Pazopanib-induced enteritis in a patient with renal cell carcinoma.

A 69-year-old woman presented to our department with the chief complaint of diarrhea. She had undergone left nephrectomy for renal cancer 14 years earlier. Three years earlier, metastasis was detected in the left retroperitoneal cavity, and pazopanib administration was initiated. In the 29th month after the start of chemotherapy, the patient developed diarrhea, and on the 31st month, computed tomography showed thickening of the intestinal wall. Colonoscopy revealed white villi, intramucosal hemorrhage in the terminal ileum, and rough inflammatory mucosa with inflammatory polyps extending from the transverse to the sigmoid colon. Suspecting pazopanib-induced enteritis, we discontinued the medication, and the diarrhea resolved within 3 days. On the 21st day after discontinuation, colonoscopy revealed that the inflammatory polyps had shrunk, and the inflammatory findings had improved. Biopsy of the white villi of the ileum revealed histiocytes. The patient resumed treatment with pazopanib at 400 mg/day and developed soft stool on the 7th day after resumption. Compared with other tyrosine-kinase inhibitor-induced enteritis cases, this case showed less bleeding and more extensive inflammatory findings. There are similarities as well as differences from cases of previously reported pazopanib-induced enteritis. The mechanisms and characteristics of this disease require further investigation.

Predictive Factors for Efficacy of Oral Tacrolimus Induction Therapy in Moderate to Severe Ulcerative Colitis Patients: Large Multicenter Retrospective Cohort Study.

BACKGROUND: Tacrolimus (TAC), a calcineurin inhibitor, is used for remission induction therapy in patients with moderate to severe ulcerative colitis (UC), with short-term efficacy and related predictive factors shown in previous cohort studies. However, most studies reported data for only a limited number of patients enrolled from a single center. We performed a large multicenter retrospective cohort study to identify factors related to prediction of clinical remission in UC patients treated with oral TAC. METHODS: The medical records of patients with moderate to severe UC treated with oral TAC as induction therapy at 7 institutions between April 2009 and March 2017 were retrospectively reviewed. RESULTS: A total of 216 patients who received TAC for induction were analyzed, of whom 123 (56.9%) showed clinical remission at week 12. Logistic regression analysis indicated that previous or current use of antitumor necrosis factor (TNF)-α antibodies (odds ratio [OR], 0.259; P = .006), and concomitant treatment with 5-aminosalicylate (5-ASA) at the baseline (OR, 0.268; P = .005) were independent predictive factors correlated with failure of clinical remission, whereas higher levels of C-reactive protein (OR, 1.124; P = .014) predicted achievement of clinical remission. CONCLUSIONS: Results of this multicenter study clearly indicate the efficacy of TAC induction therapy for patients with moderate to severe UC. Notably, previous or current use of anti-TNF-α antibodies was associated with poor achievement of clinical remission by week 12.

Endoscopic Lesions of Postoperative Anastomotic Area in Patients With Crohn's Disease in the Biologic Era: A Japanese Multi-Centre Nationwide Cohort Study.

BACKGROUND AND AIMS: Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients. METHODS: We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis. RESULTS: In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions. CONCLUSIONS: Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement.

Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model.

The risk of malignant tumor progression has been a concern associated with the use of anti-tumor necrosis factor-alpha monoclonal antibody (anti-TNFα mAb). On the contrary, recent observational studies have reported negatively on this risk and instead suggested that anti-TNFα mAb acts as a tumor suppressor in inflammatory carcinogenesis models and subcutaneous transplant models of colorectal cancer. However, no consensus has been established regarding the actual effects of anti-TNFα mAb on malignant tumors. Here, we aimed to evaluate, for the first time, the effect of anti-TNFα mAb on the tumor microenvironment in the absence of intestinal inflammation in a colorectal cancer orthotopic transplant mouse model suitable for tumor microenvironment assessment. The orthotopic transplantation model was developed by transplanting CT26 cells into the cecum of BALB/c mice. Changes in tumor size and weight were recorded 3 weeks after transplantation, and the tumor microenvironment was assessed via RNA sequencing and immunohistological staining. In the orthotopic transplant model, the administration of anti-TNFα mAb led to a reduction in colorectal cancer. The RNA sequencing analysis showed upregulation of immune-related pathways and apoptosis and suppression of stromal- and tumor growth-related pathways. Additionally, Gene Ontology analysis showed inhibition of angiogenesis. Immunohistochemical staining showed inhibition of tumor growth, increase in apoptosis, suppression of stromal response, suppression of angiogenesis, enhancement of tumor immunity, and reduction in the number of tumor-associated macrophages. Anti-TNFα mAb acts as an inhibitor of tumor progression in the tumor microenvironment of a colorectal cancer orthotopic transplant mouse model.

Two cases of ulcerative colitis that developed while using abatacept.

Abatacept (ABT) is a recombinant fusion protein consisting of the Fc domain fragment of human IgG1 and the extracellular domain of human cytotoxic T lymphocyte antigen-4 (CTLA-4). The function of ABT is similar to that of CTLA-4, which selectively regulates T-cell activation by inhibiting the co-stimulation of CD80/CD86 on antigen-presenting cells and CD28 on T lymphocytes. ABT is used for the treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis. We report two cases of ulcerative colitis (UC) that developed while using ABT. Case 1 is of a 58-year-old man who developed diarrhea and hematochezia 2 months after starting ABT therapy for RA. Case 2 is of a 66-year-old man who experienced hematochezia 15 months after starting ABT therapy for RA. In both cases, no obvious gastrointestinal symptoms were observed before ABT therapy was initiated. Colonoscopy after disease onset showed UC findings in both cases. The patients' condition improved following ABT withdrawal and treatment for UC. Several cases of UC development during ABT therapy have been reported. The complication of UC should be considered when diarrhea and hematochezia are observed in patients with RA being treated with CTLA-4Ig agents.

Promoting mechanism of serum amyloid a family expression in mouse intestinal epithelial cells.

Serum amyloid A (SAA) is an acute phase inflammatory protein that we previously described as a robust biomarker of colorectal inflammation in patients with ulcerative colitis (UC) in clinical remission. However, what induces SAA expression in UC remains unclear. This study demonstrates that SAA is significantly expressed in the intestinal tract of UC mouse models when compared with C-reactive protein, another inflammatory biomarker. Moreover, interleukin-6 and tumor necrosis factor-α were found to promote SAA1 expression, as were Toll-like receptor ligands flagellin and lipopolysaccharide. Furthermore, results suggested that the nuclear factor-kappa B (NF-κB) pathway may be involved in the promotion of SAA1 expression by flagellin, which was inhibited by treatment with 5-aminosalicylic acid (5-ASA). Therefore, the flagellin/NF-κB/SAA1 axis may represent one of the mechanisms by which 5-ASA suppresses intestinal inflammation.

Clinical characteristics of inflammatory bowel disease patients with immunoglobulin A nephropathy.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract. Some patients with this condition have been reported to present with immunoglobulin A nephropathy (IgAN), a renal complication that can cause end-stage renal failure, but the frequency of this comorbidity has not been described. Thus, the aim of this study was to investigate the frequency of IgAN in patients with IBD. METHODS: This study included 620 patients with IBD (338 with ulcerative colitis [UC] and 282 with Crohn's disease [CD]) from the Hiroshima University Hospital outpatient department. IgAN cases were identified from medical interviews, blood examinations (serum immunoglobulin A), and urinalyses (occult blood, proteinuria). Definitive IgAN cases were diagnosed by renal biopsies, while those detected through the clinical course and test results, but not clinically recommended for renal biopsy, were defined as suspected IgAN. RESULTS: We analyzed 427 cases meeting the inclusion criteria (220 with UC and 207 with CD). The incidence of IgAN across all patients with IBD was 3.0%. The frequency of IgAN was significantly higher in patients with CD (11/207, 5.3%) than in those with UC (2/220, 0.9%) (P< 0.01). Moreover, a significant correlation was found between CD patients with ileostomy or colostomy and a diagnosis of IgAN. CONCLUSIONS: Patients with IBD present a high incidence of IgAN, especially those with CD who have undergone ileostomy or colostomy.

Serum amyloid A is a better predictive biomarker of mucosal healing than C-reactive protein in ulcerative colitis in clinical remission.

BACKGROUND: Many studies have revealed that mucosal healing improves the long-term prognosis of ulcerative colitis. Frequent colonoscopy is difficult because of its invasiveness and cost. Therefore, in diagnosing and treating ulcerative colitis, noninvasive, low-cost methods for predicting mucosal healing using useful biomarkers are required in the clinical setting. This study aimed to evaluate whether serum amyloid A is a better serum biomarker than C-reactive protein in predicting mucosal healing in ulcerative colitis patients in clinical remission. METHODS: Ulcerative colitis patients whose C-reactive protein and serum amyloid A were measured within 1 month before and after colonoscopy were included in this retrospective study, and the relationship between the C-reactive protein and serum amyloid A values and the mucosal condition was analyzed. Mucosal condition was assessed using the Mayo Endoscopic Score, with score 0 or 1 indicating mucosal healing. RESULTS: A total of 199 colonoscopic examinations were conducted in 108 ulcerative colitis patients who underwent C-reactive protein and serum amyloid A blood tests. In clinical remission patients, serum amyloid A showed a strong correlation with mucosal inflammation compared to C-reactive protein and had excellent sensitivity and specificity rates with significant statistical significance. CONCLUSIONS: Serum amyloid A is a more useful marker compared to C-reactive protein in predicting mucosal inflammation in ulcerative colitis patients in clinical remission.

Evaluation of blood flow on optic nerve head after pattern scan and conventional laser panretinal photocoagulation.

To evaluate the changes in the blood flow on retina and the optic nerve head (ONH) after conventional laser treatment and to compare it to that after patterned scanning laser (PASCAL) treatment in patients with severe nonproliferative diabetic retinopathy (S-NPDR).In this prospective, cross-sectional study, the blood flow on retina and the ONH was assessed by laser speckle flowgraphy using the mean blur rate (MBR) in 39 eyes with S-NPDR before, 1, 4, 8, 12 weeks after panretinal photocoagulation (PRP). Of 39 eyes, 17eyes with 17 patients treated by conventional laser and 22 eyes with 22 patients treated by PASCAL.The mean age was 55.5 ±â€Š11.5 years in the conventional laser group, 55.6 ±â€Š11.8 years in the PASCAL group. The MBR-vessel, which can be dominantly expressed as retinal blood flow, was significantly reduced after PRP treated by conventional laser (P < .001), but did not change after PRP treated by PASCAL. The ratio of MBR-vessel to the baseline was significantly lower in the conventional laser group only at Week 1 (P = .045). The MBR-tissue, which can be dominantly expressed as the ONH blood flow, did not significantly change after PRP in the both group. The multiple stepwise regression analysis revealed that the laser burns was an independent factor significantly correlated with the ratio of MBR-vessel at Week 1 to the baseline (ß = -0.550, P = .012).The retinal blood flow was significantly reduced during the 12 weeks only after completion of PRP by conventional laser treatment. Our results indicate that short pulse on PRP treatment performed by the PASCAL would not significantly reduce the retinal blood flow.

Effect of intravitreal or sub-tenon triamcinolone acetonide injection at completion of vitrectomy on peripheral retinochoroidal thickness in eyes with proliferative diabetic retinopathy.

The effect of triamcinolone acetonide (TA) on the peripheral retinochoroidal thickness was determined after pars plana vitrectomy (PPV) with scatter photocoagulation in eyes with proliferative diabetic retinopathy. The peripheral retinochoroidal thickness was measured at 5 mm from the limbus in the four quadrants using anterior segment optical coherence tomography before, and 3 days, and 1 and 2 weeks after the surgery. The total peripheral thickness was significantly thicker than the baseline thickness after PPV alone (P < 0.001; 18 eyes), PPV combined with intravitreal TA injection (IVTA; P = 0.011; 19 eyes), and PPV combined with sub-tenon TA injection (STTA; P = 0001; 23 eyes). The total peripheral thickness in the PPV group at 3 days after surgery was significantly thicker than that of the PPV + IVTA (P = 0.015) and of the PPV + STTA groups (P = 0.016). Multiple linear regression analyses showed that the injection of TA by the two routes and the number of photocoagulation burns were significantly correlated with the total peripheral thicknesses at 3 days after the surgery. The results indicate that the PPV with large number of intraoperative scatter photocoagulation burns caused an increase in the total peripheral thickness and an administration of either IVTA and STTA can reduced the degree of thickening.

Rectal Lymphoid Follicle Aphthous Lesions Frequently Progress to Ulcerative Colitis with Proximal Extension.

Objective Rectal lymphoid follicular aphthous (LFA) lesions are related to ulcerative colitis (UC) and can be initial lesions of UC. We investigated the clinical course and prognosis of rectal LFA lesions. Methods This is a retrospective analysis of the clinical records at a single center. Patients Thirteen consecutive cases with LFA lesions treated at Hiroshima University Hospital between 1998 and 2015 were evaluated. Another 49 consecutive cases with ulcerative proctitis treated in the same period were enrolled as the control group. The clinical course and prognosis of both groups were evaluated. Results The group with LFA lesions included 9 women and 4 men with a median age of 39.9 years (range, 21-70 years). A total of 11 cases progressed to typical UC at 5-51 months. Proximal extension of these typical UC lesions was observed in 7 (53.8%) cases, which was significantly higher than in the control group (10 cases, 20.8%). Three cases (5-year accumulation incidence rate, 27.3%) progressed to steroid-intractable UC, a significantly higher incidence than that of the control group (3 cases; 5-year accumulation incidence rate, 6.9%). Conclusion Rectal LFA lesions frequently progress to typical UC with proximal extension, some of which become intractable to corticosteroid treatment.

Polysaccharides derived from Ganoderma lucidum fungus mycelia ameliorate indomethacin-induced small intestinal injury via induction of GM-CSF from macrophages.

Non-steroidal anti-inflammatory drugs often cause ulcers in the human small intestine, but few effective agents exist to treat such injury. Ganoderma lucidum Karst, also known as "Reishi" or "Lingzhi", is a mushroom. We previously reported that a water-soluble extract from G. lucidum fungus mycelia (MAK) has anti-inflammatory effects in murine colitis induced by trinitrobenzene sulfonic acid, and induction of granulocyte macrophage colony-stimulating factor (GM-CSF) by MAK may provide anti-inflammatory effects. However, its effects on indomethacin-induced small intestinal injuries are unknown. The present study investigated the preventative effects of MAK via immunological function and the polysaccharides from MAK on indomethacin-induced ileitis in mice. Peritoneal macrophages (PMs) were stimulated in vitro with MAK and adoptively transferred to C57BL/6 mice intraperitoneally, which were then given indomethacin. Intestinal inflammation was evaluated after 24h. We performed in vivo antibody blockade to investigate the preventive role of GM-CSF, which derived from PMs stimulated with MAK. We then used PMs stimulated with MAK pre-treated by pectinase in an adoptive transfer assay to determine the preventive role of polysaccharides. Indomethacin-induced small intestinal injury was inhibited by adoptive transfer of PMs stimulated in vitro with MAK. In this transfer model, pre-treatment with anti-GM-CSF antibody but not with control antibody reversed the improvement of small intestinal inflammation by indomethacin. Pectinase pretreatment impaired the anti-inflammatory effect of MAK. PMs stimulated by MAK appear to contribute to the anti-inflammatory response through GM-CSF in small intestinal injury induced by indomethacin. The polysaccharides may be the components that elicit the anti-inflammatory effect.

Significance of non-alcoholic fatty liver disease in Crohn's disease: A retrospective cohort study.

AIM: The prevalence of non-alcoholic fatty liver disease (NAFLD) and Crohn's disease (CD) is increasing. The aim of our study was to evaluate the prevalence of NAFLD in patients with CD, as well as to investigate the effect of NAFLD on the disease course of CD. METHODS: Our retrospective cohort study included 303 patients who underwent abdominal ultrasound for CD and NAFLD diagnosis at our center between November 2008 and October 2014. Serum C-reactive protein (CRP) level and rate of remission, defined by a score <150 on the Crohn's Disease Activity Index, were compared between CD patients with and without NAFLD, using multivariate logistic regression. The effect of NAFLD on the surgery-free interval was evaluated using Cox proportional hazards models, adjusted for potential demographic confounders. RESULTS: Non-alcoholic fatty liver disease was diagnosed in 66 (21.8%) patients in our study cohort and was associated with lower CRP levels (0.58 vs. 2.18 mg/dL, P < 0.0001) and a higher rate of remission (75.9% vs. 53.7%, P = 0.0024). Non-alcoholic fatty liver disease was identified as an independent predictor of a negative CRP level (<0.3 mg/dL; odds ratio, 1.85; 95% confidence interval, 1.03-3.37) and higher rate of remission (odds ratio, 2.57; 95% confidence interval, 1.21-5.80). Non-alcoholic fatty liver disease was associated with longer surgery-free interval (log-rank test, P = 0.0035), with NAFLD identified as a positive predictor of surgery-free interval (P = 0.0014). CONCLUSIONS: Non-alcoholic fatty liver disease may offer a protective effect in patients with CD and could be used as a prognostic marker in patients with CD.

Clinical usefulness of narrow band imaging magnifying colonoscopy for assessing ulcerative colitis-associated cancer/dysplasia.

Background and study aims: Colitis-associated cancer/dysplasia (CC/D) can affect the life expectancy of patients with ulcerative colitis (UC). Although the utility of magnifying chromocolonoscopy has been shown, the use of optical magnification with narrow band imaging (NBI) for distinguishing CC/D from non-neoplastic lesions in patients with UC has not been reported. We evaluated whether endoscopic findings are distinguishing and thus assessed the clinical usefulness of NBI magnification for differentiating UC-associated lesions. Patients and methods: The study involved 27 patients diagnosed and treated at Hiroshima University Hospital between September 2005 and March 2015: a neoplasia group (16 lesions) and a non-neoplasia group (17 lesions). The neoplasias comprised 9 dysplastic lesions, 5 intramucosal carcinomas, and 2 submucosal carcinomas, and 17 non-neoplastic lesions. Targeted biopsy samples of suspicious lesions detected by conventional colonoscopy were classified pathologically as neoplastic or non-neoplastic, and NBI magnifying colonoscopy findings (i. e., the surface [unclear/regular/irregular/amorphous] and vascular [same as the background mucosa/regular/irregular/avascular] patterns) of the 2 lesion types were compared. Results: Irregular/amorphous surface patterns were significantly more common in neoplastic lesions than in non-neoplastic lesions (81 % [13/16] vs. 18 % [3/17], respectively, P < 0.001). Irregular/avascular vessel pattern tended to be more common in neoplastic lesions (75 % [12/16] vs. 41 % [7/17], respectively). The surface pattern correctly predicted 82 % of neoplastic lesions, and the vessel pattern correctly predicted 67 % of non-neoplastic lesions. The 2 endoscopic findings together correctly predicted 91 % of neoplastic lesions. Conclusion: Surface pattern, determined by magnifying colonoscopy with NBI, is useful for differenting between UC-associated neoplastic and non-neoplastic lesions.

Clinical usefulness of transabdominal ultrasonography prior to patency capsule for suspected small-bowel strictures.

OBJECTIVE: Patency capsule (PC) examination has made it possible to perform capsule endoscopy (CE) in patients with a suspected small-bowel stricture. However, PC has some drawbacks, so we assessed the usefulness of transabdominal ultrasonography (TUS) prior to PC in patients with suspected small-bowel strictures to avoid unnecessary PC examination. PATIENTS AND METHODS: Fifty-two patients who underwent TUS prior to PC were enrolled in this study. TUS findings were classified as follows: intestinal narrowing and distension at the oral side (Type A); extensive bowel wall thickening (Type B); focal bowel wall thickening (Type C) or no abnormality detected (Type D). We evaluated the TUS and PC findings for the detection of small-bowel strictures. RESULTS: Double-balloon endoscopy (DBE) revealed small-bowel strictures in 13 of 50 patients (26%). TUS yielded Type B or C findings in 12 of 13 patients (92%), while PC revealed strictures in all 13 patients. In Crohn's disease (CD) patients with Type B TUS findings, 8 of 9 (89%) had small-bowel strictures on DBE. However, only two of six non-CD patients (33%) with Type B TUS findings had small-bowel strictures. The incidence of Type B strictures was significantly higher in CD patients. CONCLUSIONS: CD patients with Type B TUS findings should not undergo PC or CE because of the high rate of small-bowel strictures. Non-CD patients diagnosed with Type B TUS strictures, as well as patients diagnosed with Type C or D strictures should undergo CE after confirming small-bowel patency using PC.

A Patient with CTLA-4 Haploinsufficiency Presenting Gastric Cancer.

Cytotoxic T-lymphocyte-antigen 4 (CTLA-4) is an essential negative regulator expressed on regulatory T cells (Tregs) and activated T cells. Germline heterozygous mutations in CTLA4 lead to haploinsufficiency of CTLA-4, resulting in the development of an autosomal dominant immune dysregulation syndrome with incomplete penetrance. We report here a Japanese patient with this disorder who has a novel heterozygous single nucleotide insertion, 76_77insT (p. L28SfsX40), in the CTLA4 gene. Peripheral blood mononuclear cells from the patient showed decreased frequency of CTLA-4(high) cells in CD4(+)FOXP3(+) cells following CD3/CD28 stimulation. The patient experienced hypogammaglobulinemia, recurrent pneumonia, esophageal candidiasis, cytomegalovirus-positive chronic gastritis, chronic and severe diarrhea, and type 1 diabetes mellitus. Moreover, the patient developed multifocal gastric cancer, histologically poorly and well-differentiated adenocarcinomas, associated with chronic atrophic gastritis and intestinal metaplasia. Previously, 23 symptomatic cases with heterozygous CTLA4 mutations have been reported. Including the case presented here, 3 of the 24 cases (12.5%) developed gastric cancer. Notably, 2 of 3 patients presented similarly multifocal adenocarcinomas associated with atrophic gastritis and intestinal metaplasia. Predisposition to gastric cancer has been also reported in CVID patients. These clinical observations suggest that gastric cancer is a disease commonly associated with autosomal dominant immune dysregulation syndrome due to CTLA4 mutation.

Clinical usefulness of endocytoscopy in the remission stage of ulcerative colitis: a pilot study.

BACKGROUND: Histopathology can be used to detect ulcerative colitis (UC) relapse, but diagnosis of the disease activity by histopathology requires multiple biopsies to be taken. Magnifying endocytoscopy provides a method for real-time ultra-magnifying imaging. It was recently reported that the endocytoscopy system score (ECSS) correlates well with the histopathology of UC. Here we evaluated the clinical usefulness of endocytoscopy for accurately monitoring UC during remission. METHODS: We performed endocytoscopy on 26 patients with UC in remission that had been diagnosed by conventional colonoscopy at our institution between January and April 2013. Endocytoscopy was performed at the area of the rectum where UC had been detected with conventional endoscopy. Biopsies were also taken from the same area and histopathology was evaluated by a single pathologist according to the Matts' grading system. The correlation between the relapse rate of UC and both the ECSS and the Matts' histopathological grade was evaluated. RESULTS: The ECSS of the intestinal mucosa in UC showed a correlation with the Matts' histopathological grade (Spearman's |r| = 0.647). The patients were classified into two groups: those with an ECSS of 0-2 (Grade A, 12 cases) and those with an ECSS of 3-6 (Grade B, 10 cases). To date, three Grade B cases have relapsed and no Grade A cases have relapsed. The average post-endocytoscopy surveillance period was 446 ± 92 days. CONCLUSIONS: The ECSS may be a predictive indicator for UC relapse since there was a correlation between the ECSS and the degree of inflammation as determined by histopathology.

Pulverized konjac glucomannan ameliorates oxazolone-induced colitis in mice.

PURPOSE: Pulverized konjac glucomannan (PKGM) is a natural biologically active compound extracted from konjac, a Japanese traditional food. In the present study, we investigated the role of PKGM in intestinal immunity in a mouse model of oxazolone (OXA)-induced colitis. METHODS: C57BL/6(B6) mice were fed PKGM or control food from 2 weeks before the induction of OXA colitis. Body weight change, colon length, and histological change in the colon were examined. The mononuclear cells were purified from colon and stimulated with PMA/ionomycin. The levels of TNF-α, interferon (IFN)-γ, interleukin (IL)-4, and IL-13 from the supernatant were measured by ELISA. RESULTS: Oral administration of PKGM prevented the body weight loss and shortening of colon length associated with OXA-induced colitis. Histological analysis revealed that the colonic inflammation was improved by the administration of PKGM. The levels of IL-4 and IL-13, the critical inflammatory cytokines in OXA colitis, derived from mononuclear cells from the lamina propria of the colon were significantly suppressed by PKGM administration. PKGM-fed mice showed a significantly lower IL-4/IFN-γ ratio in the colonic lamina propria compared with that in control-fed mice. Fluorescence-activated cell sorting analysis revealed that natural killer (NK) 1.1(+) T cells in the liver were significantly decreased in PKGM-fed mice. Finally, the preventive role of PKGM in OXA-induced colitis was not observed in invariant natural killer T cell-deficient mice. CONCLUSIONS: PKGM ameliorated OXA-induced colitis in mice. This effect is associated with a decreased population of NK1.1(+) T cells and induction of Th1-polarized immune responses.

Is it possible to discriminate between neoplastic and nonneoplastic lesions in ulcerative colitis by magnifying colonoscopy?

BACKGROUND: Colitis-associated cancer/dysplasia is an intestinal tract condition that can affect the life expectancy of patients with ulcerative colitis. It is often difficult to detect neoplastic lesions. This study evaluated whether any endoscopic features are effective for distinguishing colitis-associated cancer/dysplasia from nonneoplastic lesions in patients with ulcerative colitis. METHODS: The study involved 52 patients with 61 lesions treated at Hiroshima University Hospital between September 1999 and May 2012: 10 patients with 11 dysplastic lesions, 5 patients with 5 intramucosal carcinomas, 3 patients with 3 submucosal carcinomas, and 34 patients with 42 nonneoplastic lesions. All patients had undergone targeted biopsy. Endoscopic findings were compared between patients with biopsy-determined neoplasia and those with biopsy-determined nonneoplasia. Multivariate regression analysis was performed to identify magnifying chromocolonoscopy features predictive of neoplasia. RESULTS: No significant difference was found in conventional endoscopy features between the neoplastic and nonneoplastic lesions. Under magnifying chromocolonoscopy, the pit density of the neoplastic lesions was found to be significantly greater than that of the nonneoplastic lesions (89% [17/19] versus 60% [25/42], respectively). Pit margins were more frequently irregular in the neoplastic lesions than in the nonneoplastic lesions (63% [12/19] versus 33% [14/42], respectively). CONCLUSIONS: In differentiating between colitis-associated neoplastic and nonneoplastic lesions, focus should be on the high residual density of pits and irregular pit margins observed under magnifying chromocolonoscopy.

Continued use of low-dose aspirin does not increase the risk of bleeding during or after endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: Although recent guidelines for endoscopic submucosal dissection (ESD) as treatment for early gastric cancer (EGC) recommend noninterruption of low-dose aspirin (LDA) perioperatively, this strategy is controversial. It was our practice to interrupt LDA therapy 5-7 days before to ESD until December 2010, when we instituted the new guidelines and performed ESD without interrupting LDA therapy. Our purpose in this study was to confirm the validity of noninterrupted use of LDA in patients undergoing ESD for EGC. METHODS: We studied 78 consecutive patients with 94 EGCs who were routinely taking LDA and were treated by ESD at Hiroshima University Hospital between April 2005 and June 2012. The patients were of two groups: those in whom LDA was interrupted perioperatively (53 patients with 66 EGCs) and those in whom LDA was continued perioperatively (25 patients with 28 EGCs). RESULTS: The complete resection rate was 92.4 % (61/66) in the LDA-interrupted group and 100 % (28/28) in the LDA-continued group. Incidences of poor bleeding control during the procedure and bleeding after procedure were 10.6 % (7/66) and 4.8 % (3/66), respectively, in the LDA-interrupted group and 7.1 % (2/28) and 3.6 % (1/28) in the LDA-continued group. Two patients in the interrupted-LDA group suffered cerebrovascular infarction before ESD, and 2 patients in this group suffered acute myocardial infarction after ESD. CONCLUSIONS: Our data suggest that continued use of LDA does not increase the risk of bleeding during or after ESD for EGC and does decrease the risk of ischemic events.