Taku Tomizawa

Clinical and Pharmacokinetic Factors Associated With Adalimumab-Induced Mucosal Healing in Patients With Crohn’s Disease

Background & Aims We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn’s disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. Methods We compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. Results The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04–4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77–2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72–0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84–0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14–1.58; P for trend = .001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P < .001). Conclusions In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.

Reversible Hypopituitarism Associated with Intravascular Large B-Cell Lymphoma: Case Report of Successful Immunochemotherapy

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. There have been only a limited number of reports regarding pituitary dysfunction associated with IVLBCL. We present a 71-year-old woman with hypopituitarism without any hypothalamic/pituitary abnormalities as assessed by magnetic resonance imaging. She presented with edema, abducens palsy, and elevated levels of lactate dehydrogenase and soluble interleukin-2 receptor. Provocative testing showed that the peaks of luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone and adrenocorticotropic hormone were evoked to normal levels by simultaneous administration of luteinizing hormone-releasing hormone, thyrotropin-releasing hormone and corticotropin-releasing hormone, but the responses of these four pituitary hormones showed a delayed pattern. She was diagnosed with IVLBCL with cerebrospinal invasion by pathological findings of the bone marrow, skin, and cerebrospinal fluid. She achieved hematological remission after immunochemotherapy. Pituitary function was also restored without hormonal replacement, and the improvement of the pituitary function was confirmed by dynamic testing. We reviewed the literature with respect to hypopituitarism associated with IVLBCL. There were less than 20 case reports and most of the patients died. Endocrinological course was described in only two cases, and both of them required hormonal supplementation. To our knowledge, this is the first case of hypopituitarism induced by IVLBCL that was successfully managed by immunochemotherapy alone. This case suggests that early diagnosis and treatment of IVLBCL might improve anterior pituitary function and enable patients to avoid hormone replacement therapy.

Hydroxyurea-induced Pneumonitis in a Patient with Chronic Myelomonocytic Leukemia: An Autopsy Case.

We describe the case of an 85-year-old man diagnosed with chronic myelomonocytic leukemia whose disease was treated with hydroxyurea for 3 months. He developed respiratory symptoms that were extensively investigated. Despite the intensive treatment, he died of respiratory failure eleven days later. An autopsy revealed diffuse interstitial inflammation of both lungs consistent with drug-induced inflammation. A drug lymphocyte stimulation test was positive for hydroxyurea. Taken together these findings demonstrated that severe interstitial pneumonitis was induced by this drug. Physicians using hydroxyurea must be aware of its potentially life-threatening pulmonary toxicity.

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.

Faecal lactoferrin is a useful biomarker for mucosal healing in patients with ulcerative colitis during granulocyte and monocyte adsorptive apheresis therapy.

The study investigated the value of faecal lactoferrin as a follow‐up biomarker for mucosal healing of ulcerative colitis during granulocyte and monocyte adsorptive apheresis (GMA) therapy.

A Case of Proton Pump Inhibitor-Resistant Multiple Gastric Ulcers Caused by Eosinophilic Gastroenteritis.

40-year-old woman visited a hospital after a few Amonths of epigastralgia. She was diagnosed with a gastric ulcer by upper gastrointestinal (GI) endoscopy. Despite proton pump inhibitor (PPI) therapy (esomeprazole; 20 mg/day), her symptoms and endoscopic findings worsened, and she was referred to our hospital. She had no significant past history, no allergies other than pollen, and denied the use of nonsteroidal antiinflammatory drugs. Physical examination showed tenderness in her epigastrium. Laboratory findings were normal except for a mild increase of white blood cell counts (9200/mL) and eosinophils (497/mL, 5.4%). Upper GI endoscopy showed deformation and 3 deep ulcerative lesions in the prepylorus (Figure A, arrows indicate ulcers). Endoscopic biopsy specimens showed chronic active ulcers, no malignant cells, and marked infiltration of eosinophilic leukocytes (130/high-power field) (Figure B). Serum anti–Helicobacter pylori and antiparasite antibody were negative. The plasma gastrin level was normal. The serum IgE level was 154.7 IU/ mL (<295), and radioallergosorbent tests were negative. Eosinophilic gastroenteritis was diagnosed. Oral prednisolone 30 mg was added to the PPI (rabeprazole; 20 mg) therapy. Symptoms improved immediately and the ulcers were improved 2 weeks later as assessed by endoscopy. Prednisolone was tapered gradually (5 mg/2 wk), and ulcer healing was confirmed (Figure C, arrows indicate scars). Biopsy examination showed a marked decrease of eosinophilic infiltration. The prednisolone dose was decreased to 2.5 mg/2 wk, and then ceased. The PPI was administered over the entire course of prednisolone treatment and after cessation. Eosinophilic gastroenteritis is an uncommon disorder characterized by eosinophilic infiltration of the GI tract. Gastric endoscopic findings are edema, erythema, and erosions. Gastric ulceration is rare, and multiple ulcerative lesions typically are not noted, with only 3 cases identified in the English literature. Approximately 50% of patients with eosinophilic gastroenteritis have a history of atopy and food hypersensitivity, eosinophilia, increased serum IgE level, and positive radioallergosorbent test results. In this case, mild peripheral eosinophilia was observed, however, the serum IgE level was normal and radioallergosorbent test results were negative. Raithel et al reported increased intestinal foodspecific IgEs in a case in which serum food-specific IgEs were negative. Therefore, food allergy cannot be eliminated completely in this case. The diagnosis was made by mucosal biopsy examination (eosinophils > 20/ high-power field) and differential diagnosis. Serum antiparasite antibody, antinuclear antibody, and antineutrophil cytoplasmic antibody were negative in this case, thus, parasitic infection, collagen disease, and vasculitis were eliminated. Twenty years ago, a diagnosis often was made after surgery. In recent reports, patients were diagnosed and treated successfully with prednisolone or food elimination. In this case, ulcer healing was confirmed after prednisolone, and

Photodynamic therapy for local recurrence of esophageal cancer in the esophagus after resection and free jejunal loop interposition for pharyngeal cancer

a Department of Gastroenterology, Gunma University Hospital, Address: 3-39-15 Showamachi, Maebashi, Gunma 371-8511, Japan b Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Address: 3-39-15 Showamachi, Maebashi, Gunma 371-8511, Japan c Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Address: 3-39-22 Showamachi, Maebashi, Gunma 371-8511, Japan Available online 2 June 2014