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.

Distinction between Chronic Enteropathy Associated with the SLCO2A1 Gene and Crohn's Disease

BACKGROUND/AIMS: We recently identified recessive mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1) as causative variants of chronic nonspecific multiple ulcers of the small intestine (chronic enteropathy associated with SLCO2A1, CEAS). The aim of this study was to investigate the gastroduodenal expression of the SLCO2A1 protein in patients with CEAS and Crohn’s disease (CD). METHODS: Immunohistochemical staining for SLCO2A1 was performed with a polyclonal antibody, HPA013742, on gastroduodenal tissues obtained by endoscopic biopsy from four patients with CEAS and 29 patients with CD. RESULTS: The expression of SLCO2A1 was observed in one of four patients (25%) with CEAS and in all 29 patients (100%) with CD (p C (exon 7) or c.940+1G>A (exon 10). The remaining one CEAS patient with positive expression of SLCO2A1 had compound heterozygous c.664G>A and c.1807C>T mutations. CONCLUSIONS: Immunohistochemical staining for SLCO2A1 in gastroduodenal tissues obtained by endoscopic biopsy is considered useful for the distinction of CEAS from CD.

Immunohistochemical differentiation between chronic enteropathy associated with SLCO2A1 gene and other inflammatory bowel diseases

BACKGROUND/AIMS: We recently identified recessive mutations in the solute carrier organic anion transporter family member 2A1 gene (SLCO2A1) as causative variants of chronic enteropathy associated with SLCO2A1 (CEAS). The aim of this study was to evaluate SLCO2A1 protein expression in the intestinal tissues of patients with CEAS, intestinal Behçet's disease (BD), simple ulcer (SU), and Crohn's disease (CD). METHODS: Immunohistochemical staining using a polyclonal anti-SLCO2A1 antibody was performed on the resected intestinal specimens from 13 cases of CD, 9 cases of intestinal BD/SU, and 3 cases of CEAS. The extent of SLCO2A1 expression was determined by counting positively-staining vascular endothelial cells and scored as 0 (no cells), 1 (1%–30% cells), 2 (31%–60%), or 3 (>60%). The intensity of SLCO2A1 expression was scored either as 0 (negative), 1 (intermediate), or 2 (strong). The extent score and intensity score were summed for the final score of 0, 2, 3, 4, or 5. RESULTS: SLCO2A1 protein expression was observed in 1 of 3 cases of CEAS (33%), all 13 cases of CD (100%), and all 9 cases of BD/SU (100%). The mean final expression scores of CEAS, CD, and BD/SU were 1.6 (range, 0–5), 4.8 (range, 4–5), and 4.3 (range, 4–5), respectively. The final expression score in CEAS was significantly lower than in CD (P=0.03). CONCLUSIONS: Immunohistochemical staining of the SLCO2A1 protein is considered useful to distinguish CEAS from other inflammatory bowel diseases.

Predicting outcomes to optimize disease management in inflammatory bowel disease in Japan: their differences and similarities to Western countries

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.

Characteristics of Primary and Metachronous Gastric Cancers Discovered after Helicobacter pylori Eradication: A Multicenter Propensity Score-Matched Study

BACKGROUND/AIMS: Gastric cancers develop even after successful Helicobacter pylori eradication. We aimed to clarify the characteristics of early gastric cancers discovered after H. pylori eradication. METHODS: A total of 1,053 patients with early gastric cancer treated by endoscopic submucosal dissection were included. After matching the propensity score, we retrospectively investigated the clinicopathological features of 192 patients, including 96 patients who had undergone successful H. pylori eradication (Hp-eradicated group) and 96 patients who had active H. pylori infection (Hp-positive group). RESULTS: In the Hp-eradicated group, early gastric cancers were discovered 1 to 15 years (median, 4.1 years) after H. pylori eradication. Compared with Hp-positive patients, Hp-eradicated patients showed a more frequently depressed configuration (81% vs 53%, respectively, p<0.0001) and a higher trend toward submucosal invasion (18% vs 8%, respectively, p=0.051). A multivariable analysis revealed the macroscopic depressed type to be characteristics of early gastric cancers after H. pylori eradication. Among patients in the Hp-eradicated group, metachronous cancers showed less frequent depressed lesions (68% vs 84%, respectively, p=0.049) and smaller tumor sizes (median, 11 mm vs 14 mm, respectively, p=0.014) than primary cancers. CONCLUSIONS: Early gastric cancers after H. pylori eradication are characterized by a depressed configuration. Careful follow-up endoscopies are necessary after H. pylori eradication.

Adsorptive Granulocyte/Monocyte Apheresis for the Maintenance of Remission in Patients with Ulcerative Colitis: A Prospective Randomized, Double Blind, Sham-Controlled Clinical Trial

BACKGROUND/AIMS: Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse. METHODS: Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy. They were then randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal circulation without the GMA column every 4 weeks (Sham, n=11), or no additional intervention (Control, n=11). The primary endpoint was the rate of avoiding relapse (AR) over 48 weeks. RESULTS: At week 48, the AR rates in the True, Sham, and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were steroid-free, but no statistically significant difference was seen among the three arms. However, in patients who could taper their prednisolone dose to <20 mg/day during the remission induction therapy, the AR in the True group was better than in the Sham (p<0.03) or Control (p<0.05) groups. CONCLUSIONS: Monthly GMA may potentially prevent UC relapse in patients who have achieved remission through weekly GMA, especially in patients on <20 mg/day PSL at the start of the maintenance therapy.

Infliximab Therapy Impacts the Peripheral Immune System of Immunomodulator and Corticosteroid Naive Patients with Crohn's Disease

BACKGROUND/AIMS: Infliximab (IFX), an antibody to tumor necrosis factor, (TNF)-alpha has efficacy in treating Crohn's disease (CD). However, knowledge of the potential effects of IFX on patients' immune profiles is lacking. The purpose of this study was to reveal the immunological effects of IFX. METHODS: Twenty-two patients with a CD activity index (CDAI) of 194.2+/-92.9 and an average duration of disease of 3.26 months and 21 healthy controls were included. Patients were to have their first IFX remission induction therapy with 3 infusions (5 mg/kg) at weeks 0, 2, and 6. Oral 5-aminosalicylic acid was the only ongoing medication in the patient population. Blood samples at baseline, 12 hours after the first infusion and at week 14 were labeled with anti-CD4/CD25 antibodies for immunohistochemical measurement of regulatory T-cells (Treg). Serum cytokines and chemokines were measured by suspension array and ELISA. RESULTS: CDAI significantly decreased prior to the second IFX infusion (p<0.001). Clinical remission rates were 77.3% and 91% by the second and third infusions, respectively. At baseline, interleukin (IL)-6 (p<0.03), IL-8 (p<0.03), IL-10 (p=0.050), IL-13 (p<0.01), transforming growth factor-beta1 (p<0.01), and 'regulated on activation, normal T cell expressed and secreted' (RANTES) (p<0.01) were elevated in patients. After the initial IFX infusion, TNF-alpha (p<0.04), IL-6 (p<0.03), interferon (IFN)-gamma (p<0.04), IFN-gamma-inducible protein-10 (p<0.01), monocyte chemoattractant protein-1 (p<0.01), macrophage inflammatory protein-1beta (p<0.01), and RANTES (p<0.01) were decreased. IFX infusion was associated with an increase in Treg (p<0.01) and a decrease in the Th1 (IFN-gamma)/Th2 (IL-4) ratio (p<0.03). CONCLUSIONS: IFX use was associated with restoration of the Th1/Th2 balance after a single infusion and seemed to promote induction of naive Th0 lymphocytes to Treg. This knowledge should have clinical relevance.

Analysis of the Gastrointestinal Symptoms of Uninvestigated Dyspepsia and Irritable Bowel Syndrome

BACKGROUND/AIMS: Epidemiological studies suggest that there is a considerable overlap between functional dyspepsia (FD) and irritable bowel syndrome (IBS). The aim of this study was to examine concurrent gastrointestinal symptoms in FD and IBS. METHODS: A total of 186 college students filled out a questionnaire regarding whether they had uninvestigated dyspepsia (UD, FD without endoscopic examination) and IBS based on Rome-II criteria. Gastrointestinal symptoms were measured using the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. RESULTS: A total of 181 students (98 males, mean age 24.6 years) completed both questionnaires. The prevalence of UD, IBS, and UD+IBS overlap was 12 (6.7%), 40 (22.1%), and 8 (4.4%), respectively. A significant UD+IBS overlap was observed (66.7% IBS in UD, 20.0% UD in IBS). Reflux scores of GSRS in either UD or IBS were significantly greater than in those without. Gastroesophageal reflux disease (GERD), defined as weekly occurring moderate symptoms of heartburn and/or acid regurgitation and evaluated using the GSRS, was found in 16 (8.8%) of the subjects. The prevalence of IBS was significantly higher in GERD patients than in non-GERD patients (50.0% vs 19.4%). CONCLUSIONS: The considerable overlap not only between UD and IBS, but also between GERD and IBS, suggests the involvement of common pathophysiological disturbances in the two conditions.

Cytapheresis in Patients with Severe Ulcerative Colitis after Failure of Intravenous Corticosteroid: A Long-Term Retrospective Cohort Study

BACKGROUND/AIMS: Cytapheresis (CAP) is a novel strategy for ulcerative colitis (UC). However, there is insufficient data on the long-term outcome of UC patients who achieve remission by CAP. This study involved patients with severe UC who refracted to intravenous (iv) corticosteroid. METHODS: Forty-seven UC patients who had received CAP therapy for the first time within 1 year after UC diagnosis were followed for 36 months. One of the inclusion criteria was a clinical activity index (CAI) of > or =7 points at the end of a 2-week iv course of corticosteroid therapy. CAP therapy consisted of ten sessions over 10 weeks. RESULTS: CAP induced clinical remission (CAI or =12, n=25) than for moderately severe UC at entry (7< or =CAI<12, p=15; p<0.02). The cumulative rates of avoiding surgery and relapse were 54.5% and 24.2%, respectively, at 36 months in patients who responded to CAP therapy. This was similar to that of iv cyclosporine reported recently. CONCLUSIONS: This study suggest that CAP is an effective therapy in patients who are refractory to conventional medications including iv corticosteroid. Increased remission rates should be expected in refractory patients with moderately severe UC.