Innate Immune System in the Pathogenesis of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by lipid accumulation in hepatocytes with low alcohol consumption. The development of sterile inflammation, which occurs in response to a range of cellular stressors or injuries, has been identified as a major contributor to the pathogenesis of NAFLD. Recent studies of the pathogenesis of NAFLD reported the newly developed roles of damage-associated molecular patterns (DAMPs). These molecules activate pattern recognition receptors (PRRs), which are placed in the infiltrated neutrophils, dendritic cells, monocytes, or Kupffer cells. DAMPs cause the activation of PRRs, which triggers a number of immunological responses, including the generation of cytokines that promote inflammation and the localization of immune cells to the site of the damage. This review provides a comprehensive overview of the impact of DAMPs and PRRs on the development of NAFLD.

Endoscopic Submucosal Dissection versus Surgery for Undifferentiated-Type Early Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: The use of endoscopic submucosal dissection (ESD) for treating undifferentiated-type early gastric cancer is controversial. The objective of this study was to perform a meta-analysis to compare the long-term outcomes of ESD and surgery for undifferentiated-type early gastric cancer. METHODS: The PubMed, Cochrane Library, and EMBASE databases were used to search for relevant studies comparing ESD and surgery for undifferentiated-type early gastric cancer. The methodological quality of the included publications was evaluated using the Risk of Bias Assessment tool for Nonrandomized Studies. The rates of overall survival, recurrence, adverse event, and complete resection were determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were also evaluated. RESULTS: This meta-analysis enrolled five studies with 429 and 1,236 participants undergoing ESD and surgery, respectively. No significant difference was found in the overall survival rate between the ESD and surgery groups (OR, 2.29; 95% CI, 0.98-5.36; p=0.06). However, ESD was associated with a higher recurrence rate and a lower complete resection rate. The adverse event rate was similar between the two groups. CONCLUSION: ESD with meticulous surveillance esophagogastroduodenoscopy may be as effective and safe as surgery in patients with undifferentiated-type early gastric cancer. Further large-scale, randomized, controlled studies from additional regions are required to confirm these findings.

Propofol compared with bolus and titrated midazolam for sedation in outpatient colonoscopy: a prospective randomized double-blind study.

BACKGROUND AND AIMS: The safest and most efficient method of sedation for outpatient colonoscopy remains unclear. This study aimed to compare the efficiency and safety of bolus administration of midazolam compared with titrated administration and propofol administration for patients undergoing outpatient colonoscopy. METHODS: We randomly divided patients undergoing colonoscopy into the propofol group, bolus midazolam group, and titrated midazolam group. We compared total procedure time, induction time, recovery time, and discharge time among the 3 groups. We also compared patient satisfaction and the incidence of adverse events. RESULTS: In total, 267 patients (89 in each study group) were enrolled during the study period. Patients in the propofol group had a shorter total procedure time (39.5 vs 59.4 vs 58.1 minutes; P < .001), induction time (4.6 vs 6.3 vs 7.6 minutes; P < .001), recovery time (11.5 vs 29.5 vs 29.2 minutes; P < .001), and discharge time (20.6 vs 34.9 vs 34.7 minutes; P < .001) than patients in the bolus midazolam group and titrated midazolam group. Patients in the propofol group reported higher degrees of satisfaction than patients in the bolus or titrated midazolam plus meperidine groups (9.9 vs 9.6 vs 9.6 [P = .007] and 4.9 vs 4.7 vs 4.8 [P = .008], respectively). Adverse events were not significantly different between groups. CONCLUSIONS: In this randomized trial, propofol was superior to bolus or titrated midazolam in terms of endoscopy unit efficiency and patient satisfaction during outpatient colonoscopy. (Clinical trial registration number: KCT0002805.).

The Suggestion of Revised Criteria for Endoscopic Resection of Differentiated-Type Submucosal Gastric Cancer.

BACKGROUND: Early gastric cancer that meets the expanded criteria for endoscopic resection (ER) is expected to be associated with a negligible risk for lymph node metastasis (LNM); however, recent studies have reported LNM in submucosal gastric cancer patients who met the existing criteria. In this study, we develop the revised criteria for ER of submucosal gastric cancer with the aim of minimizing LNM. METHODS: We analyzed the clinicopathological data of 2461 patients diagnosed with differentiated, submucosal gastric cancer who underwent surgery at three tertiary hospitals between March 2001 and December 2012, and re-analyzed the pathological slides of all patients. The depth of submucosal invasion was measured histopathologically in two different ways (the classic and alternative methods) to obtain accurate data. RESULTS: Of the enrolled subjects, 306 (17.0%) had LNM. The width of submucosal invasion correlated well with the LNM. We defined the depth and width of submucosal infiltration associated with the lowest incidence of LNM. None of the 254 subjects developed LNM when the following criteria were met: tumor diameter ≤ 3 cm, submucosal invasion depth < 1000 µm (as measured using the alternative method), submucosal invasion width < 4 mm, no lymphovascular invasion, and no perineural invasion; however, LNM was observed in 2.7% of subjects (6/218) who met the existing criteria. CONCLUSIONS: We revised the criteria for ER by adopting the alternative method to measure the depth of submucosal invasion and adding the width of such invasion. Our criteria better predicted LNM than the current criteria used to select ER to treat submucosal gastric cancer.

Relationship Between Sarcopenia and Prognosis in Patient With Concurrent Chemo-Radiation Therapy for Esophageal Cancer.

Background: Sarcopenia, defined as skeletal muscle loss, has been known as a poor prognosis factor in various malignant diseases The aim of this study is to investigate the effect of sarcopenia on prognosis in patients with esophageal cancer who received concurrent chemo- and radiotherapy (CCRT). Methods: We retrospectively collected clinical data of 287 patients with esophageal cancer who were treated by definite CCRT at Gangnam Severance and Severance hospital from August 2005 to December 2014. The cross-sectional area of muscle at the level of the third lumbar vertebra was measured using pre- and post-CCRT computed tomography images. Sarcopenia was defined as skeletal muscle index <49 cm2/m2 for men and of <31 cm2/m2 for women by Korean-specific cutoffs. Overall survival (OS) and progression free survival (PFS) were analyzed according to sarcopenia. Results: Sarcopenia identified before CCRT did not affect OS and PFS. However, patients with post-CCRT sarcopenia showed shorter OS and PFS than patients without it (median OS: 73 months vs. 28 months; median PFS: 34 months vs. 25 months, respectively). Post-CCRT sarcopenia was an independent prognostic factor of poor OS (hazards ratio: 1.697; 95% confidence interval: 1.036-2.780; P = 0.036). In multivariate analysis, male sex (P = 0.004) and presence of CCRT-related complications, such as esophagitis or general weakness were significantly associated with post-CCRT sarcopenia (P = 0.016). Conclusions: Sarcopenia after CCRT can be a useful predictor for long-term prognosis in patients with esophageal cancer. To control CCRT-related complications may be important to prevent skeletal muscle loss during CCRT.

Predicting lymph node metastasis for endoscopic resection of superficial esophageal squamous cell carcinoma.

OBJECTIVE: The aims of this study were to identify risk factors for lymph node metastasis and develop a reliable risk stratification system. METHODS: Between May 2001 and December 2015, 262 patients who underwent endoscopic resection or surgery for superficial esophageal squamous cell carcinoma were enrolled. We evaluated possible predictive factors for lymph node metastasis: age, gender, tumor length, tumor area, circumferential spread, tumor location, gross appearance, depth of invasion, tumor differentiation, and lymphovascular invasion. RESULTS: The incidence of lymph node metastasis was 14.5% (38/262). In multivariate analysis, tumor size (>15 mm), depth of invasion (submucosal invasion), and lymphovascular invasion were significantly associated with lymph node metastasis. These factors were included in the risk stratification system and assigned scores; the total risk stratification system score was 0 to 6. The area under the receiver operating characteristic curve for predicting lymph node metastasis was 0.869 (95% confidence interval, 0.813-0.926). The high-risk group (risk stratification system score ≥3) exhibited a significantly higher risk of lymph node metastasis than the low-risk group (score <3) (26.5% vs 1.6%). There was no lymph node metastasis in patients with a risk stratification system of 0. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the risk stratification system were 94.7%, 55.4%, 26.5%, 98.4%, and 61.1%, respectively. CONCLUSIONS: We developed a risk stratification system that should facilitate the identification of patients with a high or low risk of lymph node metastasis. This may aid the precise selection of patients who can undergo endoscopic resection.

Risk factors of electrocoagulation syndrome after esophageal endoscopic submucosal dissection.

AIM: To investigate post endoscopic submucosal dissection electrocoagulation syndrome (PEECS) of the esophagus. METHODS: We analyzed 55 consecutive cases with esophageal endoscopic submucosal dissection for superficial esophageal squamous neoplasms at a tertiary referral hospital in South Korea. Esophageal PEECS was defined as "mild" meeting one of the following criteria without any obvious perforation: fever (≥ 37.8 °C), leukocytosis (> 10800 cells/µL), or regional chest pain more than 5/10 points as rated on a numeric pain intensity scale. The grade of PEECS was determined as "severe" when meet two or more of above criteria. RESULTS: We included 51 cases without obvious complications in the analysis. The incidence of mild and severe esophageal PEECS was 47.1% and 17.6%, respectively. Risk factor analysis revealed that resected area, procedure time, and muscle layer exposure were significantly associated with PEECS. In multivariate analysis, a resected area larger than 6.0 cm2 (OR = 4.995, 95%CI: 1.110-22.489, P = 0.036) and muscle layer exposure (OR = 5.661, 95%CI: 1.422-22.534, P = 0.014) were independent predictors of esophageal PEECS. All patients with PEECS had favorable outcomes with conservative management approaches, such as intravenous hydration or antibiotics. CONCLUSION: Clinicians should consider the possibility of esophageal PEECS when the resected area exceeds 6.0 cm2 or when the muscle layer exposure is noted.

Clinical implication of endoscopic gross appearance in superficial esophageal squamous carcinoma: revisited.

BACKGROUND: Standard endoscopic appearance is essential for the diagnosis and treatment of superficial esophageal squamous carcinoma (SESC). The aim of this study was to investigate the association between the endoscopic gross appearance and the clinicopathologic characteristics of SESC. METHODS: We retrospectively analyzed the clinicopathologic characteristics of SESC according to gross endoscopic appearance in 275 patients with SESC that underwent esophagectomy or endoscopic resection (ER). RESULTS: The proportion of type I or type III gross appearance, and that of types IIa, IIb, or IIc, were 26.2 and 73.8%, respectively. Type I or type III gross appearance was significantly associated with the female sex, submucosal invasion, lymphovascular invasion (LVI), and lymph node metastasis (LNM). In addition, younger age, larger tumor size, higher proportion of circumferential extension, type I or type III endoscopic gross appearance, submucosal invasion, moderate or poorly differentiated carcinoma, and LVI were significantly associated with LNM. Multivariate logistic regression analysis determined that independent predictors of LNM in patients with SESC included endoscopic gross appearance, submucosal invasion, and presence of LVI. Additionally, type I or type III endoscopic gross appearance lesions were more likely to have submucosal invasion than types IIa, IIb, or IIc. Risk factors for submucosal invasion included a gross appearance of type I or type III, moderately or poorly differentiated tumors, and presence of LVI. CONCLUSIONS: We found that SESC clinical features are correlated with the endoscopic appearance. Therefore, we suggest that the endoscopic gross appearance may be a candidate for additive criteria in the indications for ER.

Assessment of hepatic fibrosis regression by transient elastography in patients with chronic hepatitis B treated with oral antiviral agents.

Transient elastography (TE) has been used as a non-invasive method for liver stiffness measurement (LSM) in patients with chronic liver disease. This study was performed to assess the change of LSM by TE and to assess its clinical usefulness during long-term oral antiviral therapy in patients with chronic hepatitis B (CHB). We retrospectively reviewed 83 CHB patients. The mean interval between two LSM was 411.5 ± 149.5 days. Initial and follow-up LSM was 16.15 ± 12.41 kPa and 11.26 ± 7.36 kPa, respectively (P < 0.001). The degree of regression of liver stiffness was -2.03 ± 0.36% per month. The fibrosis stage classified by LSM value improved in 37 (44.6%) patients during oral antiviral therapy. Of the 30 (36.1%) patients with LSM ≥ 14.1 kPa (cirrhosis) at 1st LSM, 12 (40%) proved to no longer have cirrhosis (≥ 1 decrease in fibrosis stage) at 2nd LSM. LSM significantly decreased in both baseline high (> upper limit of normal [ULN] × 2) and low (≤ ULN × 2) alanine aminotransferase groups during antiviral therapy (P < 0.001; P = 0.001, respectively). Long-term oral antiviral therapy resulted in the improvement of liver stiffness in a substantial portion of patients with CHB. TE may be used a useful clinical tool to assess disease progression in CHB patients.

¹8F-fluorodeoxyglucose positron emission tomography-computed tomography for the evaluation of bone metastasis in patients with gastric cancer.

BACKGROUND: The roles of positron emission tomography and bone scanning in identifying bone metastasis in gastric cancer are unclear. AIM: We compared the usefulness of positron emission tomography-computed tomography and scanning in detecting bone metastasis in gastric cancer. METHODS: Data from 1485 patients diagnosed with gastric cancer who had undergone positron emission tomography-computed tomography and scanning were reviewed. Of 170 enrolled patients who were suspected of bone metastasis in either positron emission tomography or scanning, 81.2% were confirmed to have bone metastasis. RESULTS: The sensitivity, specificity, and accuracy were 93.5%, 25.0%, and 80.6%, respectively, for positron emission tomography and 93.5%, 37.5%, and 82.9%, respectively, for scanning. 87.7% of patients with bone metastasis showed positive findings on two modalities. 15.0% of solitary bone metastases were positive on positron emission tomography only. Positron emission tomography was superior to scanning for the detection of synchronous bone metastasis, but the two modalities were similar for the detection of metachronous bone metastasis. The concordance rate of response assessment after treatment between two modalities was moderate. CONCLUSIONS: Positron emission tomography-computed tomography may be more effective for the diagnosis of bone metastasis in the initial staging workup. Conversely, bone scanning and positron emission tomography-computed tomography may be similarly effective for the detection of metachronous bone metastasis.

Synephrine-containing dietary supplement precipitating apical ballooning syndrome in a young female.

Apical ballooning syndrome (ABS) is a unique reversible cardiomyopathy that is frequently precipitated by emotional or physical stress. In addition, the few drugs reported to precipitate ABS were either illegal or strictly controlled for medical use. This paper reports a case of ABS precipitated by a dietary supplement. Our case accentuates the potential risk of dietary supplements containing synephrine, which is uncontrolled and available to the general public. Therefore, the Korea Food and Drug Administration should regulate these dietary supplements, and warn healthcare workers and the general public of the potential hazards of the indiscriminate abuse of dietary supplements.

[A case of double primary neuroendocrine tumor from duodenum and pancreas].

Gastrointestinal neuroendocrine tumors arise from cells of the diffuse neuroendocrine system and can take place almost anywhere within the gastrointestinal tract. A 40-year-old man admitted to evaluate a duodenal subepithelial lesion which was incidentally found at health check-up. The polypoid duodenal subepithelial lesion, measuring about 7 mm, was removed by the endoscopic mucosal resection and the pathology confirmed a neuroendocrine tumor. Abdominopelvic computed tomography, done for staging work up, revealed a mass in the pancreatic head and the patient received pylorus preserving pancreaticoduodenectomy. Mass at the pancreas also found out to be neuroendocrine tumor but showed different histopathologic traits under immunohistochemical staining. The patient was also diagnosed as hyperparathyroidism and pituitary microadenoma. Finally, multiple endocrine neoplasia type 1 was confirmed, which was accompanied by duodenal neuroendocrine tumor.

Prognostic significance of elevated lipoprotein(a) in coronary artery revascularization patients.

BACKGROUND: Although lipoprotein(a) [Lp(a)] has been considered a cardiovascular risk factor for many years, there is a paucity of data in regard to the potential risk of elevated Lp(a) in symptomatic patients with CAD. Therefore, we sought to evaluate whether elevated Lp(a) is associated with worse outcome in symptomatic patients with coronary artery disease (CAD), and to clarify the prognostic value of Lp(a) in the era of coronary artery revascularization. METHODS: 6252 consecutive subjects (59.2% male, mean age 61.2 ± 11.2 years) suspected of having CAD underwent coronary angiography. Laboratory values for lipid parameters including Lp(a) were obtained on the day of coronary angiography. Baseline risk factors, coronary angiographic findings, length of follow-up, and major adverse cardiovascular events (MACE), including cardiac death and non-fatal myocardial infarction were recorded. RESULTS: Over a mean follow-up period of 3.1 ± 2.2 years, there were 100 MACE (56 cardiac deaths and 44 non-fatal myocardial infarctions), with an event rate of 1.6%. In multivariate Cox regression analysis, elevated Lp(a) was a significant predictor of MACE [hazard ratio 1.773 (95% confidence interval 1.194-2.634, p=0.005)], and the addition of this factor to the model significantly increased the global х(2) value over traditional risk factors and CAD (from 79.1 to 88.7, p=0.003). CONCLUSIONS: Elevated Lp(a) is an independent prognostic risk factor for cardiovascular events, and moreover, has incremental prognostic value in symptomatic patients with coronary artery revascularization.

Outcomes of cardiac involvement in patients with late-stage Duchenne muscular dystrophy under management in the pulmonary rehabilitation center of a tertiary referral hospital.

OBJECTIVES: The purpose of this study was to investigate the clinical outcome as well as the sequential changes of cardiac function in late-stage Duchenne muscular dystrophy (DMD) patients by 2-dimensional echocardiography. METHODS: A total of 31 individuals (initial age: 21.6 ± 5.0 years, range: 15-35 years) with late-stage DMD (Swinyard-Deaver's stage 7 or 8) were enrolled. All of these patients had respiratory insufficiency and were on ventilator support. Sequential echocardiographic data were collected over at least 3 years. Repeated measures analysis of variance was used to compare changes in left ventricular ejection fraction (LVEF) over time. RESULTS: The sequential change in the mean LVEF showed no significant differences with initial, 1-, 2-, and 3-year follow-up LVEFs which were 42.2, 42.9, 43.8 and 42.6%, respectively (p = 0.320). In terms of the clinical outcome, all but 1 patient survived during the follow-up period of 46.5 ± 9.1 months. CONCLUSIONS: The cardiac function in late-stage DMD patients showed a stabilization of LVEF on adequate ventilatory support and optimal cardiac medication therapy until their mid-30s. In addition, considering the favorable clinical outcome in our study, the process of cardiac involvement in late-stage DMD may demonstrate that in some patients it is nonprogressive.