Summary
Background
Atrophic gastritis and intestinal metaplasia are premalignant conditions for gastric cancer. Their reversibility by Helicobacter pylori eradication remains controversial.
Aim
To ...evaluate the reversibility of atrophic gastritis and intestinal metaplasia by H. pylori eradication with long‐term follow‐up.
Methods
598 subjects were prospectively enrolled and followed for up to 10 years. They were categorised as H. pylori‐negative (n = 65), H. pylori non‐eradicated (n = 91), and H. pylori‐eradicated (n = 442). Histological assessment was performed for antrum and corpus by Sydney classification.
Results
Histological follow‐up was performed regularly at 1, 2, 3‐4 and ≥5 years, with mean follow‐up of 1.07 ± 0.21, 2.29 ± 0.83, 3.93 ± 1.02, and 6.45 ± 1.28 years, respectively. Atrophic gastritis in antrum and corpus gradually and significantly (both P < .05 for all timepoints) improved only in the H. pylori‐eradicated group compared to that at baseline. Significant difference in atrophic gastritis between H. pylori‐eradicated and H. pylori‐negative groups disappeared from 1‐year follow‐up. Similarly, intestinal metaplasia in antrum and corpus improved significantly (both P < .05 for all timepoints) only in the H. pylori‐eradicated group in comparison with that at baseline. Significant difference in intestinal metaplasia between H. pylori‐eradicated and H. pylori‐negative groups disappeared from ≥5 years of follow‐up in the antrum and from 3 years of follow‐up in the corpus.
Conclusion
H. pylori eradication may be a preventative strategy for intestinal‐type gastric cancer by regression of atrophic gastritis and intestinal metaplasia.
Linked ContentThis article is linked to Genta and Kim and Hwang papers. To view these articles visit https://doi.org/10.1111/apt.14491 and https://doi.org/10.1111/apt.14524.
Summary
Background
Rifaximin might decrease the risk of portal hypertension‐related complications by controlling small intestinal bacterial overgrowth.
Aim
To evaluate whether rifaximin was ...associated with the risk of death and cirrhotic complications.
Methods
We conducted a retrospective study that included 1042 patients experiencing hepatic encephalopathy (HE): 421 patients without hepatocellular carcinoma (HCC; the non‐HCC cohort) and 621 patients with HCC (the HCC cohort). The primary endpoint was overall survival and secondary endpoints were recurrence of HE and the development of spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS) and variceal bleeding.
Results
In the non‐HCC cohort, 145 patients received rifaximin plus lactulose (the rifaximin group) and 276 patients received lactulose alone (the control group). The multivariate analysis revealed that rifaximin was significantly associated with lower risk of death (adjusted hazard ratio aHR, 0.697; P = .024) and reduced the risk of recurrent HE (aHR, 0.452; P < .001), SBP (aHR, 0.210; P < .001) and variceal bleeding (aHR, 0.425; P = .011) but not HRS (aHR, 0.598; P = .08). In the HCC cohort, 173 patients received rifaximin plus lactulose and 448 patients received lactulose. Rifaximin was not associated with the risk of death (aHR, 1.177; P = .121). Rifaximin was associated with lower risk of SBP (aHR, 0.323; P < .001) but not with variceal bleeding (aHR, 0.660; P = .104) or recurrent HE (aHR, 0.689; P = .057). The risk of Clostridium difficile‐associated diarrhoea was not different between the groups (aHR, 0.028; P = .338).
Conclusions
In patients without HCC, rifaximin treatment was significantly associated with prolonged overall survival and reduced risks of spontaneous bacterial peritonitis, variceal bleeding and recurrent hepatic encephalopathy.
Linked Content
This article is linked to Juang, Kang et al, Wang et al, and Borentain et al papers. To view these papers visit https://doi.org/10.1111/apt.14325, https://doi.org/10.1111/apt.14343, https://doi.org/10.1111/apt.14353 and https://doi.org/10.1111/apt.14516.
Exosomes are enclosed compartments that are released from cells and that can transport biological contents for the purpose of intercellular communications. Research into exosomes is hindered by their ...rarity. In this article, we introduce a device that uses centrifugal force and a filter with micro-sized pores to generate a large quantity of cell-derived nanovesicles. The device has a simple polycarbonate structure to hold the filter, and operates in a common centrifuge. Nanovesicles are similar in size and membrane structure to exosomes. Nanovesicles contain intracellular RNAs ranging from microRNA to mRNA, intracellular proteins, and plasma membrane proteins. The quantity of nanovesicles produced using the device is 250 times the quantity of naturally secreted exosomes. Also, the quantity of intracellular contents in nanovesicles is twice that in exosomes. Nanovesicles generated from murine embryonic stem cells can transfer RNAs to target cells. Therefore, this novel device and the nanovesicles that it generates are expected to be used in exosome-related research, and can be applied in various applications such as drug delivery and cell-based therapy.
Aims/hypothesis The aim of this study was to confirm a link between mitochondrial dysfunction and type 2 diabetes. Materials and methods Cellular levels of mitochondrial proteins, cellular ...mitochondrial DNA content, and mitochondrial function and morphology were assessed by MitoTracker staining and electron microscopy, in white adipose tissue of 12-week-old male wild-type, obese (ob/ob), and diabetic (db/db) mice. Results Levels of mitochondrial proteins were found to be very similar in the livers and muscles of all the mice studied. However, levels were greatly decreased in the adipocytes of db/db mice, but not in those of the wild-type and ob/ob mice. Levels of mitochondrial DNA were also found to be considerably reduced in the adipocytes of db/db mice. MitoTracker staining and under electron microscopy revealed that the number of mitochondria was reduced in adipocytes of db/db mice. Respiration and fatty acid oxidation studies indicated mitochondrial dysfunction in adipocytes of db/db mice. Interestingly, there was an increase in mitochondria and mitochondrial protein production in adipocytes of db/db mice treated with rosiglitazone, an agent that enhances insulin sensitivity. Conclusions/interpretation Taken together, these data indicate that mitochondrial loss in adipose tissue is correlated with the development of type 2 diabetes.
We conducted a population-based retrospective cohort study to investigate the influence of hospital volume, delay of surgery, and both together on the long-term survival of postoperative cancer ...patients.
Using information from the Korea Central Cancer Registry from 2001 through 2005 and the National Health Insurance claim database, we determined survival for 147 682 patients who underwent definitive surgery for any of six cancers.
Regardless of cancer site, surgical patients in low- to medium-volume hospitals showed significantly worse survival adjusted hazard ratio (aHR) = 1.36–1.86 than those in high-volume hospitals in multivariable analyses. Among the latter, treatment delays > 1 month were not associated with worse survival for stomach, colon, pancreatic, or lung cancer but were for rectal aHR = 1.28; 95% confidence interval (CI), 1.17–1.40 and breast (aHR = 1.59; 95% CI, 1.37–1.84) cancer. For patients in low- to medium-volume hospitals, treatment delay was associated with worse survival for all types of cancer (aHR = 1.78–3.81).
Our findings suggest that the effect of hospital volume and surgical treatment delay on overall survival of cancer patients should be considered in formulating or revising national health policy.
We hypothesized that the pharmacodynamic (PD) characteristics of metformin would change with inhibition of the multidrug and toxin extrusion (MATE) transporter, which mediates renal elimination of ...metformin. Twenty healthy male subjects received two doses (750/500 mg) of metformin, with and without 50 mg of pyrimethamine (a potent MATE inhibitor), with 1 week of washout in between each dose. The PD characteristics of metformin were assessed using oral glucose tolerance tests (OGTTs) before and after the metformin dose. Metformin concentrations in plasma and urine were determined using liquid chromatography‐electrospray ionization‐tandem mass spectrometry. When metformin was co‐administered with pyrimethamine, its area under the concentration–time curve from 0 to 12 h was 2.58‐fold greater (p < 0.05), whereas the antihyperglycaemic effects of metformin were decreased. The mean differences (90% confidence interval) in mean and maximum serum glucose concentrations and in 2‐h‐post‐OGTT serum glucose concentration were −0.6 (−1, −0.2), −0.9 (−1.6, −0.3) and −0.5 (−1.1, 0.1) mmol/l, respectively. These findings indicate that the response to metformin is not only related to the plasma exposure of metformin but is also related to other factors, such as inhibition of uptake transporters and the gastrointestinal‐based pharmacology of metformin.
Abstract Background Tacrolimus is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), encoded by the CYP3A and ATP-binding cassette subfamily B member 1 (ABCB1) genes, respectively. ...This study was aimed to investigate the impact of CYP3A and ABCB1 polymorphisms on the tacrolimus pharmacokinetics and clinical outcomes in Korean renal transplant recipients. Methods We analyzed data from a cohort of 70 renal transplant recipients receiving tacrolimus. CYP3A4*4, CYP3A4*5, CYP3A4*18, CYP3A5*3, ABCB1 C1236>T, ABCB1 G2677>T/A, and ABCB1 C3435>T polymorphisms were genotyped and correlated to dose-adjusted tacrolimus trough concentration at months 1, 3, 6, and 12 after transplantation. Results Patients with the CYP3A5*3 alleles showed higher dose-adjusted tacrolimus concentrations for 12 months and higher trough levels until 6 months after transplantation. ABCB1 polymorphisms and haplotypes were not associated with tacrolimus concentrations. In a multivariate analysis, the presence of ≥1 CYP3A5*3 allele was a significant independent variable affecting dose-adjusted tacrolimus concentrations. Glomerular filtration rate, acute rejection, opportunistic infection, and graft survival were not affected by CYP3A5 polymorphisms. Calcineurin inhibitor toxicity, which showed higher tendency in patients with CYP3A5*1 alleles, might be associated with higher tacrolimus dose per kilogram. Conclusions The CYP3A5 genotype is a major factor in determining the dose requirement of tacrolimus, and genotyping may be of value in individualization of immunosuppressive therapy of renal transplant patients.
Treatment of cirrhotic patients with spontaneous peritonitis using antibiotics occasionally fails. Fungal infections may be one of the causes of antibiotic treatment failure in such patients. In this ...study we evaluated the clinical significance and characteristics of spontaneous fungal peritonitis (SFP). Consecutive cirrhotic patients with spontaneous peritonitis treated between 2000 and 2005 at a tertiary care center in Seoul, Korea, were included. We analyzed the clinical characteristics and the prognosis of SFP patients compared with patients with spontaneous bacterial peritonitis (SBP). During the study period 416 patients developed spontaneous peritonitis and 15 (3.6 %) had SFP. Compared with patients with SBP, nosocomial peritonitis (peritonitis that developed after hospitalization for >72 h) was more common and the Child–Pugh score was higher in SFP patients (both,
P
< 0.01). Ten patients were infected with
Candida
spp. (
C. albicans
, 8;
C. tropicalis
, 1;
C. glabrata
, 1), and 5 with
Cryptococcus neoformans
. Eleven patients were co-infected with bacteria that were susceptible to the antibiotics administered. Only 5 patients were treated using appropriate anti-fungal agents. The 1-month mortality rate for SFP patients was 73.3 % (11 out of 15; median time to death, 2 days range, 0–22), which was significantly higher than patients with SBP alone (28.7 %,
P
= 0.0007). SFP is severe complication related to high mortality in cirrhotic patients. A longer admission and a higher Child–Pugh score may be risk factors. Immediate anti-fungal treatment is warranted in patients with spontaneous peritonitis, once fungus is found in the ascitic fluid.
Summary
Nucleos(t)ide analogues (NAs) have been shown to decrease the risk of hepatocellular carcinoma (HCC) recurrence. This study evaluated whether high‐potency NAs (entecavir and tenofovir ...disoproxil fumarate TDF) reduce the risk of tumour recurrence more potently than low‐potency NAs after curative treatment of hepatitis B virus (HBV)‐related HCC. This study included 607 consecutive HBV‐related HCC patients treated with surgical resection or radiofrequency ablation. The patients were categorized into three groups according to antiviral treatment: group A (no antiviral; n = 261), group B (low‐potency NA; n = 90) and group C (high‐potency NA; n = 256). The primary end‐point was recurrence‐free survival (RFS). During the duration of follow‐up, the median RFS was 29.4, 25.1, and 88.2 months in groups A, B and C, respectively (P < .001, log‐rank test). The multivariate Cox analysis indicated that group C had a significantly longer RFS than both group A (adjusted hazard ratio HR = 0.39, P < .001) and group B (adjusted HR = 0.47, P < .001). When baseline characteristics were balanced using inverse probability weighting, group C still had a significantly longer RFS than group A (adjusted HR = 0.46, P < .001) and group B (adjusted HR = 0.59, P = .007). Group C had significantly lower risk of viral breakthrough than group B (HR = 0.19, P < .001). Viral breakthrough was an independent risk factor for shorter RFS among groups B and C (adjusted HR = 2.03, P = .007, time‐dependent Cox analysis). Antiviral agents with high genetic barrier to resistance (entecavir and TDF) reduced the risk of HCC recurrence compared with other antivirals and no antiviral treatment, especially in patients with high baseline viral load.
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