Jun-ichi Haruta

Elevation of interleukin-6 in inflammatory bowel disease is macrophage- and epithelial cell-dependent

Local interleukin-6 (IL-6) activity was studied using colonic mucosal tissues in inflammatory bowel disease (IBD) and inflammatory control patients. Active IBD specimens exhibited significantly higher IL-6 activity than control specimens in both cultures of isolated lamina propria mononuclear cells (LPMC) and mucosal tissues with an increased number of IL-6-producing cells. However, the activity in inactive IBD or inflammatory controls did not differ from controls. Northern blot analysis demonstrated IL-6 messenger RNA in LPMC and colonic epithelial cells isolated from active IBD specimens but not in control cells. Furthermore, immunofluorescent microscopic study of active IBD specimens showed more conspicuous staining of IL-6 in infiltrating LPMC (mostly CD68+ cells) and colonic epithelial cells. These results suggest that elevation of local IL-6 activity may be a characteristic feature of active IBD and both macrophages and colonic epithelial cells are the major cell types responsible for this phenomenon.

Importance of appropriate pharmaceutical management in pregnant women with ulcerative colitis

BackgroundUlcerative colitis (UC) often occurs in women of childbearing age. Compared to Western countries, however, few studies have investigated the impact of UC on the progress of pregnancy in Asian populations.MethodsWe retrospectively examined 91 pregnancies in 64 patients with UC experienced at our hospital and related institutions from 1991 to 2011, focusing on the relationship between the progression of UC during pregnancy, progress of the pregnancy itself, and the treatment of UC.ResultsIn 80 of 91 pregnancies the patient had already been diagnosed with UC at the time she became pregnant, of whom 31 (38.8%) experienced exacerbation during pregnancy. Regarding severity, moderate or severe active-stage disease during pregnancy was seen in 13.7% of those who had been in remission at the onset of pregnancy versus 58.6% of those who had been in the active stage at onset (OR 8.9: 95%CI 3.0~26.4; P<0.01). The incidence of miscarriage or abortion was 9.8% in pregnancies in which UC was in remission at onset versus 31% in those in which it was in the active stage at onset (OR 4.1: 95%CI 1.2~13.9; P=0.02). Among patients, 62.5% were receiving pharmaceutical treatment at onset of pregnancy. Exacerbation during pregnancy occurred in 26.5% of the group who continued to receive the same treatment during pregnancy versus 56.3% of those with a dose decrease or discontinuation after onset (OR 3.6: 95%CI 1.0~12.4; P=0.04).ConclusionsUC patients wishing to conceive should do so when in remission and continue appropriate pharmaceutical treatment during pregnancy.

Successful Hyperbaric Oxygen Therapy of Pneumatosis Cystoides Intestinals : A Report of Two Cases

Abstract: Two patients with pneumatosis cystoides intestinalis (PCI) successfully treated with hyperbaric oxygen are described, The first patient was a 52‐year‐old male who presented with bloody stools and was diagnosed as having primary PCI. The second was a 61‐year‐old male whose occupation entailed prolonged exposure to trichloroethylene. Following hyperbaric oxygen therapy, the colonic gas cysts completely disappeared in both patients, and there has been no evidence of recurrence. The relevant literature from 1980 to 1992 is reviewed, and hyperbaric oxygen therapy for PCI is discussed in detail. The data accumulated thus far suggest that hyperbaric oxygen is superior to high‐flow oxygen breathing in PCI therapy.

Acute Graft‐Versus‐Host Disease of the Large Intestine after Bone Marrow Transplantation

Abstract: A 13‐year old male with acute lymphocytic leukemia was admitted to our hospital for bone marrow transplantation (BMT). Lower abdominal pain and bloody diarrhea developed during the fourth post‐BMT week. Colonoscopy revealed edematous mucosa, erosions and multiple irregular ulcers in the rectum and sigmoid colon. Histologically, multiple apoptotic lesions were recognizable in the crypt basement membrane. Most infiltrating lymphoid cells were mature memory T lymphocytes bearing LFA‐la‐, CD43 and CD45RO antigens. HLA‐DR and ICAM‐1 immunostaining was seen on the vascular endothelium and the epithelium stained positively for HLA‐DR antigens.

Iodine staining and p16 immunohistochemistry as a novel screening for secondary esophageal neoplasm after hematopoietic stem cell transplantation

Regarding allogeneic hematopoietic stem cell transplantation (HSCT) survivors, several studies have reported a twofold to fourfold increased risk of secondary solid tumors, and incidence ratios of oral, pharyngeal and esophageal cancers were significantly higher than the general population [1–3]. Notably, increased risk of oral squamous cell carcinoma (SCC) has been reported in patients with chronic graft-versus-host disease (GVHD) [4–6]. Considering the dismal prognosis of esophageal cancer found in the advanced stage, detection in the asymptomatic early stages is highly desirable. Human papillomavirus (HPV) infection is suspected as an associated risk factor for oral and esophageal SCC in patients with immunodeficiency caused by the human immunodeficiency virus, solid organ transplantation, or allogeneic HSCT [5, 7, 8]. A case report has assessed the usefulness of p16 immunohistochemistry, a surrogate marker for HPV, for the early diagnosis of secondary oral and esophageal malignancy after HSCT [4]. Indeed, p16 immunohistochemistry is known as a pathologically good tool for the detection of oral and esophageal squamous cell neoplasm (SCN). The HPV-associated oncoprotein E6 and E7 interfere with cell cycle and inactivate tumor-suppressor protein p53 and pRb (retinoblastoma protein), which result in increased p16 expression levels caused by negative feedback control [9]. In patients with oral and pharyngolaryngeal SCC, the esophagus should be examined and screened for another SCN [4, 5]. In addition, esophagogastroduodenoscopy (EGD) with iodine staining and narrow band imaging (NBI) of the esophagus is a powerful tool for the detection of early esophageal SCN. In this study, we screened esophageal SCN using EGD examination with iodine staining, as well as pathological examination with p16 immunostaining, in patients after allogeneic HSCT. We performed EGD screening in patients who survived at least 1 year after the first allogeneic HSCT and who visited Japanese Red Cross Nagoya First Hospital from January 2009 to January 2017. Patients with oral mucosal lesions, primarily oral GVHD, but without gastrointestinal symptoms were selected. All patients provided informed consent in accordance with the Declaration of Helsinki. This study was designed as a prospective observational survey, and approved by the ethical committee of our institutional review board. EGD was performed by using an Olympus GIF-H290Z, GIF-H260Z, or GIF-H260 scope (Olympus Corporation, Tokyo, Japan). All patients were examined with normal white light, NBI, and iodine staining, respectively. Endoscopic biopsies were performed for abnormal endoscopic findings, even if it were minor changes. Biopsy specimens were stained with hematoxylin and eosin (HE) and p16 mouse monoclonal antibody (Ventana, Arizona, USA) immunostaining by using an autostainer BOND Max (Leica Biosystems, Newcastle, UK) according to the instruction manual, and then we compared p16 staining status with patient’s clinical characteristics. Each patient had a single-time EGD screening; however, annual EGD examinations were recommended for patients that were p16 positive. * Masafumi Ito itom@nagoya-1st.jrc.or.jp