Kazuhito Kani

The efficacy of intensive granulocyte and monocyte adsorption apheresis in a patient with Crohn's disease complicated by extensive subcutaneous aseptic neutrophilic abscesses

BACKGROUND AND AIMS Subcutaneous aseptic abscess is one phenotype of neutrophilic dermatitis. We were interested to see if a case of steroid refractory Crohns disease (CD) complicated by subcutaneous aseptic neutrophilic abscesses responds to intensive granulocyte/monocyte adsorptive apheresis (GMA). METHODS The patient was a 21-year-old male with worsening severe CD while on oral prednisolone (30 mg/day). His symptoms included fever, bloody diarrhoea and multiple painful subcutaneous nodules throughout his body. Skin biopsy showed chronic panniculitis with neutrophilic infiltrates. Further, colonoscopy showed oedematous sigmoid colon, while colonic biopsy showed non-caseous granuloma. Because biologics were feared to increase the risk of bacteraemia as the result of germ culture on his pus was not known at the time, we decided to treat this case with GMA. Five GMA sessions with the Adacolumn over 5 consecutive days (daily GMA) were initiated. RESULTS On admission, his CD activity index (CDAI) was 355, C-reactive protein (CRP) 11.2 mg/dL. After 5 GMA sessions, CDAI decreased to 170, and CRP fell to 5.0 mg/dL, with no fever. GMA was restarted at 2 sessions/week (total 10 sessions). The patients CDAI fell to <150, and the skin lesions re-epithelialized. CONCLUSIONS In this CD case complicated by subcutaneous aseptic neutrophilic abscesses, GMA appeared to be effective. Our impression is that when biopsy reveals neutrophil infiltrate is a major feature of the lesions, GMA should be considered. As GMA appears to have no safety concerns, a frequent GMA protocol, like daily followed by 2 to 3 times/week should be preferred over the routine weekly GMA.

Double balloon enteroscopy to retrieve an accidentally swallowed dental reamer deep in the jejunum.

Accidentally swallowed foreign objects are not uncommon but difficult to manage without complications. We describe the case of a 68 year old man who accidentally a swallowed sharp-pointed dental reamer that had reached deep in his jejunum. Double balloon enteroscopic retrieval was performed with polypectomy snare but the reamer was entangled in the wire loop of the snare and penetrated the jejunal wall. After releasing the reamer by pushing and pulling the snare for approximately 30 min, the reamer was retrieved with biopsy forceps. This is the first report of double balloon enteroscopic removal of a dental reamer. Furthermore, this is a novel case with regard to decision making in situations when sharp objects are swallowed.

COMPARISON OF ADJUVANT THERAPIES BY AN H2-RECEPTOR ANTAGONIST AND A PROTON PUMP INHIBITOR AFTER ENDOSCOPIC TREATMENT IN HEMOSTATIC MANAGEMENT OF BLEEDING GASTRODUODENAL ULCERS

Aim:  Upper gastrointestinal bleeding is often associated with a higher risk of serious blood loss. Both H2‐receptor antagonists and proton pump inhibitors are commonly given intravenously for endoscopic hemostatic therapies. We compared the effects of a H2‐receptor antagonist (famotidine) and a proton pump inhibitor (omeprazole) injected during the early phase (the first 3 days) on cessation of bleeding and prevention of its recurrence in patients who underwent endoscopic therapy for gastroduodenal ulcer bleeding.

Su1194 Prospective Comparison of Computed Tomography Enterography (CTE) and Double Balloon Enteroscopy (DBE) for the Assessment of Disease Activity and Mucosal Healing in the Small Intestinal Involvements in Patients With Crohn's Disease

G A A b st ra ct s study we investigated the applicability of rectal swabs for gut microbiota profiling in a clinical routine setting. We analysed optimal storage and processing of rectal swabs for clinical routine, reproducibility of profiles from rectal swabs and similarity to microbial profiles from fecal and mucosal samples. Methods Rectal swabs, mucosal biopsies, mucosal washings and fecal samples from 38 subjects were prospectively collected and analysed by IS-pro, a high-throughput molecular fingerprinting method. Two rectal swabs were stored in RTF buffer at room temperature for two hours before freezing at -20°C and one was immediately snap frozen. These samples were used to evaluate reproducibility of rectal swabs and effect of storage at room temperature. IS-profiles from rectal swabs were further compared to mucosal and fecal samples. All data analysis was performed with in-house developed software tools in combination with the Spotfire software package (TIBCO, Palo Alto, USA). Results IS-profiles from the two rectal swabs stored in RTF buffer at room temperature were highly similar (estimated correlation coefficients of IS-profiles .90%) and were equally similar to the snap frozen rectal swab. Correlation of rectal swabs to feces was low (estimated correlation coefficients of IS-profiles 40-60%) and correlations to mucosal samples were slightly higher (50-70%). Correlations of fecal samples to mucosal samples were low (4060%). Conclusion We find that rectal swabs give highly reproducible microbiota profiles that resemble mucosal adherent microbiota more closely than feces. Storage of swabs in RTF buffer of up to two hours at room temperature does not affect the results of subsequent microbiota analysis, making reproducible routine sampling in a clinical setting feasible.

Elevated serum IgE prior to acute severe infusion reaction during infliximab maintenance therapy in a Crohn's disease patient.

Intercepting tumor necrosis factor alpha (TNF-a) by antibodies to this cytokine, such as infliximab (IFX) and adalimumab, is currently the best hope for improving the treatment of patients with Crohn’s disease (CD). However, formation of antibodies to IFX (ATI), episodes of infusion reaction (IR), as well as the loss of response to the currently available anti-TNF-a biologics by a significant fraction of patients are serious issues that limit the efficacy and safety of anti-TNF-a therapy. Accordingly, identification of a marker that can predict an IR episode is desirable. A 42-year-old male patient was referred to our hospital with symptoms including diarrhea, abdominal pain, and weight loss together with polyarticular arthropathy. He was diagnosed with colonic CD based on endoscopic findings, showing large longitudinal ulcers and classic cobblestone patterns in the colon without small bowel involvement. His arthritis was judged to be a type 2 polyarticular extraintestinal manifestation without joint destruction, seronegative for rheumatoid factor. The first therapeutic regimen for this patient in our hospital was oral prednisolone (PSL, 10 mg/day), oral mesalamine (5-ASA, 1500 mg/day), and methotrexate (16 mg/week). Two months later, methotrexate was withdrawn due to nausea and was switched to azathioprine (AZA, 50 mg/day). However, his CD Activity Index (CDAI) and disease activity score (DAS28-4) for arthritis were 160 and 4.75, respectively. With these medications, neither the patient’s colonic lesions nor joint symptoms reached the remission stage. Subsequently, medication with IFX (5 mg/kg/day) was initiated together with 100 mg intravenous hydrocortisone and 50 mg intramuscular promethazene, administered 30 minutes before every scheduled IFX infusion (as a prophylactic measure). His CDAI and joint symptoms improved markedly (Fig. 1A). IFX infusion at 8week intervals was continued as maintenance therapy in this patient. Twenty-one months after initiating IFX therapy the patient developed an acute severe IR and his blood pressure fell to below 90/60 mmHg, together with pallor, breathing difficulties, and hypoxemia (indicated by a dotted line in Fig. 1A). We decided to cease IFX therapy due to this severe IR. Additionally, AZA was discontinued due to nausea after 22 months. The patient worsened with an increase in stool frequency and swollen/tender joint counts. We tried induction therapy with adalimumab at 24 months but the patient developed injection site reactions consisting of edema, erythema, and pruritus at the second adalimumab infusion and adalimumab was discontinued. Although the patient did not have any recorded history of allergic reactions such as pollinosis, he showed hypersensitivity reactions to both antiTNF-a biologics. We decided to look for serum factors potentially related to the infusion reaction. Stored sera at time 0 (patient naı̈ve for IFX), 19 months (8 weeks before IR), 21 months (the day of severe IR), and 29 months (8 months after the cessation of IFX due to IR) were prepared for the measurement of IFX according to a new fluid-phase enzyme immunoassay. In the same test samples, ATI was assayed by a doubleantigen enzyme-linked immunosorbent FIGURE 1. (A) Time course of disease activity scores, ATI, and serum IgE obtained before and after severe infusion reaction to IFX. CDAI <150, remission; DAS 28-4 <2.3, remission; ATI >1.69 lg/mL, positive; IgE <408 ng/mL, normal. (B) Changes in CDAI and DAS 28-4 following GMA therapy.

Ghrelin and Functional Dyspepsia

Food consumption is supposed to affect the onset of functional gastrointestinal disorder (FGID), particularly functional dyspepsia (FD). Many secretory fluids and digestive enzymes are secreted from digestive organs in response to food consumption and are then combined with the crushed and mixed food and transported, thereby inducing gastrointestinal motility. Gastrointestinal hormones are active substances that promote these digestive and absorptive functions. Furthermore, in recent years, many gastrointestinal hormones were found to have appetite-regulatory activity, and the abnormal secretion of gastrointestinal hormones and changes in their physiological activity have been suggested to contribute to FD onset. Although some gastrointestinal hormones have anorexic effects, only ghrelin have an orexigenic action and it also stimulates gastric motility. This short review presents the physiological activity of ghrelin as well as the regulatory mechanisms underlying appetite, acid secretion, and gastric motility via the brain–gut axis. In this review, we present the action of ghrelin on the secretion of gastric acid and its mechanism. We found that histamine mediates the stimulatory action of ghrelin on acid secretion through the mechanism based on brain–gut axis. Furthermore, we discussed the relationship between FD and ghrelin, and pathophysiology for FD in the state of stress that was simulated through animal experiments with intracerebroventricular (icv) injection of stress-related peptide urocortin 1 (UCN1). Our study has elucidated that UCN1 decreases plasma ghrelin level through CRF receptor 2. The inhibition of ghrelin secretion is mediated by sympathetic nerve through α2-adrenergic receptor in periphery. The mechanism may explain pathophysiology for FD inducing dyspepsia symptoms such as abdominal distension, fullness, and anorexia.

Changes in Treatment with Granulocyte and Monocyte Adsorptive Apheresis from the Past to Future in Patients with Inflammatory Bowel Disease

BACKGROUND Idiopathic acute-on-chronic inflammation in the gastrointestinal tract is an etiology of inflammatory bowel disease (IBD). Granulocyte and monocyte adsorptive apheresis (GMA) is a nonpharmacological treatment tool for patients with IBD. Here, we present a review of the positioning and possibilities of GMA for patients with IBD. SUMMARY GMA decreases inflammatory cytokines and upregulates regulatory T cells. Intensive GMA is significantly more effective than weekly GMA in patients with IBD. The frequency of GMA sessions per week positively correlates with treatment effects. GMA can be safely used in pregnant women and children because of its low adverse event rates. Maintenance therapy and rescue therapy for loss of response of anti-tumor necrosis factor (TNF)-α antibodies are effective. Optimal patients who responded to combination therapy with infliximab and GMA showed aggravation characteristics against infliximab treatment at week 4. Key Message: Prospective randomized blinded studies using a sham column should be performed for the loss of response against anti-TNF-α antibodies.

Seven days triple therapy for eradication of Helicobacter pylori does not alter the disease activity of patients with inflammatory bowel disease

Background/Aims The influences of Helicobacter pylori eradication therapy on the disease course of inflammatory bowel disease (IBD) are still unclear. We therefore conducted a multicenter, retrospective cohort study to evaluate the safety of H. pylori eradication therapy for IBD patients. Methods IBD patients with H. pylori eradication from 2005 to 2015 (eradication group) and control patients (non-eradication group; 2 paired IBD patients without H. pylori eradication matched with each eradicated patient) were included. IBD exacerbation (increased/additional IBD drug or IBD-associated hospitalization/surgery) and disease improvement based on the physicians’ global assessment were investigated at baseline, and at 2 and 6 months after eradication or observation. Results A total of 429 IBD (378 ulcerative colitis, 51 Crohn’s disease) patients, comprising 144 patients in the eradication group and 285 patients in the non-eradication group, were enrolled at 25 institutions. IBD exacerbation was comparable between groups (eradication group: 8.3% at 2 months [odds ratio, 1.76; 95% confidence interval, 0.78–3.92; P=0.170], 11.8% at 6 months [odds ratio, 1.60; 95% confidence interval, 0.81–3.11; P=0.172]). Based on the physicians’ global assessment at 2 months, none of the patients in the eradication group improved, whereas 3.2% of the patients in the non-eradication group improved (P=0.019). Multivariate analysis revealed that active disease at baseline, but not H. pylori eradication, was an independent factor for IBD exacerbation during 2 months’ observation period. The overall eradication rate was 84.0%–comparable to previous reports in non-IBD patients. Conclusions H. pylori eradication therapy does not alter the short-term disease activity of IBD.

Optimized Management of Ulcerative Proctitis: When and How to Use Mesalazine Suppository

Background: Ulcerative proctitis, one of the disease types of ulcerative colitis, is considered one of the initial manifestations of ulcerative colitis. Prevention of aggravation of ulcerative proctitis is important for improving the prognosis of ulcerative colitis. Here we reviewed the epidemiology, diagnosis, and management of ulcerative proctitis. Summary: The number of patients with ulcerative proctitis is increasing. Disease extension occurs in many patients with ulcerative proctitis. Differential diagnosis from other chronic proctitis is important and should be performed based on the clinical history and endoscopical and histological features. Mesalazine suppository has been the first-line therapy for patients with ulcerative proctitis because of its high effectiveness and safety. Topical treatment of ulcerative proctitis, particularly using mesalazine suppository has been underused in clinical practice. Key Messages: Mesalazine suppositories are more effective than dose intensification of oral mesalazine for relapsed patients with maintenance dose of oral mesalazine. However, low adherence to rectal mesalazine has hindered remission in patients with ulcerative proctitis.

Mo1058 Optimization of the Regimen for Granulocyte/ Monocyte Adsorptive Apheresis in Patients With Active Ulcerative Colitis

G A A b st ra ct s pain intensity and stool consistency. When only the abdominal pain component of IBS symptoms is considered, a more restricted population is still identified, even when the weekly responses to satisfactory relief are analysed according to the less stringent 50% rule. Table ISatisfactory Relief of IBS symptoms and abdominal pain/discomfort (YES to the weekly binary question) vs. combined weekly abdominal pain and stool consistency responders (FDA category)