A survey of current practices in post-polypectomy surveillance in Korea.

BACKGROUND/AIMS: We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. METHODS: In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. RESULTS: In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1-2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3-10 tubular adenomas < 10 mm, adenomas ≥ 10 mm, tubulovillous or villous adenomas, ≤ 20 hyperplastic polyps < 10 mm, 1-4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs ≥ 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5-10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%-55.1%) discontinued the surveillance at the patient age of 80-84 years. CONCLUSIONS: A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.

Risk Prediction of Post-Endoscopic Submucosal Dissection Coagulation Syndrome.

INTRODUCTION: Endoscopic submucosal dissection (ESD) has been popular worldwide to treat laterally spreading tumors and large polyps. Post-ESD coagulation syndrome (PECS) is more common than the two major ESD-related complications, perforation and bleeding. The aim of this study was to assess the prevalence of PECS, identify the risk factors for PECS, and create a risk prediction model for PECS. METHODS: Retrospective cross-sectional study analyzed a total of 986 patients who underwent colorectal ESD. Logistic regression models were used to assess risk factors with PECS. Each risk factor was scored and the 3-step risk stratification index of prediction model was assessed. RESULTS: The prevalence of PECS was 21.4% (95% confidence interval [CI]=18.9%-24.1%). The risk factors of PECS in the multivariate logistic regression were tumor size (+1 cm: odds ratio [OR], 1.29; 95% CI, 1.16 to 7.09), cecal lesion (OR, 1.96; 95% CI, 1.09 to 1.53), procedure time (+30 minutes: OR, 1.19; 95% CI, 1.02 to 1.39), and ESD with snaring (OR, 0.64; 95% CI, 0.43 to 0.95). Applying a simplified weighted scoring system based on adjusted OR increments of 1, the risk of PECS was 12.3% (95% CI, 0.3%-16.0%) for the low-risk group (score ≤ 4) and was 36.0% (95% CI=29.4%-43.2%) for the high-risk group (score ≥ 8). Overall discrimination (C-statistic=0.629; 95% CI=0.585-0.672) and calibration (p = 0.993) of the model were moderate to good. CONCLUSION: PECS occurs frequently and the prediction model can be helpful for effective treatment and prevention of PECS.

Rebamipide Prevents the Hemoglobin Drop Related to Mucosal-Damaging Agents at a Level Comparable to Proton Pump Inhibitors.

Background/Aims: : The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage. Methods: : A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data. Results: : The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI. Conclusions: : Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract.

Clinicopathologic and Endosonographic Characteristics of Colon Subepithelial Tumors Discovered Incidentally.

BACKGROUND/AIMS: Colonoscopy is commonly used for colorectal cancer screening; therefore, the detection of colon subepithelial tumors (SETs) has also increased. Several research studies have been undertaken to diagnose and treat stomach and rectal SETs. The purpose of this study was to determine a diagnostic point for colon SETs by comparing histological findings with the endoscopic characteristics of colon SETs discovered by chance. METHODS: A total 194 patients underwent an endoscopic ultrasound (EUS) for suspicious colon SETs during a colonoscopy from May 2014 to December 2021. A total of 105 colon SETs, which were histologically diagnosed, were finally included. Fisher's exact test was used to determine the factors associated with malignant SETs. RESULTS: Colon SETs were predominantly present in the right colon (n = 73, 69.5%), particularly in the transverse colon (n = 32, 30.5%). The majority were smaller than 10 mm (n = 88, 83.8%), and they had hard consistencies (n = 84, 80%) and exhibited no surface changes (n = 96, 91.4%). Most of them were found in the submucosal layers (n = 54, 51.4%) and had a hypoechoic pattern (n = 56, 53.3%) in the EUS. Of the histologically confirmed cases, only three (3/105, 2.9%) were malignant. Most benign lesions were lipomas, suspected parasitic infections, or lesions caused by various inflammatory reactions, including fibrous/fibrocalcific lesions and necrotic nodules. All soft lesions were benign. Two of the three malignant lesions were adenocarcinomas, and the other was lymphoma. For the malignant SETs, there was a statistically significant alteration in the surface of the tumors (p < 0.001), and they were located where the muscularis mucosa layer was included (p = 0.008). The potential malignant SETs, granular cell tumors, and neuroendocrine tumors (NETs) had similar features, such as yellowish hypoechoic masses. Colon NETs were only found in the rectosigmoid junction. Parasitic infections and lesions, resulting in various inflammatory reactions, were observed as pale and hard SETs and mostly revealed as mixed echogenic masses located in the muscularis mucosa, submucosa, or multi-layers in the EUS. CONCLUSION: This study showed that small colon SETs were mostly benign lesions. Despite its rarity, pathological confirmation is crucial in cases where the SET has surface changes and has been located in a position where the muscularis mucosa layer was included on the EUS, due to the risk of malignancy.

Experience of primary intestinal lymphangiectasia in adults: Twelve case series from a tertiary referral hospital.

BACKGROUND: While primary intestinal lymphangiectasia (PIL) is considered a rare condition, there have been several reported cases in adults. Nevertheless, the absence of clear guidance from diagnosis to treatment and prognosis poses challenges for both physicians and patients. AIM: To enhance understanding by investigating clinical presentation, diagnosis, treatment, complications, and prognoses in adult PIL cases. METHODS: We enrolled adult patients diagnosed with PIL between March 2016 and September 2021. The primary outcome involved examining the diagnosis and treatment process of these patients. The secondary outcomes included identifying complications (infections, thromboembolism) and assessing prognoses (frequency of hospitalization and mortality) during the follow-up period. RESULTS: Among the 12 included patients, peripheral edema (100%) and diarrhea (75%) were the main presenting complaints. Laboratory tests showed that all the patients exhibited symptoms of hypoalbuminemia and hypogammaglobulinemia. Radiologically, the predominant findings were edema of the small intestine (67%) and ascites (58%). The typical endoscopic finding with a snowflake appearance was observed in 75% of patients. Among the 12 patients, two responded positively to octreotide and sirolimus, and eight who could undergo maintenance therapy discontinued subsequently. Complications due to PIL led to infection in half of the patients, thromboembolism in three patients, and one death. CONCLUSION: PIL can be diagnosed in adults across various age groups, with different severity and treatment responses among patients, leading to diverse complications and prognoses. Consequently, tailored treatments will be necessary. We anticipate that our findings will contribute to the management of PIL, an etiology of protein-losing enteropathy.

Risk factors and management of iatrogenic colorectal perforation in diagnostic colonoscopy: a single-center cohort study.

BACKGROUND AND AIMS: Diagnostic colonoscopy plays a central role in colorectal cancer screening programs. We analyzed the risk factors for perforation during diagnostic colonoscopy and discussed the treatment outcomes. METHODS: We performed a retrospective analysis of risk factors and treatment outcomes of perforation during 74,426 diagnostic colonoscopies between 2013 and 2018 in a tertiary hospital. RESULTS: A total of 19 perforations were identified after 74,426 diagnostic colonoscopies or sigmoidoscopies, resulting in a standardized incidence rate of 0.025% or 2.5 per 10,000 colonoscopies. The majority (15 out of 19, 79%) were found at the sigmoid colon and recto-sigmoid junction. Perforation occurred mostly in less than 1000 cases of colonoscopy (16 out of 19, 84%). In particular, the incidence of perforation was higher in more than 200 cases undergoing slightly advanced colonoscopy rather than beginners who had just learned colonoscopy. Old age (≥ 70 years), inpatient setting, low body mass index (BMI), and sedation status were significantly associated with increased risk of perforation. Nine (47%) of the patients underwent operative treatment and ten (53%) were managed non-operatively. Patients who underwent surgery were often diagnosed with delayed or concomitant abdominal pain. Perforations of rectum tended to be successfully treated with endoscopic clipping. CONCLUSIONS: Additional precautions are required to prevent perforation in elderly patients, hospital settings, low BMI, sedated patients, or by a doctor with slight familiarity with endoscopies (but still insufficient experience). Endoscopic treatment should be actively considered if diagnosis is prompt, abdominal pain absent, and especially the rectal perforation is present.

Strategies to improve screening colonoscopy quality for the prevention of colorectal cancer.

The incidence and mortality of colorectal cancer (CRC) have decreased through regular screening colonoscopy, surveillance, and endoscopic treatment. However, CRC can still be diagnosed after negative colonoscopy. Such CRC is called interval CRC and accounts for 1.8-9.0% of all CRC cases. Most cases of interval CRC originate from missed lesions and incompletely resected lesions. Interval CRC can be minimized by improving the quality of colonoscopy. This has led to a growing interest in and demand for high-quality colonoscopy. It is important to reduce the risk of CRC and its associated mortality by improving the quality of colonoscopy. In this review article, we provide an overview of colonoscopy quality indicators, including bowel preparation adequacy, the cecal intubation rate, the adenoma detection rate, the colonoscopy withdrawal time, appropriate polypectomy, and complication of the procedure. Because colonoscopy is a highly endoscopist-dependent procedure, colonoscopists should be well-acquainted with quality indicators and strive to apply them in daily clinical practice for the prevention of CRC.

Trends in colorectal cancer incidence according to an increase in the number of colonoscopy cases in Korea.

BACKGROUND: The incidence of colorectal cancer (CRC) and preinvasive CRC (e.g., early colon cancer and advanced adenoma) is gradually increasing in several countries. AIM: To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in Korea. METHODS: This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC, and assess the numbers of diagnostic colonoscopies and colonoscopic polypectomies. Colonoscopy-related complications by age group were also determined. RESULTS: The incidence of CRC showed a rapid increase, then decreased after 2012 in the 50-75 year-age group. During the study period, the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of age. Since 2009, the increase has been rapid, showing a pattern similar to the increase in colonoscopies. The rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after 2007. The rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of age. CONCLUSION: The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies performed. As the risk of colonoscopy-related hospitalization and death is high in the elderly, if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75, colonoscopy-related complications can be reduced for those aged 76 years or over.

Comparison of an Endoscopic Scoring System and the Simplified Magnetic Resonance Index of Activity in Patients with Small Bowel Crohn's Disease.

Background/Aims: The newly derived simplified magnetic resonance index of activity (MARIAs) has not been verified in comparison to balloon-assisted enteroscopy (BAE) for patients with small bowel Crohn's disease (CD). We studied the correlation of MARIAs with simple endoscopic scores for CD (SES-CD) of the ileum based on magnetic resonance enterography (MRE) and BAE in patients with small bowel CD. Methods: Fifty patients with small bowel CD who underwent BAE and MRE concurrently within 3 months from September 2020 to June 2021 were enrolled in the study. The primary outcome was the correlation between the active score of ileal SES-CD (ileal SES-CDa)/ileal SES-CD and MARIAs based on BAE and MRE. The cutoff value for MARIAs identifying endoscopically active/severe disease, defined as ileal SES-CDa/ileal SES-CD of 5/7 or more, was analyzed. Results: Ileal SES-CDa/ileal SES-CD and MARIAs showed strong associations (R=0.76, p<0.001; R=0.78, p<0.001). The area under the receiver operating characteristic curve of MARIAs for ileal SES-CDa ≥5 and ileal SES-CD ≥7 was 0.92 (95% confidence interval, 0.88 to 0.97) and 0.92 (95% confidence interval, 0.87 to 0.97). The cutoff value of MARIAs for detecting active/severe disease was 3. A MARIAs index value of ≥3 identified ileal SES-CDa ≥5 with a sensitivity of 85% and specificity of 87% and detected ileal SES-CD ≥7 with a sensitivity of 87% and specificity of 86%. Conclusions: This study validated the applicability of MARIAs compared to BAE-based ileal SES-CDa/SES-CD.

Weight loss from diagnosis of Crohn's disease to one year post-diagnosis results in earlier surgery.

Malnutrition might play a key role in the prognosis of patients with Crohn's disease (CD). The aim of this study was to explore the impact of weight loss from diagnosis of CD to one-year post-diagnosis on disease prognosis in terms of surgery. Patients who were diagnosed with CD at Samsung Medical Center between 1995 to 2020 were included in this study. The study defined the "group with weight loss" as patients with weight loss in one year after diagnosis and the "group without body weight loss" as patients without weight loss in one year after diagnosis. Their data such as demographics, laboratory findings, and medical interventions were collected retrospectively. The primary outcome was confirmation of the difference in the incidence of surgery associated with CD between the group with weight loss and the group without body weight loss. We further analyzed factors associated with surgery outcomes. A total of 165 patients were analyzed in this study. Forty-one patients (24.8%) had body weight loss whereas 124 patients (75.2%) had no body weight loss. Body change at one year showed no significant association with direct surgical incidence. However, the patients with weight loss tended to undergo surgery earlier than patients without body weight loss. Among factors associated with outcomes of Crohn's surgery, the albumin was the only significant factor. Patients with weight loss had no statistically significant increase in the risk of surgery than patients without weight loss, although they tended to undergo surgery earlier than patients without body weight loss. A prospective study is needed to determine serial body weight changes during follow-up for patients with CD.

SGLT2 and DPP4 inhibitors improve Alzheimer's disease-like pathology and cognitive function through distinct mechanisms in a T2D-AD mouse model.

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D) share common features, including insulin resistance. Brain insulin resistance has been implicated as a key factor in the pathogenesis of AD. Recent studies have demonstrated that anti-diabetic drugs sodium-glucose cotransporter-2 inhibitor (SGLT2-i) and dipeptidyl peptidase-4 inhibitor (DPP4-i) improve insulin sensitivity and provide neuroprotection. However, the effects of these two inhibitors on the brain metabolism and insulin resistance remain uninvestigated. We developed a T2D-AD mouse model using a high-fat diet (HFD) for 19 weeks along with a single dose of streptozotocin (100 mg/kg, intraperitoneally) at the fourth week of HFD initiation. Subsequently, the animals were treated with SGLT2-i (empagliflozin, 25 mg/kg/day orally [p.o.]) and DPP4-i (sitagliptin, 100 mg/kg/day p.o.) for 7 weeks. Subsequently, behavioral tests were performed, and the expression of insulin signaling, AD-related, and other signaling pathway proteins in the brain were examined. T2D-AD mice not only showed increased blood glucose levels and body weight but also insulin resistance. SGLT2-i and DPP4-i effectively ameliorated insulin sensitivity and reduced body weight in these mice. Furthermore, SGLT2-i and DPP4-i significantly improved hippocampal-dependent learning, memory, and cognitive functions in the T2D-AD mouse model. Interestingly, SGLT2-i and DPP4-i reduced the hyperphosphorylated tau (pTau) levels and amyloid ß (Aß) accumulation and enhanced brain insulin signaling. SGLT2-i reduced pTau accumulation through the angiotensin converting enzyme-2/angiotensin (1-7)/ mitochondrial assembly receptor axis, whereas DPP4-i reduced Aß accumulation by increasing insulin-degrading enzyme levels. These findings suggest that SGLT2-i and DPP4-i prevent AD-like pathology and cognitive dysfunction in T2D mice potentially through affecting brain insulin signaling via different mechanisms.

Can balloon-assisted enteroscopy predict disease outcomes in patients with small-bowel Crohn's disease?

There are limited studies on the endoscopic assessment of disease activity using balloon-assisted enteroscopy (BAE) and its predictive role for long-term outcomes of patients with small bowel Crohn's disease (CD). We sought to investigate the value of BAE as a predictor of long-term outcomes in patients with small-bowel CD. A total of 111 patients with small-bowel CD whose endoscopic disease activity was assessed using BAE based on the small-bowel simple endoscopic score for Crohn's disease (small-bowel SES-CD) at Samsung Medical Center were retrospectively selected from January 2014 to August 2020. The outcome was an evaluation of the risk of surgery according to a small-bowel SES-CD of 0-6 vs. ≥ 7 and endoscopic findings (presence of any ulcer and degree of stricture) using the Cox proportional hazards model. The risk of surgery was significantly increased in patients with a small-bowel SES-CD of ≥ 7 compared to a small-bowel SES-CD of 0-6 [hazard ratio (HR) 6.31; 95% confidence interval (CI) 1.48-26.91; p = 0.013]. In addition, the risk of surgery was significantly increased in patients with stenosis with "cannot be passed" compared to the cases without stenosis (HR 12.34; 95% CI 1.66-91.92; p = 0.014), whereas there was no significance in any ulcer. The present study demonstrated the role of BAE in the endoscopic assessment of disease activity and its predictive value for the risk of surgery in small-bowel CD patients. Further optimization of BAE utilization for the assessment of disease activity is warranted in clinical practice.

Evaluation of hormonal and circulating inflammatory biomarker profiles in the year following bariatric surgery.

Background: Bariatric surgery (BS) has a superior effect on reducing body weight and fat in patients with morbid obesity. As a result, BS mitigates obesity-related complications such as type 2 diabetes (T2D). However, few studies have shown the mechanism underlying diabetes remission after surgery. This study aimed to investigate the differences in serum hormone and inflammatory cytokine levels related to diabetes before surgery and during 12 months of follow-up in Korean patients with obesity. Methods: The study participants were patients with morbid obesity (n=63) who underwent sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) between 2016 - 2017 at seven tertiary hospitals in Korea. The patients were followed for 1 year after surgery. Results: Sixty-three patients had significant weight loss after surgery and showed improvements in clinical parameters and hormonal and inflammatory profiles. Among them, 23 patients who were diabetic preoperatively showed different remission after surgery. The levels of inflammation-related clinical parameters changed significantly in the remission group, and serum inflammatory cytokine and hormones significantly decreased at certain points and showed an overall decreasing trend. Conclusions: Our study found postoperative changes of factors in blood samples, and the changes in hormones secreted from the three major metabolic tissue (pancreas, adipose, and gut) along with the differences in multi-origin inflammatory cytokines between remission and non-remission groups provide a path for understanding how the effect of BS in improving glucose metabolism is mediated.

The optimal surgery timing after stenting in colorectal cancer patients with malignant obstruction: additionally compared with emergency surgery.

BACKGROUND: This study aimed to determine short-term and long-term outcomes according to time intervals after stenting and compared them with those of emergency surgery (ES) in colorectal cancer (CRC) with malignant obstruction. METHODS: CRC with malignant obstructions was reviewed retrospectively between January 2008 and July 2018. Of a total of 539 patients who visited the emergency room and underwent ES, 133 were enrolled in the ES group. Of a total of 567 patients who initially received stenting and subsequently underwent elective surgery, 220 were enrolled in the SEMS group. The interval between SEMS placement and elective surgery was classified as < 11 days, 11-17 days, and > 17 days. RESULTS: For those who received SEMS (n = 220), those with a time interval of 11-17 days (n = 97) had fewer hospital days than those with a time interval of < 11 days (n = 68) (8 days vs. 15 days) and less stoma formation than those with a time interval of > 17 days (n = 55) (1.0% vs. 14.6%). Multivariable analysis revealed a decreased risk of death for the group with a time interval of 11-17 days (20.6%) compared to the ES group (31.6%) (hazard ratio: 0.48; 95% confidence interval: 0.24-0.97). Disease-free survival was comparable between the SEMS and ES groups regardless of the time interval (log-rank p = 0.52). CONCLUSIONS: The time interval of 11-17 days after stenting to elective surgery appeared to be associated with the most favorable outcomes.

Deep learning model for distinguishing Mayo endoscopic subscore 0 and 1 in patients with ulcerative colitis.

The aim of this study was to address the issue of differentiating between Mayo endoscopic subscore (MES) 0 and MES 1 using a deep learning model. A dataset of 492 ulcerative colitis (UC) patients who demonstrated MES improvement between January 2018 and December 2019 at Samsung Medical Center was utilized. Specifically, two representative images of the colon and rectum were selected from each patient, resulting in a total of 984 images for analysis. The deep learning model utilized in this study consisted of a convolutional neural network (CNN)-based encoder, with two auxiliary classifiers for the colon and rectum, as well as a final MES classifier that combined image features from both inputs. In the internal test, the model achieved an F1-score of 0.92, surpassing the performance of seven novice classifiers by an average margin of 0.11, and outperforming their consensus by 0.02. The area under the receiver operating characteristic curve (AUROC) was calculated to be 0.97 when considering MES 1 as positive, with an area under the precision-recall curve (AUPRC) of 0.98. In the external test using the Hyperkvasir dataset, the model achieved an F1-score of 0.89, AUROC of 0.86, and AUPRC of 0.97. The results demonstrate that the proposed CNN-based model, which integrates image features from both the colon and rectum, exhibits superior performance in accurately discriminating between MES 0 and MES 1 in patients with UC.

Increased expression of sodium-glucose cotransporter 2 and O-GlcNAcylation in hepatocytes drives non-alcoholic steatohepatitis.

AIMS: Steatosis reducing effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in non-alcoholic steatohepatitis (NASH) has been consistently reported in humans, but their mechanism remains uncertain. In this study, we examined the expression of SGLT2 in human livers and investigated the crosstalk between SGLT2 inhibition and hepatic glucose uptake, intracellular O-GlcNAcylation, and autophagic regulation in NASH. MATERIALS AND METHODS: Human liver samples obtained from subjects with/without NASH were analyzed. For in vitro studies, human normal hepatocytes and hepatoma cells were treated with SGLT2 inhibitor under high-glucose and high-lipid conditions. NASH in vivo was induced by a high-fat, -fructose, and -cholesterol Amylin liver NASH (AMLN) diet for 10 weeks followed by an additional 10 weeks with/without SGLT2 inhibitor (empagliflozin 10 mg/kg/day). RESULTS: Liver samples from subjects with NASH were associated with increased SGLT2 and O-GlcNAcylation expression compared with controls. Under NASH condition (in vitro condition with high glucose and lipid), intracellular O-GlcNAcylation and inflammatory markers were increased in hepatocytes and SGLT2 expression was upregulated; SGLT2 inhibitor treatment blocked these changes by directly reducing hepatocellular glucose uptake. In addition, decreased intracellular O-GlcNAcylation by SGLT2 inhibitor promoted autophagic flux through AMPK-TFEB activation. In the AMLN diet-induced NASH mice model, SGLT2 inhibitor alleviated lipid accumulation, inflammation, and fibrosis through autophagy activation related to decreased SGLT2 expression and O-GlcNAcylation in the liver. CONCLUSIONS: This study firstly demonstrates increased SGLT2 expression in NASH and secondly reveals the novel effect of SGLT2 inhibition on NASH through autophagy activation mediated by inhibition of hepatocellular glucose uptake and consequently decreased intracellular O-GlcNAcylation.

Small Bowel Capsule Endoscopy within 6 Hours Following Bowel Preparation with Polyethylene Glycol Shows Improved Small Bowel Visibility.

Although bowel preparation influences small bowel visibility for small bowel capsule endoscopy (SBCE), the optimal timing for bowel preparation has not been established yet. Thus, the aim of the study was to evaluate the optimal timing of polyethylene glycol (PEG) for small bowel preparation before SBCE. This multicenter prospective observational study was conducted on patients who underwent SBCE following bowel preparation with polyethylene glycol (PEG). Patients were categorized into three groups according to the time used for completing PEG ingestion: group A, within 6 h; group B, 6-12 h; and group C, over 12 h. The percentage of unclean segment in small bowel (unclean image duration / small bowel transit time × 100) and small bowel visibility quality (SBVQ) were evaluated according to the time interval between the last ingestion of PEG and swallowing of small bowel capsule endoscope. A total of 90 patients were enrolled and categorized into group A (n = 40), group B (n = 27), and group C (n = 23). The percentage of unclean segment in the entire small bowel increased gradually from group A to C (6.6 ± 7.6% in group A, 11.3 ± 11.8% in group B, and 16.2 ± 10.7% in group C, p = 0.001), especially in the distal small bowel (11.4 ± 13.6% in group A, 20.7 ± 18.7% in group B, and 29.5 ± 16.4% in group C, p < 0.001). The proportion of patients with adequate SBVQ in group A was significantly (p < 0.001) higher (30/40, 75.0%) than that in group B (17/27, 63.0%) or group C (5/23, 21.7%). In multivariate analysis, group A was associated with an increased likelihood of adequate SBVQ compared with group C (odds ratio [OR]: 13.05; 95% confidence interval [CI]: 3.53-48.30, p < 0.001). Completing PEG ingestion within 6 h prior to SBCE could enhance small bowel visibility.

Incremental Detection Rate of Dysplasia and Sessile Serrated Polyps/Adenomas Using Narrow-Band Imaging and Dye Spray Chromoendoscopy in Addition to High-Definition Endoscopy in Patients with Long-Standing Extensive Ulcerative Colitis: Segmental Tandem Endoscopic Study.

High-definition (HD) endoscopy is recommended in surveillance colonoscopy for detecting dysplasia in patients with ulcerative colitis (UC). Dye-spray chromoendoscopy (DCE) and narrow-band imaging (NBI) are often used as adjunctive techniques of white-light endoscopy (WLE) in real-world practice. However, the incremental detection ability of DCE and NBI added to HD-WLE for dysplasia and serrated lesions has not yet been evaluated using tandem endoscopy in patients with long-standing extensive UC. We enrolled patients with extensive UC for >8 years who were in clinical remission (partial Mayo score < 2) at the Samsung Medical Center in Seoul, Republic of Korea. HD-WLE was performed first. Subsequently, HD-NBI and HD-DCE with indigo carmine were performed using the segmental tandem colonoscopy technique. A total of 40 patients were eligible, and data obtained from 33 patients were analyzed. The incremental detection rates (IDRs) for dysplasia and serrated lesions were calculated. HD-WLE detected three dysplasia and five sessile serrated adenomas/polyps (SSAs/Ps). HD-NBI and HD-DCE did not detect additional dysplasia (IDR = 0%; 95% confidence interval (CI): 0-56.2%). HD-NBI identified one missed SSA/P (IDR = 7.7%; 95% CI: 1.4-33.3%), and HD-DCE detected seven missed SSAs/Ps (IDR = 53.9%; 95% CI: 29.1-76.8%). Logistic regression found that HD-DCE increased the detection of SSAs/Ps compared to HD-WLE and/or HD-NBI (odds ratio (OR) = 3.16, 95% CI: 0.83-11.92, p = 0.08). DCE in addition to HD-WLE improved the detection of SSAs/Ps, but not dysplasia, in patients with long-standing extensive UC.

Cancer risk in patients with Peutz-Jeghers syndrome in Korea: a retrospective multi-center study.

BACKGROUND/AIMS: There have been little research on the cancer risks of patients with Peutz-Jeghers syndrome (PJS) in Korea. We aimed to investigate the clinical features of PJS patients and their cancer incidence rate. METHODS: Patients with PJS from nine medical centers were enrolled. In those patients diagnosed with cancer, data obtained included the date of cancer diagnosis, the tumor location, and the cancer stage. The cumulative risks of gastrointestinal cancers and extra-gastrointestinal cancers were calculated using the Kaplan-Meier method. RESULTS: A total of 96 PJS patients were included. The median age at diagnosis of PJS was 23.4 years. Cancer developed in 21 of the 96 patients (21.9%). The age of PJS diagnosis was widely distributed (0.9 to 72.4 years). The most common cancers were gastrointestinal cancer (n = 12) followed by breast cancer (n = 6). The cumulative lifetime cancer risk was calculated to be 62.1% at age 60. The cumulative lifetime gastrointestinal cancer risk was 47.1% at age 70. The cumulative lifetime extra- gastrointestinal cancer risk was 40.3% at age 60. CONCLUSION: PJS onset may occur at any age and the risks of gastrointestinal and extra-gastrointestinal cancer are high. Thorough surveillance of PJS patients for malignancies is vital.

Biomechanical forces in the aged brain: Relationship to AD.

The pathogenesis of neurodegenerative disorders, including Alzheimer's disease, has been studied with a focus on biochemical mechanisms, such as the amyloid-ß plaque deposition and removal. Recently, the importance of brain microenvironmental cues, which comprise the sophisticated cellular and fluid system, has been emphasized in the aged brain or in pathological conditions. Especially, substrate rigidity and biomechanical forces of the brain microenvironment determine the function of glial cells and neurons; furthermore, these microenvironmental cues change with age. However, our understanding of role of the biomechanical cues on glial cells and neurons is relatively poor. In this review, we briefly introduce an overview of biomechanical forces that present in the aged brain and its sensations, and then examine the brain in Alzheimer's disease, which constitutes a representative neurodegenerative disorder, with regard to changes in the biomechanical forces associated with disease and aging.