Background
Nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction associated fatty liver disease (MAFLD) have important associations with cardiovascular disease (CVD). The main objective ...of this study was to compare the frequency of incidence rate of CVD in the NAFLD or MAFLD patients utilizing a large claims database.
Methods
Using the JMDC database from April 2013 to March 2019, we retrospectively analyzed data for 1,542,688 and 2,452,949 people to estimate the relationship between CVD and NAFLD, MAFLD, respectively.
Results
The incidence rates of CVD were 0.97 (95% CI 0.94–1.01) and 2.82 (95% CI 2.64–3.01) per 1000 person-years in the non-NAFLD and NAFLD groups, respectively, and 1.01 (95% CI 0.98–1.03) and 2.69 (95% CI 2.55–2.83) per 1000 person-years in the non-MAFLD and MAFLD groups, respectively. The overall prevalence of hypertriglyceridemia and diabetes mellitus (DM) was 13.1, and 4.2%, respectively, in the non-NAFLD group and 63.6, and 20.2%, respectively, in the NAFLD group. The overall prevalenceof hypertriglyceridemia and DM was 13.6 and 4.3%, respectively, in the non-MAFLD group and 64.1, and 20.6%, respectively, in the MAFLD group. HRs for CVD increased with hypertriglyceridemia and DM.
Conclusions
Results indicated that incident rate of CVD increased with NAFLD/MAFLD; the complication rate of DM and hypertriglyceridemia among NAFLD/MAFLD patients is high and may affect the development of CVD.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To investigate the clinical usefulness of ultrasonography-based acoustic radiation force impulse (ARFI) elastography (ie, ARFI sonoelastography) in patients with a diagnosis of nonalcoholic fatty ...liver disease (NAFLD) and compare ARFI sonoelastography results with transient sonoelastography and serum fibrosis marker test results.
Written informed consent was obtained from all subjects, and the local ethics committee approved the study. Fifty-four patients with a liver biopsy-confirmed diagnosis of NAFLD (mean age, 50.6 years +/- 13.7) were examined. All patients with NAFLD and healthy volunteers underwent ARFI sonoelastography, transient sonoelastography, and serum liver fibrosis marker testing (hyaluronic acids, type IV collagen 7 S domain). Ten healthy volunteers underwent ARFI sonoelastography. ARFI sonoelastography results were compared with liver biopsy findings, the reference standard. ARFI sonoelastography findings were compared with liver biopsy, transient sonoelastography, and serum fibrosis marker test results. Student t testing was used for univariate comparisons; Kruskal-Wallis testing, for assessments involving more than two independent groups; and areas under the receiver operating characteristic curve (A(z)), to assess the sensitivity and specificity of ARFI sonoelastography for detection of stage 3 and stage 4 fibrosis.
Median velocities in the patients with NAFLD were 1.040 m/sec for those with stage 0 fibrosis, 1.120 m/sec for those with stage 1, 1.130 m/sec for those with stage 2, 1.780 m/sec for those with stage 3, and 2.180 m/sec for those with stage 4. The A(z) for the diagnosis of hepatic fibrosis stages 3 or higher was 0.973 (optimal cutoff value, 1.77 m/sec; sensitivity, 100%; specificity, 91%), while that for the diagnosis of stage 4 fibrosis was 0.976 (optimal cutoff value, 1.90 m/sec; sensitivity, 100%; specificity, 96%). Significant correlations between median velocity measured by using ARFI sonoelastography and the following parameters were observed: liver stiffness measured with transient sonoelastography (r = 0.75, P < .0001), serum level of hyaluronic acid(r = 0.459, P = .0009), and serum level of type IV collagen 7 S domain (r = 0.445, P = .0015).
There is a significant positive correlation between median velocity measured by using ARFI sonoelastography and severity of liver fibrosis in patients with NAFLD. The results of ARFI sonoelastography were similar to those of transient sonoelastography.
Summary Background The prevalence of, and mortality from, colorectal cancer is increasing worldwide, and new strategies for prevention are needed to reduce the burden of this disease. The oral ...diabetes medicine metformin might have chemopreventive effects against cancer, including colorectal cancer. However, no clinical trial data exist for the use of metformin for colorectal cancer chemoprevention. Therefore, we devised a 1-year clinical trial to assess the safety and chemopreventive effects of metformin on sporadic colorectal cancer (assessed by adenoma and polyp recurrence) in patients with a high risk of adenoma recurrence. Methods This trial was a multicentre, double-blind, placebo-controlled, randomised phase 3 trial. Non-diabetic adult patients who had previously had single or multiple colorectal adenomas or polyps resected by endoscopy were enrolled into the study from five hospitals in Japan. Eligible patients were randomly assigned (1:1) to receive oral metformin (250 mg daily) or identical placebo tablets by a stratified computer-based randomisation method, with stratification by institute, age, sex, and body-mass index. All patients, endoscopists, doctors, and investigators were masked to drug allocation until the end of the trial. After 1 year of administration of metformin or placebo, colonoscopies were done to assess the co-primary endpoints: the number and prevalence of adenomas or polyps. Our analysis included all participants who underwent random allocation, according to the intention-to-treat principle. This trial is registered with University Hospital Medical Information Network (UMIN), number UMIN000006254. Findings Between Sept 1, 2011, and Dec 30, 2014, 498 patients who had had single or multiple colorectal adenomas resected by endoscopy were enrolled into the study. After exclusions for ineligibility, 151 patients underwent randomisation: 79 were assigned to the metformin group and 72 to the placebo group. 71 patients in the metformin group and 62 in the placebo group underwent 1-year follow-up colonoscopy. The prevalence of total polyps (hyperplastic polyps plus adenomas) and of adenomas in the metformin group was significantly lower than that in the placebo group (total polyps: metformin group 27 38·0%; 95% CI 26·7–49·3 of 71 patients, placebo group 35 56·5%; 95% CI 44·1–68·8 of 62; p=0·034, risk ratio RR 0·67 95% CI 0·47–0·97; adenomas: metformin group 22 30·6%; 95% CI 19·9–41·2 of 71 patients, placebo group 32 51·6%; 95% CI 39·2–64·1 of 62; p=0·016, RR 0·60 95% CI 0·39–0·92). The median number of polyps was zero (IQR 0–1) in the metformin group and one (0–1) in the placebo group (p=0·041). The median number of adenomas was zero (0–1) in the metformin group and zero (0–1) in the placebo group (p=0·037). 15 (11%) of patients had adverse events, all of which were grade 1. We recorded no serious adverse events during the 1-year trial. Interpretation The administration of low-dose metformin for 1 year to patients without diabetes was safe. Low-dose metformin reduced the prevalence and number of metachronous adenomas or polyps after polypectomy. Metformin has a potential role in the chemoprevention of colorectal cancer. However, further large, long-term trials are needed to provide definitive conclusions. Funding Ministry of Health, Labour and Welfare, Japan.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
Few studies have investigated measures to prevent small bowel injuries induced by aspirin. Our aim was to evaluate the effect of probiotic treatment on the small bowel injuries induced by ...chronic low-dose aspirin use.
Methods
Thirty-five patients who took low-dose enteric-coated aspirin 100 mg daily (for more than 3 months) plus omeprazole 20 mg daily and were diagnosed as having unexplained iron deficiency anemia participated in this prospective randomized controlled trial. We assigned the patients to receive probiotic treatment with
Lactobacillus casei
for 3 months (
L. casei
group) or not receive the probiotic (control group). Patients underwent capsule endoscopy (CE) before and after treatment.
Results
Twenty-five patients, including 13 in the
L. casei
group and 12 in the control group, underwent the full analysis. Significant decreases in the number of mucosal breaks and the CE score were observed at the 3-month evaluation in the
L. casei
group as compared with the results in the control group (
P
= 0.039). The change from the baseline in the median number of mucosal breaks in the
L. casei
group was −2, as compared with 0.5 in the control group. The change from the baseline in the median CE score in the
L. casei
group was −228 compared with −4 in the control group (
P
= 0.026).
Conclusions
Co-administration of
L. casei
is effective for the treatment of aspirin-associated small bowel injury.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Importance The COVID-19 pandemic has delayed medical consultations, possibly leading to the diagnosis of gastrointestinal cancer at advanced stages. Objective To evaluate stage at diagnosis among ...patients with gastrointestinal cancer in Japan before and during the COVID-19 pandemic. Design, Setting, and Participants This retrospective cohort study included patients in a hospital-based cancer registry who were diagnosed with gastrointestinal cancer (ie, esophageal, gastric, colorectal, pancreatic, liver, and biliary tract cancers) between January 2016 and December 2020 at 2 tertiary Japanese hospitals. Exposures The pre–COVID-19 period was defined as January 2017 to February 2020, and the COVID-19 period was defined as March 2020 to December 2020. Main Outcome and Measure Monthly numbers of patients with newly diagnosed cancer were aggregated, classified by stage, and compared. Results The study evaluated 5167 patients, including 4218 patients (2825 67.0% men; mean SD age, 71.3 10.9 years) in the pre–COVID-19 period and 949 patients (607 64.0% men; mean SD age, 71.8 10.7 years) in the COVID-19 period. Comparing the pre–COVID-19 period with the COVID-19 period, significant decreases were observed in the mean (SD) number of patients with newly diagnosed gastric cancer (30.63 6.62 patients/month vs 22.40 5.85 patients/month; –26.87% change;P < .001) and colorectal cancer (41.61 6.81 patients/month vs 36.00 6.72 patients/month; –13.47% change;P = .03). Significant decreases were also observed in the mean (SD) number of cases of stage I gastric cancer (21.55 5.66 cases/month vs 13.90 5.99 cases/month; –35.51% change;P < .001), stage 0 colorectal cancer (10.58 3.36 cases/month vs 7.10 4.10 cases/month; –32.89% change;P = .008), and stage I colorectal cancer (10.16 3.14 cases/month vs 6.70 2.91 cases/month; –34.04% change;P = .003). No significant increases were observed for esophageal, gastric, pancreatic, liver, or biliary tract cancers. A significant decrease was observed in the mean (SD) number of cases per month of stage II colorectal cancer (7.42 3.06 cases/month vs 4.80 1.75 cases/month; –35.32% change;P = .01); a significant increase was observed for the mean (SD) number of cases per month of stage III colorectal cancer (7.18 2.85 cases/month vs 12.10 2.42 cases/month; 68.42% change;P < .001). Conclusions and Relevance In this cohort study of patients in a hospital-based cancer registry form Japan, significantly fewer patients were diagnosed with stage I gastric and colorectal cancers during the COVID-19 pandemic. Thus, the number of screening-detected cancers might have decreased, and colorectal cancer may have been diagnosed at more advanced stages.
The liver directly accepts blood from the gut and is, therefore, exposed to intestinal bacteria. Recent studies have demonstrated a relationship between gut bacteria and nonalcoholic fatty liver ...disease (NAFLD). Approximately 10–20% of NAFLD patients develop nonalcoholic steatohepatitis (NASH), and endotoxins produced by Gram-negative bacilli may be involved in NAFLD pathogenesis. NAFLD hyperendotoxicemia has intestinal and hepatic factors. The intestinal factors include impaired intestinal barrier function (leaky gut syndrome) and dysbiosis due to increased abundance of ethanol-producing bacteria, which can change endogenous alcohol concentrations. The hepatic factors include hyperleptinemia, which is associated with an excessive response to endotoxins, leading to intrahepatic inflammation and fibrosis. Clinically, the relationship between gut bacteria and NAFLD has been targeted in some randomized controlled trials of probiotics and other agents, but the results have been inconsistent. A recent randomized, placebo-controlled study explored the utility of lubiprostone, a treatment for constipation, in restoring intestinal barrier function and improving the outcomes of NAFLD patients, marking a new phase in the development of novel therapies targeting the intestinal barrier. This review summarizes recent data from studies in animal models and randomized clinical trials on the role of the gut–liver axis in NAFLD pathogenesis and progression.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background/Purpose
Placement of uncovered self‐expandable metallic stents (U‐SEMSs) of patients with unresectable perihilar cholangiocarcinoma (UPHC) is recommended as the treatment of first choice ...to address bile stasis. The aim of this study was to determine which of the following two endoscopic stents might be the stent of first choice for the treatment of biliary stasis in patients with UPHC: plastic stents (PSs) or U‐SEMSs.
Methods
U‐SEMSs, deployed as a stent‐in‐stent, were selected as the stents of first choice from 2013 and 2014, while PSs began to be selected as the stents of first choice from 2015 onward.
Results
The median time to recurrent biliary obstruction were 66 days in the PS group (N = 38) and 105 days in the U‐SEMS group (N = 37; P = .04). Emergency endoscopy was necessitated in 76.3% (29/38) of patients of the PS group and 54.1% (20/37) of patients of the U‐SEMS group (P = .0434). The success rate of the first reintervention was 96.5% (27/29) in the PS group and 55% (11/20) in the U‐SEMS group (P = .0002). Sustainable chemotherapy could be carried out in 55.2% of patients in the PS group and 32.4% of patients in the U‐SEMS group (P = .0472). Multivariate analysis identified selection of U‐SEMS as the stent of first choice as the only independent factor predictive of successful reintervention (P = .0016, odds ratio = 0.058). However, the stent selection was not an independent factor for feasible chemotherapy.
Conclusions
Plastic stent placement could enhance the success rate of reintervention in patients with UPHC and might be facilitated by sustainable chemotherapy. However, stent selection might not have an influence on the prognosis.
Highlight
Placement of uncovered self‐expandable metallic stents is recommended as the treatment of choice in patients with unresectable perihilar cholangiocarcinoma. Iwasaki and colleagues conclude that plastic stent placement could enhance the success rate of reintervention in these patients and might facilitate sustainable chemotherapy. Stent selection, however, may not affect the prognosis.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Diagnosing distal bile duct obstruction remains challenging. This study aimed to examine the diagnostic ability of artificial intelligence (AI) based on clinical biomarkers in diagnosing malignant ...distal bile duct obstruction. A total of 206 patients with distal bile duct obstruction were included in this study. Clinical laboratory parameters were collected from the patients and evaluated using AI. All clinical parameters were input into the AI algorithm, and the AI value for malignant distal bile duct obstruction was calculated. The benign and malignant diagnostic capabilities of AI and other factors (alkaline phosphatase ALP, intrahepatic bile duct IHBD diameters, and total bile duct CBD diameters) were compared. Benign and malignant bile duct obstruction were diagnosed in 142 and 64 patients, respectively. The median AI value of malignant distal bile duct obstruction was significantly greater than that of benign distal bile duct obstruction (0.991 vs. 0.002, p < 0.001). The area under the receiver operating characteristic curve of AI, ALP, IHBD diameter, and CBD diameter were 0.908, 0.795, 0.794, and 0.775, respectively. AI showed a sensitivity, specificity, and accuracy of 83.1%, 87.2%, and 85.9%. AI-based on clinical biomarkers could serve as an auxiliary for diagnosing malignant bile duct obstruction.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective The effectiveness of everolimus for the management of pancreatic neuroendocrine neoplasms (PNENs), including the G3/NEC types, remains unclear. We therefore investigated the effectiveness ...of the drug for the management of PNENs. Methods We analyzed the progression-free survival (PFS) and overall survival (OS) associated with everolimus and factors influencing the PFS and OS. Results One hundred patients were evaluated. The PFS associated with the G1/G2 types tended to be significantly longer than that associated with the G3/NEC types hazard ratio (HR), 0.45; p=0.005. A multivariate analysis showed that the significant factors influencing the PFS were age (<65 years old; HR, 0.44; p=0.002), grade (G1/G2; HR, 0.42; p=0.006), everolimus treatment line (≤2nd; HR, 0.55; p=0.031), and presence of treatment with metformin (yes; HR, 0.29; p=0.044). The median OS was 63.8 months. In the multivariate analysis, the significant factors influencing the OS were grade (G1/G2; HR, 0.21; p<0.001), volume of liver metastasis (≤25%; HR, 0.27; p<0.001), everolimus treatment line (≤2nd; HR, 0.27; p<0.001), and presence of primary tumor resection (yes; HR, 0.33; p=0.005). Conclusion The effectiveness of everolimus in the management of G3/NEC types and prognoses tended to be poorer than those associated with the G1/G2 types. Everolimus combined with metformin and early-line treatment with everolimus may be effective for managing advanced PNENs.
Since pancreatic steatosis is reported as a possible risk factor for pancreatic cancer, the development of a non-invasive method to quantify pancreatic steatosis is needed. Proton density fat ...fraction (PDFF) measurement is a magnetic resonance imaging (MRI) based method for quantitatively assessing the steatosis of a region of interest (ROI). Although it is commonly used for quantification of hepatic steatosis, pancreatic PDFF can greatly vary depending on the ROI's location because of the patchy nature of pancreatic fat accumulation. In this study, we attempted to quantify pancreatic steatosis by fat-water MRI with improved reproducibility.
Using the MRI images of 159 patients with nonalcoholic fatty liver disease, we attempted to calculate the average PDFF of whole pancreas. We set ROIs covering the entire area of the pancreas appearing in every slice and calculated the average PDFF from all the voxels included in the pancreas. We named this average value as whole-pancreatic PDFF and evaluated the reproducibility of the measured values. In addition to whole-pancreatic PDFF, we measured the average PDFF of the pancreatic head (head-PDFF) and that of the pancreatic body plus tail separately and analyzed their correlation with the clinical characteristics of the patients.
The mean inter-examiner coefficient of variation of the whole-pancreatic PDFF was 11.39%. The whole-pancreatic PDFF was correlated with age (p = 0.039), body mass index (p = 0.0093) and presence/absence of diabetes (p = 0.0055). The serum level of low-density lipoprotein cholesterol was inversely correlated with the head-PDFF.
We developed a new measurement method of the pancreatic PDFF with greater reproducibility. Using this method, we characterized pancreatic steatosis in detail. This novel measurement method allows accurate estimation of the severity of pancreatic steatosis and is therefore useful for the detailed characterization of pancreatic steatosis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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