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There is some dissatisfaction with the term “nonalcoholic fatty liver disease (NAFLD),” which overemphasizes alcohol and underemphasizes the importance of metabolic risk factors in this disease. Recently, a consensus recommended “metabolic (dysfunction)-associated fatty liver disease (MAFLD)” as a more appropriate term to describe fatty liver diseases (FLD) associated with metabolic dysfunction. During the definition change from NAFLD to MAFLD, subjects with FLD and metabolic abnormalities, together with other etiologies of liver diseases such as alcohol, virus, or medication who have been excluded from the NAFLD criteria, were added to the MAFLD criteria, while subjects with FLD but without metabolic abnormality, who have been included in the NAFLD criteria, were excluded from the MAFLD criteria. This means that there is an emphasis on the metabolic dysfunction in MAFLD which may underestimate the prognostic value of hepatic steatosis itself, whereas the MAFLD criteria might better identify subjects who are at a higher risk of hepatic or cardiovascular outcomes. However, non-metabolic risk NAFLD subjects who are excluded from the MAFLD criteria are missed from the diagnosis, and their potential risk can be the cause of future diseases. Although huge controversies remain, this review focused on summarizing recent studies that compared the clinical and prognostic characteristics between subjects with NAFLD and MAFLD.

Background and study aims Sessile serrated lesion (SSL) detection rate has been variably reported and unlike adenoma detection rate (ADR) is not currently a quality indicator for screening colonoscopy. Composite detection rates of SSL in patients undergoing average risk screening colonoscopy are not available. Methods Electronic database search (Medline, Embase and Cochrane) was conducted for studies reporting detection rates of serrated polyps (SSL, Hyperplastic polyp, traditional serrated adenoma) among average risk subjects undergoing screening colonoscopy. Primary outcomes were pooled SDR (SSL detection rate) and proximal serrated polyp detection rate (PSPDR). Pooled proportion rates were calculated with 95 %CI with assessment of heterogeneity (I2). Publication bias, regression test and 95 %prediction interval were calculated. Results A total of 280,370 screening colonoscopies among average risk subjects that were eligible with 48.9 % males and an average age of 58.7 years (± 3.2). The pooled SDR was available from 16 studies: 2.5 % (1.8 %–3.4 %) with significant heterogeneity (I2 = 98.66 %) and the 95 % prediction interval ranging from 0.6 % to 9.89 %. When analysis was restricted to large (n > 1000) and prospective studies (n = 4), SDR was 2 % (1.1 %–3.3 %). Pooled PSPDR was 10 % (8.5 %–11.8 %; 12 studies). There was evidence of publication bias (P Conclusion Definitions of SSL have been varying over years and there exists significant heterogeneity in prevalence reporting of serrated polyps during screening colonoscopy. Prevalence rate of 2 % for SSL and 10 % for proximal serrated polyps could serve as targets while robust high-quality data is awaited to find a future benchmark showing reduction in colorectal cancer arising from serrated pathway.

The clinicopathological features of carcinomas expressing AT-rich interaction domain 1a (ARID1A) and programmed death ligand 1 (PD-L1) in HCC are poorly understood. Here, we examined ARID1A and PD-L1 expression in surgically resected primary hepatocellular carcinoma (HCC) and the association of ARID1A and PD-L1 expression with clinicopathological features and patient outcomes. Their association with ARID1A expression and tumor-associated CD68-positive macrophage was further explored. Using a database of 255 patients who underwent hepatic resection for HCC, immunohistochemical staining of ARID1A, PD-L1, and CD68 was performed. We also analyzed the expression PD-L1 after ARID1A knockdown in HCC cell lines. Samples from 81 patients (31.7%) were negative for ARID1A. Negative ARID1A expression was significantly associated with male sex, high alpha-fetoprotein, high des-gamma-carboxyprothrombin, large tumor size, high rate of poor differentiation, microscopic intrahepatic metastasis, and PD-L1 expression. In addition, negative ARID1A expression was an independent predictor for recurrence-free survival, overall survival, and positive PD-L1 expression. Stratification based on ARID1A and PD-L1 expression in cancer cells was also significantly associated with unfavorable outcomes. PD-L1 protein expression levels were increased through phosphoinositide 3-kinase/AKT signaling after ARID1A knockdown in HCC cells. HCC with ARID1A-low expression was significantly correlated with high levels of tumor-associated CD68-positive macrophage. Conclusion: Our large cohort study showed that ARID1A expression in cancer cells was associated with a poor clinical outcome in patients with HCC, PD-L1 expression in cancer cells, and tumor microenvironment. Therefore, ARID1A may be a potential molecular biomarker for the selection of patients with HCC for anti-programmed death 1/PD-L1 antibody therapy.

Background and study aims The primary objective was to measure the effect of music as an adjunct to sedation in patient anxiety levels during pediatric endoscopic examinations. Patients and methods We performed a single-blind randomized controlled trial comparing music with no music in children aged 2 to 18 years. Anxiety was measured using the Modified Yale Preoperative Anxiety Scale (m-YPAS) and the Visual Analog Anxiety Scale (VAS-anxiety). Patient perception of pain was evaluated with the Wong-Baker Faces Pain Rating Scale (WBFPRS). Patient experience, family satisfaction, and endoscopist perception of difficulty were evaluated. Sedative doses were recorded. Results A total of 51 children were randomized to the experimental group and 49 children to the control group. The mean ages were 10.5 years and 12.3 years, respectively. There were 63 % female subjects with no differences between groups. Overall, there were 85 upper endoscopies and 15 colonoscopies. In the recovery unit, the experimental group had lower average m-YPAS scores (mean score 27.7 vs 34.7; P Conclusions The study results show that music reduces anxiety and pain associated with endoscopic procedures in children. It also facilitates these procedures and improves patient satisfaction.

Background/Aims: Current evidence suggests that liver cirrhosis (LC) causes severe psychological stress and depression, which are risk factors for suicide. Although previous studies reported the association between LC and suicidal thoughts, little is known of its effect on suicidal deaths. Therefore, this study was undertaken to investigate the effect of new-onset LC on suicide.Methods: From the National Health Insurance Service-National Sample Cohort of South Korea, 5,809 incident LC patients and 11,618 risk-set controls matched by propensity score were selected for follow-up. The incidence rate of suicide was estimated using a generalized estimating equation with a Poisson distribution. Effect size was presented as a hazard ratio (HR) using Cox’s proportional hazards model.Results: The incidence rate of suicide was 143.3 cases per 100,000 person years (95% confidence interval [CI], 100.2–205.1) among the LC cohort. The LC patients were 2.37 times more likely to commit suicide compared with matched controls (HR, 2.37; 95% CI, 1.44–3.88). Increased suicide risk was evident within the first 2 years of the follow-up period (HR, 2.59; 95% CI, 1.20–5.60) and among the 18–49-year-old age group (HR, 3.72; 95% CI, 1.45–9.56).Conclusions: Our study found increased risk of suicide in patients with new onset LC, especially during the early period following diagnosis and in younger patients. To decrease this suicide risk, a regular and continuous social support system is required.

Chronic hepatitis C infection is a major cause of liver disease and hepatocellular carcinoma worldwide. While hepatitis C has been treated for decades with some success, the introduction of direct acting antiviral agents has revolutionized the treatment of hepatitis C with finite, highly effective, well-tolerated therapy and there are few populations that cannot be successfully treated now or are complicated to manage. The World Health Organization has released elimination targets in an effort to eliminate viral hepatitis and reduce dramatically the morbidity and mortality caused by both viral hepatitis. While hepatitis C is straightforward to treat, it remains problematic to eliminate on a global scale. Diagnosis of hepatitis C remains the major gap in the cascade of care and numerous screening strategies will be required to reduce this gap. While historically, treatment of hepatitis C has been centralized, decentralized approaches will be required to diagnose, evaluate, and link to care the large population of individuals worldwide with hepatitis C across low-, middle-, and high-income countries. With the introduction of multiple pangenotypic treatment options and reduced cost for these therapies, assessment and treatment for those with hepatitis C has been simplified and made more accessible worldwide. There are multiple populations for whom care models are being developed and refined, including those when inject drugs, those who are incarcerated, those who present with sexually transmitted disease including the men who have sex with men population, amongst many others. While a vaccine for hepatitis C remains elusive these efforts continue. Multiple successful elimination efforts have been reported.

The immune-tolerant (IT) phase of chronic hepatitis B (CHB) patients is not generally indicative of antiviral therapy (AVT). We assessed and compared the risk of hepatocellular carcinoma (HCC) during the IT-phase stringently defined by a low fibrosis-4 (FIB-4) index, compared to that in patients undergoing AVT.Among 125 untreated patients that were hepatitis B e-antigen positive, hepatitis B virus-DNA20,000 IU/mL, with normal alanine aminotransferase level from 2012 to 2018, those with a FIB-4 index of1.45 were classified into the IT-group. The cumulative probability of HCC was estimated using Kaplan-Meier analysis. All patients were assessed until HCC development (intention-to-treat [ITT] analysis), whereas those suspected of experiencing CHB phase switch were assessed using the per-protocol (PP) and censored at the time of phase switch.The cumulative probability of HCC at 1-, 3-, and 5-years among the IT-group was zero, compared to AVT-treated patients with FIB-4 indices1.45 during the same period: 0.2%, 0.6%, and 1.4%, respectively (P=0.264 for ITT and P=0.533 for PP). Among the initially screened 125 untreated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to the IT-group (P=0.005). Furthermore, among AVT-treated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to their counterpart (P0.001).The risk of HCC was negligible in the IT-group stringently defined by a low FIB-4 index. However, given that a higher HCC risk exists among untreated patients with higher FIB-4, appropriate criteria for AVT should be established.

Background and aims Endoscopic resections are associated with bleeding and perforation and may be managed with through-the-scope (TTS) clips, over-the-scope clips and endoscopic suturing. The aim of this preclinical study was to compare technical success of closure using a novel TTS tissue helix tack and suture device (X-Tack) to TTS clips in a porcine model. Materials and methods Four subjects underwent 40 mucosal resections, diameter range 25–50 mm, in the stomach (n = 24) and colon (n = 16). Closures were randomized to X-Tack (n = 24) or clip (n = 16). Animals underwent weekly endoscopic follow-up for 4 weeks. Results Technical closure with X-Tack was successful in 24 of 24 (100 %) cases and with clips in 13 of 16 cases (81.3 %) (P = 0.0001). One colonic perforation occurred and was successfully managed using X-Tack. The rate of healing was not statistically different between the groups, and all sites healed at 4 weeks including the perforation and were confirmed by histology. Conclusions Compared to TTS clip, X-Tack is superior for effecting large mucosal defect closure, including durable sealing of full-thickness perforation. There was no difference in rate of healing between devices.

Compared with each monoinfection, coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) is well known to increase the risks of developing liver cirrhosis and hepatocellular carcinoma. However, the mechanism by which HBV/HCV coinfection is established in hepatocytes is not well understood. Common cell culture models for coinfection are required to examine viral propagation. In this study, we aimed to establish a cell line permissive for both HBV and HCV infection. We first prepared a HepG2 cell line expressing sodium taurocholate cotransporting polypeptide, an HBV receptor, and then selected a cell line highly permissive for HBV infection, G2/NT18-B. After transduction with a lentivirus-encoding microRNA-122, the cell line harboring the highest level of replicon RNA was selected and then treated with anti-HCV compounds to eliminate the replicon RNA. The resulting cured cell line was transduced with a plasmid-encoding CD81. The cell line permissive for HCV infection was cloned and then designated the G2BC-C2 cell line, which exhibited permissiveness for HBV and HCV propagation. JAK inhibitor I potentiated the HCV superinfection of HBV-infected cells, and fluorescence-activated cell-sorting analysis indicated that HBV/HCV double-positive cells accounted for approximately 30% of the coinfected cells. Among several host genes tested, cyclooxygenase-2 showed synergistic induction by coinfection compared with each monoinfection. Conclusion: These data indicate that our in vitro HBV/HCV coinfection system provides an easy-to-use platform for the study of host and viral responses against coinfection and the development of antiviral agents targeting HBV and HCV.

Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC.Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed.Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C.Conclusions: Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.

Background and study aims Endoscopic balloon dilation (BD) and temporary stent placement for pancreaticojejunostomy anastomotic stricture (PJAS) achieves good short-term outcomes; however, stricture recurrences remain frequent. We examined the feasibility of performing radial incision and cutting (RIC) combined with BD for refractory PJAS. Patients and methods Five consecutive patients with refractory PJAS who underwent RIC with BD between 2015 and 2018 were retrospectively investigated. We evaluated the technical and clinical success, adverse event (AE), and recurrence rates associated with RIC with BD. Results In all five patients, technical and clinical success were achieved. Pancreatic stone removal was simultaneously performed in one patient. The mean procedure time was 18 minutes (range 12–23 minutes). There were no procedure-related AEs. All patients were followed for over 2 years, with a mean follow-up period of 33 months (range 24–40 months). During the follow-up period, none of the patients developed stricture recurrence and all anastomoses remained patent. Conclusions This is the first report of RIC with BD for the treatment of refractory PJAS, showing favorable results. This combined procedure might be a useful option for treating refractory PJAS.

Background/aims Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus (HBV). Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (p = 0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (p = 0.75 and p = 0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (Date: September 10, 2013).

Background and study aims Endoscopic submucosal dissection (ESD) is widely performed for superficial esophageal cancer, but stricture after extensive resection is a major clinical problem. Using an ultrathin endoscope would enable endoscopists to approach lesions beyond the stricture. We evaluated the feasibility of an ultrathin endoscope for esophageal ESD. Methods To perform ESD with an ultrathin endoscope, we developed a transparent hood and ESD knife. A total of 24 esophageal ESDs were performed by two endoscopists with excised and live porcine esophaguses. A GIF-Q260 J and Dual knife were used in the conventional group and the GIF-XP260NS and a newly developed knife were used in the ultrathin group. En bloc resection rates, perforation rates, and procedure times were compared. Results All 24 lesions were resected en bloc without perforation. The mean procedure time was longer in the ultrathin group, although not significantly so (274.3 ± 81.8 s vs 435.8 ± 313.9 s, respectively; P = 0.22). Conclusion Although the procedure time was longer in the ultrathin group, en bloc resection was performed without any perforation. The findings indicate that esophageal ESD with an ultrathin endoscope is feasible.

Eosinophilic colitis (EC) belongs to a group of idiopathic diseases called eosinophilic gastrointestinal disorders, which are characterized by eosinophil-predominant inflammation in the gastrointestinal tract. Corticosteroids is the first-line pharmacotherapy for EC refractory to diet therapy. We report an infant with steroid-resistant EC, who successfully returned to a healthy growth trajectory under the combined therapy of montelukast and ketotifen. An 8-month-old boy presented with bloody diarrhea, anemia, and failure to thrive (FTT) that started 6 days after birth. The patient has no known allergies. A trial of elementary diet was unsuccessful. The results of several stool cultures were unremarkable. Similarly, lower gastrointestinal series failed to identify anything significant. At 3 months of age, an esophagogastroduodenoscopy with biopsies from the distal duodenum and proximal jejunum were unremarkable. The diarrhea and FTT persisted. A rectosigmoidoscopy with biopsies was performed; the results led to the diagnosis of EC at 5 months of age. Oral prednisolone 1 mg/kg/day was prescribed; however, 3 months into the treatment, persistent bloody diarrhea and FTT were still noted. Montelukast and ketotifen were added, after which diarrhea and weight gain started to improve. Prednisolone and montelukast/ketotifen were tapered off 6 months after. He remains symptom free and has normal growth and development in a 5-year follow-up.

Celiac disease (CD) is a systemic disease triggered by gluten ingestion in genetically predisposed individuals. It manifests primarily as an autoimmune enteropathy associated with specific circulating autoantibodies and a human leukocyte antigen haplotype (HLA-DQ2 or HLA-DQ8). It afflicts roughly 1% of the population, though the majority of patients remain undiagnosed. Diarrhea and malabsorption are classic manifestations of CD; however, both children and adults can be paucisymptomatic and present extraintestinal manifestations such as anemia, osteoporosis, and abnormal liver tests. CD screening is not recommended for the general population, and it should be focused on high-risk groups. CD diagnosis is challenging and relies on serological tests, duodenal histology, and genetic testing. Particularly difficult presentations to manage are seronegative patients, seropositive patients without villus atrophy, and patients who have started a gluten-free diet before the diagnostic workup. The only proven treatment is a lifelong gluten-free diet. We present an in-depth review on the physiopathology and management of CD, with a particular emphasis on diagnostic challenges.A doença celíaca (DC) é uma doença sistémica desencadeada pela exposição ao glúten em doentes geneticamente susceptíveis. Manifesta-se maioritariamente por uma enteropatia auto-imune associada a auto-anticorpos e aos haplotipos HLA-DQ2 ou HLA-DQ8. A DC afecta aproximadamente 1% da população mundial admitindose, no entanto, que a maioria dos doentes não esteja diagnosticada. As manifestações clássicas de DC são a diarreia e sintomas de malabsorção, no entanto tanto crianças como adultos podem ser pauci-sintomáticos ou apresentar manifestações extra-intestinais incluindo anemia, osteoporose ou alteração das provas hepáticas. O rastreio de base populacional não está recomendado, devendo o foco ser nos grupos de risco para DC. O diagnóstico de DC é um desafio e assenta em três pilares: testes serológicos, histologia duodenal e testes genéticos. Apresentações particularmente difíceis de manejar são os doentes sero-negativos, doentes sero-positivos sem atrofia vilositária e doentes que iniciam dieta sem glúten antes da marcha diagnóstica. O único tratamento com eficácia comprovada é a dieta sem glúten. Apresentamos uma revisão aprofundada da fisiopatologia e manejo da DC, com particular ênfase nos desafios diagnósticos.

Background and study aims The optimal intragastric pressure (IP) for strong gastric wall extension is unclear. We aimed to develop an accurate method to measure IP using endoscopy and determine the pressure required for strong gastric wall extension. Methods An in vitro experiment using an endoscope with a rubber attached at its tip was conducted. The process of inserting the pressure measurement probe into the forceps channel was skipped, and the tube of the pressure measurement device was directly connected to the forceps channel. In vivo, the pressure in 51 consecutive patients at the time of strong gastric wall extension was measured. Strong extension of the gastric wall was defined as when the folds in the greater curvature were flattened as a result of sufficient extension of the gastric wall by insufflated air during upper gastrointestinal endoscopy. The IP at that time was measured. Results In vitro, 20 mL of tap water was injected once into the forceps channel and then aspirated for 10 seconds. Pressure measurement after irrigation of the forceps channel as well as the measurement by inserting the probe procedure were accurately performed. In vivo, among the 51 included patients, the mean IP (range) was 14.7 mmHg (10–23). Strong extension of the gastric wall was obtained in 96.1 % of patients when the IP was 20 mmHg. Conclusions We developed an accurate method to measure IP using upper gastrointestinal endoscopy. Strong extension of the gastric wall was obtained in almost all patients when the IP was 20 mmHg.

Downhill esophageal varices (DEV) are a rare form of esophageal varices associated with superior vena cava obstruction. Obstruction leads to retrograde blood flow through collateral venous channels, including the esophageal venous plexus, to redirect blood flow to the right atrium via the inferior vena cava. This leads to the formation of DEV. It is a rare phenomenon to have gastrointestinal bleeding, especially hematemesis, on a patient’s first presentation with this disease process. We describe such a case here involving a patient with DEV secondary to metastatic renal cell carcinoma presenting with hematemesis.

Intrahepatic cholelithiasis, which is defined as stones proximal to the confluence of the hepatic ducts, is considered endemic in Southeast Asia. Its pathogenesis is not completely understood yet. A 19-year-old female was admitted to the hospital with a history of recurrent biliary pancreatitis. Abdominal ultrasound detected normal gallbladder while magnetic resonance cholangiopancreatography revealed lithiasis at the hepatic duct of liver segment V. After preoperative evaluation a typical segmentectomy was done. The postoperative period was uneventful and the patient was well at 6-month follow-up.

With the comprehensive application of a variety of treatment methods, the survival time of patients with primary liver cancer is gradually increasing. For patients with early-stage liver cancer and portal hypertension, local ablation therapy can achieve long-term survival and play a positive role in stabilizing portal venous pressure, preserving liver function, and reducing complications. In addition, it can be combined with other techniques such as transarterial chemoembolization, transjugular intrahepatic portosystemic shunt, splenectomy, and pericardial devascularization to further improve treatment outcome. Several measures can be taken in the perioperative period to improve the management efficiency of patients after ablation, such as objective evaluation of portal venous pressure, prevention of esophagogastric variceal bleeding, correction of hypersplenism, prevention of postoperative liver failure, and multidisciplinary team management.

Background and study aims The safety of transpapillary biliary drainage by stent placement through endoscopic retrograde cholangiography (ERC) may be compromised by the occurrence of stent migration-induced perforation of the duodenal wall (SMDP). We aimed to assess the prevalence rate, risk factors and clinical course of SMDP.Patients and methods This retrospective cohort study included all patients who underwent an ERC with biliary plastic stent placement, between January 2014 and December 2018. Patients with an SMDP were identified from our endoscopy complication registry.Results 1227 patients underwent an ERC, of whom 629 patients (51 %) with biliary plastic stent placement; in 304 patients (25 %) stents were placed for perihilar strictures. Thirteen patients with SMDP were identified. The prevalence was 2.1 % for patients with biliary plastic stent placement and 4.3 % for patients stented for a perihilar stricture. All SMDPs occurred in patients with a perihilar stricture and with stents ≥ 12 cm (range 12–20 cm). Another potential risk factor was stent insertion into the left liver lobe, which was present in 10 of 13 patients. In 10 of 13 patients, SMDP was clinically suspected. Three of 13 patients were asymptomatic and diagnosed at elective stent retrieval. Eight patients could be endoscopically treated with an over-the-scope clip. Four patients died due to abdominal sepsis despite repeated interventions.Conclusion SMDP is a rare but potentially life-threatening complication of ERC after transpapillary drainage for perihilar biliary strictures. Stents ≥ 12 cm and stent insertion into the left liver lobe may be associated risk factors.

Gastrointestinal (GI) symptoms of SARS-CoV-2/COVID-19 in the form of anorexia, nausea, vomiting, abdominal pain and diarrhea are usually preceded by respiratory manifestations and are associated with a poor prognosis. Hematochezia is an uncommon clinical presentation of COVID-19, and we hypothesize that older patients with significant comorbidities (obesity and cardiovascular) and prolonged hospitalization are susceptible to ischemic injury to the bowel. We reviewed the clinical course, key laboratory data including acute-phase reactants, and drug/medication history in 2 elderly male patients admitted for COVID-19 respiratory failure. Both patients had a complicated clinical course and suffered from hematochezia, acute blood loss, and anemia which led to hemodynamic instability requiring blood transfusion around day 40 of their hospitalization. Colonoscopic impressions were correlated with the histopathological findings in the colonic biopsies that included changes compatible with ischemia and nonspecific acute inflammation, edema, and increased eosinophils in the lamina propria. Both patients were hemodynamically stable, on prophylactic anticoagulants, multiple antibiotics, and antifungal agents due to respiratory infections at the time of lower GI bleeding. Hematochezia resolved spontaneously with supportive care. Both patients eventually recovered and were discharged. Elderly patients with significant comorbid conditions are uniquely at risk for ischemic injury to the bowel. This case report highlights hematochezia as an uncommon GI manifestation of spectrum of COVID-19 complications. The causes of bleeding in these COVID-19 associated cases are likely multifactorial and can be attributed to concomitant etiologies based on their age, multiple comorbid conditions, prolonged hospitalization compounded by lung injury, and hypoxia precipitated by the virus. We hypothesize that rather than a direct viral cytopathic effect, ischemia and hypoperfusion may be unleashed due to the cytokine storm orchestrated by the virus that leads to abnormal coagulation profile. Additional factors that may contribute to ischemic injury are prophylactic use of anticoagulants and polypharmacy. There were no other causes to explain the brisk lower GI bleeding. Presentation of hematochezia was followed by hemodynamic instability that may further increase the mortality and morbidity of COVID-19 patients, and prompt consultation and management by gastroenterology is therefore warranted.

In order to standardize the effective prevention, early screening, and diagnosis of primary liver cancer, Chinese Society of Hepatology, Chinese Medical Association, organized relevant experts to develop consensus on the secondary prevention for primary liver cancer (2021 edition) based on the advances in the basic, clinical, and preventive researches on primary liver cancer in China and globally and the actual situation in China at this stage, so as to provide an important basis for the prevention, screening, and early diagnosis of primary liver cancer in patients with chronic liver diseases.

ObjectiveTo investigate the features of liver injury and related influencing factors in adolescents and adults with infectious mononucleosis (IM). MethodsA retrospective analysis was performed to investigate the features of liver injury in adolescents and adults with IM who were hospitalized in Peking University First Hospital from January 1,2005 to December 31,2018, and the patients were divided into subgroups based on age, Epstein-Barr virus (EBV) DNA level, and presence or absence of jaundice or infection with cytomegalovirus or hepatitis E virus (HEV). The t-test was used for comparison of continuous data meeting analytical conditions between two groups, and the Mann-Whitney U test was used for comparison of continuous data which did not meet analytical conditions between two groups; the chi-square test was used for comparison of categorical data between two groups, and the Fisher’s exact test was used for comparison of categorical data which did not meet the analytical conditions of the chi-square test. A logistic regression analysis was used for multivariate analysis. ResultsA total of 274 patients were enrolled, with 154 male patients (56.2%) and 120 female patients (43.8%), and the mean age of onset was 22.3±67 years. The incidence rate of liver injury ［defined as alanine aminotransferase (ALT) ＞50 U/L and/or aspartate aminotransferase (AST)＞40 U/L］ was 97.4% (267/274), and that of jaundice was 27.6% (74/268). The patients, aged ≥20 years, tended to have a higher level of gamma-glutamyl transpeptidase (GGT) (Z=2.070, P=0.038). Serum EBV DNA was measured for 167 patients, among whom 90 had positive results and 77 had negative results. The positive serum EBV DNA group had significantly higher levels of GGT (Z=3.005, P=0.003) and lactate dehydrogenase (Z=2.162, P=0.031) than the negative serum EBV DNA group. The patients with cytomegalovirus infection tended to have a higher level of alkaline phosphatase (Z=2.351, P=0.019), and the patients with HEV infection presented with a higher level of GGT (Z=1.988, P=0.047). AST (odds ratio ［OR］=1.006, 95% confidence interval ［CI］: 1.002-1.010, P=0.005) and ALP (OR=1.012, 95%CI: 1.005-1.020, P=0.001) were independent risk factors for jaundice. ConclusionThere is a high incidence rate of liver injury in adolescents and adults with IM, and the patients with an older age or positive serum EBV DNA tend to have more severe liver injury.

One of the approaches to cure human immunodeficiency virus (HIV) is the use of therapeutic vaccination. We have launched the Provir/Latitude 45 study to identify conserved CTL epitopes in archived HIV-1 DNA according to the HLA class I alleles in aviremic patients under antiretroviral therapy (ART). A HIV-1 polypeptidic therapeutic vaccine based on viral sequence data obtained from circulating blood was proposed; here, our aim was to compare the proviral DNA in blood and gut-associated lymphoid tissue (GALT). Peripheral blood mononuclear cells and gut biopsies were obtained from two HIV-1 infected patients under successful antiretroviral therapy. Total DNA was extracted including the proviral DNA. The HIV-1 reverse transcriptase was sequenced in both compartments using next generation sequencing followed by single genome sequencing; phylogenetic trees were established and compared. The proviral sequences of both compartments intra-patient exhibited a very low genetic divergence while it was possible to differentiate the sequences inter-patients; single genome sequencing analysis of two couples of samples confirmed that there was no compartmentalization of the sequences intra-patient. We conclude that, considering these two cases, the proviral DNA sequences in blood and GALT are similar and that the epitope analysis of HIV-1 provirus in blood should be considered as relevant to that observed in the GALT, a hard-to-reach major compartment, and can therefore be used for therapeutic vaccine approaches.

Herpes esophagitis (HE) is a rare condition in immunocompetent adolescents. However, it commonly occurs as a primary infection in younger individuals. Herein, we report a 16-year-old female patient who had a history of fever for 5 days, odynophagia, and orolabial herpes infection for 7 days. Clusters of painful vesicles on an erythematous base on the lips, gingiva, and palate were observed on physical examination. Further, esophagogastroduodenoscopy revealed diffuse linear ulcerations in the distal esophagus. The patient then received the following treatment: intravenous (I.V.) acyclovir 5 mg/kg three times a day, I.V. omeprazole 40 mg two times a day, and acyclovir 5% cream four times a day. After 8 days of admission, the patient was discharged. A follow-up esophagogastroduodenoscopy was performed 7 weeks after discharge, and the results revealed that the esophageal mucosa had a normal appearance. The effect of antiviral treatment against HE remains unknown in these patients. Nevertheless, it is believed to accelerate the healing process in individuals with esophageal mucosal barrier damage. To the best of our knowledge, this case of a female adolescent with an intact immune system is the sixth case of herpes simplex esophagitis to be reported in the literature.

Background The diagnosis of pediatric pancreatitis has been increasing over the last 20 years. We aimed to compare the clinical characteristics for pediatric acute pancreatitis (AP) with adult AP, and investigate the risk factor for acute recurrent pancreatitis (ARP) in children. Method From June 2013 to June 2019, a total of 130 pediatric patients with AP at the inpatient database were enrolled. Univariate analysis and multivariate Cox regression analysis were performed to identify the risk factors for ARP in children. Result Major etiologic factors in 130 patients were biliary (31.5%), idiopathic (28.5%). The etiology of pancreatitis in children was markedly different from that in adults (p p = 0.018) and occurrence rate of pancreatic necrosis (p = 0.041), SIRS (p = 0.021), acute peripancreatic fluid collection (p = 0.014). Univariate and Multivariate Cox regression analysis showed that female (p = 0.020; OR 3.821; 95% CI 1.231–11.861), hypertriglyceridemia (p = 0.045; OR 3.111; 95% CI 1.024–9.447), pancreatic necrosis (p = 0.023; OR 5.768; 95% CI 1.278–26.034) were the independent risk factors of ARP. Hypertriglyceridemia AP had the highest risk of recurrence compared to other etiology (p = 0.035). Conclusion Biliary and idiopathic disease were the major etiologies of AP in children. Children have simpler conditions than adults. Female, hypertriglyceridemia, and pancreatic necrosis were associated with the onset of ARP.

ObjectiveTo investigate the clinical effect of laparoscopic splenectomy and pericardial devascularization (LSPD) in patients with portal hypertension and the long-term effect of LSPD. MethodsA total of 40 portal hypertension patients with Child-Pugh A/B liver function who received LSPD in The First Hospital of Jilin University from August to December 2017 were enrolled as surgical group, and 44 portal hypertension patients with Child-Pugh A/B liver function who received conservative treatment during the same period of time was enrolled as internal medicine group. The patients were followed up to June 30, 2019, and liver function parameters, upper gastrointestinal bleeding, and portal vein thrombosis were recorded for all patients at each time point. The t-test was used for comparison of normally distributed continuous data between two groups; an analysis of variance was used for comparison between multiple groups, and the Bonferroni test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution; between multiple groups, and the Mann-Whitney U test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups. ResultsAt 6, 12, and 24 months after discharge, compared with the internal medicine group, the surgical group had a significantly higher level of cholinesterase (t=3.527, 3.849, and 5.555, all P＜0.05) and a significantly lower Child-Pugh score (t=2.498, 2.138, and 2.081, all P＜0.05). Compared with the internal medicine group at 12 and 24 months after discharge, the surgical group had a significantly higher level of albumin (t=3.120 and 2.587, both P＜0.05) and a significantly lower incidence rate of upper gastrointestinal bleeding (χ2=4.947 and 5.155, both P＜0.05). At 24 months after discharge, the surgical group had a significantly lower number of patients who had a significant increase in alpha-fetoprotein level than the internal medicine group (χ2=4.648, P=0.031). At 12 months after discharge, the surgical group had a significantly higher incidence rate of portal vein thrombosis than the internal medicine group (χ2=4.395, P=0.036). The surgical group had significant improvements in albumin (F=2.959, P=0.013), cholinesterase (F=11.022, P＜0001), prothrombin time (H=94.100, P＜0.001), and Child-Pugh score (F=3.742, P=0.003) from admission to 12 and 24 months after surgery. ConclusionIn portal hypertension patients with Child-Pugh A/B liver function, LSPD can improve liver function and reduce the incidence rate of upper gastrointestinal bleeding, and the high incidence rate of portal vein thrombosis can be effectively reduced by oral aspirin and rivaroxaban.

Background and study aims Despite its widespread adoption, colonoscope still has its limitations. Advancement is often limited by the looping of colon. The isolation of SARS-CoV-2 in stool raises concern for the risk of disease transmission. A single-use robotic colonoscope, the NISInspire-C System, that features a balloon-suction anchorage mechanism was developed to address these. Methods The NISInspire-C balloons are designed to provide anchorage for straightening of the colon during advancement. Angulation at the bending section is tendon-wire driven by servo mechanisms integrated into a robotic control console. This was a pilot, prospective trial to evaluate the safety and feasibility of this system. Healthy volunteers underwent examination with the NISInspire-C, followed by the conventional colonoscope. The procedure time, cecal intubation rates (CIR), complications, and level of pain were measured. Results A total of 19 subjects underwent the examination. The cecal intubation rate was 89.5 % (17/19) and the overall time-to-cecum was 26.3 minutes (SD: 17.9 mins). There were no procedure-related complications. Polyps were detected in seven of 19 (36.8 %) subjects during the NISInspire-C procedure. Three more subjects were found to have adenomatous polyps with the conventional colonoscope. There was minimal variation in level of pain during the procedures with the two colonoscopes. Conclusion The single-use robotic colonoscope NISInspire-C is a safe and feasible alternative to the conventional colonoscope. Further technical refinement is needed to improve the CIR. This study was limited by its small sample size.

Aim:The risk of acute diverticulitis (AD) increases with each attack and the decision of therapeutic management is getting more complicated. We aimed to investigate the effective features of the number of attacks.Method:Two hundred thirty six patients with AD defined by computerized tomography were retrospectively analyzed according to the number of attacks (1, 2, and ≥3).Results:45.8% patients were female. The mean age was 58.3±12.7 years old, mean body mass index was 28.8±6.5 kg/m2. Elective colonoscopy of AD was mostly localized in the left colon (p

Background Calcium carbonate antacids are potent over-the-counter antacids, made more effective by adding magnesium carbonate (as in Rennie, Bayer). However, published studies on their onset of action are scarce. Therefore, we carried out an in vitro study comparing Rennie and placebo under simulated conditions of the human stomach (artificial stomach model) to reconfirm the onset of action of Rennie. Methods The validated Simulator of the Human Intestinal Microbial Ecosystem apparatus (SHIME, ProDigest, Belgium) was used, comprising five reactors simulating different parts of the human gastrointestinal tract. Both Rennie and placebo were dosed at two tablets per incubation over six independent, 2-h stomach incubations each. Primary objectives: to evaluate the time required to achieve pH 3.0, 3.5, 4.0 and 4.5, as well as the maximum pH reached. Secondary objective: to evaluate pepsin activity over the entire 2-h gastric incubation. Results After addition of Rennie, the gastric medium reached a pH of 3.0 within 40 s. The maximum pH of 5.24 was maintained for almost 10 min. In contrast, the maximum pH with placebo was 1.28 during the entire gastric simulation. Furthermore, Rennie strongly reduced the activity of mucosa-damaging pepsin during the period of increased pH. With placebo, the lower pH resulted in consistently high loads of digested peptides, reflecting the high cumulative and instantaneous pepsin activity. Conclusions New data is a critical component in informed decision making. Our data confirm the high efficacy and fast onset of acid-neutralizing action of Rennie, which begins to work within seconds.

Background Tumor-associated macrophages (TAMs), inflammatory cells in tumor microenvironment, are crucial for the tumor occurrence and progression which in turn increase the expression of soluble CD163 (sCD163). Nevertheless, not much has been established regarding sCD163 and its connection to HCC diagnosis and prognosis. This study was conducted to evaluate the diagnostic and prognostic role of sCD163 in patients with HCC on top of HCV-related liver cirrhosis. Forty adult patients with HCV-related liver cirrhosis and HCC (HCC group) were randomly selected and subjected to locoregional therapies, either transarterial chemoembolization (TACE) or radiofrequency ablation (RFA). Four patients were excluded because of portal vein invasion. Another group of 20 patients with liver cirrhosis only served as controls (LC group). Routine laboratory studies and abdominal ultrasound were done for all. Alpha-fetoprotein (AFP) and sCD163 were measured twice, at baseline and 1-month post-intervention, using a commercially available enzyme-linked immunosorbent assay kit. Results At baseline, sCD163 showed an insignificant higher value in HCC group (p > 0.05). The best cutoff value for sCD163 and AFP was 6.2 mg/L and 195 ng/mL, respectively. AFP had a larger area under the curve (0.88 vs. 0.767). An overall significant decline was seen in sCD163 after treatment (6.5±1.5 to 3.1±2.5 mg/L; p < 0.001), while AFP showed an insignificant decrease (p > 0.05). Also, sCD163 decreased significantly in the eradicated cases (6.1±1.4 mg/L before intervention vs. 2.3±1.4 mg/L after intervention, p < 0.01), while there was a significant increase in the recurrent cases (8.4±0.4 mg/L before intervention vs. 10.3±1.6 after intervention; p < 0.05). Moreover, sCD163 showed a significant difference in its pre-intervention and post-intervention values between recurrent and eradicated HCC cases (p < 0.01). Conclusions It is concluded that sCD163 has a minor role as a diagnostic marker for HCC, yet it could be used as a good prognostic marker in predicting the tumor response to locoregional therapies.

Systemic treatment and local treatment of metastatic lesion can improve the survival of patients with colorectal cancer liver metastasis (CRLM). Stereotactic body radiotherapy, also known as stereotactic ablative radiotherapy (SABR), is an effective method for local treatment of metastatic lesion and also has a certain impact on systemic immune status. SABR can directly kill tumor cells and change tumor immune microenvironment through influence on tumor cells and non-tumor cells. SABR combined with immunotherapy may increase the incidence rate of abscopal effect outside the irradiated area by affecting different links of immune response. Stereotactic ablative brachytherapy (SABT) is an independent minimally invasive treatment system with the characteristics of short treatment course, high accuracy, and definite therapeutic effect. This article reviews the application of SABR and SABT in CRLM.

Coronavirus disease 2019 (COVID-19) is associated with adverse outcomes, including need for invasive mechanical ventilation and death in people with risk factors. Liver enzyme elevation is commonly seen in this group, but its clinical significance remains elusive. In this study, we calculated the Fibrosis-4 (FIB-4) score for a cohort of hospitalized patients with COVID-19 and assessed its association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, inflammatory cytokine levels, and clinical outcome. A total of 202 hospitalized participants who tested positive for SARS-CoV-2 by nasopharyngeal sampling were included in this analysis. FIB-4 was calculated for each participant using the alanine aminotransferase, aspartate aminotransferase, age, and platelet count. We evaluated the association between FIB-4 and mortality using both multivariate logistic regression and Cox proportional hazards model. Correlations between FIB-4 and SARS-CoV-2 RNA and cytokine levels were evaluated using the Spearman test. Among the 202 participants, 22 died. The median FIB-4 in participants who survived and died were 1.91 and 3.98 (P

The hepatic mesenchyme has been studied extensively in the context of liver fibrosis; however, much less is known regarding the role of mesenchymal cells during liver regeneration. Single‐cell genomics approaches have recently uncovered both spatial and functional zonation of the hepatic mesenchyme in homeostasis and following liver injury. Here we discuss how the use of preclinical models are helping to shape our understanding of the role of the mesenchyme during liver regeneration, and how these approaches should facilitate the precise identification of highly targeted, pro‐regenerative therapies for patients with liver disease., The hepatic mesenchyme has been studied extensively in the context of liver fibrosis; however, much less is known regarding the role of mesenchymal cells during liver regeneration. As our knowledge of the cellular and molecular mechanisms driving hepatic regeneration deepens, the key role of the mesenchymal compartment during the regenerative response has been increasingly appreciated. Single‐cell genomics approaches have recently uncovered both spatial and functional zonation of the hepatic mesenchyme in homeostasis and following liver injury. Here we discuss how the use of preclinical models, from in vivo mouse models to organoid‐based systems, are helping to shape our understanding of the role of the mesenchyme during liver regeneration, and how these approaches should facilitate the precise identification of highly targeted, pro‐regenerative therapies for patients with liver disease.

Hepatitis C virus (HCV) infection is common in the United States and leads to significant morbidity, mortality, and economic costs. Simplified screening recommendations and highly effective direct-acting antivirals for HCV present an opportunity to eliminate HCV. The objective of this study was to increase testing, linkage to care, treatment, and cure of HCV. This was an observational, prospective, population-based intervention program carried out between September 2014 and September 2018 and performed in three community health centers, three large multiclinic health care systems, and an HCV patient education and advocacy group in King County, WA. There were 232,214 patients included based on criteria of documented HCV-related diagnosis code, positive HCV laboratory test or prescription of HCV medication, and seen at least once at a participating clinical site in the prior year. Electronic health record (EHR) prompts and reports were created. Case management linked patients to care. Primary care providers received training through classroom didactics, an online curriculum, specialty clinic shadowing, and a telemedicine program. The proportion of baby boomer patients with documentation of HCV testing increased from 18% to 54% during the project period. Of 77,577 baby boomer patients screened at 87 partner clinics, 2,401 (3%) were newly identified HCV antibody positive. The number of patients staged for treatment increased by 391%, and those treated increased by 1,263%. Among the 79% of patients tested after treatment, 95% achieved sustained virologic response. Conclusion: A combination of EHR-based health care system interventions, active linkage to care, and clinician training contributed to a tripling in the number of patients screened and a more than 10-fold increase of those treated. The interventions are scalable and foundational to the goal of HCV elimination.

ObjectiveTo investigate the effect of entecavir (ETV) antiviral therapy on the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) receiving transcatheter arterial chemoembolization (TACE). MethodsA total of 170 HCC patients who received TACE for the first time in Liver Cancer Center of Nanfang Hospital from January 2011 to March 2018 were enrolled, among whom 114 patients were treated with ETV (ETV treatment group) and 56 patients did not receive antiviral therapy (control group). Baseline demographic data, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), albumin (Alb), platelet count (PLT), Child-Pugh class, HBeAg and HBV DNA levels, alpha-fetoprotein, and BCLC stage were recorded before treatment, and the changes in HBV DNA level, ALT, AST, TBil, Alb, and Child-Pugh class were observed at weeks 4-8 after treatment; long-term survival was also observed after treatment. Short- and long-term clinical benefits (overall survival) were observed for all patients. The t-test or the Mann-Whithey U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Multivariate logistic regression analyses were performed for related clinical indices before treatment to identify the risk factors for HBV reactivation. The Kaplan-Meier method was used to analyze the survival curves of overall survival, and the log-rank test was used for comparison of survival curves. ResultsThere was no significant difference in the incidence rate of HBV reactivation between the ETV treatment group and the control group (15.79% vs 16.07%, χ2=0.002，P=0962). The univariate analysis showed that PLT was a risk factor for HBV reactivation (Z=-2.183,P=0.029), and the multivariate analysis showed that HBV DNA level was an independent risk factor for HBV reactivation (hazard ratio =1.000, P=0.015). The 1-, 3-, and 5-year survival rates were 56.20%, 30.30%, and 13.20%, respectively, in the ETV treatment group and 60.60%, 27.20%, and 16.30%, respectively, in the control group. There was no significant difference in overall survival rate between the two groups (χ2=0049,P=0.755). ConclusionAntiviral therapy can inhibit HBV replication after TACE in patients with HBV-related HCC, thereby reducing the hepatotoxicity of TACE.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China, and when a single tumor is larger than 5 cm in diameter, it is defined as large HCC. Large HCC has the characteristics of high degree of tumor malignancy and high risk of tumor metastasis and vascular invasion, which increases the difficulty of treatment. Surgical resection is the preferred treatment regimen for large HCC, but only 20%-30% of patients are candidates for surgical treatment. Transarterial chemoembolization (TACE) is recommended as the treatment regimen for unresectable large HCC in Chinese and international guidelines. It can control tumor progression and prolong the survival time of patients; however, repeated TACE has limited efficacy and may cause serious damage to liver function, and TACE alone can no longer meet clinical needs. With the development of tumor ablation techniques such as radiofrequency ablation, microwave ablation, and cryoablation, TACE combined with tumor ablation has become an important treatment method for large HCC. However, there are still controversies over the effect of ablation on large HCC, and therefore, how to choose the appropriate ablation time, reduce tumor residue and recurrence after ablation, and finally bring survival benefits to patients remains a difficult problem to be solved in clinical and scientific research. This article reviews the current status, predicaments, and future development trends of ablation therapy for large HCC.

Neil Hawkes,1,2 Umakant Dave,3 Mesbah Rahman,2,3 Dafydd Richards,3 Mahmud Hasan,4,5 AHM Rowshon,4 Faruque Ahmed,4,6 M Masudur Rahman,6 MG Kibria,6 Phedra Dodds,7 Bethan Hawkes,8 Stuart Goddard,9 Imdadur Rahman,10 Peter Neville,1 Mark Feeney,11 Gareth Jenkins,12 Keith Lloyd,12 Krish Ragunath,13 Cathryn Edwards,2,11 Simon D Taylor-Robinson14 1Department of Gastroenterology, Cwm Taf Morgannwg University Health Board, Llantrisant, South Wales, UK; 2British Society of Gastroenterology Central Office, London, UK; 3Department of Gastroenterology, Swansea Bay University Health Board, Swansea, UK; 4Office of the Central Secretariat, Bangladesh Gastroenterology Society, Dhaka, Bangladesh; 5Office of Central Secretariat, Gastroliver Foundation, Dhaka, Bangladesh; 6Department of Gastroenterology, Sheikh Russel National Gastroliver Institute and Hospital, Dhaka, Bangladesh; 7Department of Endoscopy Nursing, Office of the JAG GRS Team, Powys Health Board, Brecon, UK; 8Office of the Wales Cancer Network Pathway, Welsh Cancer Network, Cardiff, UK; 9Welsh Institute of Minimal Access Therapy, Cardiff MediCentre, Welsh Institute for Minimal Access Therapy, Cardiff University, Cardiff, UK; 10Department of Gastroenterology, Southampton NHS Trust, Southampton, UK; 11Department of Gastroenterology and Liver Medicine, Torbay and South Devon NHS Foundation Trust, Devon, UK; 12Faculty of Health and Life Sciences, Medicine, Swansea University, Swansea, UK; 13Office of the Provost, Faculty of Health Sciences, Bentley Campus, Curtin Medical School, Curtin University, Perth, Western Australia, Australia; 14Department of Surgery and Cancer, Imperial College London, London, UKCorrespondence: Neil Hawkes Email neil.hawkes@wales.nhs.ukAbstract: The British Society of Gastroenterology (BSG) and the Bangladesh Gastroenterology Society (BGS) have collaborated on an endoscopy training programme, which has grown up over the past decade from a small scheme borne out of the ideas of consultant gastroenterologists in Swansea, South Wales (United Kingdom) to improve gastroenterology services in Bangladesh to become a formalised training programme with broad reach. In this article, we document the socioeconomic and historical problems that beset Bangladesh, the current training needs of doctors and how the BSG-BGS collaboration has made inroads into changing outcomes both for gastroenterologists in Bangladesh, but also for the populations they serve.Keywords: endoscopy training, Bangladesh, training programmes, gastroenterology training

ObjectiveTo investigate the association of Modified Response Evaluation Criteria in Solid Tumors (mRECIST) response with the prognosis of patients with unresectable hepatocellular carcinoma (HCC) after transarterial embolization (TACE). MethodsA retrospective analysis was performed for the clinical data of 190 patients with unresectable HCC who were consecutively admitted to Department of Liver Disease and Digestive Interventional Radiology, The First Affiliated Hospital of Air Force Medical University, and treated with TACE from January 2010 to December 2014. The mRECIST criteria were used to evaluate imaging response after TACE; the patients with complete response (CR) or partial response (PR) were enrolled as response group(n=89), and those with progressive disease (PD) or stable disease (SD) were enrolled as non-response group(n=101). The Kaplan-Meier method was used to calculate median survival time, and the log-rank test was used for comparison between groups; the Cox regression model was used to identify the influencing factors for prognosis. ResultsAccording to the mRECIST criteria, 39 patients (20.5%) achieved CR, 50 (26.3%) achieved PR, 67 (35.3%) had SD, and 34 (17.9%) had PD. The objective response rate based on mRECIST was 46.8% for the whole population. The response group had a significantly longer survival time than the non-response group, and the median survival time was 29.9 (95% confidence interval ［CI］: 25.0-34.8) months for the response group and 7.5 (95% CI: 5.7-9.3) months for the non-response group (P＜0.001). The multivariate analysis showed that mRECIST response (hazard ratio ［HR］=2.02, P＜0.001), hepatitis B (HR=4.03, P＜0.001), and portal invasion (HR=2.12, P=0.008) were independent risk factors for survival. ConclusionThe mRECIST response has a certain value in predicting the prognosis of patients with unresectable HCC after TACE.

ObjectiveTo investigate the clinical effect of transcatheter arterial chemoembolization (TACE) in the treatment of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus and the value of existing prognostic evaluation models for HCC. Methods Screening was performed for HCC patients who underwent TACE in 24 tertiary hospitals in China from January 2010 to May 2016, and finally 266 HCC patients with portal vein tumor thrombus were included for retrospective analysis. The Kaplan-Meier method was used to plot survival curves and the log-rank test was used for comparison; a Cox regression analysis was used to perform univariate and multivariate analyses and establish a Cox regression model; area under the ROC curve (AUC) and C-index were calculated for HAP score, mHAP score, mHAP2 score, mHAP3 score, and 6&12 criteria to compare their prediction performance. ResultsThe median survival time was 9.867 months for all patients, and according to Child-Pugh class, the patients with Child-Pugh class A HCC had a significantly longer median survival time than those with Child-Pugh class B HCC (10.067 months vs 5.967 months, χ2=5.181, P=0.023). The patients with alpha-fetoprotein (AFP) ≤800 ng/ml had a significantly longer median survival time than those with AFP ＞800 ng/ml (13.10 months vs 8.13 months, χ2=8.643, P=0.003). The univariate analysis showed that number of tumors, tumor diameter, total bilirubin, serum albumin, alanine aminotransferase (AST), and alanine aminotransferase (ALT) were associated with the survival of patients (all P＜0.05), and the multivariate analysis showed that number of tumors (hazard ratio ［HR］=1.186, 95% confidence interval ［CI］: 1.058-1.329, P＜0.05) and tumor diameter (HR=1.047, 95% CI: 1.001-1.095, P＜0.05) were independent influencing factors for the survival of patients. The 1-, 2-, and 3-year AUCs of 6&12 criteria were 0.651, 0.655, and 0.641, respectively, which were higher than those of the other models; 6&12 criteria and the new model had a C-index of 0.577 and 0.579, respectively, which were higher than C-index of the other models. ConclusionTACE is safe and effective in HCC patients with portal vein tumor thrombus who have a low AFP level and good liver function. Tumor diameter and number of tumors provide a reliable basis for screening out the patients suitable for TACE. Among the existing prognostic evaluation models for primary liver cancer, 6&12 criteria have a better predictive capability than the other models.

Aim:In this study, we aimed to share our surgical experiences and clinical results in non-traumatic small bowel perforations.Method:Patients who underwent surgical treatment for non-traumatic small bowel perforation between 2009-2019 were included in the study. Patients were divided into two groups according to postoperative 90-day mortality status: Group 1 (no mortality), Group 2 (mortality). The demographic, clinical features, treatment methods and results of the patients were compared between the groups.Results:Forty-two patients participated in our study. Group 1 consisted of 25, and Group 2 consisted of 17 patients. Male sex was dominant in Group 2 (48% vs 76.5%, p=0.062). Mean age was higher in Group 2 (54 vs 61, p=0.218). American Anesthesiology Association score (ASA) was statistically significantly higher in Group 2 (12% vs 58.8%). Forty-two percent of patients had abdominal surgery and 30% had a history of malignancy. The presence of electrolyte imbalance was similar in the groups (56% vs 76.5%, p=0.049). The days between the first complaint and laparotomy were similar between the groups (6.40 vs. 5.70 p=0.699). In perforated areas, jejunum was dominant in Group 2 with 64.7%, and ileum in Group 1 with 68%. The multiple perforation rate was higher in Group 2, but was not statistically significant (12% vs 23.5%, p=0.284). From postoperative complications, anastomosis leakage was higher in Group 1, but it was not statistically significant (12% vs 5.9%, p=0.501).Conclusion:Morbidity and mortality of non-traumatic small bowel perforations is high. While the ASA score and hypoalbuminemia were associated with postoperative mortality in non-traumatic small bowel perforations, we did not find the localization of the perforation and the time between the first complaint and laparotomy to be related to mortality.

ObjectiveTo investigate the mechanism of Xiaozheng Huoluo prescription (XZHLF) in the prevention and treatment of liver fibrosis based on network pharmacology. MethodsTCMSP database, Chemistry Database, ETCM database, chemical source network database, ChemSrc database, and PubChem database were searched and a literature review was performed to collect the chemical components of each traditional Chinese medicine of XZHLF, Swiss ADME database was used to screen out the active components of each traditional Chinese medicine of XZHLF, and Swiss Target Prediction database was used to predict the targets of these active components; GeneCards and OMIN databases were used to collect the disease targets of liver fibrosis, and Venn diagrams were used to obtain the potential targets of XZHLF in the prevention and treatment of liver fibrosis. Cytoscape 3.7.1 software was used to establish a “drug-active component” network for XZHLF and an “active component-potential target” network for XZHLF in the prevention and treatment of liver fibrosis. Metascape database was used to perform GO and KEGG enrichment analysis of potential targets, and bubble charts were plotted for the top 20 pathways with the highest number of enriched genes. The MAPK signaling pathway among the top 20 KEGG pathways was analyzed to plot an “active component-potential target-pathway” network. Healthy Sprague-Dawley rats were randomly divided into blank control group (K group), model group (M group), colchicine-positive control group (Y group), high-dose XZHLF group (G group), middle-dose XZHLF group (Z Group), and low-dose XZHLF group (D group), and a rat model of liver fibrosis was established by CCl4; the drug was administered simultaneously for 8 weeks. Western blot was used to measure the protein expression of ERK5, p-ERK5, MEK5, and MEKK3 in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsA total of 110 active components were screened out from XZHLF and they acted on 923 targets, which were mapped to 6823 disease targets of liver fibrosis to obtain 647 potential targets. XZHLF might act on multiple protein targets such as EGFR, AKT1, IKBKB, MAPK8, and PDGFRB through the pathways including the MAPK signaling pathway and the biological processes including the regulation of MAPK cascade, thereby playing a role in the prevention and treatment of liver fibrosis. The M group had significant increases in the protein levels of ERK5, p-ERK5, MEK5, and MEKK3 in liver tissue compared with the K, Y, G, Z, and D groups (all P ＜0.05), and the K group had significant reductions in the protein levels of ERK5, p-ERK5, MEK5, and MEKK3 in liver tissue compared with the Y, G, Z, and D groups (all P ＜0.05). ConclusionBased on the method of network pharmacology, it is predicted that XZHLF may prevent and treat liver fibrosis via the MAPK signaling pathway, and it is verified through experiments that XZHLF prevents and treats liver fibrosis via the ERK5 pathway in the MAPK signaling pathway family. The high-dose XZHLF group shows the most obvious anti-liver fibrosis effect.

Double pylorus, also known as acquired double pylorus, is a rare condition defined as a gastrointestinal fistula connecting stomach antrum and duodenal bulb. The prevalence of double pylorus ranges from 0.001 to 0.4% by esophagogastroduodenoscopy (EGD). Although the etiology is unknown, the formation of double pylorus is related to Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs (NSAID). The development of the occurrence of double pylorus is still unknown, but many systemic diseases play a role. We present the case of a 59-year-old man who was admitted to Dr. Soetomo General Hospital with hematemesis and melena. The patient had a history of diabetes mellitus since 3 years and consumption of medicinal herbs for myalgia, which was suspected of NSAIDs for the past 5 months. The patient had anemia with hemoglobin at 8.3 g/dL, enterogenous azotemia with blood urea nitrogen 28 mg/dL and serum creatinine 1.14 mg/dL. At EGD, double pylorus was found and accompanied by gastric ulcer, a giant white base ulcer, part of it covered by clotting without any sign of active bleeding. Biopsy revealed chronic inactive gastritis, and no H. pylori was found. Treatment mainly depends on gastrointestinal acid suppression through a proton pump inhibitor (PPI). The patient was given a high-dose PPI and a mucosal protective agent. He was treated for 1 week and had improved complaints.

A 77-year-old female who had an acute severe abdominal pain was taken to the emergency room in the previous hospital. CT scans showed jejunum and ileum wall thickening and fatty deposits around the small intestinal tract, and gastrointestinal perforation could not be ruled out. By using single anal and oral balloon endoscopy, we observed mild edema with petechial erythema, shallow erosions with edematous mucosa and ulcers with surrounded disrupted villous structures at the jejunum and ileum. Histological analysis revealed atypical lymphocytes infiltrating the small intestinal mucosa demonstrating intraepithelial lymphocytosis. Immunohistochemical staining revealed that CD3, CD7, and CD56 staining was positive, and CD4, CD5, and CD8 staining was negative in infiltrated lymphocytes. We made the diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) with the combination of HE staining and IHC. PET-CT showed abnormal uptake in irregular wall thickening of the small intestine, lymph nodes, ribs, spine and pelvic bone. She was treated with chemotherapy (etoposide, prednisolone, oncovin, cyclophosphamide, hydroxydaunorubicin) and is still alive 1 year after the diagnosis. We reported the various endoscopic findings in the same MEITL patient by using single balloon endoscopy. We also summarized endoscopic characteristics of MEITL patients.

Aim:The aim of our study was to assess the outcome of hemorrhoidal dearterialization, achieved by a dedicated laser energy device.Method:From February 2013 to December 2017, 441 patients with second- or third-degree hemor-rhoids were studied. The primary end point was a reduction in the bleeding rate; secondary end points were; reduction in pain and recurrence of the symptoms which patients complaint. The procedure was carried out as 1-day surgery. A 1,470 nm diode laser device was employed to seal the terminal branch-es of the hemorrhoidal arteries. Follow-up was scheduled at 1 and 4 weeks, 3 and 6 months.Results:Two early postoperative bleeding (2/441) which recquired surgical intervention, Late com-plications were Eight (8/441) thrombosed hemorrhoids that resolved medically and recurrence of the symptoms which patients suffer in 10 patients (10/441). Postoperative pain was recorded by using a 10-point visual analog scale (VAS) on which 0 represents no pain and 10 represents the worst pain imaginable. VAS protocol was followed up after 1 week, 1 month. Mean pain score was 0.65 in postoperative 1 week and decreased gradually. All patients were discharged on the day of surgery.Conclusion:The hemorrhoid laser procedure was effective in improving bleeding and pain symp-toms in patients with Grade II and III hemorrhoids, but prospective randomized controlled studies are needed for evidence based conclusions.

NSAIDs (non-steroidal anti-inflammatory drugs) are one of the most used medications worldwide. Every day they are used by more than 30 million Americans. Here, we report a rare and interesting case of a 63-year-old woman with a history of NSAID use who presented to our emergency room with lower abdominal pain. Computed tomography (CT) scan of the abdomen with intravenous contrast revealed focal mucosal thickening in the cecum which was highly suspicious for colonic malignancy. She had a colonoscopy which showed two masses and ulcers in the right colon, pathology was negative for malignancy and showed inflammation consistent with NSAID colopathy.

Background The role of IL-12/23 in the pathogenesis of ulcerative colitis (UC) is unclear. We analyzed mucosal IL-12/23 expression and its relationship with endoscopic severity, histological activity, and UC relapse. Methods Rectal biopsies were collected from 70 UC patients with clinical remission. IL-12, IL-23, IFN-γ, IL-17A, and IL-17F mRNA expression was measured by real-time PCR. Endoscopic severity and histological activity were evaluated using the Mayo endoscopic subscore (MES) and the Geboes score, respectively. Results The longest follow-up period was 51 months. Thirty-four patients relapsed during the study period. Samples from these subsequently relapsed patients formed the “relapse” group, while those from patients that did not relapse formed the “remission” group. IL-12 (P = 0.0003) and IL-23 (P = 0.014) mRNA expression was significantly higher in the relapse than the remission group. Expression of IL-23 (P = 0.015) but not IL-12 (P = 0.374) was correlated with MES. However, in patients with an MES of 0 and 1, IL-12 expression was statistically higher in the relapse than the remission group (P = 0.0015, P = 0.0342). IL-12 and IL-23 expression did not vary significantly between histologically active and inactive mucosa; both were higher in histologically inactive patients in the remission group (IL-12: P = 0.0002, IL-23: P = 0.046). Conclusions Rectal IL-12 and IL-23 expression was elevated in the relapse group, but IL-12 was more strongly associated with UC relapse, irrespective of endoscopic severity and histological activity. Mucosal IL-12 was elevated in patients with deep mucosal healing. Our results suggest an important role of IL-12 in UC pathogenesis and the molecular mechanism of UC relapse.

ObjectiveTo systematically evaluate the association between vitamin D level and nonalcoholic fatty liver disease (NAFLD) in children and adolescents. MethodsRelated English and Chinese databases, including PubMed, Cochrane Library, Embase, CNKI, CBM, Wanfang Data, and VIP, were searched for studies on the association between vitamin D level and NAFLD in children and adolescents published up to August 2020. Newcastle-Ottawa Scale (NOS) was used to evaluate quality of studies, and RevMan 5.3 software was used for data analysis. ResultsA total of 10 articles were included in the meta-analysis, with 622 patients in the NAFLD group and 1608 in the healthy control group. All 10 articles had an NOS score of ≥6. A pooled analysis of the 10 articles was performed using a random effects model (I2=97%, P＜0.05). The NAFLD group had a significantly lower serum 25(OH) D level than the healthy control group (standardized mean difference=-1.40, 95% confidence interval: -2.07 to -0.72). ConclusionThere is a significant reduction in serum vitamin D level in children and adolescents with NAFLD, which may be associated with the progression and severity of NAFLD.