Kenichiro Nishikawa

Interleukin-17 Induces an Atypical M2-Like Macrophage Subpopulation That Regulates Intestinal Inflammation

Interleukin 17 (IL-17) is a pleiotropic cytokine that acts on both immune and non-immune cells and is generally implicated in inflammatory and autoimmune diseases. Although IL-17 as well as their source, mainly but not limited to Th17 cells, is also abundant in the inflamed intestine, the role of IL-17 in inflammatory bowel disease remains controversial. In the present study, by using IL-17 knockout (KO) mice, we investigated the role of IL-17 in colitis, with special focus on the macrophage subpopulations. Here we show that IL-17KO mice had increased susceptibility to DSS-induced colitis which was associated with decrease in expression of mRNAs implicated in M2 and/or wound healing macrophages, such as IL-10, IL-1 receptor antagonist, arginase 1, cyclooxygenase 2, and indoleamine 2,3-dioxygenase. Lamina propria leukocytes from inflamed colon of IL-17KO mice contained fewer CD11b+Ly6C+MHC Class II+ macrophages, which were derived, at least partly, from blood monocytes, as compared to those of WT mice. FACS-purified CD11b+ cells from WT mice, which were more abundant in Ly6C+MHC Class II+ cells, expressed increased levels of genes associated M2/wound healing macrophages and also M1/proinflammatory macrophages. Depletion of this population by topical administration of clodronate-liposome in the colon of WT mice resulted in the exacerbation of colitis. These results demonstrate that IL-17 confers protection against the development of severe colitis through the induction of an atypical M2-like macrophage subpopulation. Our findings reveal a previously unappreciated mechanism by which IL-17 exerts a protective function in colitis.

Second and Third-look Endoscopy for the Prevention of Post-ESD Bleeding

AbstractThe efficacy of 2nd-look esophagogastroduodenoscopy (EGD) with endoscopic hemostatic therapy (EHT) for the prevention of postendoscopic submucosal dissection (ESD) clinical bleeding remains controversial. The aim of this study was to estimate post-ESD bleeding rate using 2nd and 3rd-look strategy, and to determine risk factors for clinical bleeding, and for EHT at 2nd and 3rd-look EGDs.Three hundred forty-four consecutive patients with early gastric cancer or adenoma underwent ESD from January 2006 through March 2012. Second and 3rd-look EGDs were performed on day 1 (D1) and day 7 (D7), respectively, with EHT as needed.Post-ESD clinical bleeding rate was 2.6% (95% confidence interval [CI] 1.2%–4.9%). For clinical bleeding, adjusted odds ratios (ORs) for age <65 years and antithrombotic drug uses were 4.40 (95% CI 1.07–19.93) and 7.34 (95% CI 1.80–32.48), respectively. For D1 EHT, adjusted ORs of tumor location in the lower part of the stomach and maximum tumor diameter ≥60 mm were 2.16 (95% CI 1.35–3.51) and 2.20 (95% CI 1.05–4.98), respectively. For D7 EHT, adjusted OR of D1 EHT was 4.65 (95% CI 1.56–20.0).Post-ESD clinical bleeding rate was relatively low using 2nd and 3rd-look strategy. Age <65 years and antithrombotic drug use are significant risk factors for clinical bleeding. Regarding EHT, tumor location in the lower part of the stomach and maximum diameter of resected specimen ≥60 mm are significant predictors for D1 EHT. D1 EHT in turn is a significant risk factor for D7 EHT. The efficacy of sequential strategy for preventing post-ESD bleeding is promising.

Magnifying endoscopy for diagnosis of residual/local recurrent gastric neoplasms after previous endoscopic treatment

BackgroundIncomplete resection of gastric neoplasms by endoscopic treatment could lead to residual/local recurrence, which may be difficult to identify. This study aimed to evaluate the usefulness of magnifying endoscopy for identifying and demarcating residual/local recurrent gastric neoplasms after endoscopic treatment.MethodsBetween December 2004 and November 2010, magnifying endoscopy was performed in 15 patients with residual/local recurrent gastric neoplasms. All patients underwent conventional magnifying endoscopy (CME) and enhanced-magnification endoscopy with acetic acid instillation (EME) after conventional endoscopy (CE). Eleven patients additionally underwent magnifying endoscopy using narrow-band imaging (NBI-ME) and a combination of narrow-band imaging and acetic acid instillation (NBI-EME). For each procedure, it was recorded whether the location and circumferential demarcation of the lesions were identified. All lesions were resected by endoscopic submucosal dissection.ResultsEleven lesions were identified using CE. However, two and four additional lesions were identified using CME and EME, respectively. In 11 cases, NBI-ME and NBI-EME were performed and all lesions were identified. Three lesions, which were identified by CME, were not demarcated circumferentially. All 15 lesions were well demarcated by EME and 11 by NBI-ME and NBI-EME. Of the resected specimens, histopathology indicated that ten lesions were differentiated tubular adenocarcinomas and five lesions were adenomas. The histopathological diagnosis of the location and demarcation of all neoplasms corresponded to endoscopic findings.ConclusionsMagnifying endoscopy techniques (CME, EME, NBI-ME, and NBI-EME) may be useful for identifying and demarcating residual/local recurrent gastric neoplasms after previous endoscopic treatment.

Splenectomy increases the number of circulating hematopoietic stem/progenitor cells in patients with hepatitis C virus-associated liver cirrhosis

The spleen is not believed to contribute to hematopoiesis in healthy adults. However, several reports have demonstrated that the spleen in adults contains a large number of hematopoietic stem/progenitor cells (HSC). Although splenectomy increases platelet and leukocyte counts, the effects of splenectomy on circulating HSC have not been elucidated. In this study, we evaluated the association between the number of circulating HSC and splenectomy in patients with hepatitis C virus (HCV)‐associated liver cirrhosis (LC).

A Rare Form of Intraductal Papillary Mucinous Carcinoma

A 69-year-old-woman presented with febrile epigastric pain. A laboratory analysis indicated inflammation (WBC, 19,000/μL; CRP, 34.64 mg/dL). CT showed a 50-mm cyst and an enhanced mass in the pancreatic head (Picture 1). MRI demonstrated a fluid-fluid-level inside the cyst with edematous wall-thickness (Picture 2). Endoscopic retrograde pancreatography showed the irregular pancreatic duct leading to the cyst (Picture 3). Endoscopic transpapillary nasopancreatic drainage (ENPD) was performed; her symptoms were alleviated and the cyst became smaller. Pancreaticoduodenectomy was performed based on a cytological diagnosis of adenocarcinoma. The histological examination showed a 29-mm-mass occupying the pancreatic duct; which was well-differentiated papillary adenocarcinoma. Inside the