequent in patients with IgAV (18.2 %) than in those with EGPA (0 %, P  = 0.0481). Duodenal mucosal erythema (IgAV 54.6 %; EGPA 21.1 %, P  = 0.0227), ulcer (IgAV 33.3 %; EGPA 0 %, P  = 0.0041), and hematoma-like protrusion (IgAV 21.1 %; EGPA 0 %, P  = 0.039) were more frequently observed in patients with IgAV than in those with EGPA. Conclusions Frequent duodenal involvement, gastric mucosal erythema, and duodenal lesions including erythema, ulcer, and hematoma-like protrusion are characteristic of patients with IgAV. Because jejunoileal involvement was frequent in both groups of patients, small-bowel endoscopies should be performed for diagnosis of small-bowel lesions in patients with IgAV and EGPA.

Practical fecal calprotectin cut-off value for Japanese patients with ulcerative colitis.

AIM: To determine appropriate fecal calprotectin cut-off values for the prediction of endoscopic and histologic remission in Japanese patients with ulcerative colitis (UC). METHODS: We performed a cross-sectional observational study of 131 Japanese patients with UC and measured fecal calprotectin levels by fluorescence enzyme immunoassay. The clinical activity of UC was assessed with the partial Mayo score (PMS). Relapse was defined as increase of PMS by 2 points or more in stool frequency or rectal bleeding subscore. The endoscopic and histologic activities of UC were evaluated in 50 patients within a 2-mo period from fecal sampling. Endoscopic activity was determined by Mayo endoscopic subscore, Rachmilewitz endoscopic index, and ulcerative colitis endoscopic index of severity. The histologic grade of inflammation was evaluated with biopsy specimens obtained from the endoscopically most severely inflamed site, according to the scheme by Matts grade and Riley's score. RESULTS: Fecal calprotectin levels varied from 1-20783 µg/g. There was a significant correlation between the partial Mayo score and fecal calprotectin levels (r = 0.548, P < 0.001). In 50 patients who underwent colonoscopy with biopsy, levels were significantly correlated with the Mayo endoscopic subscore (r = 0.574, P < 0.001), Rachmilewitz endoscopic index (r = 0.628, P < 0.001), ulcerative colitis endoscopic index of severity (r = 0.613, P < 0.001), Riley's histologic score (r = 0.400, P = 0.006), and Matts grade (r = 0.586, P < 0.001). Receiver-operating characteristic analyses identified the best cut-off value for the prediction of endoscopic remission as 288 µg/g, with an area under the curve of 0.777 or 0.823, while that for histologic remission was 123 or 125 µg/g, with an AUC of 0.881 or 0918, respectively. Of the 131 study patients, 88 patients in clinical remission were followed up 6 mo. During the follow-up period, 19 patients relapsed. The best fecal calprotectin cut-off value for predicting relapse was 175 µg/g. CONCLUSION: Fecal calprotectin is a predictive biomarker for endoscopic and histologic remission in Japanese patients with UC.

[Quality of life in irritable bowel syndrome].

Irritable bowel syndrome (IBS) is a chronic disorder of unknown origin, which is a very common disease and a frequent complaint among patients consulting general practitioners or gastroenterologists. It is primary characterized by abdominal pain, alteration in bowel habit, abdominal discomfort that can significantly affect quality of life (QOL). Measurements of QOL in IBS patients are more complete than a symptomatic score for the evaluation of patient status, which would increase to use as the assessment of therapeutic effects.

Characterization of follicular lymphoma in the small intestine using double-balloon endoscopy.

Follicular lymphomas occur rarely in the gastrointestinal tract, representing only 1-3% of all gastrointestinal tract B-cell non-Hodgkin lymphomas. We describe endoscopic analysis of 3 cases of follicular lymphoma in the small intestine using double-balloon endoscopy. Double-balloon endoscopy revealed multiple nodular lesions and elevated white patches, multiple polypoid lesions, and scattered white polypoid and nodular lesions in the duodenum and small intestine. Fuji Intelligent Chromo Endoscopy demonstrated small, whitish nodules, and narrow-band imaging showed a coiled, elongated vascular pattern within the elevated lesions. These cases are the first follicular lymphomas in the small intestine evaluated using narrow-band imaging or Fuji Intelligent Chromo Endoscopy to be reported.

Ventriculography using ECG-gated multiple diastolic injection of contrast material in pediatric angiocardiography.

In pediatric patients, the lower body weight limits the volume of contrast medium. Conventionally, angiocardiography is carried out with a single large bolus injection of contrast material. Angiocardiograms are used in pediatric patients with complex congenital heart diseases. In patients with complex congenital heart disease, especially with MAPCA, the volume of contrast medium used may be excessive. This would allow further injection to provide additional information. To reduce contrast medium used in the angiocardiogram in pediatric patients, we decided to use electrocardiogram (ECG)-gated multiple diastolic injection (EMDI). Three small boluses were injected during the diastolic phase of three consecutive cardiac cycles using a commercially-available power injector. Seventy-eight ventriculograms (47 left ventriculograms and 31 right ventriculograms) using EMDI were carried out on 53 patients with congenital heart disease. Total contrast medium volume with EMDI ventriculograms (mean [+/- SD] per body weight: 0.72 [+/- 0.25] ml/kg) was significantly smaller than with conventional injection (1.01 [+/- 0.36] ml/kg) (p <0.001). The grades of ventriculograms with EMDI tended to be slightly better than those with conventional injection (statistically not significant, p = 0.478). No short-run type premature ventricular contraction (PVC)s or intramural injection occurred in the ventriculograms with EMDI. PVCs tended to be less frequent in the ventriculograms with EMDI than in those with conventional injection (statistically not significant, p = 0.131). EMDI may be worthwhile in reducing ventricular ectopy when checking ventricular function by angiography, since hemodynamic conditions are less affected by small quantities of contrast medium and only during the filling phase of the ventricles. In conclusion, EMDI may be a useful method for reducing complications of ventriculography in pediatric angiocardiography.