Impact of comprehensive optical diagnosis training using Workgroup serrAted polypS and Polyposis classification on detection of adenoma and sessile serrated lesion.

OBJECTIVES: Many interventions have been attempted to improve adenoma detection rate (ADR) and sessile serrated lesion detection rate (SDR), and one of these interventions is educational training to recognize polyp characteristics. This study aimed to investigate the change in polyp detection rates of endoscopists before and after comprehensive training through the Gangnam-Real Time Optical Diagnosis (Gangnam-READI) program. METHODS: Fifteen gastroenterologists participated in a 1-year comprehensive training program that consisted of ex vivo and in vivo training that encompasses knowledge and skills in endoscopic characterization of colonic polyps using the Workgroup serrAted polypS and Polyposis (WASP) classification. We evaluated the impact of the training program by comparing the overall and individual ADR and SDR 6 months before and after the training. RESULTS: Overall, 18,280 polyps (9337 adenomas and 855 sessile serrated lesion) were collected. The optical diagnosis training had no significant impact on the difference in ADR after training compared to before training (47.7% vs. 46.5%, P = 0.608). A tendency for a decrease in ADR variance was noted among the endoscopists after training (74.9 vs. 32.7, P = 0.121). The overall pre-training period SDR was 4.5% and showed a statistically significant increase to 5.6%, 8.0%, and 7.1% in the first and second half of the training period, and post-training period, respectively (P = 0.003). The optical diagnosis training did not decrease variance in SDR (8.9 vs. 8.8, P = 0.985). CONCLUSION: Comprehensive optical diagnosis training with WASP classification has a significant impact on increasing the overall SDR of expert endoscopists.

Improved Accuracy in Optical Diagnosis of Colorectal Polyps Using Convolutional Neural Networks with Visual Explanations.

BACKGROUND & AIMS: Narrow-band imaging (NBI) can be used to determine whether colorectal polyps are adenomatous or hyperplastic. We investigated whether an artificial intelligence (AI) system can increase the accuracy of characterizations of polyps by endoscopists of different skill levels. METHODS: We developed convolutional neural networks (CNNs) for evaluation of diminutive colorectal polyps, based on efficient neural architecture searches via parameter sharing with augmentation using NBIs of diminutive (≤5 mm) polyps, collected from October 2015 through October 2017 at the Seoul National University Hospital, Healthcare System Gangnam Center (training set). We trained the CNN using images from 1100 adenomatous polyps and 1050 hyperplastic polyps from 1379 patients. We then tested the system using 300 images of 180 adenomatous polyps and 120 hyperplastic polyps, obtained from January 2018 to May 2019. We compared the accuracy of 22 endoscopists of different skill levels (7 novices, 4 experts, and 11 NBI-trained experts) vs the CNN in evaluation of images (adenomatous vs hyperplastic) from 180 adenomatous and 120 hyperplastic polyps. The endoscopists then evaluated the polyp images with knowledge of the CNN-processed results. We conducted mixed-effect logistic and linear regression analyses to determine the effects of AI assistance on the accuracy of analysis of diminutive colorectal polyps by endoscopists (primary outcome). RESULTS: The CNN distinguished adenomatous vs hyperplastic diminutive polyps with 86.7% accuracy, based on histologic analysis as the reference standard. Endoscopists distinguished adenomatous vs hyperplastic diminutive polyps with 82.5% overall accuracy (novices, 73.8% accuracy; experts, 83.8% accuracy; and NBI-trained experts, 87.6% accuracy). With knowledge of the CNN-processed results, the overall accuracy of the endoscopists increased to 88.5% (P < .05). With knowledge of the CNN-processed results, the accuracy of novice endoscopists increased to 85.6% (P < .05). The CNN-processed results significantly reduced endoscopist time of diagnosis (from 3.92 to 3.37 seconds per polyp, P = .042). CONCLUSIONS: We developed a CNN that significantly increases the accuracy of evaluation of diminutive colorectal polyps (as adenomatous vs hyperplastic) and reduces the time of diagnosis by endoscopists. This AI assistance system significantly increased the accuracy of analysis by novice endoscopists, who achieved near-expert levels of accuracy without extra training. The CNN assistance system can reduce the skill-level dependence of endoscopists and costs.

Multidirectional Colonoscopy Quality Improvement Increases Adenoma Detection Rate: Results of the Seoul National University Hospital Healthcare System Gangnam Center Colonoscopy Quality Upgrade Project (Gangnam-CUP).

BACKGROUND: To prevent colorectal cancer, high-quality colonoscopy is advocated, undertaken by endoscopists with high adenoma detection rates (ADRs). Despite reports that various factors may impact ADRs, the significance of such factors is still unclear. AIMS: The analysis was aimed at quality-oriented interventions for boosting ADRs. METHODS: Study enrollees were adults subjected to screening colonoscopy between September 2013 and August 2016 at the Gangnam Center of Seoul National University Hospital Healthcare System. The investigation entailed six periods (P1-6) of 6 months each, during which serial multidirectional quality improvement efforts were instituted. In particular, we sought to further educate endoscopists, provide feedback on individual ADRs, and introduce a split-dose regimen, gauging results via the Boston Bowel Preparation Score. Changes in polyp detection rates (PDRs) and ADRs were then analyzed. RESULTS: A total of 13,430 colonoscopies were undertaken by 15 experienced endoscopists. Overall, the ADR increased from 45.6% (P1) to 48.2% (P6, p < 0.001). The PDR, ADR, and advanced adenoma detection rate (AdvADR) showed the greatest increases between P3 and P4 [PDR 67.8% → 71.2% (p < 0.001); ADR 44.1% → 47.7% (p = 0.001); AdvADR 2.3% → 3.3% (p = 0.028)] in keeping with the introduction of a split-dose regimen. The sessile serrated adenoma detection rate (SSADR) increased substantially from 2.1% (P1) to 7.9% (P6, p < 0.001), with the largest gain between P1 and P2, just after education (p = 0.023). CONCLUSIONS: Successful quality improvement in colonoscopy was achieved through comprehensive multidirectional efforts in education, feedback, and enhanced bowel preparation. Achieving high-level bowel preparation was paramount in ADR improvement. The SSADR was improved through education.

Nonalcoholic Fatty Liver Disease Is Associated with Benign Prostate Hyperplasia.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with a wide spectrum of metabolic abnormalities. This study aimed to evaluate whether NAFLD is associated with benign prostatic hyperplasia (BPH) independent of other risk factors. METHODS: A total of 3,508 subjects who underwent prostate and hepatic ultrasonography were enrolled. NAFLD was diagnosed and graded by ultrasonographic findings. BPH was defined by total prostate volume. RESULTS: The prevalence of BPH was significantly increased according to NAFLD severity (P < 0.001). The multivariate analysis showed that NAFLD was associated with a 22% increase in the risk of BPH (odds ratio [OR], 1.22; 95% confidence interval [CI], 1.02-1.45). In non-obese subjects, NAFLD was associated with a 41% increase in the risk of BPH (OR, 1.41; 95% CI, 1.14-1.73), and an incremental increase in the risk of BPH according to NAFLD severity was pronounced (adjusted OR [95% CI], 1.32 [1.05-1.68] for mild NAFLD, 1.55 [1.15-2.10] for moderate to severe NAFLD vs. no NAFLD, P for trend = 0.004). However, in the obese population, the association of NAFLD in the risk of BPH was insignificant (P = 0.208). CONCLUSION: NAFLD is associated with an increased risk of BPH regardless of metabolic syndrome, especially in non-obese subjects. An incrementally increased risk of BPH according to NAFLD severity is prominent in non-obese subjects with NAFLD. Thus, physicians caring for non-obese patients with NAFLD may consider assessing the risk of BPH and associated urologic conditions.

Improved Real-Time Optical Diagnosis of Colorectal Polyps Following a Comprehensive Training Program.

BACKGROUND & AIMS: The optimal training method for endoscopic characterization of colorectal polyps using narrow-band imaging is uncertain, and sessile serrated lesions (SSLs) optical diagnosis data are lacking. We aimed to evaluate a comprehensive training program for real-time optical diagnosis of colorectal polyps, including SSLs. METHODS: We performed a single-institution prospective study of 15 endoscopists trained with the Workgroup Serrated Polyps and Polyposis classification system. After the first phase of in vivo optical diagnosis, their performances were evaluated. After re-education for insufficient competency, they began the second phase. The learning curves and performance on 2 preservation and incorporation of valuable endoscopic innovations benchmarks were assessed. RESULTS: A total of 7294 polyps, including 486 SSLs, were diagnosed in real-time. The overall accuracy improved from 73.5% in the first phase to 77.1% in the second. The accuracy with high confidence was 79.4% and 85.1% in the first and second phases, respectively. In the first and second phases, the negative predictive values for diminutive neoplastic polyps were 82.1% and 92.5%, respectively, and concordances of the surveillance intervals were 80.7% and 89.7%, respectively. Eight endoscopists achieved the preservation and incorporation of valuable endoscopic innovations benchmarks after the second phase compared with none after the first. In contrast, the high confidence rate decreased from 74.6% to 70.2% as training progressed. CONCLUSION: A comprehensive training program for real-time optical diagnosis significantly improved performance and reduced individual variability in less-experienced endoscopists. ClinicalTrials.gov no: NCT02516748.

Clinical implications of controlled attenuation parameter in a health check-up cohort.

BACKGROUND & AIMS: Evaluation of the controlled attenuation parameter (CAP) is a promising noninvasive method for assessing hepatic steatosis. Despite the increasing reliability of the CAP for assessing steatosis in subjects with chronic liver disease, few studies have evaluated the CAP in asymptomatic subjects without overt liver disease. Therefore, we aimed to evaluate the usefulness of the CAP for a health check-up population. METHODS: We enrolled subjects who underwent abdominal ultrasonography (US), FibroScan (Echosens, France) and blood sampling during medical health check-ups. The CAP was measured using FibroScan, and increased CAP was defined as CAP ≥ 222 dB/m. RESULTS: A total of 1133 subjects were included; 589 subjects (52.0%) had fatty liver based on US, and 604 subjects (53.3%) had increased CAP. Increased CAP was significantly associated with metabolic abnormalities, including higher body mass index (BMI)[odds ratio (OR) = 1.33;95% confidence interval (CI),1.24-1.43; P < .001], higher alanine aminotransferase (ALT) (OR = 1.02; 95% CI, 1.01-1.04; P = .003), higher insulin (OR = 1.04; 95% CI, 1.00-1.08; P = .037), higher triglyceride (OR = 1.00; 95% CI, 1.00-1.01; P = 0.042) and older age (OR = 1.02; 95% CI, 1.00-1.03; P = .05). Furthermore, a comparison of clinical parameters among three groups (normal vs no fatty liver by US but increased CAP vs fatty liver based on US) revealed that metabolic parameters, including blood pressure, BMI, waist circumference, aspartate aminotransferase (AST), ALT, triglycerides, fasting glucose, uric acid, insulin, homeostasis model assessment-estimated insulin resistance and liver stiffness measurements, gradually increased across the three groups (all P < .001). CONCLUSIONS: In conclusion, increased CAP could be an early indicator of fatty liver disease with metabolic abnormalities that manifests even before a sonographic fatty change appears.

Long-term Outcome of Small, Incidentally Detected Rectal Neuroendocrine Tumors Removed by Simple Excisional Biopsy Compared With the Advanced Endoscopic Resection During Screening Colonoscopy.

BACKGROUND: Incidental, small rectal neuroendocrine tumors during colonoscopy screening are sometimes removed using biopsy forceps. Few studies have examined the clinical course of rectal neuroendocrine tumors removed by simple excisional biopsy. OBJECTIVE: We investigated the long-term outcome of rectal neuroendocrine tumors removed by simple excisional biopsy compared with standard endoscopic resection. DESIGN: This was a cohort study. SETTINGS: This study was performed at a healthcare center in Korea. PATIENTS: We enrolled patients with rectal neuroendocrine tumors detected during a screening colonoscopy between 2003 and 2015. MAIN OUTCOME MEASURES: The clinical characteristics and long-term outcomes (overall survival and disease-free survival) of small neuroendocrine tumors <10 mm were compared between the simple excisional biopsy group and advanced endoscopic resection group. RESULTS: In total, 166 patients were diagnosed with rectal neuroendocrine tumors (≤5 mm, n = 100; 6-9 mm, n = 50; 10-19 mm, n = 15; ≥20 mm, n = 1). Among the 150 patients with neuroendocrine tumors <10 mm, follow-up endoscopy was performed on 99 (59.6%). All of the tumors were confined to the mucosa or submucosa. Thirty-one and 68 patients were included in the simple excisional biopsy and advanced endoscopic resection groups. The overall follow-up duration was 6.5 years (range, 1.0-12.8 y). Neither overall nor disease-related death occurred. Two patients exhibited local recurrence (6.5%, at 8 and 11 y) in the simple excisional biopsy group and 1 patient (1.5%, at 7 y) in the advanced endoscopic resection group, resulting in no significant difference (p = 0.37). All of the recurrences were diagnosed >5 years from initial diagnosis and successfully treated endoscopically. LIMITATIONS: More long-term data should be warranted. CONCLUSIONS: The long-term outcome of small rectal neuroendocrine tumors <10 mm removed by simple excisional biopsy was excellent. Neither overall survival nor disease-free survival significantly differed between the simple excisional biopsy group and the advanced endoscopic resection group. Thus, simple excisional biopsy and long-term follow-up can be cautiously applied for small rectal neuroendocrine tumors in clinical practice. See Video Abstract at http://links.lww.com/DCR/A406.

Training Effect on the Inter-observer Agreement in Endoscopic Diagnosis and Grading of Atrophic Gastritis according to Level of Endoscopic Experience.

BACKGROUND: Endoscopic diagnosis of atrophic gastritis can contribute to risk stratification and thereby tailored screening for gastric cancer. We aimed to evaluate the effect of training on inter-observer agreement in diagnosis and grading of endoscopic atrophic gastritis (EAG) according to the level of endoscopists' experience. METHODS: Twelve endoscopists (six less-experienced and six experienced) participated in this prospective study. The training session consisted of 1) four interventions with two-week intervals, and 2) a follow-up period (two follow-up assessments without feedback). EAG was categorized as C1 to O3 according to the Kimura-Takemoto classification. Kappa statistics were used to calculate inter-observer agreement. RESULTS: At baseline, kappa indexes were 0.18 in the less-experienced group and 0.32 in the experienced group, respectively. After four interventions with feedback, the kappa index improved in both groups and was sustained during the follow-up period. Overall diagnostic yields of EAG were 43.1% ± 10.7% in pre-intervention and 46.8% ± 5.9% in post-intervention. Variability in the rate of diagnosis of EAG significantly decreased in the less-experienced group (r = 0.04, P = 0.003). CONCLUSION: Irrespective of experience level, inter-observer agreement for diagnosis and grading of EAG improved after training and remained stable after intervention.

Clinical characteristics of primary gastric lymphoma detected during screening for gastric cancer in Korea.

BACKGROUND AND AIM: The role of screening endoscopy in primary gastric lymphoma (PGL) has not been investigated. This study aimed to evaluate the clinical characteristics and outcomes of PGLs detected by screening endoscopy in the high prevalence area of Helicobacter pylori (H. pylori) infection. METHODS: This retrospective cohort study enrolled consecutive subjects who were diagnosed with PGL by endoscopic screening in Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea, between October 2003 and September 2013. The characteristics and outcome of screening-detected patients (screening group) were compared with consecutive subjects diagnosed with PGL in the outpatient clinic (outpatient group). RESULTS: Of the 105 194 recipients of screening upper endoscopy, 52 (0.049%) were found to have PGL. The median age was 54.2 years (range 23-79), and 65.4% were women. The proportion of PGL to gastric malignancy was 12.1% (52/429) overall, but >30% (25/73) in middle-aged (40-59) women. PGLs in the screening group were more likely to be mucosa-associated lymphoid tissue lymphoma (98.1% vs 60.0%, P < 0.001) and treated with H. pylori eradication alone (90.0% vs 48.1%, P < 0.001) than those in the outpatient group. Moreover, the screening group showed better 5-year overall survival (100.0% vs 89.3%, P = 0.016) and progression-free survival (94.9% vs 83.4%, P = 0.040) than the outpatient group. CONCLUSIONS: In Korea, a high prevalence area of H. pylori infection, PGL seems more prevalent than in Western countries. Endoscopic screening may help to detect early stage H. pylori-positive mucosa-associated lymphoid tissue lymphoma. A high index of suspicion is needed, especially in middle-aged women.

Management of Suspicious Mucosa-Associated Lymphoid Tissue Lymphoma in Gastric Biopsy Specimens Obtained during Screening Endoscopy.

It is often difficult to differentiate gastric mucosa-associated lymphoid tissue (MALT) lymphoma from Helicobacter pylori-associated follicular gastritis, and thus, it becomes unclear how to manage these diseases. This study aimed to explore the management strategy for and the long-term outcomes of suspicious gastric MALT lymphoma detected by forceps biopsy during screening upper endoscopy. Between October 2003 and May 2013, consecutive subjects who were diagnosed with suspicious gastric MALT lymphomas by screening endoscopy in a health checkup program in Korea were retrospectively enrolled. Suspicious MALT lymphoma was defined as a Wotherspoon score of 3 or 4 upon pathological evaluation of the biopsy specimen. Of 105,164 subjects who underwent screening endoscopies, 49 patients with suspicious MALT lymphomas who underwent subsequent endoscopy were enrolled. Eight patients received a subsequent endoscopy without H. pylori eradication (subsequent endoscopy only group), and 41 patients received H. pylori eradication first followed by endoscopy (eradication first group). MALT lymphoma development was significantly lower in the eradication first group (2/41, 4.9%) than in the subsequent endoscopy only group (3/8, 37.5%, P = 0.026). Notably, among 35 patients with successful H. pylori eradication, there was only one MALT lymphoma patient (2.9%) in whom complete remission was achieved, and there was no recurrence during a median 45 months of endoscopic follow-up. H. pylori eradication with subsequent endoscopy would be a practical management option for suspicious MALT lymphoma detected in a forceps biopsy specimen obtained during screening upper endoscopy.

Genome-wide association study of metabolic dysfunction-associated fatty liver disease in a Korean population.

Genome-wide association studies have identified several genetic variants associated with nonalcoholic fatty liver disease. To emphasize metabolic abnormalities in fatty liver, metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been introduced; thus, we aimed to investigate single-nucleotide polymorphisms related to MAFLD and its subtypes. A genome-wide association study was performed to identify genetic factors related to MAFLD. We used a Korean population-based sample of 2282 subjects with MAFLD and a control group of 4669. We replicated the results in a validation sample which included 639 patients with MAFLD and 1578 controls. Additionally, we categorized participants into three groups, no MAFLD, metabolic dysfunction (MD)-MAFLD, and overweight/obese-MAFLD. After adjusting for age, sex, and principal component scores, rs738409 [risk allele G] and rs3810622 [risk allele T], located in the PNPLA3 gene, showed significant associations with MAFLD (P-values, discovery set = 1.60 × 10-15 and 4.84 × 10-10; odds ratios, 1.365 and 1.284, validation set = 1.39 × 10-4, and 7.15 × 10-4, odds ratios, 1.299 and 1.264, respectively). An additional SNP rs59148799 [risk allele G] located in the GATAD2A gene showed a significant association with MAFLD (P-values, discovery set = 2.08 × 10-8 and validation set = 0.034, odds ratios, 1.387 and 1.250). rs738409 was significantly associated with MAFLD subtypes ([overweight/obese-MAFLD; odds ratio (95% confidence interval), P-values, 1.515 (1.351-1.700), 1.43 × 10-12 and MD-MAFLD: 1.300 (1.191-1.416), 2.90 × 10-9]. There was a significant relationship between rs3810622 and overweight/obese-MAFLD and MD-MAFLD [odds ratios (95% confidence interval), P-values, 1.418 (1.258, 1.600), 1.21 × 10-8 and 1.225 (1.122, 1.340), 7.06 × 10-6, respectively]; the statistical significance remained in the validation set. PNPLA3 was significantly associated with MAFLD and MAFLD subtypes in the Korean population. These results indicate that genetic factors play an important role in the pathogenesis of MAFLD.

Guggulsterone attenuates activation and survival of hepatic stellate cell by inhibiting nuclear factor kappa B activation and inducing apoptosis.

BACKGROUND AND AIM: Liver fibrosis is associated with the deposition of the extracellular matrix, and hepatic stellate cells (HSCs) are the major source of these matrix proteins. Guggulsterone has recently been shown to induce apoptosis in several cell lines. Thus, the aim of this study was to evaluate whether guggulsterone has antifibrotic activities by reducing the activation and survival of HSCs. METHODS: Apoptotic and fibrosis-related signaling pathways and nuclear factor kappa B (NF-κB) activity were explored in LX-2 cells, an immortalized human HSC line, and in a mice model of liver fibrosis. RESULTS: Guggulsterone suppressed LX-2 cell growth in a dose- and activation-dependent manner. This growth suppression was due to the induction of HSC apoptosis, which was mediated by the activation of c-Jun N-terminal kinase and mitochondrial apoptotic signaling. Additionally, guggulsterone regulated phosphorylation of Akt and adenosine monophosphate-activated protein kinase, which were subsequently proven responsible for the guggulsterone-induced HSC growth suppression. Guggulsterone inhibited NF-κB activation in LX-2 cells, which is one of the major mediators in HSC activation. Indeed, guggulsterone decreased collagen α1 synthesis and α-smooth muscle actin expression in these cells. Compared with the control mice or mice treated with a low dose of guggulsterone, high dose of guggulsterone significantly decreased the extent of collagen deposition and the percentage of activated HSCs undergoing apoptosis. CONCLUSIONS: These results demonstrate that guggulsterone suppressed HSC activation and survival by inhibiting NF-κB activation and inducing apoptosis. Therefore, guggulsterone may be useful as an antifibrotic agent in chronic liver diseases.

Status of primary liver cancer found through routine health check-up.

This study aimed to investigate the status of primary liver cancers found through a routine health check-up. The data of subjects who were diagnosed with primary liver cancer for the first time through a routine health check-up during a period of 8-yr were analyzed. Primary liver cancers were detected for the first time in 34 subjects among 91,219 routine health check-up subjects. Only 11.8% of primary liver cancer subjects had been under previous surveillance. Of them, 55.8% were positive for HBsAg, 17.7% were positive for anti-HCV, and 8.8% were heavy alcohol comsumers. However, 17.7% of the subjects were neither heavy alcohol consumers nor positive for both HBsAg and anti-HCV. Of the subjects, 50.0% had a single nodular tumor, 23.5% had multi-nodular tumors, and 26.5% had an infiltrative tumor. A routine health check-up may provide beneficial opportunities to detect a liver cancer in a very early stage. It is beneficial to start surveillance in high-risk subjects for liver cancer or to detect any liver cancer in subjects without risk factors of chronic viral hepatitis or heavy alcohol consumption.

Enhancement of hexokinase II inhibitor-induced apoptosis in hepatocellular carcinoma cells via augmenting ER stress and anti-angiogenesis by protein disulfide isomerase inhibition.

3-bromopyruvate (3-BP), a hexokinase (HK) II inhibitor, promotes tumor cell death by inducing endoplasmic reticulum (ER) stress in human hepatocellular carcinoma (HCC) cell lines. Protein disulfide isomerase (PDI) is an essential folding catalyst and attenuates ER stress by folding the misfolded proteins. We examined if PDI is expressed in hypoxic HCC cells, and evaluated its inhibition potentiated HK II inhibitor-induced ER stress in hypoxic HCC cells. HCC apoptotic cell death was assessed by DAPI staining and apoptotic signaling pathways were explored by immunoblot analysis. An in vivo model of HCC was established in C3H mice intradermally with implanted MH134 cells. 3-BP with/without a PDI inhibitor (bacitracin) was subsequently administered. The anti-tumor efficacies were evaluated by measuring tumor volumes and quantifying apoptotic cells and microvessel densities (MVDs). HCC cells were found to express PDI in a hypoxia-inducible manner. The simultaneous treatment of bacitracin and 3-BP enhanced 3-BP-induced apoptosis. This enhancement was attributed to increased ER stress and JNK activation compared to the cells treated with just 3-BP. In an in vivo model of HCC, tumor growth was significantly suppressed in mice co-treated with bacitracin and 3-BP, and the percentages of apoptotic cells significantly increased and MVDs significantly decreased. These results demonstrated that PDI was induced in hypoxic HCC tissue and that PDI inhibition enhanced HK II inhibitor-induced anti-tumor efficacy synergistically via augmenting ER stress and anti-angiogenesis in vivo. Thus, blockage of PDI activity in combination with HK II inhibitor may be therapeutically useful in HCCs.

Inverse correlation between gastroesophageal reflux disease and atrophic gastritis assessed by endoscopy and serology.

BACKGROUND: Helicobacter pylori (H. pylori) infection is known to prevent the occurrence of gastroesophageal reflux disease (GERD) by inducing gastric mucosal atrophy. However, little is known about the relationship between atrophic gastritis (AG) and GERD. AIM: To confirm the inverse correlation between AG and the occurrence and severity of GERD. METHODS: Individuals receiving health checkups who underwent upper gastrointestinal endoscopy at Seoul National University Healthcare System Gangnam Center were included. The grade of reflux esophagitis was evaluated according to the Los Angeles classification. Endoscopic AG (EAG) was categorized into six grades. Serologic AG (SAG) was defined as pepsinogen I ≤ 70 ng/mL and pepsinogen I/II ratio ≤ 3.0. The association between the extent of EAG and SAG and the occurrence and severity of GERD was evaluated using multivariate logistic regression analysis. RESULTS: In total, 4684 individuals with GERD were compared with 21901 healthy controls. In multivariate logistic regression analysis, advanced age, male sex, body mass index > 23 kg/m2, presence of metabolic syndrome, current smoking, and alcohol consumption were associated with an increased risk of GERD. Seropositivity for H. pylori immunoglobulin G antibodies was associated with a decreased risk of GERD. There was an inverse correlation between the extent of EAG and occurrence of GERD: Odds ratio (OR), 1.01 [95% confidence interval (CI): 0.90-1.14] in C1, 0.87 (0.78-0.97) in C2, 0.71 (0.62-0.80) in C3, 0.52 (0.44-0.61) in O1, 0.37 (0.29-0.48) in O2, and 0.28 (0.18-0.43) in O3. Additionally, the extent of EAG showed an inverse correlation with the severity of GERD. The presence of SAG was correlated with a reduced risk of GERD (OR = 0.49, 95%CI: 0.28-0.87, P = 0.014). CONCLUSION: The extent of EAG and SAG exhibited strong inverse relationships with the occurrence and severity of GERD. AG followed by H. pylori infection may be independently protect against GERD.

The relationship between metabolic dysfunction-associated fatty liver disease and low muscle mass in an asymptomatic Korean population.

BACKGROUND: Metabolic (dysfunction)-associated fatty liver disease (MAFLD) emphasizes the metabolic dysfunction in nonalcoholic fatty liver disease (NAFLD). Although the relationship between low muscle mass and NAFLD has been suggested, the effect of MAFLD on low muscle mass is yet to be investigated. In this study, we examined the relationship between MAFLD and low muscle mass in an asymptomatic Korean population. METHODS: Examinees who underwent FibroScan® and bioelectrical impedance analyses on the same day during the period of June 2017 to December 2019 were included. Hepatic steatosis was diagnosed using controlled attenuation parameter (CAP) with two cut-off values of 248 and 294 dB/m. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight (wt) or body mass index (BMI) ratios of two standard deviations below the sex-specific mean for healthy young adults. Subjects were divided into four subgroups: diabetic MAFLD (presence of diabetes mellitus [DM]), metabolic dysfunction (MD) MAFLD (≥2 metabolic abnormalities without DM), overweight MAFLD (overweight/obese without DM and <2 metabolic abnormalities) and no MAFLD. RESULTS: Among all of the 6414 subjects (mean 53.9 years of age; 85.4% male), the prevalence of MAFLD was 49.9% and 22.7% for CAP cut-off values of 248 and 294 dB/m, respectively. In the multivariate analysis, MAFLD was associated with an increased risk of both low muscle mass_wt (odds ratio [OR] 1.80, 95% confidence interval [CI] 1.38-2.35, P < 0.001) and low muscle mass_BMI (OR 1.31, 95% CI 1.01-1.70, P = 0.042). The risk of low muscle mass_wt and low muscle mass_BMI increased the most in the diabetic MAFLD subgroup compared with the no-MAFLD group (OR 2.11, 95% CI 1.51-2.96, P < 0.001 and OR 1.51, 95% CI 1.08-2.13, P = 0.017). There was an increased risk of low muscle mass_wt in the MD MAFLD subgroup (OR 1.73, 95% CI 1.31-2.28, P < 0.001). Comparable results were observed when the CAP cut-off value of 294 dB/m was applied. CONCLUSIONS: The presence of MAFLD is significantly associated with increased risk of low muscle mass with varying risks according to the MAFLD subgroups. Clinicians should be aware of the differentiated risk of low muscle mass across the subgroups of MAFLD.

Clinical differentiation of acute cutaneous graft-versus-host disease from drug hypersensitivity reactions.

BACKGROUND: The early diagnosis of acute cutaneous graft-versus-host disease (GVHD) is challenging as there are no specific features. Drug hypersensitivity reaction (DHR) is the most frequently encountered condition to differentiate from GVHD. OBJECTIVES: We sought to investigate the clinical characteristics of acute cutaneous GVHD in comparison with DHR. METHODS: A retrospective chart review was conducted for allogeneic hemopoietic-cell transplantation recipients with maculopapular rashes who had undergone hemopoietic-cell transplantation less than 100 days earlier. We analyzed the clinical characteristics of 22 patients with acute cutaneous GVHD in comparison with 17 patients with DHR. RESULTS: Facial involvement was more frequent in the GVHD group (59%) than in the DHR group (24%). The difference was more significant when both the face and palms/soles were involved (36% in the GVHD group, no patients in the DHR group). Diarrhea was significantly more common in the GVHD group (73%) than in the DHR group (12%). The presence of both diarrhea and hyperbilirubinemia occurred only in the GVHD group (41%). In the GVHD group, the patients developed diarrhea and hyperbilirubinemia gradually with most patients exhibiting diarrhea and hyperbilirubinemia after 2 days. LIMITATIONS: A retrospective design, small number of patients, and single-center design are limitations. CONCLUSIONS: Facial involvement, and moreover involvement of the face and palms/soles, suggests the diagnosis of GVHD versus DHR. The presence of diarrhea, and diarrhea accompanied by hyperbilirubinemia is thought to favor the diagnosis of GVHD. Rashes with more than 2 to 3 days of duration and not accompanied by diarrhea and hyperbilirubinemia are less likely to be GVHD.

Clinical features and prognosis of early colorectal cancer treated by endoscopic mucosal resection.

BACKGROUND AND AIMS: The incidence of early colorectal cancer (ECC) has been increasing. The aim of this study was to evaluate the clinical outcome and prognosis of ECC treated by endoscopic mucosal resection (EMR). METHODS: A total of 129 ECC patients who were initially treated by EMR between April 2005 and August 2007 were enrolled. Clinicopathological characteristics and prognoses were evaluated retrospectively. RESULTS: En bloc resection was performed in 85% of ECC patients, and piecemeal resection was performed in 15% of patients. Clear lateral and deep margins were achieved in 86% of cases. Of the 129 patients, 64 were found to have intramucosal cancer and 65 had submucosal cancer. Clinical characteristics were not different between patients with intramucosal cancer and submucosal cancer; however, poor differentiation and the absence of background adenoma showed significant association with submucosal cancer. Seven patients with submucosal cancer underwent subsequent surgical resection; five had lymphovascular invasion or a positive resection margin, one had perforation, and one patient requested surgical resection. Of these seven patients, one had residual cancer and two had lymph node metastasis. All patients with intramucosal cancer had no recurrence during the follow-up period. Seven patients with submucosal cancer showed adverse outcomes within 3 years, such as residual/recurrence of primary cancer or lymph node metastasis; five showed lymphovascular invasion or a positive deep margin, and two had no histological risk factors. CONCLUSIONS: Our results suggest that intramucosal cancer shows good prognosis, and a cure could be expected after EMR; however, adverse outcomes can occur in submucosal cancer. Therefore, meticulous endoscopic follow up is needed in patients with submucosal cancer for at least 3 years after EMR.

Prospective evaluation of a new stool antigen test for the detection of Helicobacter pylori, in comparison with histology, rapid urease test, (13)C-urea breath test, and serology.

BACKGROUND AND AIMS: This study aimed to evaluate the efficacy of a new polyclonal enzyme immunoassay for the detection of Helicobacter pylori (H. pylori) antigen in stool by determination of the optimal cut-off value in the screening population. METHODS: A consecutive 515 patients undergoing a routine health check-up were prospectively enrolled. H. pylori infection was defined if at least two of four tests (histology, rapid urease test, (13)C-urea breath test, and serology) were positive. A stool antigen test (EZ-STEP H. pylori) was performed for the detection of H. pylori. The optimal cut-off value was determined by the receiver-operator characteristic curve. The diagnostic performance of each test was evaluated with regard to the histological diagnosis of atrophic gastritis (AG)/intestinal metaplasia (IM), degree of AG/IM, and old age. RESULTS: Sensitivity, specificity, positive and negative predictive values, and accuracy of the stool antigen test were 93.1%, 94.6%, 95.1%, 92.3%, and 93.8%, respectively. The sensitivity of histology, rapid urease test, and the (13)C-urea breath test ranged from 89.1% to 97.6%, and their specificity was > 98%, while serology had high sensitivity, but low specificity. The accuracy of the stool antigen test was comparable to that of other methods (93.6-95.9%), whereas it was higher than that of serology. The stool antigen test still showed good diagnostic performance in the setting of progression of AG/IM and in patients over 40 years. CONCLUSIONS: The performance of a new stool antigen test was comparable to that of other methods in the diagnosis of H. pylori infection for the screening population, even with the presence of AG/IM.

Body weight gain rather than body weight variability associated with increased risk of nonalcoholic fatty liver disease.

Weight loss, the most established therapy for nonalcoholic fatty liver disease (NAFLD), is frequently followed by weight regain and fluctuation. The aim of this study was to investigate whether body weight change and variability were independent risk factors for incident NAFLD. We conducted a longitudinal cohort study. Among the 1907 participants, incident NAFLD occurred in 420 (22.0%) cases during median follow-up of 5.6 years. In the multivariate analysis, there was no significant association between weight variability and the risk of incident NAFLD. The risk of incident NAFLD was significantly higher in subjects with weight gain ≥ 10% and 7% < gain ≤ 10% [hazard ratios (HR), 2.43; 95% confidence intervals (CI), 1.65-3.58 and HR, 1.73; 95% CI, 1.26-2.39, respectively], while the risk of incident NAFLD was significantly lower in those with -7% < weight loss ≤ --3% (HR, 0.33; 95% CI, 0.22-0.51). Overall body weight gain rather than bodyweight variability was independently associated with the risk of incident NAFLD. Understanding the association between body weight variability and incident NAFLD may have future clinical implications for the quantification of weight loss as a treatment for patients with NAFLD.