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1.
J Gastroenterol ; 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35031857

RESUMO

BACKGROUND: The aim of this multicenter retrospective study was to evaluate the impact of the eradication of hepatitis C virus (HCV) on the clinical outcomes of patients with hepatocellular carcinoma (HCC) treated with molecular-targeted agents (MTAs). METHODS: Among 877 patients who received any MTA as first-line systemic therapy for HCC between June 2009 and March 2019, 569 patients with HCV-related HCC were enrolled in this retrospective study. Of these, 109 patients achieved sustained virological response (SVR) before starting MTA. After propensity score matching, the clinical outcomes of 109 patients in the SVR group and 109 patients in the non-SVR group were compared. RESULTS: The median time to progression in the SVR group (7.8 months) was similar to that in the non-SVR group (5.6 months) (p = 0.212). The median time to treatment failure in the SVR group (5.3 months) was longer than that in the non-SVR group (2.8 months) (p = 0.059), and post-progression survival and overall survival in the SVR group were significantly longer than those in the non-SVR group (12.0 months vs 7.2 months; p = 0.039, and 18.1 months vs 11.3 months; p = 0.019). At the end of first-line MTA therapy, the albumin-bilirubin (ALBI) score in the SVR group ( - 2.25) was significantly lower than that in the non-SVR group ( - 2.10) (p = 0.008). CONCLUSIONS: The eradication of HCV before MTA therapy maintained liver function and led to a prolonged treatment period and improved overall survival of HCV-related HCC patients. We should not overlook the benefits of HCV eradication in HCC patients.

2.
Turk J Gastroenterol ; 33(1): 74-79, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35040791

RESUMO

BACKGROUND: The precise pathogenesis of irritable bowel syndrome (IBS) remains unresolved; however, recent studies have reported that patients with diarrhea-predominant IBS exhibit an increased small intestinal permeability and increased number of enterochromaffin cells containing high 5-hydroxytryptamine (5HT; serotonin) levels. In this study, we investigated whether 5HT has the potential to modulate small intestinal epithelial cell permeability, focusing on tight junction-associated proteins. METHODS: The differentiated Caco-2 cell monolayer on porous filters (Millicell) was used. Then, 5HT was added to the lower Millicell compartment for 7 days. Intestinal epithelial cell permeability was assessed by measuring the flux of paracellular permeability markers. We further assessed the expression of occludin in the 5HT-stimulated Caco-2 monolayer. RESULTS: We found that 5HT did not affect the viability of Caco-2 cells at concentrations up to 100 µM during the experimental period. Administration of 5HT to the basal side of Caco-2 cells increased the flux of 3H-labeled mannitol (182 Da) but did not increase that of FITC-dextran (4000 Da). Among the tight junction proteins, the expression of occludin was specifically decreased by stimulation with 5HT at a concentration of 100 µM. CONCLUSION: In conclusion, excessive 5HT in the basal side increased the permeability of intestinal epithelial cells via reduction of occludin expression.

3.
J Gastroenterol ; 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35059853

RESUMO

BACKGROUND: Direct-acting antiviral (DAA) therapy enables a high rate of sustained virologic response (SVR) in patients with hepatitis C virus associated cirrhosis. However, the impact of DAA therapy on liver-related events in patients with cirrhosis is unclear. METHODS: A total of 350 patients with compensated and decompensated cirrhosis administered DAA therapy at 29 Japanese hospitals were enrolled (Child-Pugh class A [CP-A]: 195 patients, CP-B: 131 patients and CP-C: 24 patients). RESULTS: The SVR rates of patients with CP-A, CP-B and CP-C were 96.9%, 93.1% and 83.3%, respectively (p = 0.006). Seventy patients developed hepatocellular carcinoma (HCC), and male sex, previous HCC treatment, platelet counts < 10.0 × 104/µl, alpha-fetoprotein levels ≥ 5.0 ng/ml and CP-C were identified as significant factors in the multivariate analysis. The cumulative HCC occurrence/recurrence rates at 1 year were 6.6%/45.2%. The cumulative rate of decompensated cirrhotic events requiring hospital admission at 1 year was 9.1%. In the multivariate analysis, CP-B and CP-C were identified as significant factors. During the median observation period of 14.9 months, 13 patients died and one patient received liver transplant. The overall survival rates at 1 year were 98.4% in patients with CP-A, 96.4% in those with CP-B and 85.6% in those with CP-C (CP-A vs. CP-B: p = 0.759, CP-A vs. CP-C: p = 0.001 and CP-B vs. CP-C: p = 0.005). CONCLUSIONS: HCC development and mortality in patients with CP-B were not different from those with CP-A. On the other hand, in patients with CP-C, the development of HCC and decompensated cirrhotic events requiring hospital admission, and death were frequent. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN000036150).

4.
Int J Mol Sci ; 22(24)2021 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-34948151

RESUMO

Chronic liver injury may result in hepatic fibrosis, which can progress to cirrhosis and eventually liver failure. There are no drugs that are specifically approved for treating hepatic fibrosis. The natural product honokiol (HNK), a bioactive compound extracted from Magnolia grandiflora, represents a potential tool in the management of hepatic fibrosis. Though HNK has been reported to exhibit suppressive effects in a rat fibrosis model, the mechanisms accounting for this suppression remain unclear. In the present study, the anti-fibrotic effects of HNK on the liver were evaluated in vivo and in vitro. In vivo studies utilized a murine liver fibrosis model, in which fibrosis is induced by treatment with carbon tetrachloride (CCl4). For in vitro studies, LX-2 human hepatic stellate cells (HSCs) were treated with HNK, and expression of markers of fibrosis, cell viability, the transforming growth factor-ß (TGF-ß1)/SMAD signaling pathway, and autophagy were analyzed. HNK was well tolerated and significantly attenuated CCl4-induced liver fibrosis in vivo. Moreover, HNK decreased HSC activation and collagen expression by downregulating the TGF-ß1/SMAD signaling pathway and autophagy. These results suggest that HNK is a new potential candidate for the treatment of hepatic fibrosis through suppressing both TGF-ß1/SMAD signaling and autophagy in HSCs.


Assuntos
Autofagia/efeitos dos fármacos , Compostos de Bifenilo/farmacologia , Intoxicação por Tetracloreto de Carbono , Células Estreladas do Fígado , Lignanas/farmacologia , Cirrose Hepática , Fígado/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Intoxicação por Tetracloreto de Carbono/metabolismo , Intoxicação por Tetracloreto de Carbono/patologia , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos
5.
Dig Dis Sci ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731360

RESUMO

BACKGROUND AND AIMS: Recurrence after cold snare polypectomy (CSP) sometimes occurs. We assessed the feasibility of repeat CSP for recurrence after CSP. METHODS: We retrospectively reviewed recurrent lesions after CSP which were resected by repeat CSP from 2016 to 2021 in our institution and analyzed clinical outcomes of repeat CSP, comparing those of non-recurrent 454 lesions receiving standard CSP in 2016 and follow-up colonoscopy. We also analyzed the recurrent rate among cases receiving follow-up in both groups. Indication of repeat CSP was lesions diagnosed as benign tumors of ≤ 10 mm. RESULTS: We analyzed 80 lesions receiving repeat CSP. The polyp size (mean ± standard deviation: SD) was 4.1 ± 2.3 mm (range 2-10 mm). The right-sided colon and non-polypoid morphology rates were 66.3% and 43.8%, respectively. Histopathological diagnosis was 66 adenomas, 12 sessile serrated lesions (SSLs), 1 SSL with dysplasia, and 1 high-grade dysplasia. The procedure time (min, mean ± SD) of repeat CSP was 0.9 ± 0.8. Regarding the comparison of repeat CSP/ standard CSP group, the en bloc resection and histopathological complete resection rates were 78.8%/ 98.0% (p < 0.001) and 43.8%/59.6% (p = 0.007) and the rates of perioperative hemorrhage requiring endoscopic clipping were 1.3%/ 1.0% (p = 0.646). There were no postoperative hemorrhage and perforation in both groups (p = 1.0). Among lesions receiving follow-up colonoscopy, the mean recurrence rates (number, median follow-up period: interquartile) of repeat CSP and standard CSP group were 2.0% (1/50, 12 months: 12-24) versus 0.7% (3/454, 12 months: 12-24) (p = 0.862). CONCLUSIONS: Repeat CSP for benign recurrent lesions after CSP was safe and feasible.

6.
Clin J Gastroenterol ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34727339

RESUMO

BACKGROUND: Hemophilia A causes a bleeding tendency due to the congenital absence of coagulation factor VIII or the production of antibodies against it. It is challenging to perform invasive procedures in patients with hemophilia A. Walled-off necrosis (WON) is a serious complication of acute pancreatitis. Recently, a new metallic stent has been used to drain WON. CLINICAL COURSE: We treated a 32-year-old man who developed WON due to acute pancreatitis and has severe congenital hemophilia A. Since conservative treatment was ineffective, he underwent endoscopic ultrasonography (EUS)-guided transgastric WON drainage using a new metallic stent Hot AXIOS System. The procedure was successful without any severe hemorrhagic complications. Before and after the procedure, his clotting factors were strictly monitored by a hemophilia specialist. CONCLUSION: EUS-guided pancreatic cyst drainage can be an effective option for WON in patients with severe congenital hemophilia, under adequate management.

7.
Front Oncol ; 11: 758549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796113

RESUMO

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. HCC cells consume large amounts of glutamine to survive, but can adapt to glutamine depletion in the presence of an exogenous asparagine. L-asparaginase (ASNase) converts glutamine and asparagine to glutamate and aspartate, respectively, and has been used to treat leukemia. Here we examined the effects of ASNase treatment on HCC cells and explored the potential impact of combining ASNase with the tyrosine kinase inhibitor lenvatinib (Len) for HCC treatment. Cell viability and death of HCC cell lines treated with either Len or ASNase alone or with Len and ASNase combined were determined. We assessed mRNA and protein expression levels of glutamine synthetase (GS) and asparagine synthetase (ASNS) by real-time quantitative PCR and immunoblotting. The antitumor effect of the combination therapy relative to Len or ASNase monotherapy was also evaluated in a xenograft tumor mouse model. ASNase treatment inhibited growth of SNU387 and SNU398 HCC cells, which have low GS and high ASNS expression levels, respectively, but did not clearly inhibit growth of the other cell lines. Len plus ASNase combination therapy synergistically inhibited proliferation and induced oxidative stress leading to cell death of some HCC cells lines. However, cell death of Huh7 cells, which express ASCT2, an important glutamine transporter for cancer cells, was not affected by the combination treatment. In a xenograft model, Len combined with ASNase significantly attenuated tumor development relative to mice treated with Len or ASNase alone. ASNase-mediated targeting of two amino acids, glutamine and asparagine, which are indispensable for HCC survival, induces oxidative stress and can be a novel cancer treatment option that exerts a synergistic effect when used in combination with Len.

8.
J Infect Chemother ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34799238

RESUMO

INTRODUCTION: The assessment of the risk of virus transmission through papers, such as postcards, is important. However, the stability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) on different types of papers is currently unknown. Investigation of the survival time of these viruses on different types of papers will provide insights into their risk of long-distance transport by postal items. METHODS: We evaluated the stability of SARS-CoV-2 and IAV, mixed with a culture medium, on the surface of postcards with various coatings, including plain paper (PP), inkjet paper (IP), and inkjet photo paper (IPP). The surface structure of each paper was microscopically assessed. RESULTS: The surface structures of PP, IP, and IPP varied greatly depending on the presence or absence, and type, of coat layer, regardless of the base material. IP and IPP surfaces were less conducive to virus survival than PP surfaces, because of the difference in surface shapes. The survival times of SARS-CoV-2 on each paper were approximately 59.8 (PP), 6.5 (IP), and 9.8 h (IPP), and significantly longer than those of IAV (10.3, 1.8, and 3.3 h, respectively). CONCLUSIONS: The risk of SARS-CoV-2 transmission via paper, such as postcards, is significantly higher than that of IAV transmission. While PP, IP, and IPP have the same base material, their surface structures differ, which affects viral stability. The IP and IPP surfaces are less suitable for virus survival. This study provides novel insights into the risks of viral transmission via paper.

9.
Environ Sci Technol ; 55(23): 16044-16055, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34841856

RESUMO

Lasting disinfection effects, that is, the residual disinfection effects (RDEs), of skin-coated disinfectants have rarely been considered for infection control owing to the challenges involved in the accurate evaluation of RDEs. In this study, we constructed a new skin evaluation model and determined the RDEs of existing disinfectants against viruses. Our results showed that ethanol and isopropanol had no RDE, whereas povidone-iodine, chlorhexidine gluconate, and benzalkonium chloride (BAC) exhibited RDEs, with 10% povidone-iodine and 0.2% BAC showing particularly strong RDEs. The RDE of 0.2% BAC was strong enough to reduce the median survival times of severe acute respiratory syndrome coronavirus-2, human coronavirus-OC43, and influenza virus from 670 to 5.2, 1300 to 12, and 120 to 4.2 min, respectively. Additionally, this strong RDE was maintained even 4 h after coating the skin. Clinical data also showed that the strong RDE of 0.2% BAC was maintained for more than 2 h. Thus, applying disinfectants with strong RDEs on the skin correlates with a reduction in virus survival time and appears to create a skin surface environment that is not conducive to virus survival. A prolonged reduction in virus survival decreases the contact transmission risk, thereby enabling stronger infection control.

10.
Esophagus ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34773554

RESUMO

BACKGROUND AND STUDY AIM: This study aimed to evaluate endoscopic findings using non-magnifying blue laser imaging (BLI) to determine the risk factors for metachronous esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: All consecutive patients who underwent endoscopic submucosal dissection (ESD) for primary superficial ESCC (SESCC) without a history of ESCC between January 2013 and January 2016 were enrolled. Three highly experienced endoscopists investigated seven endoscopic findings using non-magnifying BLI as follows: (1) a brownish area with unclear margin, (2) white flat deposits, (3) multiple foci of dilated vessels, (4) low capillary permeability, (5) multiple glycogenic acanthosis, (6) horizontal lines, and (7) a nonuniform color tone. Furthermore, Lugol-voiding lesions (LVLs) were graded according to the number of LVLs per endoscopic view (A, no lesions; B, 1-9 lesions; C, ≥ 10 lesions). RESULTS: A total of 102 SESCC patients who underwent ESD were included. Multivariate analyses showed that multiple foci of dilated vessels, low capillary permeability, and a nonuniform color tone were significantly associated with metachronous ESCC (hazard ratio [HR] 2.30; 95% confidence interval [CI] 1.01-5.46; P = 0.049, HR 5.25; 95% CI 1.86-15.01; P = 0.002 and HR 3.17; 95% CI 1.11-9.43; P = 0.032, respectively). The three-year cumulative incidence of metachronous ESCC was significantly higher in patients with low capillary permeability and a nonuniform color tone than in patients without these findings. (41.1% vs. 6.0%, 45.0% vs. 12.7%, respectively, P < 0.001 for both). CONCLUSION: BLI findings of multiple foci of dilated vessels, low capillary permeability, and a nonuniform color tone in the background esophageal mucosa were risk factors for patients with metachronous ESCC after ESD.

11.
Lab Invest ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732847

RESUMO

Fibroblast growth factor (FGF) 21 is an endocrine growth factor mainly secreted by the liver in response to a ketogenic diet and alcohol consumption. FGF21 signaling requires co-receptor ß-klotho (KLB) co-acting with FGF receptors, which has pleiotropic metabolic effects, including induced hepatic fatty acid oxidation and ketogenesis, in human and animal models of obesity. We examined the hepatocyte-specific enhancer/promoter of FGF21 expression plasmids in high-fat diet-fed mice for 12 weeks. Hydrodynamic injection for FGF21 delivery every 6 weeks sustained high circulating levels of FGF21, resulting in marked reductions in body weight, epididymal fat mass, insulin resistance, and liver steatosis. FGF21-induced lipolysis in the adipose tissue enabled the liver to be flooded with fat-derived FFAs. The hepatic expression of Glut2 and Bdh1 was upregulated, whereas that of gluconeogenesis-related genes, G6p and Pepck, and lipogenesis-related genes, Srebp-1 and Srebp-2, was significantly suppressed. FGF21 induced the phosphorylation of AMPK at Thr172 and Raptor at ser792 and suppressed that of mTOR at ser2448, which downregulated mTORC1 signaling and reduced IRS-1 phosphorylation at ser1101. Finally, in the skeletal muscle, FGF21 increased Glut4 and Mct2, a membrane protein that acts as a carrier for ketone bodies. Enzymes for ketone body catabolism (Scot) and citrate cycle (Cs, Idh3a), and a marker of regenerating muscle (myogenin) were also upregulated via increased KLB expression. Thus, FGF21-induced lipolysis was continuously induced by a high-fat diet and fat-derived FFAs might cause liver damage. Hepatic fatty acid oxidation and ketone body synthesis may act as hepatic FFAs' disposal mechanisms and contribute to improved liver steatosis. Liver-derived ketone bodies might be used for energy in the skeletal muscle. The potential FGF21-related crosstalk between the liver and extraliver organs is a promising strategy to prevent and treat metabolic syndrome-related nonalcoholic steatohepatitis.

12.
Free Radic Biol Med ; 177: 391-403, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34715296

RESUMO

Non-alcoholic steatohepatitis (NASH), a severe form of non-alcoholic fatty liver disease (NAFLD), can progress to cirrhosis, hepatocellular carcinoma (HCC), and hepatic failure/liver transplantation. Indeed, NASH will soon be the leading cause of HCC and liver transplantation. Lifestyle intervention represents the cornerstone of NASH treatment, but it is difficult to sustain. However, no pharmacotherapies for NASH have been approved. Oxidative stress has been implicated as one of the key factors in the pathogenesis of NASH. Systematic reviews with meta-analyses have confirmed that vitamin E reduces transaminase activities and may resolve NASH histopathology without improving hepatic fibrosis. However, vitamin E is not recommended for the treatment of NASH in diabetes, NAFLD without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis. Nevertheless, vitamin E supplementation may improve clinical outcomes in patients with NASH and bridging fibrosis or cirrhosis. Further studies are warranted to confirm such effects of vitamin E and that it would reduce overall mortality/morbidity without increasing the incidence of cardiovascular events. Future clinical trials of the use of vitamin E in combination with other anti-fibrotic agents may demonstrate an additive or synergistic therapeutic effect. Vitamin E is the first-line pharmacotherapy for NASH, according to the consensus of global academic societies.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34716962

RESUMO

BACKGROUND: Food allergy (FA) is a common disease in children; thus, a high level of safety is required for its prevention and treatment. Colonic regulatory T cells (Tregs) have been suggested to attenuate FA. We investigated the Treg-inducing ability and anti-FA effects of carotenoids, a pigment contained in vegetables and fruits. METHODS: C57BL/6N mice were fed a diet containing 0.01% (w/w) of lycopene, ß-carotene, astaxanthin or lutein for 4 weeks, and the population of colonic Tregs was assessed. Subsequently, to evaluate the Treg-inducing ability of lycopene, splenic naïve CD4+ T cells from BALB/c mice were cultured with anti-CD3/CD28 antibody, TGF-ß and lycopene, and the frequencies of Tregs were examined. The effect of 0.1% (w/w) lycopene containing diet on FA was investigated in OVA-induced FA model BALB/c mice. RESULTS: In screening, only lycopene significantly increased the frequency and number of colonic Tregs. Lycopene also increased Treg differentiation in splenic naïve CD4+ T cells. In FA mice, lycopene feeding significantly increased the number of colonic Tregs and attenuated allergic symptoms. The expression levels of IL-4, IL-9 and IL-13 mRNA in colonic mucosa were also significantly reduced by lycopene. IL-9 is known to induce proliferation of mast cells, and we found that lycopene feeding significantly reduced the number of mast cells in the colonic mucosa of FA mice. CONCLUSION: Our results suggest that lycopene, a carotenoid present in many common foods on the market, may have the potential to induce colonic Tregs and suppress FA symptoms.

14.
Hepatol Res ; 51(10): 1013-1025, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34533266

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non-viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow-up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary pro- vides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan.

15.
J Gastroenterol ; 56(11): 951-963, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34533632

RESUMO

Nonalcoholic fatty liver disease (NAFLD) has become a serious public health issue not only in Western countries but also in Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease that often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma (HCC). While a definite diagnosis of NASH requires liver biopsy to confirm the presence of hepatocyte ballooning, hepatic fibrosis is the most important prognostic factor in NAFLD. With so many NAFLD patients, it is essential to have an effective screening method for NAFLD with hepatic fibrosis. As HCC with non-viral liver disease has increased markedly in Japan, effective screening and surveillance of HCC are also urgently needed. The most common death etiology in NAFLD patients is cardiovascular disease (CVD) event. Gastroenterologists must, therefore, pay close attention to CVD when examining NAFLD patients. In the updated guidelines, we propose screening and follow-up methods for hepatic fibrosis, HCC, and CVD in NAFLD patients. Several drug trials are ongoing for NAFLD/NASH therapy, however, there is currently no specific drug therapy for NAFLD/NASH. In addition to vitamin E and thiazolidinedione derivatives, recent trials have focused on sodium glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, and effective therapies are expected to be developed. These practical guidelines for NAFLD/NASH were established by the Japanese Society of Gastroenterology in conjunction with the Japan Society of Hepatology. Clinical evidence reported internationally between 1983 and October 2018 was collected, and each clinical and background question was evaluated using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. This English summary provides the core essentials of these clinical practice guidelines, which include the definition and concept, screening systems for hepatic fibrosis, HCC and CVD, and current therapies for NAFLD/NASH in Japan.

16.
J Mech Behav Biomed Mater ; 124: 104816, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34509904

RESUMO

As a viscous high-performance submucosal injection material (SIM) used in endoscopic submucosal dissection (ESD), sodium alginate-based SIM (SA-SIM) was recently introduced as high-performance SIM equivalent to sodium hyaluronate-based SIM (HA-SIM) in Japan. However, a comprehensive, detailed comparison of SA and HA is yet to be performed. In this study, we precisely measured the viscoelastic properties, submucosal elevation height (SEH), and injection pressure (IP). Furthermore, we compared the outcomes of ESD using an ex vivo ESD model. There was no significant difference in SEHs between HA-SIM and SA-SIM at all post-injection times, and the IP of the SA-SIM injection was significantly higher than that of the HA-SIM injection in all conditions (P < 0.0001). The viscosity at high shear rates of SA-SIM was higher than that of HA-SIM; this result was consistent with SEH/IP measurement results. No significant difference was observed in ESD procedure time and total volume of injected SIM between HA-SIM and SA-SIM (18.1 ± 6.7 and 17.8 ± 6.0 min, P = 0.8987; 13.3 ± 5.3 and 11.6 ± 5.9 ml, P = 0.4658, respectively). Although SA-SIM was slightly more difficult to inject than HA-SIM, there was no significant difference in performance between the materials. Thus, this basic study demonstrated that SA-SIM can be used for endoscopic treatment as well as HA-SIM, and supported previous clinical research data.


Assuntos
Alginatos , Ácido Hialurônico , Endoscopia , Injeções , Reologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-34477242

RESUMO

BACKGROUND AND AIM: Efficient intestinal wound healing is essential for good prognoses of ulcerative colitis (UC). Although bile acids and the transmembrane G-protein-coupled receptor (TGR) 5 have been reported to affect wound healing in intestinal epithelial cells, the detailed underlying mechanisms are unclear. Here, we investigated the role of TGR5 in wound healing in the context of colonic epithelial cells in the presence of bile acids. METHODS: The expression of TGR5 in the colonic epithelium of both a dextran sulfate sodium (DSS)-induced colitis mouse model (recovery phase), and UC patients in clinical remission, was evaluated. Young adult mouse colonic epithelial (YAMC) cells were then used to evaluate wound healing after treatment with deoxycholic acid (DCA); TGR5 was silenced in YAMC cells via shRNA-transfection, and a wound-healing assay in the presence of DCA was performed. Furthermore, we investigated the role of the activation of AKT in the context of wound healing. RESULTS: The expression of TGR5 was decreased in the colonic epithelium of both mice with DSS-induced colitis and UC patients. Additionally, DCA significantly delayed wound healing in YAMC cells but not in TGR5 silenced ones. Of note, the DCA-induced activation of AKT signaling in YAMC cells was inhibited by TGR5 silencing, and AKT inhibitors prevented the wound healing delay induced by DCA. CONCLUSIONS: Overall, we show that DCA delays wound healing in the context of colonic epithelial cells through AKT activation. These results may support the development of new therapeutic approaches for epithelial regeneration in UC.

19.
Gastric Cancer ; 24(6): 1365-1369, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34379230

RESUMO

Recent advances in magnifying endoscopy with narrow-band imaging/blue laser imaging have aided in the diagnosis of gastrointestinal lesions. However, it requires knowledge of the relationship between magnifying endoscopic and histopathological images. We propose a novel method which makes possible a complete correspondence between magnifying endoscopic and histopathological images at the single glandular duct level. The KOTO method II enables three-dimensional visualization of the correlation between the endoscopic surface pattern of the mucosa and histopathological images. This method may be helpful in the development of diagnosis using magnifying endoscopy.

20.
Int J Colorectal Dis ; 36(10): 2237-2245, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34406437

RESUMO

OBJECTIVES: Recently, CAD EYE (Fujifilm, Tokyo, Japan), an artificial intelligence for the lesion recognition (CADe) and the optical diagnosis (CADx) of colorectal polyps, was released. We evaluated the function of CADe and CADx of CAD EYE. METHODS: In this single-center retrospective study, we examined consecutive polyps ≤ 10 mm detected from March to April 2021 to determine whether CAD EYE could recognize them live with both normal- and high-speed observation using white-light imaging (WLI) and linked-color imaging (LCI). We then examined whether the polyps were neoplastic or hyperplastic live with magnified or non-magnified blue-laser imaging (BLI-LASER) or blue-light imaging (BLI-LED) under CAD EYE, comparing the retrospective evaluations with 5 experts and 5 trainees using still images. All polyps were histopathologically examined. RESULTS: We analyzed 100 polyps (mean size 3.9 ± 2.6 mm; 55 neoplastic and 45 hyperplastic lesions) in 25 patients. Regarding CADe, the respective detection rates of CAD EYE with normal- and high-speed observation were 85.0% and 67.0% for WLI (p = 0.002) and 89.0% and 75.0% for LCI (p = 0.009). Regarding CADx for differentiating neoplastic and hyperplastic lesions, the diagnostic accuracy values of CAD EYE with non-magnified and magnified BLI-LASER/LED were 88.8% and 87.8%. Regarding magnified BLI-LASER/LED, the diagnostic accuracy value of CAD EYE was not significantly different from that of experts (92.0%, p = 0.17), but that of trainees (79.0%, p = 0.04). We also found no significant differences in CADe or CADx between LED (53 lesions) and LASER (47 lesions). CONCLUSIONS: CAD EYE was a helpful tool for CADe and CADx in clinical practice.


Assuntos
Pólipos do Colo , Inteligência Artificial , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Humanos , Imagem de Banda Estreita , Estudos Retrospectivos
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