Publications by authors named "Shuji Terai"

360 Publications

Severe steatosis and mild colitis are important for the early occurrence of hepatocellular carcinoma.

Biochem Biophys Res Commun 2021 Jun 8;566:36-44. Epub 2021 Jun 8.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan. Electronic address:

The number of patients with non-alcoholic steatohepatitis (NASH) and inflammatory bowel disease (IBD) is increasing. This study elucidates the effect of both NASH and IBD on hepatocellular carcinoma (HCC) using a mouse model combining NASH and IBD. The melanocortin 4 receptor-deficient (Mc4r-KO) mice were divided into four groups with or without a high-fat diet (HFD) and with or without dextran sulfate sodium (DSS) to induce colitis, and the differences in liver damage and occurrence of HCC were analyzed. In the HFD + DSS group, the body weight, liver weight/body weight ratio, and serum levels of albumin and alanine aminotransferase were significantly lower than those in the HFD group. We further found that steatosis was significantly lower and lobular inflammation was significantly higher in the HFD + DSS group than those in the HFD group, and that individual steatosis and lobular inflammation state in the HFD + DSS mice varied. We detected HCC only in the HFD + DSS group, and mice with severe steatosis and mild colitis were found to be at high risk of HCC. Presently, the prediction of HCC is very difficult. In some cases, severe colitis reverses the fat accumulation due to appetite loss. Our findings clearly showed that severe steatohepatitis and mild colitis are simultaneously essential for the occurrence of HCC in patients with NASH and IBD.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.097DOI Listing
June 2021

A case of -negative early gastric adenocarcinoma with gastrointestinal phenotype.

Endosc Int Open 2021 Jun 27;9(6):E863-E866. Epub 2021 May 27.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

A 40-year-old man with slightly depressed (0-IIc) type gastric cancer of the pyloric anterior gastric area underwent pre-operative screening for tetralogy of Fallot and endoscopic submucosal dissection (ESD) and was tested for antigens and antibodies. Both tests were negative. He did not have a history of eradication. Pathological diagnosis of ESD showed a well-differentiated adenocarcinoma. The tumor was CD10-positive, MUC5AC-negative, and MUC6-confocal positive; it showed differentiation with gastrointestinal phenotype. Moreover, the tumor cells were lysozyme-positive, resembling Paneth cells. Mucosal glands exhibited intestinal metaplasia on the anal side of the tumor lesion. On the oral side of the tumor, metaplasia was non-existent, with normal pyloric glands present in the mucosal layer. The patient was not infected with ; however, intestinal metaplasia existed around the early gastric cancer. This suggested that the intestinal metaplasia occurred due to bile reflux, and the gastric neoplasia arose with the metaplasia without an infection. This case may potentially help explain gastric cancer development in the absence of infection.
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http://dx.doi.org/10.1055/a-1396-3854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159579PMC
June 2021

Effectiveness of EUS-Guided Fine-Needle Biopsy versus EUS-Guided Fine-Needle Aspiration: A Retrospective Analysis.

Diagnostics (Basel) 2021 May 27;11(6). Epub 2021 May 27.

Department of Gastroenterology and Hepatology, Graduate School of Medicine and Dental sciences, Niigata University, Niigata 951-8510, Japan.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic tumors and subepithelial lesions (SEL) of the gastrointestinal tract are effective for histological diagnosis. There are also reports that tissue sampling is possible with a smaller number of punctures by EUS-guided fine-needle biopsy (EUS-FNB). In this study, we retrospectively compared the diagnostic abilities of EUS-FNA and EUS-FNB. We examined 130 patients who underwent EUS-FNA/EUS-FNB for pancreatic tumors and SEL from July 2018 to January 2021. None of the cases underwent rapid on-site evaluation. There were 94 and 36 cases in the EUS-FNA and EUS-FNB groups, respectively. The median tumor size in the EUS-FNB group was 30 mm, which was significantly larger than the EUS-FNA group ( = 0.02). In addition, transgastric puncture was significantly more common in the EUS-FNB group ( = 0.01). The EUS-FNA and EUS-FNB groups had a sensitivity of 82.9% and 91.7% and an accuracy rate of 85.1% and 91.7%, respectively. However, both procedures had a comparable diagnostic ability.
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http://dx.doi.org/10.3390/diagnostics11060965DOI Listing
May 2021

Endoscopic retrieval of multiple sewing needles by using the tip of a magnetic tube.

VideoGIE 2021 May 24;6(5):228-230. Epub 2021 Feb 24.

Department of Gastroenterology and Hepatology, Niigata University Hospital, Niigata, Japan.

Video 1Multiple sewing needles are retrieved from the stomach endoscopically using the tip of a magnet tube.
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http://dx.doi.org/10.1016/j.vgie.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120008PMC
May 2021

Rapid decline in visceral adipose tissue over 1 month is associated with poor prognosis in patients with unresectable pancreatic cancer.

Cancer Med 2021 May 16. Epub 2021 May 16.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Background: Involuntary weight loss related to cachexia is common in patients with advanced cancer, but the association between body composition changes and survival is still unclear in pancreatic cancer.

Methods: We retrospectively reviewed the clinical outcomes of 55 patients with advanced pancreatic cancer undergoing palliative therapy or best supportive care (BSC). The skeletal muscle index (SMI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue area ratio (VSR) were calculated based on the cross-sectional area on two sets of computed tomography images obtained at cancer diagnosis and 1 month later before treatment. The prognostic value of body composition indexes at diagnosis and the changes in those indexes over 1 month was then evaluated.

Results: In total, 45 patients (81.8%) received chemotherapy, chemoradiation, or radiation therapy, whereas the remaining patients underwent BSC. There were 27 patients (49.1%) who had low SMI at cancer diagnosis. Univariate analysis showed no significant associations between the baseline body composition indexes including SMI, VATI, SATI, and VSR and survival. Meanwhile, male sex (HR, 2.79; 95% CI, 1.16-6.71, p = 0.022) and higher decrease in VATI over 1 month (HR, 2.41; 95% CI, 1.13-5.13, p = 0.023) were identified as independent risk factors for mortality in multivariate analysis.

Conclusion: Rapid decline in VAT over 1 month is closely associated with poorer survival in unresectable advanced pancreatic cancer. A short-term assessment of body composition changes may be a rational approach to predict prognosis in these patients.
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http://dx.doi.org/10.1002/cam4.3964DOI Listing
May 2021

Transoral surgery for superficial head and neck cancer: National Multi-Center Survey in Japan.

Cancer Med 2021 Jun 15;10(12):3848-3861. Epub 2021 May 15.

Department of Gastroenterology, Kobe City Medical Center General Hospital, Kobe, Japan.

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1-75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2-357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1-113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.
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http://dx.doi.org/10.1002/cam4.3927DOI Listing
June 2021

Long-term survival of 11 years with multidisciplinary therapy for hepatocellular carcinoma metastasis to the ovary and peritoneum: a case report.

Clin J Gastroenterol 2021 May 12. Epub 2021 May 12.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.

We herein report a rare case of HCC metastases to the ovary and peritoneum in a 61-year-old female patient who has achieved 11-year survival with multidisciplinary therapy. The patient was diagnosed with HCC during balloon angioplasty performed for Budd-Chiari syndrome in 1994 and underwent partial hepatectomy twice. Five years after the second hepatectomy, allochronic recurrence of a single nodule detected in S8 was treated by radiofrequency ablation, followed by percutaneous ethanol injection therapy and stereotactic body radiotherapy. However, her α-fetoprotein level rose to 1862 ng/mL within one year and computed tomography revealed a large pelvic tumor suggesting HCC metastasis to the ovary. The subsequent laparotomy revealed one 11-cm left ovarian tumor, one small right ovarian nodule, and numerous peritoneal nodules. Bilateral salpingo-oophorectomy and peritoneal resection of as many nodules as possible were performed. Combination therapy with intravenous 5-fluorouracil plus cisplatin and ramucirumab monotherapy effectively suppressed tumor progression with maintenance of hepatic functional reserve, and she has achieved long-term survival of 11 years, illustrating that multidisciplinary therapy with favorable hepatic functional reserve maintenance can contribute to long-term survival in HCC with extrahepatic spread.
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http://dx.doi.org/10.1007/s12328-021-01434-2DOI Listing
May 2021

Comparison of Oral and Esophageal Microbiota in Patients with Achalasia Before and After Peroral Endoscopic Myotomy.

Turk J Gastroenterol 2021 Jan;32(1):42-52

Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Background/aims: Patients with achalasia have a high incidence of esophageal squamous cell carcinoma (ESCC), which may be associated with alterations in oral and esophageal microbiota caused by food stasis. This study compared the oral and esophageal microbiota of patients with achalasia before and after peroral endoscopic myotomy (POEM). It also compared patients with achalasia to those with ESCC.

Materials And Methods: The study prospectively examined 6 patients with achalasia and 14 with superficial ESCC. Oral samples obtained from the buccal mucosa using a swab and esophageal samples obtained from the mid-esophagus using a brush via endoscopy were analyzed by 16S rRNA metagenome sequencing. Additionally, endoscopic and histological findings of patients with achalasia before and after POEM were prospectively compared.

Results: In patients with achalasia, Streptococcus was most abundant in both the oral and the esophageal microbiota, and these microbiota were significantly different. Although the overall structure of the oral and esophageal microbiota did not change after POEM, the relative abundance rate of Haemophilus and Neisseria increased in the esophagus, and endoscopic findings of inflammation improved after POEM (P = .04). The relative abundance of microbiota was not different among patients with achalasia from those with ESCC.

Conclusions: The oral and esophageal microbiota were significantly different in patients with achalasia, and some of the composition of the esophageal microbiota changed after POEM. However, these findings and disease-specific microbiota should be further evaluated in large-scale studies.
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http://dx.doi.org/10.5152/tjg.2020.19995DOI Listing
January 2021

Paris II and Rotterdam criteria are the best predictors of outcomes in patients with primary biliary cholangitis in Japan.

Hepatol Int 2021 Apr 16;15(2):437-443. Epub 2021 Apr 16.

Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.

Background: Biochemical response to treatment in patients with primary biliary cholangitis (PBC) reflects prognosis. However, the best predictive criteria to detect biochemical response remain undetermined. In addition, because these criteria need > 6 months until definition, parameters that can estimate its results before initiating treatment are needed.

Methods: We conducted a single-center retrospective study on 196 patients with PBC, followed up for at least 12 months after initiating treatment.

Results: Kaplan-Meier analysis showed that Paris II (p = 0.002) and Rotterdam criteria (p = 0.001) could estimate the overall survival of PBC patients, whereas Paris II (p = 0.001), Rotterdam (p = 0.001), and Rochester criteria (p= 0.025) could estimate liver-related deaths. Cox hazard analysis revealed Paris II and Rotterdam criteria as significantly independent predictors of overall survival (hazard ratio (HR) 3.948, 95% CI 1.293-12.054, p = 0.016 and HR 6.040, 95% CI 1.969-18.527, p = 0.002, respectively) and liver-related deaths (HR 10.461, 95% CI 1.231-88.936, p = 0.032 and HR 10.824, 95% CI 1.252-93.572, p = 0.032, respectively). The results of Paris II criteria could be estimated by serum prothrombin time (Odds ratio (OR) 1.052, 95% CI 1.008-1.098, p = 0.021) and alanine transaminase level (OR 0.954, 95% CI 0.919-0.991, p = 0.014) whereas, those of Rotterdam criteria could be estimated by serum albumin level (OR 3.649, 95% CI 1.098-12.128, p = 0.035) at the time of diagnosis.

Conclusions: This study highlights the best prediction criteria and pre-treatment parameters that facilitate the prognosis of PBC patients.
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http://dx.doi.org/10.1007/s12072-021-10163-0DOI Listing
April 2021

Analysis of the safety of pretransplant corticosteroid therapy in patients with acute liver failure and late-onset hepatic failure in Japan.

JGH Open 2021 Apr 5;5(4):428-433. Epub 2021 Mar 5.

Department of Gastroenterology and Hepatology Yamaguchi University Graduate School of Medicine Ube Japan.

Background And Aim: In Japan, corticosteroids have been commonly used as a part of multidisciplinary therapy for patients with acute liver failure and late-onset hepatic failure. However, there is controversy regarding the development of infections and other complications. In this study, the influence of corticosteroids on patient outcomes after liver transplantation was investigated.

Methods: This study included 167 patients with acute liver failure and late-onset hepatic failure who underwent liver transplantation between 2010 and 2015. The effects of pretransplant corticosteroid therapy on patient outcomes were evaluated using a database constructed by the subcommittee for fulminant hepatitis in the Intractable Hepato-Biliary Diseases Study Group of Japan.

Results: The subacute type and the median total bilirubin levels were higher in those receiving corticosteroids than in those not receiving corticosteroids. Although infections tended to be higher in patients receiving corticosteroids, pretransplant corticosteroid administration did not affect the survival rates. The duration from corticosteroid initiation to liver transplantation was longer in patients who developed infections. The survival rates, however, did not differ between patients with and without infections.

Conclusions: Corticosteroids were administered to patients with poor prognoses. Otherwise, the overall outcome in those administered corticosteroids was not significantly different from that in those administered without corticosteroids. Although infectious complications tended to occur, they were generally controllable and nonfatal. Pretransplant corticosteroid therapy may be permissible, with regarding for infections and performed within the minimum duration.
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http://dx.doi.org/10.1002/jgh3.12508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035437PMC
April 2021

Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver.

Dis Model Mech 2021 Mar 28;14(3). Epub 2021 Mar 28.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Japan.

The etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect of modulation of this axis in this study. To test the contribution of the gut-liver neural axis, we examined NAFLD progression with respect to body weight, hepatic steatosis, fibrosis, intestinal tight junction, microbiota and short-chain fatty acids in NAFLD models of choline-deficient defined L-amino-acid and high-fat diet-fed mice with or without blockades of autonomic nerves from the liver. Blockade of the neural signal from the liver to the gut in these NAFLD mice models ameliorated the progression of liver weight, hepatic steatosis and fibrosis by modulating serotonin expression in the small intestine. It was related to the severity of the liver pathology, the tight junction protein expression, microbiota diversity and short-chain fatty acids. These effects were reproduced by administrating serotonin antagonist, which ameliorated the NAFLD progression in the NAFLD mice models. Our study demonstrated that the gut-liver neural axis is involved in the etiologies of NAFLD progression and that serotonin expression through this signaling network is the key factor of this axis. Therefore, modulation of the gut-liver neural axis and serotonin antagonist ameliorates fatty and fibrotic changes in non-alcoholic fatty liver, and can be a potential therapeutic target of NAFLD.This article has an associated First Person interview with the first author of the paper.
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http://dx.doi.org/10.1242/dmm.048922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084356PMC
March 2021

Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis.

NPJ Regen Med 2021 Mar 30;6(1):19. Epub 2021 Mar 30.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.

Mesenchymal stromal cells (MSCs) are used for ameliorating liver fibrosis and aiding liver regeneration after cirrhosis; Here, we analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs). γ-sEVs effectively induced anti-inflammatory macrophages with high motility and phagocytic abilities in vitro, while not preventing hepatic stellate cell (HSC; the major source of collagen fiber) activation in vitro. The proteome analysis of MSC-derived sEVs revealed anti-inflammatory macrophage inducible proteins (e.g., annexin-A1, lactotransferrin, and aminopeptidase N) upon IFN-γ stimulation. Furthermore, by enabling CXCR1+ macrophage accumulation in the damaged area, γ-sEVs ameliorated inflammation and fibrosis in the cirrhosis mouse model more effectively than sEVs. Single cell RNA-Seq analysis revealed diverse effects, such as induction of anti-inflammatory macrophages and regulatory T cells, in the cirrhotic liver after γ-sEV administration. Overall, IFN-γ pre-conditioning altered sEVs resulted in efficient tissue repair indicating a new therapeutic strategy.
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http://dx.doi.org/10.1038/s41536-021-00132-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010072PMC
March 2021

Successful treatment of positive-sense RNA virus coinfection with autoimmune hepatitis using double filtration plasmapheresis.

BMJ Case Rep 2021 Mar 25;14(3). Epub 2021 Mar 25.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40-60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.
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http://dx.doi.org/10.1136/bcr-2020-236984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006769PMC
March 2021

Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers.

Sci Rep 2021 Mar 18;11(1):6255. Epub 2021 Mar 18.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, Niigata, 951-8510, Japan.

Cisplatin (CDDP) is one of the chemotherapeutic drugs being used to treat various cancers. Although effective in many cases, as high doses of CDDP cause cytotoxic effects that may worsen patients' condition, therefore, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. This study focused on adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues and serum of HCC patients (n = 71) treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The predictability of serum APM2 for CDDP sensitivity was assessed in additional 54 HCC patients and 14 gastric cancer (GC) patients. APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of ERCC6L (DNA excision repair protein ERCC6-like) by APM2, which accounts for the degree of APM2 expression. The serum APM2 level and chemosensitivity for CDDP were assessed and cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 µg/mL. The value was assessed in HCC (n = 54) and GC (n = 14) patients for its predictability of CDDP sensitivity, resulted in predictive value of 77.3% and 100%, respectively. Our study demonstrated that APM2 expression is related to CDDP sensitivity and serum APM2 can be an effective biomarker of HCC and GC for determining the sensitivity to CDDP.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028487).
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http://dx.doi.org/10.1038/s41598-021-85498-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973578PMC
March 2021

Potential Effect of a Selective Peroxisome Proliferator-activated Receptor Alpha Modulator on Metabolic Dysfunction-associated Fatty Liver Disease.

Intern Med 2021 Feb 22. Epub 2021 Feb 22.

Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Japan.

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http://dx.doi.org/10.2169/internalmedicine.6906-20DOI Listing
February 2021

Molecular Mechanisms and Treatment of Sarcopenia in Liver Disease: A Review of Current Knowledge.

Int J Mol Sci 2021 Jan 31;22(3). Epub 2021 Jan 31.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan.

Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength that occurs with aging or in association with various diseases. The condition is prevalent worldwide and occurs more frequently in patients with chronic diseases owing to the intrinsic relationship of muscles with glucose, lipid, and protein metabolism. Liver cirrhosis is characterized by the progression of necro-inflammatory liver diseases, which leads to fibrosis, portal hypertension, and a catabolic state, which causes loss of muscle tissue. Sarcopenia is of significant concern in the state of liver cirrhosis because sarcopenia has been associated with higher mortality, increased hospital admissions, worse post-liver transplant outcomes, decreased quality of life, and increased risk for other complications associated with cirrhosis. Therefore, sarcopenia is also an important feature of liver cirrhosis, representing a negative prognostic factor and influencing mortality. An increased understanding of sarcopenia could lead to the development of novel therapeutic approaches that could help improve the cognitive impairment of cirrhotic patients; therefore, we present a review of the mechanisms and diagnosis of sarcopenia in liver disease and existing therapeutic approaches.
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http://dx.doi.org/10.3390/ijms22031425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867020PMC
January 2021

Tuberculous Spondylitis in a Woman without Pulmonary Lesions.

Intern Med 2021 Feb 8. Epub 2021 Feb 8.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan.

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http://dx.doi.org/10.2169/internalmedicine.5054-20DOI Listing
February 2021

Rare paraneoplastic syndromes in digestive systems caused by lung cancer.

BMJ Case Rep 2021 Feb 5;14(2). Epub 2021 Feb 5.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences Niigata University, Niigata, Japan.

We observed a rare case of two different digestive paraneoplastic syndromes that improved with the treatment of the neoplasms. The first syndrome was chronic intestinal pseudo-obstruction (CIPO), which is a subtype of paraneoplastic syndromes called a paraneoplastic neurological syndrome (PNS). The second was Stauffer's syndrome, which is a unique paraneoplastic syndrome characterised by non-metastatic intrahepatic cholestasis associated with neoplasms. Here, we report the case of a 55-year-old man who presented with two concurrent paraneoplastic syndromes in the digestive system. The intestinal pseudo-obstruction and elevated biliary enzyme levels improved as the lung cancer responded to chemotherapy. In this case, CIPO as a PNS led to the detection of lung cancer. To our knowledge, this is the first report of Stauffer's syndrome caused by lung adenocarcinoma.
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http://dx.doi.org/10.1136/bcr-2020-240161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871262PMC
February 2021

Achalasia and esophageal cancer: a large database analysis in Japan.

J Gastroenterol 2021 Apr 4;56(4):360-370. Epub 2021 Feb 4.

Digestive Diseases Center, Showa University Koto Toyosu Hospital, Tokyo, Japan.

Background: Achalasia has been reported to be associated with esophageal cancers (ECs). However, owing to the rarity of achalasia, details of achalasia-related ECs are not well investigated.

Method: The incidence of ECs in Japanese patients with achalasia and achalasia-related esophageal motility disorders (EMDs) was estimated, and risk factors for achalasia-related ECs were determined. Characteristics of ECs and treatment courses were also analyzed.

Results: Between 2010 and 2019, 2714 Japanese patients with achalasia and achalasia-related EMDs were recorded in 7 high-volume centers; 24 patients (21 men, 3 women) developed ECs. The incidence of ECs was estimated at 0.078 and 0.28 per 100 person-years from the onset and the diagnosis of disease, respectively. Kaplan-Meier estimate suggested that, in addition to a long history of achalasia, advanced age, male sex, and regular alcohol consumption were statistically significant risk factors for EC development. A prevalence of 40 ECs (12.5% multiple lesions, and 22.7% metachronal lesions) was also noted, predominantly distributed over the thoracic esophagus. All were histologically diagnosed as squamous cell carcinoma. Superficial ECs were successfully treated with endoscopic treatment in all cases, except one. Achalasia-related Barret esophagus was extremely rare, and Barret adenocarcinoma was not detected in our cohort.

Conclusion: The high relative risk of ECs was clarified in Japanese achalasia patients, although the absolute risk remained low. Therefore, surveillance endoscopy may be recommended in limited patients with several aforementioned risk factors determined. Superficial cancer can be treated with endoscopic treatment. Multiple and metachronal ECs should be screened.
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http://dx.doi.org/10.1007/s00535-021-01763-6DOI Listing
April 2021

Immunoglobulin therapy for successful management of prolonged, recurrent jaundice in a young adult male with combined immunodeficiency.

Clin J Gastroenterol 2021 Feb 2. Epub 2021 Feb 2.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757, Aasahimachi-Dori, Chuo-Ku, Niigata, 9518510, Japan.

Jaundice may be persistent in drug-induced liver injury associated with vanishing bile duct syndrome. However, recurrent jaundice is atypical, following bile flow restoration. Here, we report a 28-year-old man with prolonged, recurrent jaundice (more than 300 days) and combined immunodeficiency (CID) of B-cells, T-cells, and natural killer (NK) cells. Hypogammaglobulinemia was observed throughout his hospitalization, and peripheral blood flow cytometry detected a few B-cells (2% of CD19 + cells and 2% of CD20 + cells). We further detected the dysfunction of T-cells and NK cells. Based on these findings, CID was diagnosed. We presumed that hypogammaglobulinemia was related to the jaundice. After regular injections of intravenous immunoglobulin (IVIG), the stool color gradually turned brown. However, the color returned to white as IgG levels decreased. The brown-to-white stool pattern was repeated with another IVIG administration, suggesting that the patient's serum immunoglobulin levels were related to the jaundice. On follow-up, IVIG was performed every two to three weeks, and his total bilirubin improved gradually. Immunoglobulin replacement therapy could be one of the treatment choices for jaundice with CID.
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http://dx.doi.org/10.1007/s12328-021-01347-0DOI Listing
February 2021

Usefulness of an artificial intelligence system for the detection of esophageal squamous cell carcinoma evaluated with videos simulating overlooking situation.

Dig Endosc 2021 Jan 27. Epub 2021 Jan 27.

AI Medical Service Inc, Tokyo, Japan.

Objectives: Artificial intelligence (AI) systems have shown favorable performance in the detection of esophageal squamous cell carcinoma (ESCC). However, previous studies were limited by the quality of their validation methods. In this study, we evaluated the performance of an AI system with videos simulating situations in which ESCC has been overlooked.

Methods: We used 17,336 images from 1376 superficial ESCCs and 1461 images from 196 noncancerous and normal esophagi to construct the AI system. To record validation videos, the endoscope was passed through the esophagus at a constant speed without focusing on the lesion to simulate situations in which ESCC has been missed. Validation videos were evaluated by the AI system and 21 endoscopists.

Results: We prepared 100 video datasets, including 50 superficial ESCCs, 22 noncancerous lesions, and 28 normal esophagi. The AI system had sensitivity of 85.7% (54 of 63 ESCCs) and specificity of 40%. Initial evaluation by endoscopists conducted with plain video (without AI support) had average sensitivity of 75.0% (47.3 of 63 ESCC) and specificity of 91.4%. Subsequent evaluation by endoscopists was conducted with AI assistance, which improved their sensitivity to 77.7% (P = 0.00696) without changing their specificity (91.6%, P = 0.756).

Conclusions: Our AI system had high sensitivity for the detection of ESCC. As a support tool, the system has the potential to enhance detection of ESCC without reducing specificity. (UMIN000039645).
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http://dx.doi.org/10.1111/den.13934DOI Listing
January 2021

Comorbidities and healthcare costs and resource use of patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in the Japan medical data vision database.

J Gastroenterol 2021 Mar 26;56(3):274-284. Epub 2021 Jan 26.

Gilead Sciences Inc, Foster City, CA, USA.

Background: This study examined demographics, comorbidities and healthcare resource use (HCRU) and costs among Japanese patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

Methods: We conducted a repeated cross-sectional analysis of the Medical Data Vision (MDV) claims database, from January 2011 to March 2018. Demographics were described at index date and by calendar year; a "NASH" subpopulation included patients with ≥ 1 claim for NASH at any time. Prevalence of pre-specified comorbidities of interest and data-emergent top comorbidities were estimated. All-cause HCRU and costs were quantified by calendar year. Outcomes were compared between 2011 and 2017 using partially overlapping t tests.

Results: 58,958 patients (mean age 61.6 years; 55.5% male) were included. 1139 patients (2%) were in the NASH subpopulation. At baseline, comorbid cardiovascular disease (69.4%), diabetes (62.1%) and hyperlipidaemia (54.4%) were most prevalent; comorbidity prevalence increased with age. Mean outpatient visits decreased from 9.36 per patient in 2011 to 7.80 in 2017; mean inpatient admissions increased (both p < 0.001 for 2011 vs 2017). Mean total all-cause healthcare costs ranged from ¥322,206 to ¥340,399 per patient per year between 2011 and 2017. Although total all-cause healthcare costs did not change significantly (p = 0.552), cost burden shifted from the outpatient to inpatient setting between 2011 and 2017. All-cause healthcare resource use/costs were generally higher for the NASH subgroup compared with the overall population.

Conclusions: There is a high burden of disease among Japanese NAFLD/NASH patients, including a high prevalence of comorbidities which generally increase with age. Accordingly, substantial all-cause HCRU and costs were incurred.
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http://dx.doi.org/10.1007/s00535-021-01759-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932941PMC
March 2021

Evaluation of intestinal microbiota, short-chain fatty acids, and immunoglobulin a in diversion colitis.

Biochem Biophys Rep 2021 Mar 30;25:100892. Epub 2020 Dec 30.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

It is reported that an increase in aerobic bacteria, a lack of short-chain fatty acids (SCFAs), and immune disorders in the diverted colon are major causes of diversion colitis. However, the precise pathogenesis of this condition remains unclear. The aim of the present study was to examine the microbiota, intestinal SCFAs, and immunoglobulin A (IgA) in the diverted colon. Eight patients underwent operative procedures for colostomies. We assessed the diverted colon using endoscopy and obtained intestinal samples from the diverted colon and oral colon in these patients. We analyzed the microbiota and SCFAs of the intestinal samples. The bacterial communities were investigated using a 16S rRNA gene sequencing method. The microbiota demonstrated a change in the proportion of some species, especially , which significantly decreased in the diverted colon at the genus level. We also showed that intestinal SCFA values were significantly decreased in the diverted colon. Furthermore, intestinal IgA levels were significantly increased in the diverted colon. This study was the first to show that intestinal SCFAs were significantly decreased and intestinal IgA was significantly increased in the diverted colon. Our data suggest that SCFAs affect the microbiota and may play an immunological role in diversion colitis.
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http://dx.doi.org/10.1016/j.bbrep.2020.100892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797511PMC
March 2021

[Problems and future questions in the clinical practice of liver cirrhosis].

Nihon Shokakibyo Gakkai Zasshi 2021 ;118(1):41-45

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University.

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http://dx.doi.org/10.11405/nisshoshi.118.41DOI Listing
February 2021

The first case of balloon-occluded retrograde transvenous obliteration and partial splenic embolization for gastric varices in situs inversus abdominus.

Clin J Gastroenterol 2021 Apr 5;14(2):656-661. Epub 2021 Jan 5.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Situs inversus abdominus is a congenital abnormality characterized by the mirror image positioning of the abdominal organs, making it difficult to diagnosis and treatment of many diseases. Here, we report a rare case of gastric varices in situs inversus abdominus patient. A 55-year-old man was diagnosed with F2-shaped gastric varices associated with alcoholic cirrhosis. Abdominal dynamic computed tomography showed situs inversus abdominus, and gastric varices with a gastrorenal shunt. Due to the complex anatomy, emergency interventional radiology during bleeding was extremely difficult. Therefore, after thorough consultation, we decided to treat gastric varices prophylactically by balloon-occluded retrograde transvenous obliteration. After treatment, the patient's clinical course was generally good, with no adverse events, and the gastric varices disappeared. It is important to assess anatomical positioning using three-dimensional reconstruction computed tomography images before treatment, to adequately prepare, including selecting appropriate devices (i.e., catheters and sheath). Although preventive treatment of gastric varices is controversial, in cases with anatomical complexity, preventive treatment with sufficient preparation would be recommended. To the best of our knowledge, there are no reports of treatment for gastric varices in situs inversus abdominus patient. This case will serve as a reference for successful treatment in future cases.
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http://dx.doi.org/10.1007/s12328-020-01332-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016758PMC
April 2021

Effect of Lenvatinib on a Hepatocellular Carcinoma with Fibroblast Growth Factor Receptor 4 Expression: A Case Report and Review of the Literature.

Intern Med 2021 Jun 29;60(11):1709-1715. Epub 2020 Dec 29.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Japan.

Basic and clinical research have shown that the expression of molecules involved in the hepatocellular carcinoma (HCC) cell signaling pathway is related to the sensitivity to molecular-targeted agents. We herein report a case of HCC that was effectively treated with lenvatinib after a poor response to sorafenib. The tumor showed a high expression of fibroblast growth factor receptor 4, which is reportedly related to the sensitivity to lenvatinib in vitro. The information obtained from this case and from our literature review highlights the importance of assessing the expression of the molecules involved in tumors for effective precision medicine.
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http://dx.doi.org/10.2169/internalmedicine.6580-20DOI Listing
June 2021

Usefulness of ultrasonography to assess the response to steroidal therapy for the rare case of type 2b immunoglobulin G4-related sclerosing cholangitis without pancreatitis: A case report.

World J Clin Cases 2020 Nov;8(22):5821-5830

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 9518510, Japan.

Background: A type 2b immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) without autoimmune pancreatitis is a rare condition with IgG4-SC. While the variety of the imaging modalities have tested its usefulness in diagnosing the IgG4-SC, however, the usage of ultrasonography for the assessment of the response to steroidal therapy on the changes of bile duct wall thickness have not been reported in the condition. Therefore, the information of our recent case and reported cases have been summarized.

Case Summary: We report the case of an 82-year-old Japanese man diagnosed with isolated IgG4-related SC based on the increase of serum IgG4, narrowing of the bile duct, its wall thickness, no complication of autoimmune pancreatitis, and IgG4 positive inflammatory cell infiltration to the wall with the fibrotic changes. The cholangiogram revealed type 2b according to the classification. Corticosteroid treatment showed a favorable effect, with the smooth decrease in serum IgG4 and the improvement of the bile duct wall thickness.

Conclusion: As isolated type 2b, IgG4-SC is rare, the images, histological findings, and clinical course of our case will be helpful for physicians to diagnose and treat the new cases appropriately.
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http://dx.doi.org/10.12998/wjcc.v8.i22.5821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716308PMC
November 2020

Choledochocele observed on direct peroral cholangioscopy using an ultra-slim endoscope.

J Hepatobiliary Pancreat Sci 2020 Dec 15. Epub 2020 Dec 15.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Science, Niigata University, Niigata, Japan.

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http://dx.doi.org/10.1002/jhbp.884DOI Listing
December 2020

The development of mesenchymal stem cell therapy in the present, and the perspective of cell-free therapy in the future.

Clin Mol Hepatol 2021 01 3;27(1):70-80. Epub 2020 Dec 3.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Cirrhosis is a chronic condition that can lead to liver failure. Currently, the viable option for decreasing mortality is liver transplantation. However, transplant surgery is highly invasive. Therefore, cell-based therapy has been developed as an alternative. Based on promising findings from preclinical research, some new trials have been registered. One of them was autologous bone marrow cell infusion therapy and found that ameliorating liver fibrosis activated liver regeneration. Now, majority of trials focus on low-immunogenicity mesenchymal stem cells (MSCs) appropriate for allogeneic administration. However, despite about 20 years of research, only a limited number of cell-based therapies have entered routine practice. Furthermore, potential shortcomings of cell-based therapy include a limit on the number of cells, which may be administered, as well as their failure to infiltrate target organs. On the other hand, these research show that MSCs act as "conducting cells" and regulate host cells including macrophages via extracellular vesicles (EVs) or exosome signals, leading to ameliorate liver fibrosis and promote regeneration. Therefore, the concept of cell-free therapy, which makes use of cell-derived EVs or exosomes, is attracting attention. Cell-free therapies may be safely administered in large doses and are able to infiltrate target organs. However, development of cell-free therapy exhibits its own set of challenges and such therapy may not be completely curative in the context of liver disease. This review describes the history of cell-based therapy research and recent advances in cell-free therapy, as well as discussing the need for more effective therapies.
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http://dx.doi.org/10.3350/cmh.2020.0194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820202PMC
January 2021

Effectiveness of Endoscopic Pancreatic Stenting for Pancreatic Pseudocyst-Portal Vein Fistula.

Case Rep Gastroenterol 2020 Sep-Dec;14(3):570-576. Epub 2020 Oct 30.

Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Pancreatic pseudocyst-portal vein (PP-PV) fistula, mostly occurring after pseudocyst formation following acute/chronic pancreatitis, is a rare but life-threatening condition. The majority of treatments are based on conservative or surgical interventions. We report the case of a 70-year-old man with a PP-PV fistula and PV thrombosis. We adopted conservative treatment at first due to his mild symptoms. However, after resuming food intake, the patient had severe abdominal pain. Following endoscopic retrograde cholangiopancreatography, we found that the pseudocyst was connected with the PV through the fistula. Subsequently, an endoscopic nasopancreatic drainage (ENPD) catheter was inserted into the main pancreatic duct to establish pancreatic drainage, which resulted in a decrease in the abdominal pain. After the ENPD tube had been exchanged for endoscopic pancreatic stenting, his abdominal pain did not recur. Therefore, this case demonstrated endoscopic treatment as an effective treatment option for PP-PV fistula.
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http://dx.doi.org/10.1159/000510331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670380PMC
October 2020