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1.
Eur J Clin Pharmacol ; 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34085115

RESUMO

BACKGROUND AND AIM: Low-dose aspirin (LDA) administration prevents cerebral infarction and myocardial infarction, but many studies found an association with mucosal injury. Proton-pump inhibitors (PPIs) can prevent gastric and duodenal mucosal damage, but they may exacerbate small-intestinal mucosal injury by altering the microbiota. We aimed to assess the effect of PPIs on the intestinal flora of LDA users. METHODS: Thirty-two recruited patients, who received LDA (100 mg/day) but did not take PPIs, were divided into 15 patients additionally receiving esomeprazole (20 mg/day) and 17 patients additionally receiving vonoprazan (10 mg/day). On days 0, 30, 90, and 180, the microbiota of each patient was examined by terminal restriction fragment length polymorphism analysis, and the serum gastrin, hemoglobin, and hematocrit levels were measured. RESULTS: Additional PPI administration increased the proportion of Lactobacillales in the microbiota of LDA users. This trend was more prevalent in the vonoprazan group (p < 0.0001) than in the esomeprazole group (p = 0.0024). The Lactobacillales proportion was positively correlated with the gastrin level (r = 0.5354). No significant hemoglobin or hematocrit level reduction was observed in subjects receiving LDA with additional PPI. CONCLUSIONS: Additional PPI administration increased the Lactobacillales proportion in the microbiota of LDA users. The positive correlation between the gastrin level and the proportion of Lactobacillales suggested that the change in the intestinal flora was associated with the degree of suppression of gastric acid secretion. Additional oral PPI did not significantly promote anemia, but the risk of causing PPI-induced small-intestinal mucosal injury in LDA users should be considered.

2.
Anticancer Res ; 41(5): 2227-2237, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952449

RESUMO

Lifestyle-related factors play a major role in the development of cancer. In recent years, obesity has become widespread in the world and has attracted attention not only as a cause of diabetes mellitus and atherosclerotic diseases but also as a factor in carcinogenesis. In Japan, the number of obesity-related malignancies has been increasing with the westernization of lifestyle. On the other hand, it is estimated that there are more than 10 million nonalcoholic fatty liver disease (NAFLD) patients in Japan. NAFLD is classified into simple fatty liver and nonalcoholic steatohepatitis (NASH), and 10-20% of NASH patients will progress to liver cirrhosis and 2-3% of them will develop hepatocellular carcinoma (HCC) per year. Research interest in metabolism-associated liver cancer has been increasing in recent years. Here in this review, we will comprehensively summarize the current knowledge with regard to the relationship between obesity and HCC in Japan.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Neoplasias Hepáticas/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/epidemiologia , Diabetes Mellitus/epidemiologia , Humanos , Incidência , Japão/epidemiologia , Estilo de Vida , Prevalência
4.
Artigo em Inglês | MEDLINE | ID: mdl-34021720

RESUMO

BACKGROUND AND AIM: Recombinant thrombomodulin (rhTM) is potentially effective in the treatment of disseminated intravascular coagulation (DIC). Several studies related to drugs for the treatment of acute cholangitis have shown negative results in improvement of overall survival (OS) with rhTM. The aim of this multicenter study was to evaluate the clinical effectiveness of rhTM in patients with acute cholangitis and sepsis-induced DIC who underwent biliary drainage. METHODS: A total of 284 consecutive patients, who were complicated with sepsis-induced DIC due to severe acute cholangitis, were included (rhTM group, n = 173; non-rhTM, n = 111) in this study. The primary outcome was the DIC resolution rate at 7 days after starting treatment. The 28-day survival rate was secondarily evaluated. RESULTS: DIC scores in the rhTM group improved significantly compared with the non-rhTM group on day 7 (P = .020). According to multivariate analysis, etiology of cholangitis (malignant, HR 2.28), rhTM (non-administration, HR 4.13), and DIC score (≥5, HR 2.46) were significant factors associated with failed DIC resolution on day 7. Propensity score matching created 103 matched pairs. Survival rate at day 28 was significantly higher in rhTM group (94.3%) compared with non-rhTM group (82.6%; P = .048) after propensity score matching. rhTM (non-administration, HR 2.870), DIC score (≥5, HR 2.751), and APACHE II score (≥20, HR 9.310) were significant factors associated with decreasing survival rate at day 28. CONCLUSION: In conclusion, rhTM seemed to improve patient survival, but future studies should only include patients with benign or malignant disease and should be performed according to APACHE II scores.

5.
Clin Endosc ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33896154

RESUMO

Endoscopic ultrasound-guided biliary drainage has been developed as an alternative method for biliary drainage. EUS-guided hepaticogastrostomy (EUS-HGS) can be attempted via the trans-gastric route. These procedures are technically complex for two reasons. First, puncture of the intrahepatic bile duct via the trans-gastric route can be more difficult than that by other approaches because of the small diameter of the target site, and guidewire insertion or manipulation is challenging during EUS-HGS. Second, critical adverse events, such as stent migration into the abdominal cavity, could occur because of the greater mobility of the stomach compared to the duodenum. Therefore, endoscopists should be cautious when performing EUS-HGS. An advantage of EUS-HGS is that it can be performed in patients with complications such as duodenal bulb obstruction or surgically altered anatomy. Recent advances in technique and improvements in devices and stents for EUS-HGS have shown promise for improving the technical success rate of EUS-HGS and reducing the rate of adverse events. However, endoscopists should remain aware of the possibility of critical adverse events such as stent migration.

6.
J Leukoc Biol ; 109(5): 943-952, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33899953

RESUMO

Gut-associated sepsis is a major problem in patients undergoing abdominal radiation therapy; the majority of pathogens causing this type of sepsis are translocated from the gut microbiota. While treating sepsis, bacterial clearance must be achieved to ensure patient survival, and the hepatic immune response is responsible for this process. In particular, Kupffer cells play a crucial role in the hepatic immune response against infectious agents. Recently, two populations of Kupffer cells have been described: liver-resident macrophages (Mϕ) (F4/80+ CD11b- CD68+ cells) and hepatic Mϕ derived from circulating monocytes (F4/80+ CD11b+ CD68- cells). We examined the properties of both types of hepatic Mϕ obtained from irradiated and normal mice and their role in sepsis. Hepatic F4/80+ CD11b- CD68+ cells from both normal and irradiated mice did not show any antibacterial activity. However, F4/80+ CD11b+ CD68- cells from normal mice behaved as effector cells against sepsis by Enterococcus faecalis, although those from irradiated mice lost this ability. Moreover, hepatic F4/80+ CD11b+ CD68- cells from normal infected mice were shown to be IL-12+ IL-10- CD206- CCL1- (considered M1Mϕ), and hepatic F4/80+ CD11b- CD68+ cells from the same mice were shown to be IL-12- IL-10+ CD206+ CCL1- (considered M2aMϕ). When normal mice were exposed to radiation, hepatic F4/80+ CD11b+ CD68- cells altered their phenotype to IL-12- IL-10+ CD206- CCL1+ (considered M2bMϕ), independent of infection, but hepatic F4/80+ CD11b- CD68+ cells remained IL-12- IL-10+ CD206+ CCL1- (M2aMϕ). In addition, hepatic F4/80+ CD11b+ CD68- cells from irradiated mice acquired antibacterial activity upon treatment with CCL1 antisense oligodeoxynucleotides. Therefore, the characteristics of hepatic F4/80+ CD11b+ CD68- cells play a key role in the antibacterial response against gut-associated sepsis.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antígeno CD11b/metabolismo , Enterococcus faecalis/fisiologia , Fígado/metabolismo , Sepse/imunologia , Sepse/microbiologia , Irradiação Corporal Total , Animais , Polaridade Celular/efeitos dos fármacos , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Oligonucleotídeos Antissenso/farmacologia , Sepse/patologia
9.
Ther Apher Dial ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33885215

RESUMO

Several adsorptive type devices for ulcerative colitis are used for the induction of remission in patients with active severe disease worldwide. In 2020, the novel apheresis device Immunopure for ulcerative colitis was launched in Japan. Immunopure, like the polyethylene terephthalate column, uses polyarylate, a type of polyester resin, as the adsorbent. Similar to the cellulose acetate column, Immunopure is filled with adsorbent beads and expected to provide ease of use, with minimal risk of column clogging. Immunopure adsorbs leukocytes and platelets, especially activated platelets and platelet-leukocyte aggregates. In this article, the capability of Immunopure is evaluated from clinical perspective based on a clinical trial in Japan/Europe. As a result, Immunopure is comparable to other products in clinical effectiveness and indicated for the treatment of patients with refractory moderate ulcerative colitis, making it highly useful in clinical practice.

11.
Asian Pac J Cancer Prev ; 22(3): 871-877, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773552

RESUMO

BACKGROUND: Fosaprepitant, an NK1 receptor antagonist, inhibits and induces cytochrome P450 3A4 (CYP3A4) as its substrate. Contrarily dexamethasone is metabolized by CYP3A4. Therefore, in combination therapy wherein both agents interact with each other, it is recommended that the dexamethasone dose be reduced in the first two days. Thus far, there are only a few studies on the optimum dose of dexamethasone after day 3. Thus, we aimed to determine the pharmacokinetics of dexamethasone on day3 when administered together with fosaprepitant and investigate the dose-dependent differences in its antiemetic effect in patients with cancer. METHODS: Twelve patients with esophageal, stomach, or lung cancer received primary highly emetogenic chemotherapy (HEC). We intravenously administered 9.9 mg and 6.6 mg of dexamethasone on days 1 and 2, respectively, and 6.6 mg or 13.2 mg on day 3 together with the administration of 150 mg fosaprepitant and 0.75 mg palonosetron. We assessed the pharmacokinetics of dexamethasone on day 3 by dose and examined the dose-dependent antiemetic effect. RESULTS: No differences were observed in the time-to-maximum concentration and blood half-life of dexamethasone between patient groups that received dexamethasone at doses of 6.6 mg and 13.2 mg. In contrast, the area under the blood concentration-time curve and the maximum concentration of dexamethasone correlated with its dose. Moreover, the blood dexamethasone concentration on day 3 increased by twofold after the administration of a higher dose than after a lower dose. The severity of nausea in the delayed phase significantly decreased in a dose-dependent manner. CONCLUSION: Administration of a higher dexamethasone dose on day 3 improved the antiemetic effect of the combined regimen in patients with cancer who underwent HEC.
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12.
Dig Endosc ; 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33772880

RESUMO

The Japan Gastroenterological Endoscopy Society held four serial symposia between 2019 and 2020 on the state-of-the-art of issues related to upper GI inflammatory diseases. This review discusses some of the topics addressed in these symposia. The papers regarding nonerosive reflux disease, recent improvements in intraesophageal pH-impedance monitoring and endoscopic diagnosis using image-enhanced endoscopy have been published. Many publications have addressed its usefulness in endoscopic treatment of gastroesophageal reflux disease such as anti-reflux mucosectomy. In the management of eosinophilic esophagitis, since the symptoms are subjective, objective indicators have been sought, and ultrasonography and high-resolution manometry may be useful tools for evaluation. The natural course of this condition, especially of asymptomatic cases, is not well clarified. Some newly developed anti-acid or anti-inflammatory medicines are now under investigation. With regard to autoimmune gastritis, because of widespread medical examinations, diagnosis of asymptomatic cases has been increasing. Recently, its endoscopic characteristics have become clear and the natural history of these conditions is being elucidated. The Kyoto Classification of Gastritis has been reported to be useful not only for Helicobacter pylori diagnosis but also for identification of risks of gastric cancer. Its usefulness is now recognized in Asia and Europe.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33529462

RESUMO

EUS-guided biliary drainage (EUS-BD) has been indicated for benign biliary strictures. However, the intrahepatic bile duct is sometimes much narrower in benign biliary strictures. In this situation, puncture of the intrahepatic bile duct using a 19-G needle is sometimes challenging. Several reports have described attempts at EUS-BD using a 22-G needle, but fistula dilation with a 22-G needle is challenging because the 0.018-inch guidewire is not stiff enough to perform dilatation. Recently, a thin mechanical dilator has become available. After its insertion into the biliary tract, the 0.018-inch guidewire can be replaced with a 0.025-inch guidewire. We herein describe the technical procedure of EUS-guided hepaticogastrostomy using a 22-G needle with a thin mechanical dilator.

16.
In Vivo ; 35(2): 977-985, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622892

RESUMO

BACKGROUND/AIM: Neoadjuvant chemotherapy without radiation (NAC) shows favorable outcomes for locally advanced rectal cancer (LARC), however, the optimal regimen has not been determined yet. This study aimed to compare the efficacy and safety of oxaliplatin, irinotecan, folinic acid, and 5-fluorouracil (mFOLFOXIRI) with capecitabine/S-1 and oxaliplatin (XELOX/SOX) in rectal cancer patients. PATIENTS AND METHODS: We retrospectively examined patients with LARC who received mFOLFOXIRI or XELOX/SOX as NAC. RESULTS: Between January 2015 and July 2019, 49 patients received mFOLFOXIRI and 37 patients received XELOX/SOX. The pathological response rates (over two-thirds affected tumor area) were 36.7% and 40.5% in the mFOLFOXIRI and XELOX/SOX groups, respectively. Grade 3/4 neutropenia was experienced by 45.0% of the patients in the mFOLFOXIRI group and 8.0% in the XEOX/SOX group. CONCLUSION: Although pathological responses were comparable between two groups, mFOLFOXIRI tended to be more toxic compared to XELOX/SOX as NAC for LARC.

17.
Intern Med ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33456043

RESUMO

Objective Although colorectal polyps (CPs) can be observed with colon capsule endoscopy (CCE), it is difficult to determine the type of polyp using CCE. The objective of this study was to differentiate adenomatous polyps (APs) from hyperplastic polyps (HPs) with CCE. Methods In this single-center retrospective study, an analysis was conducted on the same CPs with both CCE and colonoscopy (CS) and histopathologically diagnosed as AP or HP. The color difference (ΔE) between the polyp surface and the surrounding mucosa was calculated using the CIELAB color space method on white light (WL), flexible spectral imaging color enhancement (FICE), and blue mode (BM) CP images. We investigated the ability of the ratio of the color differences (ΔE') to differentiate between APs and HPs. Results The size of all 51 polyps (34 APs, 17 HPs) was 7.5±4.6 mm with CCE and 7.3±4.2 mm with CS, and this difference was not significant (p=0.28). The FICEΔE' of APs was 3.3±1.8, which was significantly higher than the FICEΔE' of HPs (1.3±0.6; p<0.001). A receiver operating characteristic analysis showed that FICEΔE' was useful for differentiating between APs and HPs, with an area under the curve of 0.928 (95% confidence interval, 0.843-1). The sensitivity was 91.2%, and the specificity was 88.2% with a cut-off value of 1.758. Conclusion Using FICE on CCE images of CPs and applying the CIELAB color space method, we were able to differentiate between APs and HPs with high accuracy. This method has the potential to reduce unnecessary CS procedures.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33471258

RESUMO

BACKGROUND: Hepatectomy is currently recommended as the most reliable treatment for hepatocellular carcinoma. However, the association between the choice of treatment for recurrence and the timing of recurrence remains controversial. METHODS: Three-hundred thirty-nine patients who underwent hepatectomy were retrospectively analyzed using a propensity score matching analysis for the risk factors and outcomes for early recurrences within 6 months. The remnant liver volumes and laboratory data were measured postoperatively using multidetector computed tomography on days 7 and months 1, 2, and 5 after surgery. The Student's t test and chi-square test, the likelihood-ratio test, Fisher's exact test, Mann-Whitney U test, or Wilcoxon signed-rank test were used in the statistical analyses. RESULTS: Early recurrence developed in 41/312 patients (13.1%). Vascular invasion and non-curative resection were independent risk factors for the occurrence of early recurrence (P < 0.001 and < 0.001, respectively). Patients with early recurrence had a poorer prognosis than patients who developed later recurrences (P < 0.001). Patients who underwent surgery or other local treatments had better outcomes (P < 0.001). The changes in remnant liver volumes and laboratory data after postoperative month 2 were not significantly different between the two groups. CONCLUSION: Patients with early recurrence within 6 months had a poorer prognosis than patients who developed a later recurrence. However, patients who underwent repeat hepatectomy for recurrences had a better prognosis than did those who underwent other treatments, with good prospects for long-term survival.

19.
Gastrointest Endosc ; 93(2): 537-538, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33478675
20.
Artigo em Inglês | MEDLINE | ID: mdl-33283470

RESUMO

Endoscopic-ultrasound-guided gallbladder drainage (EUS-GBD) is increasingly attempted for acute cholecystitis. Recently, the lumen-apposing metal stent (LAMS) has been developed. However, in many countries, LAMSs are not indicated for EUS-GBD. Several studies on EUS-GBD using a self-expandable metal stent (SEMS) have been reported, although braided SEMSs have the risk of stent migration during stent deployment.

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