Details of a Researcher - NAKASE Hiroshi

Papers - NAKASE Hiroshi

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Can Trainees Safely Perform Endoscopic Treatments for Common Bile Duct Stones? A Single-center Retrospective Study.

Tomoya Iida, Hiroyuki Kaneto, Kohei Wagatsuma, Hajime Sasaki, Yumiko Naganawa, Suguru Nakagaki, Shuji Satoh, Haruo Shimizu, Hiroshi Nakase

Internal medicine (Tokyo, Japan) 57 ( 7 ) 923 - 928 2018.04 [Refereed] [Domestic journal]

Objective There are no reports on whether or not trainees can safely carry out endoscopic procedures for the removal of common bile duct (CBD) stones. The aim of this study was to investigate the efficacy and safety of endoscopic treatments for CBD stones by trainees. Methods Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 1,016 consecutive patients at our institution during the 6-year study period. The endoscopically treated patients with CBD stones were included in this study. Physicians who had experienced ≥300 ERCP procedures were defined as experts, while those who had experienced <300 procedures were defined as trainees. The trainees were replaced by an expert when they could not achieve the established criteria. Patients were divided into the following three groups to retrospectively examine the patients' backgrounds, details of endoscopic treatments, and intra-/post-operative complications: Group A, completed by trainees under supervision of an expert; B, treated by an expert who switched in for a trainee in the middle of the procedure; and C, completed by an expert. Results A total of 325 patients with CBD stones underwent endoscopic treatments. The number included in Groups A, B, and C was 176, 102, and 47, respectively. The bile duct catheter insertion successes rates for Groups A, B, and C were 99.0%, 97.1%, and 100% (p=0.09), and the complete stone removal rates were 94.2%, 94.8%, and 100%, respectively (p=0.07), showing no significant difference among the three groups. Furthermore, the frequency of intra-/post-operative complications was not significantly different among the three groups (p=0.48, p=0.12, respectively). Conclusion This study showed that trainees could safely perform endoscopic procedures in accordance with our facility's criteria during ERCP.

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

Taku Kobayashi, Tadakazu Hisamatsu, Yasuo Suzuki, Haruhiko Ogata, Akira Andoh, Toshimitsu Araki, Ryota Hokari, Hideki Iijima, Hiroki Ikeuchi, Yoh Ishiguro, Shingo Kato, Reiko Kunisaki, Takayuki Matsumoto, Satoshi Motoya, Masakazu Nagahori, Shiro Nakamura, Hiroshi Nakase, Tomoyuki Tsujikawa, Makoto Sasaki, Kaoru Yokoyama, Naoki Yoshimura, Kenji Watanabe, Miiko Katafuchi, Mamoru Watanabe, Toshifumi Hibi

Intestinal research 16 ( 2 ) 168 - 177 2018.04 [Refereed] [International journal]

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.

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

Kenji Watanabe, Takayuki Matsumoto, Tadakazu Hisamatsu, Hiroshi Nakase, Satoshi Motoya, Naoki Yoshimura, Tetsuya Ishida, Shingo Kato, Tomoo Nakagawa, Motohiro Esaki, Masakazu Nagahori, Toshiyuki Matsui, Yuji Naito, Takanori Kanai, Yasuo Suzuki, Masanori Nojima, Mamoru Watanabe, Toshifumi Hibi

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 16 ( 4 ) 542 - 549 2018.04 [Refereed] [International journal]

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.

胆管癌の術前診断におけるSpyGlassDSの有用性

柾木喜晴, 志谷真啓, 我妻康平, 沼田泰尚, 阿久津典之, 本谷雅代, 佐々木茂, 木村康利, 武政伊知朗, 仲瀬裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 60 ( Suppl.1 ) 668 - 668 2018.04

当院におけるステロイド投与によるB型肝炎再活性化への対応の現状と再活性化例の検討

沼田泰尚, 佐々木基, 石上敬介, 若杉英樹, 阿久津典之, 佐々木茂, 仲瀬裕志

肝臓 ( (一社)日本肝臓学会 ) 59 ( Suppl.1 ) A323 - A323 2018.04

Efficacy of Endoscopic Balloon Dilation for Small Bowel Strictures in Patients With Crohn's Disease: A Nationwide, Multi-centre, Open-label, Prospective Cohort Study.

Fumihito Hirai, Akira Andoh, Fumiaki Ueno, Kenji Watanabe, Naoki Ohmiya, Hiroshi Nakase, Shingo Kato, Motohiro Esaki, Yutaka Endo, Hironori Yamamoto, Toshiyuki Matsui, Mitsuo Iida, Toshifumi Hibi, Mamoru Watanabe, Yasuo Suzuki, Takayuki Matsumoto

Journal of Crohn's & colitis 12 ( 4 ) 394 - 401 2018.03 [Refereed] [International journal]

Background and Aims: Endoscopic balloon dilation [EBD] is an alternative to surgery for Crohn's strictures. However, there have been no prospective studies of EBD for small bowel strictures in patients with Crohn's disease [CD]. The aim of this study was to clarify the efficacy and safety of EBD using balloon-assisted enteroscopy for small bowel strictures in CD. Methods: This was a nationwide, multi-centre, open-label, prospective cohort study. The subjects were CD patients with at least one symptom [abdominal pain, abdominal bloating, nausea] attributable to small bowel stricture. The primary endpoint related to short-term outcomes was the level of improvement of symptoms evaluated using a 10-cm visual analogue scale [VAS]. Cases in which VAS scores for all symptoms improved 4 weeks after EBD compared with baseline were considered to have short-term symptomatic improvement. Factors related to short-term treatment outcomes and safety were investigated as secondary endpoints. Results: A total of 112 patients were enrolled. Seventeen were later excluded because they did not meet the criteria, and the analysis was conducted with the remaining 95 patients. Of these 95 patients, procedure failure occurred in six [6.3%], and short-term symptomatic improvement was achieved in 66 patients [69.5%]. Adverse events were seen in five patients [5%] and all of these improved with conservative treatment. A large dilation diameter of the balloon was a factor contributing to the success of EBD. Conclusions: EBD using balloon-assisted enteroscopy for small bowel strictures in CD patients was shown to be an effective and safe procedure. Clinical trial registry: UMIN000005946.

Elevation of Plasmin-α2-plasmin Inhibitor Complex Predicts the Diagnosis of Systemic AL Amyloidosis in Patients with Monoclonal Protein.

Kazuya Ishiguro, Toshiaki Hayashi, Yoshihiro Yokoyama, Yuka Aoki, Kei Onodera, Hiroshi Ikeda, Tadao Ishida, Hiroshi Nakase

Internal medicine (Tokyo, Japan) 57 ( 6 ) 783 - 788 2018.03 [Refereed] [Domestic journal]

Objective The complication of systemic immunoglobulin light chain (AL) amyloidosis in patients with monoclonal immunoglobulin affects the prognosis, but amyloid deposition in tissues is sometimes difficult to detect due to bleeding tendencies and preferential distributions. However, fibrinolysis is known to be exacerbated in patients with systemic AL amyloidosis specifically. We therefore explored new biomarkers for predicting a diagnosis of systemic AL amyloidosis focusing on coagulation and fibrinolysis markers. Methods We reviewed the clinical features and treatment outcomes of patients with serum monoclonal protein, including primary systemic AL amyloidosis and multiple myeloma (MM), treated at our hospital between January 2008 and December 2014. Results Among several biomarkers, only the serum level of plasmin-α2-plasmin inhibitor complex (PIC) in patients with systemic AL amyloidosis (n=26) at the diagnosis was significantly higher than in patients with MM without AL amyloidosis (n=26) (mean±standard deviation, 3.69±2.82 μg/mL vs. 1.23±0.97 μg/mL, p<0.01). The cut-off for predicting a diagnosis of systemic AL amyloidosis in patients with serum monoclonal protein was 1.72 μg/mL with 84.6% sensitivity and 80.8% specificity. Hepatic involvement resulted in a significantly higher PIC level than no involvement in patients with systemic AL amyloidosis. The serum PIC level was also associated with the hematological response of systemic AL amyloidosis. Conclusion PIC is a useful biomarker for the diagnosis and management of patients with systemic AL amyloidosis.

Predicting therapeutic response in IgG4-related disease based on cluster analysis.

Motohisa Yamamoto, Ken-Ichi Takano, Ryuta Kamekura, Chisako Suzuki, Tetsuya Tabeya, Rieko Murakami, Saho Honda, Masaya Mukai, Masanori Nojima, Shingo Ichimiya, Tetsuo Himi, Hiroshi Nakase, Hiroki Takahashi

Immunological medicine 41 ( 1 ) 30 - 33 2018.03 [Refereed] [International journal]

To bring the clinical practice of immunoglobulin (Ig)G4-related disease (IgG4-RD) close to personalized medicine, we classified the patient groups and clarified the therapeutic responses of each group. A total of 147 patients enrolled in our registry were classified into four groups by cluster analysis with the software. The therapeutic responses and prognosis of each group were examined. The cluster analysis classified the subjects into four groups: Cluster 1, patients who presented with prominent hypergammaglobulinemia, elevated levels of serum IgG4, and hypocomplementemia; Cluster 2, patients who presented with eosinophilia, elevated concentrations of serum IgG, IgG4, and IgE, and in whom CRP tended to be positive; Cluster 3, patients with younger onset and serum levels of IgG, IgG4, and IgE and peripheral eosinophil counts lower than the other clusters; and Cluster 4, patients with elder onset and low peripheral eosinophil counts. The amounts of glucocorticoid for maintenance treatment were from 5 to 7 mg/d in all groups, but the amounts were significantly greater in Cluster 1 (patients with hypergammaglobulinemia, elevated levels of serum IgG4, and hypocomplementemia) than in Cluster 4 (elder onset patients, relatively low concentrations of peripheral eosinophils). With regard to the use of immunosuppressants and the relapse rate, there were high frequencies in Cluster 1 and Cluster 3 (younger onset patients who presented with mild elevations of serum IgG and IgG4). On the other hand, Cluster 4 showed a low rate of relapse and often could discontinue steroids. The present results suggest that personalized medicine could be provided in IgG4-RD by classifying patients based on their clinical features.

Systemic amyloidosis with gastrointestinal involvement: Diagnosis from endoscopic and histological views.

Tomoya Iida, Hiroo Yamano, Hiroshi Nakase

Journal of gastroenterology and hepatology 33 ( 3 ) 583 - 590 2018.03 [Refereed] [International journal]

Amyloid tends to deposit in the gastrointestinal tract, which, being easily accessible, is often the target organ for a pathological diagnostic examination. Although a mucosal biopsy is necessary for a definitive diagnosis and several studies have reported positive results for each possible biopsy site, there remain many unclear features in various aspects. This review focuses on the current literature to determine a better understanding of the diagnosis from endoscopic and histological views in patients with systemic amyloidosis with gastrointestinal involvement. A literature search was performed using PubMed to identify relevant studies; linked references were also reviewed. Endoscopic findings vary based on the organ and the depositing amyloids. A fine granular appearance or polypoid protrusions are likely to occur in the duodenum. AL, Aβ2M, and ATTR amyloids are likely to deposit submucosally, while AA amyloid is easily deposited in the superficial layer of the mucous membrane. Furthermore, it is necessary to consider the collection of biopsy specimens from the duodenum, which has high positive biopsy rates. However, the difference in the positive biopsy rates depends on whether endoscopic findings are available or whether the appropriate number has not been fully elucidated. A duodenal biopsy is strongly recommended to confirm the deposition of amyloid in patients with systemic amyloidosis having gastrointestinal involvement. Because amyloidosis is a disease with a poor prognosis, early diagnosis and treatment are required; gastroenterologists and endoscopists play important roles.

Evidence-based clinical practice guidelines for inflammatory bowel disease.

Katsuyoshi Matsuoka, Taku Kobayashi, Fumiaki Ueno, Toshiyuki Matsui, Fumihito Hirai, Nagamu Inoue, Jun Kato, Kenji Kobayashi, Kiyonori Kobayashi, Kazutaka Koganei, Reiko Kunisaki, Satoshi Motoya, Masakazu Nagahori, Hiroshi Nakase, Fumio Omata, Masayuki Saruta, Toshiaki Watanabe, Toshiaki Tanaka, Takanori Kanai, Yoshinori Noguchi, Ken-Ichi Takahashi, Kenji Watanabe, Toshifumi Hibi, Yasuo Suzuki, Mamoru Watanabe, Kentaro Sugano, Tooru Shimosegawa

Journal of gastroenterology 53 ( 3 ) 305 - 353 2018.03 [Refereed] [Domestic journal]

Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn's disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.

術前CTにおける右肝動脈周囲の脂肪織濃度上昇所見に関する検討

志谷真啓, 風間友江, 我妻康平, 柾木喜晴, 阿久津典之, 本谷雅代, 佐々木茂, 山口洋志, 永山稔, 今村将史, 木村康利, 水口徹, 竹政伊知朗, 仲瀬裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 ) 115 ( 臨増総会 ) A391 - A391 2018.03

A case of a rectal stricture related to ischemic proctitis following rupture of an aortic aneurysm.

Tomoya Iida, Yosuke Ohkubo, Toshiyuki Kubo, Kentaro Yamashita, Kei Onodera, Eiichiro Yamamoto, Katsuhiko Nosho, Toshiro Ito, Hiroo Yamano, Hiroshi Nakase

Endoscopy international open 6 ( 2 ) E186-E189 2018.02 [Refereed] [International journal]

Background and study aims Ischemic proctitis is a rare disease and comprises 2 % to 5 % of cases of ischemic colitis, because the rectum has abundant blood supply and rich collaterals. Herein, we report a case of a 73-year-old male patient with a pronounced rectal stricture caused by ischemic proctitis resulting from an abdominal aortic rupture and treated by endoscopic balloon dilation therapy. To date, only 3 cases of rectal stricture related to ischemic proctitis including our case have been reported, and this is the first case of rectal stricture related to ischemic proctitis, which was successfully treated by endoscopic balloon dilation.

Epigenetic silencing of SMOC1 in traditional serrated adenoma and colorectal cancer.

Hironori Aoki, Eiichiro Yamamoto, Akira Takasawa, Takeshi Niinuma, Hiro-O Yamano, Taku Harada, Hiro-O Matsushita, Kenjiro Yoshikawa, Ryo Takagi, Eiji Harada, Yoshihito Tanaka, Yuko Yoshida, Tomoyuki Aoyama, Makoto Eizuka, Akira Yorozu, Hiroshi Kitajima, Masahiro Kai, Norimasa Sawada, Tamotsu Sugai, Hiroshi Nakase, Hiromu Suzuki

Oncotarget 9 ( 4 ) 4707 - 4721 2018.01 [Refereed] [International journal]

Colorectal sessile serrated adenoma/polyps (SSA/Ps) are well-known precursors of colorectal cancer (CRC) characterized by BRAF mutation and microsatellite instability. By contrast, the molecular characteristics of traditional serrated adenoma (TSAs) are not fully understood. We analyzed genome-wide DNA methylation in TSAs having both protruding and flat components. We identified 11 genes, including SMOC1, methylation of which progressively increased during the development of TSAs. SMOC1 was prevalently methylated in TSAs, but was rarely methylated in SSA/Ps (p < 0.001). RT-PCR and immunohistochemistry revealed that SMOC1 was expressed in normal colon and SSA/Ps, but its expression was decreased in TSAs. Ectopic expression of SMOC1 suppressed proliferation, colony formation and in vivo tumor formation by CRC cells. Analysis of colorectal lesions (n = 847) revealed that SMOC1 is frequently methylated in TSAs, high-grade adenomas and CRCs. Among these, SMOC1 methylation was strongly associated with KRAS mutation and CpG island methylator phenotype (CIMP)-low. These results demonstrate that epigenetic silencing of SMOC1 is associated with TSA development but is rarely observed in SSA/Ps. SMOC1 expression could thus be a diagnostic marker of serrated lesions, and SMOC1 methylation could play a role in neoplastic pathways in TSAs and conventional adenomas.

Identification of genomic alterations in oral squamous cell carcinomas using amplicon-based whole-exome sequencing

Sasaki Yasushi, Tamura Miyuki, Nakagaki Takafumi, Koyama Ryota, Idogawa Masashi, Ogi Kazuhiro, Hiratsuka Hiroyoshi, Nakase Hiroshi, Tokino Takashi

CANCER SCIENCE 109 990 2018.01 [Refereed]

Clinicopathological comparison between acute gastrointestinal-graft-versus-host disease and infectious colitis in patients after hematopoietic stem cell transplantation.

Sae Ohwada, Tomoya Iida, Daisuke Hirayama, Gota Sudo, Toshiyuki Kubo, Masanori Nojima, Kentaro Yamashita, Hiroo Yamano, Hiroshi Nakase

PloS one 13 ( 7 ) e0200627 2018 [Refereed] [International journal]

The aim of this study is to elucidate the differences of the clinicopathological characteristics between acute gastrointestinal (GI)-graft-versus-host disease (GVHD) and infectious colitis (IC) after hematopoietic stem cell transplantation (HSCT). Of the 282 patients who underwent HSCT at our institution between January 1991 and December 2015, we could investigate 182 patients in detail. Of the 182 patients, we selected those who underwent colonoscopy and were diagnosed with acute GI-GVHD or IC after HSCT. Patients' backgrounds, colonoscopic findings, and pathological findings were retrospectively analyzed. There were 30 patients who had colonoscopy performed and diagnosed with acute GI-GVHD or IC after HSCT. Of the 30 patients, 20 had acute GI-GVHD and 10 had IC. All the cases of acute GI-GVHD were diagnosed by endoscopic biopsy and 4 of the IC patients had Clostridium difficile associated colitis. In the IC group, the period from the transplantation up to diagnosis was significantly shorter than acute GI-GVHD group (10.0 days vs. 43.2 days, p = 0.03). In the acute GI-GVHD group, tortoiseshell-like mucosal patterns were significantly more common than the IC group (70% vs. 0%, p < 0.001). Furthermore, there were some cases presenting normal mucosal appearance despite the diagnosis with acute GI-GVHD by pathological findings. Clinically, we should consider IC when abdominal symptoms appeared in the early period after HSCT. Endoscopically, tortoiseshell-like mucosal pattern was a characteristic feature of acute GI-GVHD. In addition, it is essential to perform mucosal biopsy for diagnose of acute GI-GVHD even in patients showing the normal mucosal appearance.

Efficacy and safety of endoscopic procedures for common bile duct stones in patients aged 85 years or older: A retrospective study.

Tomoya Iida, Hiroyuki Kaneto, Kohei Wagatsuma, Hajime Sasaki, Yumiko Naganawa, Suguru Nakagaki, Shuji Satoh, Haruo Shimizu, Hiroshi Nakase

PloS one 13 ( 1 ) e0190665 2018 [Refereed] [International journal]

The Endoscopic procedures for common bile duct (CBD) stones are reportedly safe in the elderly patients. However, the definition of the elderly is different in each report. If the elderly are defined as people aged 85 years or older, data on the effectiveness and safety of endoscopic retrograde cholangiopancreatography (ERCP) for CBD stones are limited. This study investigated the efficacy and safety of endoscopic procedures for CBD stones in patients aged 85 years or older. 1,016 consecutive ERCP procedures were performed at our institution from January 2009 to December 2014. Of these, 235 cases with CBD stones were finally analyzed. Group A patients were younger than 85 years and Group B patients were 85 years or older. Patient background, details of endoscopic therapy, complications, and related factors were retrospectively reviewed for 185 cases in Group A, and 50 cases in Group B. Patients in Group B showed high rates of dementia and cerebrovascular disorders and larger CBD stones and diameters, in comparison with patients in Group A. The complete removal rate of bile duct stones was slightly higher in Group A. However, there was no difference between the two groups in recurrence rate of CBD stones, complication and mortality rates, and length and cost of hospitalization. Despite some differences between the two groups, endoscopic procedures for CBD stones in patients aged 85 years or older can be performed effectively and safely without increasing medical costs.

The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis.

Daisuke Hirayama, Tomoya Iida, Hiroshi Nakase

International journal of molecular sciences 19 ( 1 ) 2017.12 [Refereed] [International journal]

Macrophages are effector cells of the innate immune system that phagocytose bacteria and secrete both pro-inflammatory and antimicrobial mediators. In addition, macrophages play an important role in eliminating diseased and damaged cells through their programmed cell death. Generally, macrophages ingest and degrade dead cells, debris, tumor cells, and foreign materials. They promote homeostasis by responding to internal and external changes within the body, not only as phagocytes, but also through trophic, regulatory, and repair functions. Recent studies demonstrated that macrophages differentiate from hematopoietic stem cell-derived monocytes and embryonic yolk sac macrophages. The latter mainly give rise to tissue macrophages. Macrophages exist in all vertebrate tissues and have dual functions in host protection and tissue injury, which are maintained at a fine balance. Tissue macrophages have heterogeneous phenotypes in different tissue environments. In this review, we focused on the phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis for a better understanding of the role of tissue macrophages in several pathological conditions.

Is Osteopontin a Friend or Foe of Cell Apoptosis in Inflammatory Gastrointestinal and Liver Diseases?

Tomoya Iida, Kohei Wagatsuma, Daisuke Hirayama, Hiroshi Nakase

International journal of molecular sciences 19 ( 1 ) 2017.12 [Refereed] [International journal]

Osteopontin (OPN) is involved in a variety of biological processes, including bone remodeling, innate immunity, acute and chronic inflammation, and cancer. The expression of OPN occurs in various tissues and cells, including intestinal epithelial cells and immune cells such as macrophages, dendritic cells, and T lymphocytes. OPN plays an important role in the efficient development of T helper 1 immune responses and cell survival by inhibiting apoptosis. The association of OPN with apoptosis has been investigated. In this review, we described the role of OPN in inflammatory gastrointestinal and liver diseases, focusing on the association of OPN with apoptosis. OPN changes its association with apoptosis depending on the type of disease and the phase of disease activity, acting as a promoter or a suppressor of inflammation and inflammatory carcinogenesis. It is essential that the roles of OPN in those diseases are elucidated, and treatments based on its mechanism are developed.

Editorial: therapeutic drug monitoring for anti-TNF agents—has it all been said? Author's reply

H. Nakase

Alimentary Pharmacology and Therapeutics ( Blackwell Publishing Ltd ) 46 ( 11-12 ) 1114 - 1115 2017.12 [Refereed]

Endoscopic and molecular characterization of colorectal sessile serrated adenoma/polyps with cytologic dysplasia.

Yoshihito Tanaka, Hiro-O Yamano, Eiichiro Yamamoto, Hiro-O Matushita, Hironori Aoki, Kenjiro Yoshikawa, Ryo Takagi, Eiji Harada, Michiko Nakaoka, Yuko Yoshida, Makoto Eizuka, Tamotsu Sugai, Hiromu Suzuki, Hiroshi Nakase

Gastrointestinal endoscopy ( MOSBY-ELSEVIER ) 86 ( 6 ) 1131 - 1138 2017.12 [Refereed] [International journal]

BACKGROUND AND AIMS: Sessile serrated adenoma/polyps (SSA/Ps), which are precursor lesions of colorectal cancer (CRC) with BRAF mutation and the CpG island methylator phenotype (CIMP), develop cytologic dysplasia (CD) during the progression of colorectal tumorigenesis. In the present study we aimed to clarify the endoscopic and molecular signatures of SSA/Ps, with and without CD. METHODS: A series of 208 serrated lesions, including 41 hyperplastic polyps, 90 SSA/Ps, 33 SSA/Ps with CD, and 44 traditional serrated adenomas, were observed and resected using magnifying endoscopy. BRAF and KRAS mutations and methylation of CIMP markers (MINT1, MINT2, MINT12, MINT31, and p16) were analyzed through pyrosequencing. Molecular alterations were then compared with endoscopic and pathologic characteristics. RESULTS: Among SSA/Ps without CD, the Type II-Open pit pattern (Type II-O), BRAF mutation, and CIMP were tightly associated with a proximal colon location. SSA/Ps in the distal colon infrequently exhibited Type II-O and CIMP. By contrast, most SSA/Ps with CD showed Type II-O plus adenomatous pit patterns (Type III or IV), BRAF mutation, and CIMP, irrespective of their locations. CONCLUSIONS: Our results suggest that the Type II-O plus III/IV pit pattern is a common feature of SSA/Ps with CD in both the proximal and distal colon and that this pit pattern is a hallmark of serrated lesions at high risk of developing into CRCs.

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