Publications by authors named "Kohei Wagatsuma"

19 Publications

  • Page 1 of 1

Association of the Low-density Lipoprotein Cholesterol/High-density Lipoprotein Cholesterol Ratio with Glecaprevir-pibrentasvir Treatment.

Intern Med 2021 May 22. Epub 2021 May 22.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Japan.

Objective The change in serum lipid levels by direct-acting antiviral (DAA) treatment for chronic hepatitis C varies depending on the type of DAA. How the lipid level changes induced by glecaprevir-pibrentasvir (G/P) treatment contribute to the clinical outcome remains unclear. We conducted a prospective observational study to evaluate the effectiveness of G/P treatment and the lipid level changes. Methods The primary endpoint was a sustained virologic response at 12 weeks (SVR12). The total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and LDL-C/HDL-C (L/H) ratio were measured every two weeks. Patients This study included 101 patients. Seventeen cases of liver cirrhosis and nine cases of DAA retreatment were registered. The G/P treatment period was 8 weeks in 74 cases and 12 weeks in 27 cases. Results SVR12 was evaluated in 96 patients. The rate of achievement of SVR12 in the evaluable cases was 100%. We found significantly elevated TC and LDL-C levels over the observation period compared to baseline. The serum levels of HDL-C did not change during treatment but were significantly increased after treatment compared to baseline. The L/H ratio was significantly increased two weeks after the start of treatment but returned to the baseline after treatment. Conclusion The primary endpoint of the SVR12 achievement rate was 100%. G/P treatment changed the serum lipid levels. Specifically, the TC and LDL-C levels increased during and after treatment, and the HDL-C levels increased after treatment. G/P treatment may be associated with a reduced thrombotic risk. Therefore, validation in large trials is recommended.
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http://dx.doi.org/10.2169/internalmedicine.7098-21DOI Listing
May 2021

Gastrointestinal involvement in a patient with familial Mediterranean fever mimicking Crohn's disease: a case report.

Clin J Gastroenterol 2021 May 11. Epub 2021 May 11.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.

Familial Mediterranean fever (FMF) in gastrointestinal involvement has been considered rare, but resent reports suggest that FMF causes enterocolitis which is similar endoscopic findings to inflammatory bowel disease. The clinical characteristics and endoscopic findings of FMF with enterocolitis remain unclear. Here, we report a case of an FMF patient who had enterocolitis with stricture of the terminal ileum whose endoscopic and clinical features mimicked Crohn's disease. A 23-year-old man who was diagnosed with FMF 10 years ago presented with abdominal pain and diarrhea. Colonoscopy showed terminal ileitis and aphthous colitis; however, these findings, including the histopathology, did not confirm Crohn's disease. Therefore, we diagnosed FMF with enterocolitis and administered anti-interleukin-1β monoclonal antibody (canakinumab). The patient's symptoms improved with treatment, but after 1 year, lower abdominal pain recurred. Colonoscopy revealed a stricture of the terminal ileum. Endoscopic balloon dilation relieved his symptoms. At present, he has been followed up without surgical treatment by endoscopic balloon dilation every 6 month. Clinicians should be aware that FMF accompanied with enterocolitis may resemble Crohn's disease.
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http://dx.doi.org/10.1007/s12328-021-01426-2DOI Listing
May 2021

The characteristics of gastrointestinal symptoms in patients with severe COVID-19: a systematic review and meta-analysis.

J Gastroenterol 2021 05 23;56(5):409-420. Epub 2021 Mar 23.

Department of Gastroenterology and Hepatology, Sapporo Medical University of Medicine, S-1, W16, Chuoku, Sapporo, Hokkaido, 060-8543, Japan.

Although primarily a respiratory illness, several studies have shown that COVID-19 causes elevation of liver enzymes and various gastrointestinal (GI) symptoms. The aim of this study was to undertake a systematic review and meta-analysis to determine whether the presence of gastrointestinal (GI) symptoms contributed toward COVID-19 severity, and identify the GI symptoms characteristic of severe COVID-19. We conducted a literature search of PubMed from December 1, 2019, to June 30, 2020, and identified all reports with GI symptoms reported. A meta-analysis comparing the severity of COVID-19 with the presence of liver enzyme elevation and GI symptoms was performed using RevMan version 5.4. Pooled data from 15,305 unique reverse transcriptase-polymerase chain reaction positive COVID-19 patients from 44 studies were analyzed. We found that the severe COVID-19 patients significantly had abdominal pain compared to the non-severe COVID-19 patients (OR = 2.70, 95% CI 1.17-6.27, Z = 2.32, p = 0.02, I = 0%) by analyzed 609 patients of 4 studies who reported both abdominal pain and COVID-19 severity. However, there was no significant difference in the incidence of diarrhea, nausea, or vomiting between the two groups. Thus, this systematic review and meta-analysis demonstrated that abdominal pain could be characteristic of severe COVID-19 infections. Compared with other viral infections that primarily infect the respiratory system, patients with COVID-19 have a slightly lower frequency of diarrheal symptoms with abdominal pain. However, to confirm this, further studies with COVID-19 patients across various countries and ethnicities are required.
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http://dx.doi.org/10.1007/s00535-021-01778-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987120PMC
May 2021

Idiopathic retroperitoneal fibrosis diagnosed by endoscopic ultrasonography-guided fine-needle biopsy.

JGH Open 2021 Jan 14;5(1):151-152. Epub 2020 Oct 14.

Department of Gastroenterology and Hepatology Sapporo Medical University School of Medicine Sapporo Japan.

We demonstrate a case, in which endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) was useful for determining the diagnosis of lesions of retroperitoneal fibrosis. In our case, accessing the retroperitoneal lesions by conventional percutaneous biopsy procedures was not feasible due to the difficulty of avoiding the inferior vena cava and ureter. We believe that our case demonstrates a unique approach for performing histological analysis in a challenging case.
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http://dx.doi.org/10.1002/jgh3.12431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812448PMC
January 2021

Autophagy and Autophagy-Related Diseases: A Review.

Int J Mol Sci 2020 Nov 26;21(23). Epub 2020 Nov 26.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.

Autophagy refers to the process involving the decomposition of intracellular components via lysosomes. Autophagy plays an important role in maintaining and regulating cell homeostasis by degrading intracellular components and providing degradation products to cells. In vivo, autophagy has been shown to be involved in the starvation response, intracellular quality control, early development, and cell differentiation. Recent studies have revealed that autophagy dysfunction is implicated in neurodegenerative diseases and tumorigenesis. In addition to the discovery of certain disease-causing autophagy-related mutations and elucidation of the pathogenesis of conditions resulting from the abnormal degradation of selective autophagy substrates, the activation of autophagy is essential for prolonging life and suppressing aging. This article provides a comprehensive review of the role of autophagy in health, physiological function, and autophagy-related disease.
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http://dx.doi.org/10.3390/ijms21238974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729615PMC
November 2020

Contradictory Effects of NLRP3 Inflammasome Regulatory Mechanisms in Colitis.

Int J Mol Sci 2020 Oct 30;21(21). Epub 2020 Oct 30.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Minami 1-jo Nishi 16-chome, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.

The inflammasome is an intracellular molecular complex, which is mainly involved in innate immunity. Inflammasomes are formed in response to danger signals, associated with infection and injury, and mainly regulate the secretion of interleukin-1β and interleukin-18. Inflammasome dysregulation is known to be associated with various diseases and conditions, and its regulatory mechanisms have become of great interest in recent years. In the colon, inflammasomes have been reported to be associated with autophagy and the microbiota, and their dysregulation contributes to colitis and. However, the detailed role of inflammasomes in inflammatory bowel disease is still under debate because the mechanisms that regulate the inflammasome are complex and the inflammasome components and cytokines show seemingly contradictory multiple effects. Herein, we comprehensively review the literature on inflammasome functioning in the colon and describe the complex interactions of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome components with inflammatory cytokines, autophagy, and the microbiota in experimental colitis models and patients with inflammatory bowel disease.
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http://dx.doi.org/10.3390/ijms21218145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662299PMC
October 2020

Artificial intelligence-assisted endoscopy changes the definition of mucosal healing in ulcerative colitis.

Dig Endosc 2020 Sep 10. Epub 2020 Sep 10.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Hokkaido, Japan.

The relevance of endoscopic monitoring of ulcerative colitis (UC) has been translated into the new concept of "mucosal healing (MH)" as the therapeutic goal to achieve because a large amount of scientific data have revealed the favorable prognostic value of a healed mucosa in determining the clinical outcome of UC. Recent interest in MH has skewed toward not only endoscopic remission but also histological improvement (so called histological MH). However, we should recognize that there have been no prospectively validated endoscopic scoring systems of UC activity in previous clinical trials. Artificial intelligence (AI)-assisted endoscopy has been developed for gastrointestinal cancer surveillance. Recently, several AI-assisted endoscopic systems have been developed for assessment of MH in UC. In the future, the development of a new endoscopic scoring system based on AI might standardize the definition of MH. Therefore, "The road to an exact definition of MH in the treatment of UC has begun only now".
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http://dx.doi.org/10.1111/den.13825DOI Listing
September 2020

Immunological Mechanisms in Inflammation-Associated Colon Carcinogenesis.

Int J Mol Sci 2020 Apr 26;21(9). Epub 2020 Apr 26.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Minami 1-jo Nishi 16-chome, Chuo-ku, Sapporo 060-8543, Japan.

Patients with chronic inflammatory bowel diseases are at an increased risk of developing colitis-associated cancer (CAC). Chronic inflammation positively correlates with tumorigenesis. Similarly, the cumulative rate of incidence of developing CAC increases with prolonged colon inflammation. Immune signaling pathways, such as nuclear factor (NF)-κB, prostaglandin E2 (PGE2)/cyclooxygenase-2 (COX-2), interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3), and IL-23/T helper 17 cell (Th17), have been shown to promote CAC tumorigenesis. In addition, gut microbiota contributes to the development and progression of CAC. This review summarizes the signaling pathways involved in the pathogenesis following colon inflammation to understand the underlying molecular mechanisms in CAC tumorigenesis.
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http://dx.doi.org/10.3390/ijms21093062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247693PMC
April 2020

Current Diagnostic and Therapeutic Approaches to Cytomegalovirus Infections in Ulcerative Colitis Patients Based on Clinical and Basic Research Data.

Int J Mol Sci 2020 Mar 31;21(7). Epub 2020 Mar 31.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus (the human herpesvirus 5) and an opportunistic pathogen that primarily infects HIV-positive and other immuno-compromised patients. Retrospective studies in the field of inflammatory bowel disease (IBD) have suggested a relationship between a concomitant colonic HCMV infection and poor outcomes in patients with an ulcerative colitis (UC) due to the presence of HCMV in surgical specimens of patients with a toxic megacolon or a steroid-resistant UC. Therefore, gastroenterologists have focused on the contribution of HCMV infections in the exacerbation of UC. Numerous studies have addressed the benefits of treating colonic HCMV reactivation in UC using an antiviral treatment. However, its clinical relevance remains uncertain as only a few prospective studies have assessed the direct relationship between clinical outcomes and the viral load of HCMV in colonic tissues. HCMV reactivation can be triggered by inflammation according to fundamental research studies. Thus, optimal control of intestinal inflammation is essential for preventing an HCMV reactivation in the intestinal mucosa. Indeed, several reports have indicated the effectiveness of an anti-tumor necrosis factor-alpha (TNFα) treatment in patients with an active UC and concomitant HCMV infections. In this review, we describe the mechanism of HCMV reactivation in UC cases and discuss the current issues regarding diagnosis and treatment of HCMV infections in UC patients.
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http://dx.doi.org/10.3390/ijms21072438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177554PMC
March 2020

Down-regulation of RalGTPase-Activating Protein Promotes Colitis-Associated Cancer via NLRP3 Inflammasome Activation.

Cell Mol Gastroenterol Hepatol 2020 15;9(2):277-293. Epub 2019 Oct 15.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address:

Background & Aims: Ral guanosine triphosphatase-activating protein α2 (RalGAPα2) is the major catalytic subunit of the negative regulators of the small guanosine triphosphatase Ral, a member of the Ras subfamily. Ral regulates tumorigenesis and invasion/metastasis of some cancers; however, the role of Ral in colitis-associated cancer (CAC) has not been investigated. We aimed to elucidate the role of Ral in the mechanism of CAC.

Methods: We used wild-type (WT) mice and RalGAPα2 knockout (KO) mice that showed Ral activation, and bone marrow chimeric mice were generated as follows: WT to WT, WT to RalGAPα2 KO, RalGAPα2 KO to WT, and RalGAPα2 KO to RalGAPα2 KO mice. CAC was induced in these mice by intraperitoneal injection of azoxymethane followed by dextran sulfate sodium intake. Intestinal epithelial cells were isolated from colon tissues, and we performed complementary DNA microarray analysis. Cytokine expression in normal colon tissues and CAC was analyzed by quantitative polymerase chain reaction.

Results: Bone marrow chimeric mice showed that immune cell function between WT mice and RalGAPα2 KO mice was not significantly different in the CAC mechanism. RalGAPα2 KO mice had a significantly larger tumor number and size and a significantly higher proportion of tumors invading the submucosa than WT mice. Higher expression levels of matrix metalloproteinase-9 and matrix metalloproteinase-13 were observed in RalGAPα2 KO mice than in WT mice. The expression levels of interleukin 1β, NLRP3, apoptosis associated speck-like protein containing a CARD, and caspase-1 were apparently increased in the tumors of RalGAPα2 KO mice compared with WT mice. NLRP3 inhibitor reduced the number of invasive tumors.

Conclusions: Ral activation participates in the mechanism of CAC development via NLRP3 inflammasome activation.
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http://dx.doi.org/10.1016/j.jcmgh.2019.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957823PMC
May 2021

Diversity of Gut Microbiota Affecting Serum Level of Undercarboxylated Osteocalcin in Patients with Crohn's Disease.

Nutrients 2019 Jul 8;11(7). Epub 2019 Jul 8.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.

Several reports have indicated a possible link between decreasing plasma levels of vitamin K and bone mineral density. It has been suggested that intestinal bacteria contribute to maintenance of vitamin K. Several factors are involved in the reduction of vitamin K in patients with Crohn's disease (CD). We aimed to assess the relationship between gut microbiota and alternative indicators of vitamin K deficiency in patients with CD. We collected the feces of 26 patients with clinically inactive CD. We extracted 16S rRNA from the intestinal bacteria in the feces and amplified it by polymerase chain reaction. The generated polymerase chain reaction product was analyzed using a 16S metagenomic approach by Illumina Miseq platform. Serum undercarboxylated osteocalcin concentration was used as an alternative indicator of vitamin K deficiency. There was a significant negative correlation between serum undercarboxylated osteocalcin and mean Chao1 index in cases of low activity. The diversity of the gut microbiota was significantly lower, and and were significantly decreased in the vitamin K-deficient group in comparison to the vitamin K-normal group. Taken together, these data suggested the significance of investigating the gut microbiota even in patients with clinically inactive CD for improving patients' vitamin K status.
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http://dx.doi.org/10.3390/nu11071541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683014PMC
July 2019

The Etiology of Pancreatic Manifestations in Patients with Inflammatory Bowel Disease.

J Clin Med 2019 Jun 26;8(7). Epub 2019 Jun 26.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.

Inflammatory bowel disease (IBD) is an idiopathic chronic and recurrent condition that comprises Crohn's disease and ulcerative colitis. A pancreatic lesion is one of the extraintestinal lesions in patients with IBD. Acute pancreatitis is the representative manifestation, and various causes of pancreatitis have been reported, including those involving adverse effects of drug therapies such as 5-aminosalicylic acid and thiopurines, gall stones, gastrointestinal lesions on the duodenum, iatrogenic harm accompanying endoscopic procedures such as balloon endoscopy, and autoimmunity. Of these potential causes, autoimmune pancreatitis (AIP) is a relatively newly recognized disease and is being increasingly diagnosed in IBD. AIP cases can be divided into type 1 cases involving lymphocytes and IgG4-positive plasma cells, and type 2 cases primarily involving neutrophils; the majority of AIP cases complicating IBD are type 2. The association between IBD and chronic pancreatitis, exocrine pancreatic insufficiency, pancreatic cancer, etc. has also been suggested; however, studies with high-quality level evidence are limited, and much remains unknown. In this review, we provide an overview of the etiology of pancreatic manifestation in patients with IBD.
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http://dx.doi.org/10.3390/jcm8070916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679036PMC
June 2019

Impact of Autophagy of Innate Immune Cells on Inflammatory Bowel Disease.

Cells 2018 12 22;8(1). Epub 2018 Dec 22.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.

Autophagy, an intracellular degradation mechanism, has many immunological functions and is a constitutive process necessary for maintaining cellular homeostasis and organ structure. One of the functions of autophagy is to control the innate immune response. Many studies conducted in recent years have revealed the contribution of autophagy to the innate immune response, and relationships between this process and various diseases have been reported. Inflammatory bowel disease is an intractable disorder with unknown etiology; however, immunological abnormalities in the intestines are known to be involved in the pathology of inflammatory bowel disease, as is dysfunction of autophagy. In Crohn's disease, many associations with autophagy-related genes, such as , , , and others, have been reported. Abnormalities in the gene, in particular, have been reported to cause autophagic dysfunction, resulting in enhanced production of inflammatory cytokines by macrophages as well as abnormal function of Paneth cells, which are important in intestinal innate immunity. In this review, we provide an overview of the autophagy mechanism in innate immune cells in inflammatory bowel disease.
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http://dx.doi.org/10.3390/cells8010007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6356773PMC
December 2018

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

Intern Med 2018 Apr 9;57(7):923-928. Epub 2018 Feb 9.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Japan.

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.
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http://dx.doi.org/10.2169/internalmedicine.9737-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5919847PMC
April 2018

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

PLoS One 2018 3;13(1):e0190665. Epub 2018 Jan 3.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190665PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752008PMC
February 2018

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

Int J Mol Sci 2017 Dec 21;19(1). Epub 2017 Dec 21.

Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Minami 1-jo Nishi 16-chome, Chuo-ku, Sapporo 060-8543, Japan.

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.
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http://dx.doi.org/10.3390/ijms19010007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795959PMC
December 2017

[Four cases of 5-fluorouracil-related hyperammonemia in patients with large intestinal cancer and multiple liver metastases, including a case of hyperammonemia treated using hemodialysis].

Nihon Shokakibyo Gakkai Zasshi 2015 Feb;112(2):287-96

Department of Gastroenterology, Muroran City General Hospital.

Systemic chemotherapy based on 5-fluorouracil (5-FU) is a standard treatment for unresectable or recurrent large intestinal cancer. Although hyperammonemia is a known side effect of 5-FU that can cause serious pathological conditions, only a few cases have been reported. We describe 4 cases of 5-FU-related hyperammonemia with impairment of consciousness in patients who received 5-FU chemotherapy for large intestinal cancer with multiple liver metastases. Hemodialysis was effective in 1 severe case. There have been no detailed reports on the use of hemodialysis for hyperammonemia caused by 5-FU. Renal dysfunction is considered to be a risk factor for hyperammonemia caused by 5-FU and it is necessary to pay particular attention in patients with renal dysfunction who receive chemotherapy with 5-FU. Here we summarize our cases together with 16 previously reported cases of hyperammonemia caused by 5-FU in Japan.
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http://dx.doi.org/10.11405/nisshoshi.112.287DOI Listing
February 2015

[A case of primary mediastinal (Thymic) B-cell lymphoma successfully treated with the DA-EPOCH-R Regimen].

Gan To Kagaku Ryoho 2015 Jan;42(1):119-22

Dept. of Gastroenterology, Rheumatology, and Clinical Immunology, Sapporo Medical University School of Medicine.

Primary mediastinal (thymic) B-cell lymphoma (PMBL) is resistant to treatment when compared with diffuse large B-cell lymphoma (DLBCL). Moreover, the optimal first -line treatment of PMBL has not yet been determined. Herein, we report a case of PMBL that was successfully treated with the dose adjusted (DA) etoposide, prednisolone, vincristine, doxorubicin, and cyclophosphamide with rituximab (EPOCH-R) regimen. A-29-year-old woman was referred to our hospital with an anterior mediastinal tumor. Eight months before admission, she had visited a clinic for pain in the chest and back, but no abnormalities were found. Subsequently, her chest pain got worse, and she went to another clinic, where she was detected with an anterior mediastinal tumor and was referred to our hospital. Tumor biopsy with a thoracoscope was performed, and a diagnosis of PMBL was made. The tumor diameter was 90 mm, with invasion to the lungs and superior vena cava. The tumor had a clinical stage of IEA, and the International Prognostic Index (IPI) was low risk. She was treated with the DA-EPOCH-R regimen for 8 courses, and a complete response was achieved. A recent retrospective study of DA-EPOCH-R treatment without radiotherapy for PMBL was recently published. It showed that the event-free survival rate was 93% and the overall survival rate was 97% during a median 5-year follow-up. Thus, DA-EPOCH-R may be a potential standard treatment for PMBL.
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January 2015