Review and expert opinion on MAFLD, oxidative stress and multifunctional management.

Metabolic-associated fatty-liver disease (MAFLD), previously known as non-alcoholic fatty liver disease, is the most widespread and emerging chronic liver disease worldwide, with increasing prevalence rates also in the Asia-Pacific region. The disease has a high socio-economic burden as it negatively impacts the finances and quality of life of individuals affected and has a major burden on healthcare systems. The most important pathological event in MAFLD aetiopathogenesis is oxidative stress, which leads to functional and structural abnormalities in the liver as well as being involved in the development of other concomitant cardiometabolic diseases. MAFLD is a rather complex multisystemic clinical condition involving liver damage and a wide spectrum of extrahepatic manifestations such as obesity, type 2 diabetes, metabolic syndrome and cardiovascular diseases. This complexity requires the cooperation of multiple experts to identify MAFLD at an early stage, treat associated comorbidities, and promptly refer the patient to the hepatologist when needed. This review summarizes the current knowledge about MAFLD and reports the opinion of a group of experts on the increasing prevalence and burden of the disease in the southeast Asia region, the current journey of patients with MAFLD in developing countries, the role of oxidative stress and antioxidant treatment, and the importance of a multidisciplinary approach for early diagnosis and disease management. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.

Comparison of LED and LASER Colonoscopy About Linked Color Imaging and Blue Laser/Light Imaging of Colorectal Tumors in a Multinational Study.

INTRODUCTION: In light-emitting diode (LED) and LASER colonoscopy, linked color imaging (LCI) and blue light/laser imaging (BLI) are used for lesion detection and characterization worldwide. We analyzed the difference of LCI and BLI images of colorectal lesions between LED and LASER in a multinational study. METHODS: We prospectively observed lesions with white light imaging (WLI), LCI, and BLI using both LED and LASER colonoscopies from January 2020 to August 2021. Images were graded by 27 endoscopists from nine countries using the polyp visibility score: 4 (excellent), 3 (good), 2 (fair), and 1 (poor) and the comparison score (LED better/similar/LASER better) for WLI/LCI/BLI images of each lesion. RESULTS: Finally, 32 lesions (polyp size: 20.0 ± 15.2 mm) including 9 serrated lesions, 13 adenomas, and 10 T1 cancers were evaluated. The polyp visibility scores of LCI/WLI for international and Japan-expert endoscopists were 3.17 ± 0.73/3.17 ± 0.79 (p = 0.92) and 3.34 ± 0.78/2.84 ± 1.22 (p < 0.01) for LED and 3.30 ± 0.71/3.12 ± 0.77 (p < 0.01) and 3.31 ± 0.82/2.78 ± 1.23 (p < 0.01) for LASER. Regarding the comparison of lesion visibility about between LED and LASER colonoscopy in international endoscopists, a significant difference was achieved not for WLI, but for LCI. The rates of LED better/similar/LASER better for brightness under WLI were 54.5%/31.6%/13.9% (International) and 75.0%/21.9%/3.1% (Japan expert). Those under LCI were 39.2%/35.4%/25.3% (International) and 31.3%/53.1%/15.6% (Japan expert). There were no significant differences in the diagnostic accuracy and the comparison score of BLI images between LED and LASER. CONCLUSIONS: The differences of lesion visibility for WLI/LCI/BLI between LED and LASER in international endoscopists could be compared to those in Japanese endoscopists.

Recurrence rate and lesions characteristics after cold snare polypectomy of high-grade dysplasia and T1 lesions: A multicenter analysis.

BACKGROUND AND AIM: High-grade dysplasia (HGD) and T1 lesions are accidentally resected by cold snare polypectomy (CSP) and the characteristics, and follow-up of them has not been reported. In this study, we analyzed the histopathological findings and recurrence of them. METHODS: This was a multicenter retrospective-cohort study. We collected HGD and T1 lesions of ≤ 10 mm resected by CSP among 15 520 patients receiving CSP from 2014 to 2019 at nine related institutions, and we extracted only cases receiving definite follow-up colonoscopy after CSP of HGD and T1 lesions. We analyzed these tumor's characteristics and therapeutic results such as R0 resection and local recurrence and risk factors of recurrence. RESULTS: We collected 103 patients (0.63%) and extracted 80 lesions in 74 patients receiving follow-up colonoscopy for CSP scar. Mean age was 68.4 ± 12.0, and male rate was 68.9% (51/80). The mean tumor size (mm) was 6.6 ± 2.5, and the rate of polypoid morphology and rectum location was 77.5% and 25.0%. The rate of magnified observation was 53.8%. The rates of en bloc resection and R0 resection were 92.5% and 37.5%. The local recurrence rate was 6.3% (5/80, median follow-up period: 24.0 months). The recurrence developed within 3 months after CSP for four out of five recurrent cases. Comparing five recurrent lesions to 75 non-recurrent lesions, a positive horizontal margin was a significant risk factor (60.0% vs 10.7%, P < 0.001). CONCLUSIONS: High-grade dysplasia and T1 resected by CSP were analyzed, and the local recurrence rate of them was substantially high.

A case of urgent colonoscopic hemostasis of a cecal hemorrhagic ulceration in a patient receiving heparin for COVID-19 coagulopathy.

COVID-19 rarely causes lower gastrointestinal bleeding even though its RNA has been detected in patient's stool. Urgent colonoscopy in a COVID-19 patient with massive bloody stool requires various procedural and equipment considerations. Here, we present a case of colonoscopic hemostasis of a cecal hemorrhagic ulceration in a patient on heparin for COVID-19 coagulopathy. We also share various management methods for the prevention of COVID-19 contamination. A 71-year-old man was diagnosed with COVID-19 pneumonia and subsequently underwent hemodiafiltration. Heparin was initiated for COVID-19 coagulopathy. At day 42, the patient experienced 2000 mL of bloody stool. An operator performed urgent colonoscopy with three assistants in a negative-pressure room with full personal protective equipment. A hemorrhagic ulceration was detected at the cecum, and endoscopic hemostasis was performed. Immunohistochemistry was positive for cytomegalovirus. Postprocedure, the endoscopic systems were thoroughly cleaned, and specific measures for endoscope reprocessing and disinfection were performed to prevent contamination with COVID-19.

The Efficacy and Safety of Elobixibat for the Elderly with Chronic Constipation: A Multicenter Retrospective Cohort Study.

MATERIALS AND METHODS: This was a multicenter retrospective cohort study. The subjects were patients aged ≥20 years treated for chronic constipation from May 2018 to November 2019 at 12 related institutions. Patients were divided into ≤74 years and ≥75 years old. Elobixibat at 10 mg/day was prescribed for two weeks. We then analyzed the discontinuation due to ineffectiveness, change of spontaneous bowel movements (SBM), stool consistency, the time until the first SBM, adverse events, and effect-related factors. RESULTS: There were 140 cases (61 males) evaluated, with an average age of 72.1 ± 13.6 years (≤74 years: 71 cases; ≥75 years: 69 cases). The discontinuation rate was 7.9%. The SBM (times/week) increased from 2.86 to 6.08 (p < 0.001). The overall SBM improvement rate was 74.0% (≤74 years: 78.2% vs. ≥75 years: 68.9%, p = 0.31; male: 75.0% vs. female: 73.3%, p = 0.78). The overall improvement rate of stool consistency was 59.6% (≤74 years: 62.9%, ≥75 years: 56.1%, p = 0.42). The time until the first SBM (hours) for those ≤74 years and ≥75 years was 17.2 ± 14.3 and 11.2 ± 8.4 (p = 0.04). Adverse event rates for those ≤74 years and ≥75 years were 28.2% and 10.1% (p < 0.01). There were no significant effect-related factors for gender, age, and use of laxatives. CONCLUSIONS: Short-period elobixibat is shown to be effective also for the elderly and male.

Blue Laser Imaging, Blue Light Imaging, and Linked Color Imaging for the Detection and Characterization of Colorectal Tumors.

A laser endoscopy system was developed in 2012. The system allows blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI) to be performed as modes of narrow-band light observation; these modes have been reported to be useful for tumor detection and characterization. Furthermore, an innovative endoscopy system using four-light emitting diode (LED) multilight technology was released in 2016 to 2017 in some areas in which laser endoscopes have not been approved for use, including the United States and Europe. This system enables blue light imaging (this is also known as BLI) and LCI with an LED light source instead of a laser light source. Several reports have shown that these modes have improved tumor detection. In this paper, we review the efficacy of BLI and LCI with laser and LED endoscopes in tumor detection and characterization.

An Additional 30-s Observation of the Right-Sided Colon with Narrow Band Imaging Decreases Missed Polyps: A Pilot Study.

INTRODUCTION: Previous narrow-band imaging (NBI) was dark and reported not to be useful for polyp detection. In this study, we analyzed the efficacy of an additional 30-s observation of the right-sided colon with the recent bright high-resolution NBI. METHODS: We enrolled patients undergoing colonoscopy from February 2015 to May 2017 in two institutions. All procedures were performed with the latest system (EVIS LUCERA ELITE, Olympus). The cecum and ascending colon were first observed with white light imaging (WLI) in both the NBI and WLI group. Then, the colonoscope was re-inserted, and the cecum and ascending colon were observed for an additional 30 s. In this second observation, NBI was performed for the first 130 patients in the NBI group and WLI for the next 130 in the WLI group. The number of adenoma and sessile serrated polyps (ASPs) in the second observation were examined in both groups. According to our initial pilot study, the sample size was estimated at 126. RESULTS: In the first observation, the number of ASPs was 72 in the NBI group and 72 in the WLI group (p = 1.0). In the second observation, the number of ASPs was 23 in the NBI group and 10 in the WLI group (p = 0.02). The polyp and adenoma detection rates in the second observation were 16.2% and 12.3% in the NBI group and 7.7% (p = 0.03) and 6.2% (p = 0.09) in the WLI group. CONCLUSIONS: The additional 30-s observation with recent NBI decreased missed polyps in the right-sided colon.

The efficacy of the pocket-creation method for cases with severe fibrosis in colorectal endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: Severe fibrosis poses a challenge in colorectal endoscopic submucosal dissection (ESD). Recently, the pocket-creation method (PCM) has been developed for overcoming various difficulties of ESD. A specific tapered hood is used for adequate traction in the PCM, and endoscopic operability becomes stable in the pocket. In this study, we investigated the efficacy of the PCM in ESD for cases with severe fibrosis. PATIENTS AND METHODS: We retrospectively reviewed 1000 consecutive colorectal ESD cases (April 2006 to January 2017). Since 2016, the PCM was performed in 58 cases. The indications for ESD included (1) tumors ≥ 20 mm in size diagnosed as intramucosal cancer or high-grade dysplasia and part of T1a cancer using magnifying endoscopic examinations and (2) tumors that appeared impossible to resect with endoscopic mucosal resection because of suspected fibrosis. We identified 120 cases with severe fibrosis and compared them to cases without severe fibrosis. Additionally, the 120 severe fibrosis cases were divided into the PCM and non-PCM groups. En bloc resection, procedure time, discontinuation, and complications were analyzed between these 2 groups. RESULTS: Among all 1000 ESDs, severe fibrosis and discontinuation rates were 12.0 % (120 cases) and 1.8 % (18 cases), respectively. Regarding the comparison between cases with severe fibrosis and with no severe fibrosis, there were significant differences about en bloc resection rate (78.3 % vs. 95.7 %, P  < 0.001), discontinuance rate (12.5 % vs. 0.3 %, P  < 0.001), and perforation rate (8.3 % vs. 2.6 %, P  = 0.001). Among the 120 cases with severe fibrosis, 21 and 99 cases were in the PCM and non-PCM groups, respectively. The PCM group had a higher en bloc resection rate (95.2 vs. 74.7, P  =  0.03), a shorter mean procedure time (min) (79.6 ± 26.5 vs. 118.8 ± 71.0, P  = 0.001), and no cases of discontinuation. An analysis of the interobserver agreement for the diagnosis of severe fibrosis among the 3 endoscopists showed kappa values of > 0.6. CONCLUSIONS: In cases with severe fibrosis, the PCM with ESD improved en bloc resection rates and shortened the procedure time compared to the conventional non-PCM method. Additionally, the PCM reduced the discontinuation rate.

A Diminutive T1 Cancer 4 mm in Size Resected by Cold Snare Polypectomy.

Cold snare polypectomy (CSP) should be performed for benign lesions, though an accurate diagnosis is sometimes difficult with only white light observation. Irregular findings by narrow-band imaging (NBI) are useful for differentiating malignant lesions from benign lesions, and cases with this finding are not expected for CSP. We present a diminutive T1 cancer resected by CSP as a reflection case. A 68-year-old man underwent colonoscopy for surveillance after polypectomy. A reddish polyp 4 mm in size was detected at the rectum. White light observation showed no depression, but a slight, heterogeneous color change. NBI magnification showed irregular vessel and surface patterns. The polyp was diagnosed as intramucosal cancer. Even though cancerous lesions are regularly resected by endoscopic mucosal resection (EMR), this polyp was resected by CSP in daycare surgery because the patient requested not to be treated by EMR but by CSP, which needed an admission to our institution. The surgeon thought the polyp could be completely resected by CSP. It was thoroughly resected, and a histological examination showed submucosal cancer with a positive vertical margin. Additional surgical resection was not accepted by the patient, since he had received total gastrectomy for gastric cancer and a right hemicolectomy for colonic cancer in the past 7 years. He underwent follow-up colonoscopy 2 months after the CSP. Although there were no recurrent endoscopic findings, endoscopic submucosal dissection was performed to the scar area. The histological examination showed no residual tumor. In conclusion, CSP should only be adopted for benign cases, as cancerous lesions have a possibility for invading the submucosa, like in our case.

A novel lens cleaner to prevent water drop adhesions during colonoscopy and esophagogastroduodenoscopy.

BACKGROUND AND STUDY AIMS: Water drop adhesions (WDA) impair endoscopic view during gastrointestinal endoscopy. We developed a novel lens cleaner designed using two types of harmLess surfactants and it is reported to be useful for preventing lens cloudiness during colorectal ESD. In the current study, we examined the ability of it for preventing and removing WDA. PATIENTS AND METHODS: During laboratory experiments, the cleaner (Cleash; Fujifilm Co., Tokyo, Japan and Nagase Medicals Co., Hyogo, Japan) was applied to the endoscopic lens and an air/water device (AWD) (water 200 mL, dimethicone 1 mL, Cleash 1 mL). The endoscope was submerged in water 100 times for 5 cycles. Rates of WDA were calculated for various groups (lens and AWD with or without Cleash) and compared to a normal cleaner (SL cleaner). During clinical research, 30 colonoscopies and 30 esophagogastroduodenoscopies were analyzed. For the Cleash group, the cleaner was applied to both lens and AWD. The numbers of WDA and WDA with non-rapid removal were calculated, compared to those of the SL cleaner group. RESULTS: The mean WDA rate for the Cleash setting (lens: Cleash; AWD: Cleash) was 11.0 %, which was significantly lower than other settings (lens: SL cleaner; AWD: water, 31.0 %; P  < 0.001) (lens: Cleash; AWD: water, 19.0 %; P  < 0.001). Clinical research of colonoscopies indicated that the numbers of WDA (number/15 sec) and WDA with non-rapid removal were 0.38 and 0.17 for the Cleash group and 0.91 and 0.46 for the SL cleaner groups ( P  < 0.001, P  < 0.001). For esophagogastroduodenoscopies, the results were 0.47 and 0.24 for the Cleash group and 0.54 and 0.42 for the SL cleaner group ( P  = 0.72, P  = 0.018). CONCLUSION: A clear and beautiful image without WDA is useful not only for routine endoscopy but also, more importantly, for magnifying endoscopy and other endoscopic treatments. The use of Cleash to lens and AWD showed positive results for preventing and removing WDA during laboratory experiments and clinical research involving CS. Additionally, it also showed positive results for the removal of WDA during EGD.

Serum pepsinogen and gastrin-17 as potential biomarkers for pre-malignant lesions in the gastric corpus.

There is a lack of non-invasive screening modalities to diagnose chronic atrophic gastritis (CAG) and intestinal metaplasia (IM). Thus, the aim of the present study was to determine the sensitivity and specificity of serum pepsinogen I (PGI), PGI:II, the PGI:II ratio and gastrin-17 (G-17) in diagnosing CAG and IM, and the correlations between these serum biomarkers and pre-malignant gastric lesions. A cross-sectional study of 72 patients (82% of the calculated sample size) who underwent oesophageal-gastro-duodenoscopy for dyspepsia was performed in the present study. The mean age of the participants was 56.2±16.2 years. Serum PGI:I, PGI:II, G-17 and Helicobacter pylori antibody levels were measured by enzyme-linked immunosorbent assay. Median levels of PGI:I, PGI:II, the PGI:II ratio and G-17 for were 129.9 µg/l, 10.3 µg/l, 14.7 and 4.4 pmol/l, respectively. Subjects with corpus CAG/IM exhibited a significantly lower PGI:II ratio (7.2) compared with the control group (15.7; P<0.001). Histological CAG and IM correlated well with the serum PGI:II ratio (r=-0.417; P<0.001). The cut-off value of the PGI:II ratio of ≤10.0 demonstrated high sensitivity (83.3%), specificity (77.9%) and area under the receiver operating characteristic curve of 0.902 in detecting the two conditions. However, the sensitivity was particularly low at a ratio of ≤3.0. The serum PGI:II ratio is a sensitive and specific marker to diagnose corpus CAG/IM, but at a high cut-off value. This ratio may potentially be used as an outpatient, non-invasive biomarker for detecting corpus CAG/IM.

Efficacy of a Novel Narrow Knife with Water Jet Function for Colorectal Endoscopic Submucosal Dissection.

BACKGROUNDS: With respect to the knife's design in colorectal endoscopic submucosal dissection (ESD), diameter, water jet function, and electric power are important because these relate to efficient dissection. In this study, we analyzed a novel, narrow ball tip-typed ESD knife with water jet function (Flush knife BT-S, diameter: 2.2 mm, length: 2000 mm, Fujifilm Co., Tokyo, Japan) compared to a regular diameter knife (Flush knife BT, diameter: 2.6 mm, length: 1800 mm). METHODS: In laboratory and clinical research, electric power, knife insertion time, vacuum/suction amount with knife in the endoscopic channel, and water jet function were analyzed. We used a knife 2.0 mm long for BT-S and BT knives. RESULTS: The BT-S showed faster mean knife insertion time (sec) and better vacuum amount (ml/min) compared to the BT (insertion time: 16.7 versus 21.6, p < 0.001, vacuum amount: 38.0 versus 14.0, p < 0.01). Additionally, the water jet function of the BT-S was not inferior. In 39 colorectal ESD cases in two institutions, there were mean 4.7 times (range: 1-28) of knife insertion. Suction under knife happened 59% (23/39) and suction of fluid could be done in 100%. CONCLUSIONS: Our study showed that the narrow knife allows significantly faster knife insertion, better vacuum function, and effective clinical results.

Linked color imaging improves the visibility of various featured colorectal polyps in an endoscopist's visibility and color difference value.

PURPOSE: Linked color imaging (LCI) by laser endoscopy is a novel narrow band light observation. In this study, we analyzed the efficacy of LCI for improving the various featured colorectal polyp's visibility utilizing a subjective endoscopist's visibility scoring and objective color difference (CD) value. METHODS: We retrospectively reviewed two pictures both with white light (WL) and LCI for 54 consecutive neoplastic polyps 2-20 mm in size. All pictures were evaluated by four endoscopists according to a published polyp visibility score from four (excellent visibility) to one (poor visibility). Additionally, we calculated CD value between each polyp and surrounding mucosa in LCI and WL using an original software. RESULTS: The mean polyp visibility scores of LCI (3.11 ± 1.05) were significantly higher than those of WL (2.50 ± 1.09, P < 0.001). The ratio of an endoscopist's poor visibility (polyp visibility scores 1 and 2) was significantly lower in LCI (27.9%) than WL (55.6%, P < 0.001). With respect to the CD analysis, the CD value of LCI was significantly higher than that of WL (33.3 ± 13.9 vs. 20.7 ± 13.6, P < 0.001). In a subgroup analysis, the polyp visibility scores and CD values of LCI about 24 diminutive polyps (≤5 mm) were higher than those of WL (3.29 ± 0.99 vs. 2.12 ± 0.99, P < 0.001; 31.6 ± 12.8 vs. 14.7 ± 7.6, P < 0.001). Additionally, the polyp visibility scores and CD values of LCI for polyps with any location, size, histology, and morphology were significantly higher than those of WL. CONCLUSIONS: LCI improved the various featured polyp's visibility compared to WL in both polyp visibility scores and CD value.

Correction: A novel lens cleaner to prevent water drop adhesions during colonoscopy and esophagogastroduodenoscopy.

[This corrects the article DOI: 10.1055/s-0043-120659.].