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ObjectiveTo evaluate the efficacy and safety of rifaximin in the prevention of spontaneous bacterial peritonitis (SBP). MethodsCNKI, Wanfang Data, CBM, PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) and cohort studies on rifaximin in the prevention of SBP published up to July 5, 2020. The articles were screened according to the inclusion and exclusion criteria, and data extraction and quality assessment were performed. RevMan 5.3 software was used to conduct the meta-analysis. Results A total of 13 studies (with 2207 patients in total) were included, among which there were 6 RCTs and 7 cohort studies. The results of the meta-analysis showed that compared with the non-prevention group, the rifaximin group had significantly lower incidence rate of SBP (odds ratio ［OR］=0.36, 95% confidence interval ［CI］: 0.14-0.96, P=0.04) and mortality rate (OR=0.59, 95% CI: 037-0.95, P=0.03); compared with the norfloxacin group, the rifaximin group had significantly lower incidence rate of SBP (OR=039, 95% CI: 025-0.62, P＜0.001), mortality rate (OR=0.55, 95% CI: 0.34-0.92, P=0.02), and adverse reactions (OR=0.36, 95% CI: 0.22-059, P＜0.001). The subgroup analysis based on the type of prevention showed that there was no significant difference in primary prevention between the two groups (OR=0.56, 95% CI: 0.23-1.35, P=0.20), and in secondary prevention, the rifaximin group had a significantly lower incidence rate of SBP (OR=0.18, 95% CI: 0.08-0.43, P＜0.001). In addition, it was also found that rifaximin significantly reduced the incidence rate of hepatorenal syndrome (OR=0.34, 95% CI: 0.15-0.77, P=0.01) and hepatic encephalopathy (OR=0.55, 95% CI: 0.32-0.95, P=0.03). ConclusionRifaximin is safe and effective for the primary and secondary prevention of SBP. Rifaximin is superior to norfloxacin in secondary prevention, which still needs to be confirmed by high-quality multicenter RCTs.

Background and study aims The Japan Narrow-band imaging (NBI) Expert Team (JNET) classification was proposed for evaluating colorectal lesions. However, it remains unknown whether the JNET classification can be applied to magnifying endoscopy with image-enhanced endoscopies other than NBI. This study aimed to compare the diagnostic ability of JNET classification by magnifying endoscopy with blue laser imaging (ME-BLI) and with ME-NBI. Patients and methods We retrospectively assessed consecutive patients diagnosed per the JNET classification by ME-BLI (BLI group) or ME-NBI (NBI group) between March 2014 and June 2017. We compared the diagnostic value of JNET classification between the groups with one-to-one propensity score matching. Results Four hundred and seventy-one propensity score-matched pairs of lesions were analyzed. In the BLI and NBI groups, the overall diagnostic accuracies were 92.1 % and 91.7 %, respectively, and those for differentiating between neoplastic and non-neoplastic polyps were 96.6 % and 96.8 %, respectively. The positive predictive value by each JNET classification in BLI vs. NBI group was 90.6 % vs. 96.2 % in Type 1, 94.3 % vs. 94.6 % in Type 2A, 57.7 % vs. 42.3 % in Type 2B, and 100 % vs. 91.7 % in Type 3. The negative predictive value was 97.0 % vs. 96.9 % in Type 1, 88.1 % vs. 82.8 % in Type 2A, 98.0 % vs. 98.2 % in Type 2B, and 98.5 % vs. 98.7 % in Type 3. No statistical difference in the diagnostic results was found between the groups. Conclusions The diagnostic ability of the JNET classification by ME-BLI and ME-NBI was comparable, with the former also applicable for diagnosis of colorectal lesions.

Giant biliary calculus in the common bile duct (CBD) is rare. Giant calculus of choledochal cyst (CC) is even rarer, and no case of giant calculus of CC with more than 100 calculi has been reported in the indexed literature. We present the case of a 8.0 × 4.5 × 4.0 cm sized giant calculus with >100 small calculi in type IVa CCs with heterotopic pancreas in a 45-year-old male, which is a surprisingly rare occurrence. Magnetic resonance cholangiopancreatography showed multifocal irregular dilatation of intrahepatic biliary radicles with multiple filling defects with a giant calculus in CC with cholelithiasis. The case was successfully managed with open cholecystectomy and choledochotomy with retrieval of 1 giant and more than 100 small calculi with excision of CC with Roux-en-Y hepaticojejunostomy. Histopathological examination (HPE) showed inflamed CC identified with focal areas of surface ulceration with increased fibrosis areas in the wall and few pancreatic acini. A bile duct calculus is defined as “giant” when the size is 5 cm or more. Stone formation within is the most frequent complication of CC. Most intracystic calculi have been described as soft, earthy, and pigmented in appearance, supporting bile stasis as a primary etiologic factor. The only treatment for giant calculus of CBD or CC is surgical. Endoscopic treatment is mostly unsuccessful and open surgery is the treatment of choice due to giant size, increased load of calculus, and presence of calculi in the left and right hepatic ducts.

ObjectiveTo investigate the clinical and genetic features of patients with glycogen storage disease type Ⅸa (GSD Ⅸa), and to improve the clinical understanding of the disease. MethodsA retrospective analysis was performed for the clinical data of 20 patients who were hospitalized and genetically diagnosed with GSD Ⅸa in Children’s Hospital of Fudan University from January 2015 to December 2018, and their clinical and genetic features were summarized. ResultsAll 20 patients with GSD Ⅸa were male, with a median age of 2.5 years at the time of confirmed diagnosis. All patients had hepatomegaly and elevated aminotransferases; of all patients, there were 5 patients (250%) with growth retardation, 19 (95.0%) with fasting hypoglycemia, 14 (70.0%) with hyperlactatemia, 9 (45.0%) with hypertriglyceridemia, and 5 (25.0%) with hypercholesterolemia. Fasting blood ketone was measured for 8 patients and all of these patients had an increase in blood ketone; all patients had normal uric acid, and 5 patients (25.0%) had positive urine ketone. Liver biopsy was performed for 18 patients, among whom 15 had mild to moderate liver fibrosis. A total of 16 mutations were detected in the PHKA2 gene, among which 5 were known pathogenic mutations and 11 were novel mutations, and most of the mutations were detected in the c.3614 locus. All patients were treated with uncooked cornstarch, and most patients achieved an improvement in clinical manifestations. ConclusionGSD Ⅸa is more common in male patients. This disease should be considered for patients with hepatomegaly, elevated aminotransferases, growth retardation, fasting hypoglycemia, elevated fasting blood ketone, and normal uric acid. Liver biopsy may help with the diagnosis of this disease, and clinical biochemical parameters and gene detection can be used to confirm diagnosis and classification. Most patients have mild clinical manifestations, while some patients may have liver fibrosis, and treatment with uncooked cornstarch can improve the condition of this disease.

Background Amyloid deposition in pancreas is rare. Lactoferrin amyloid deposition has not been reported in pancreas, till date. Presence of enhancing mural nodule in a cyst on imaging is a worrisome feature for malignancy, and warrants surgical resection in a surgically fit candidate, as per Fukuoka guidelines for management of cystic lesions in pancreas. Case report We report a case of localized amyloidosis presenting as a mural nodule in a 1.6 cm cyst located in the head of pancreas, which led to pancreatoduodenectomy in a 69 year old woman. Histological evaluation revealed a simple mucinous cyst with localized lactoferrin amyloid deposition corresponding to the mural nodule identified on imaging. Conclusions We report the first case of localized lactoferrin amyloid deposition in pancreas that presented as a mural nodule in a cystic lesion and prompted pancreatoduodenectomy. This unique case illustrates that on rare occasion mural nodule in a cyst can be benign. It adds amyloid deposition to the differential diagnosis of mural nodules in pancreatic cystic lesions seen on imaging.

Background Inflammatory bowel disease (IBD) is increasing in the Asia-Pacific region, with changes in disease phenotype and course. We aimed to assess the changing phenotypes of IBD over ten years, describe the early clinical course (ECC) and identify the clinical predictors (CP) of poor outcomes among a large, multi-centre, cohort of Sri Lankan IBD patients. Methods We included patients [diagnosed between June/2003–December/2009-Group-1(G1), January/2010–June/2016-Group-2(G2)] with ulcerative colitis (UC) and Crohn disease (CD) from five national-referral centres. Changing phenotype from G1 to G2, ECC (disease duration Results 375 (UC-227, CD-148) patients were recruited. Both G1/G2 had more UC than CD (77% vs 23%, 54.5 vs 45.5 respectively, p p p p p Conclusion There was an increase in CD over time without change in disease phenotype for both UC and CD. A relatively benign ECC was observed. Family history (UC), EIMs (UC/CD), severe disease at presentation (UC/CD), younger age (CD/UC) CPs of poor outcomes.

A 79-year-old man presented with high fever, marked eosinophilia, altered biochemical liver function tests (LFT) with predominance of biliary enzymes, and severe wall thickening of the gallbladder. Magnetic resonance cholangiopancreatography (MRCP) suggested cholecystitis, without signs of biliary strictures. Laparoscopic cholecystectomy and exploratory liver excision revealed eosinophilic cholangitis and cholecystitis, complicated with hepatitis and portal phlebitis. Prednisolone monotherapy rapidly improved peripheral eosinophilia, but not LFT. Liver biopsy showed that infiltrating eosinophils were replaced by lymphocytes and plasma cells. Treatment with ursodeoxycholic acid improved LFT abnormalities. Nevertheless, after 2 months, transaminase-dominant LFT abnormalities appeared. Transient prednisolone dose increase improved LFT, but biliary enzymes’ levels re-elevated and jaundice progressed. The second and third MRCP within a 7-month interval showed rapid progression of biliary stricture. The repeated liver biopsy showed lymphocytic, not eosinophilic, peribiliary infiltration and hepatocellular reaction to cholestasis. Eighteen months after the first visit, the patient died of hepatic failure. Autopsy specimen of the liver showed lymphocyte-dominant peribiliary infiltration and bridging fibrosis due to cholestasis. Though eosinophil-induced biliary damage was an initial trigger, repeated biopsy suggested that lymphocytes played a key role in progression of the disease. Further studies are needed to elucidate the relationship between eosinophils and lymphocytes in eosinophilic cholangitis.

There are discrepancies regarding the clinical impact of age at Kasai portoenterostomy (KP) on surgical outcomes. Hence, we re-assessed the clinical significance of age at KP. We analyzed 224 patients with type III (atresia of bile duct at the porta hepatis) biliary atresia at Tohoku University Hospital. We classified patients into two groups: KP at ≤60 days of age (group TE) and >60 days of age (group TL). Group TE was subdivided into three groups (TE1, TE2, and TE3) according to age at time of surgery. Subsequently, 2,643 patients in the Japanese Biliary Atresia Registry were classified similarly. Background and surgical outcomes were compared. Of the 2,643 cases, 323 patients who underwent revision KP were analyzed separately. The jaundice clearance rates (JCRs) were 81.4%, 100%, 64.7%, 83.0%, and 65.2% of patients in the TE, TE1, TE2, TE3, and TL groups, respectively. The 15-year native liver survival rates of patients in the TE, TE1, TE2, TE3, and TL groups were 62.2%, 88.9%, 33.9%, 64.4%, and 42.9%, respectively. The 30-year native liver survival rates of patients in the TE, TE1, TE2, TE3, and TL groups were 38.6%, 74.1%, 25.4%, 35.8%, and 31.7%, respectively. The JCRs were 66.2%, 69.4%, 64.1%, 66.7%, and 59.7% for patients in groups JE, JE1, JE2, JE3, and JL, respectively. The 15-year native liver survival rates were 48.1%, 56.7%, 43.9%, 48.9%, and 37.2% for patients in groups JE, JE1, JE2, JE3, and JL, respectively. The JCRs following revision KP were higher in the JE1 group than in the other groups. Conclusion: Early KP was associated with favorable outcomes except in patients aged 31-45 days.

A 57-year-old man with a 10-year history of proton pump inhibitor (PPI) use presented with multiple fundic gland polyps (FGPs) including one >20 mm, whitish, semi-pedunculated polyp. Black spots and cobblestone-like mucosa were also observed in the stomach upon endoscopy; therefore, the lesion was considered to result from long-term PPI administration. Endoscopically, we diagnosed this polyp as a neoplastic lesion with gastric phenotype rather than a non-neoplastic lesion. Biopsy revealed an atypical glandular lesion that was indeterminate for neoplasia; therefore, we performed en bloc resection via endoscopic submucosal dissection (ESD) of the 22 × 22 × 10 mm-sized polyp. Histologically, the polyp was composed of hyperplastic foveolar epithelia in the upper half of the mucosa and hyperplastic fundic glands in the lower half of the mucosa, with luminal dilatation and parietal cell protrusion. The pathological diagnosis for this ESD specimen was FGP associated with PPI administration. We herein describe this rare case of a large FGP in Helicobacter pylori-uninfected gastric mucosa associated with long-term PPI administration, which was mimicking gastric-type neoplasm and resected by endoscopy.

CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) was identified as a regulator of programmed death ligand 1 (PD-L1), which induces antitumor immunity in several cancers. This study aimed to clarify the relationship between CMTM6 and PD-L1 expression and clinical outcomes in patients with hepatocellular carcinoma (HCC). In total, 259 patients with HCC who had undergone hepatic resection were enrolled. Immunohistochemical staining for CMTM6 and PD-L1 was performed. The relationships between CMTM6 expression and the clinicopathological characteristics and outcomes were analyzed. Additionally, the stabilization of PD-L1 expression and regulation of malignant activities by CMTM6 were examined in vitro. Our patients were divided into high (n = 65, 25.1%) and low (n = 194, 74.9%) CMTM6 expression groups. High CMTM6 expression was significantly associated with malignant aggregates, including poor differentiation (P < 0.0001), microscopic intrahepatic metastasis (P = 0.0369), and multiple intrahepatic recurrences (P = 0.0211). CMTM6 expression was significantly correlated with PD-L1 expression in HCC tissues (P < 0.0001). The patients were classified into three groups: high CMTM6/PD-L1 positive (n = 21), high CMTM6/ PD-L1 negative (n = 44), and low CMTM6 (n = 194) expression pattern groups. Overall survival was significantly different among the three groups (P < 0.0001). Additionally, immunohistochemical double staining revealed that CMTM6 and PD-L1 were co-expressed on HCC cells. In vitro, PD-L1 expression was enhanced at late time points in the presence of CMTM6 expression. CMTM6 also regulated epithelial-to-mesenchymal transition and stemness phenotypes in HCC cells. Conclusion: Our large cohort study found that CMTM6 co-expressed with PD-L1 was strongly associated with the clinical outcome in patients with HCC. The evaluation of CMTM6 combined with PD-L1 in HCC might be useful for patient selection in immune checkpoint therapy.

In patients with decompensated cirrhosis, procedure‐related bleeding is a potentially lethal complication. Routine coagulation tests such as international normalized ratio and platelet count do not predict bleeding risk. We investigated whether thromboelastography (TEG) can identify patients with cirrhosis who are at risk of procedure‐related bleeding. As a part of a prospective study on hemostasis in decompensated cirrhosis, patients had TEG performed on admission and were followed prospectively during hospitalization for the development of procedure‐related bleeding. Eighty patients with cirrhosis were included. Among the 72 who had procedures performed, 7 had procedure‐related bleeding, which was major in three cases (two following paracentesis and one following thoracentesis). Conventional coagulation tests were comparable between bleeding and nonbleeding patients, whereas TEG parameters of k‐time (4.5 minutes vs. 2.2 minutes; P = 0.02), α‐angle (34° vs. 59°; P = 0.003), and maximum amplitude (37 mm vs. 50 mm; P = 0.004) were significantly different (all indicative of hypocoagulability). TEG maximum amplitude (MA), a marker of overall clot stability, accurately discriminated between patients who had major, life‐threatening bleeding (all with MA 30 mm), whereas a platelet count

Neurofibromatosis type 1 (NF-1) is strongly associated with neurofibromas and malignancies. Solid pancreatic neuroendocrine tumors (PanNETs) have been recently reported in patients with NF-1. PanNETs are always solid and rarely present with a cystic appearance due to central necrosis and hemorrhage caused by rapid growth. A 33-year-old female diagnosed with NF-1 at age 16 was referred for evaluation of a pelvic mass found on abdominal ultrasound. Magnetic resonance imaging showed a 6 cm solid pelvic mass adjacent to the left external iliac artery, and contrast-enhanced computed tomography scan showed a 3-cm solid para-aortic mass and a 3-cm cystic mass in the pancreatic tail. Endoscopic ultrasonography showed a cystic tumor with necrotic tissue and septa. Preoperative diagnosis was pancreatic cystic malignancy with para-aortic lymph node metastasis accompanied with a pelvic neurofibroma. These lesions were resected simultaneously. The specimen resected from the pancreas showed a necrotizing cystic tumor invading abutting lymph nodes. Immunohistochemical analysis showed positive chromogranin A and synaptophysin. The Ki-67 index was

Background and study aims Quality in colonoscopy has been promoted in last decade with definition of different quality indicators (QI) as benchmarks. Currently, automatized monitoring systems are lacking, especially for merging pathologic and endoscopic data, which limits quality monitoring implementation in daily practice. We describe an adapted endoscopy reporting system that allows continuous QI recording, with automatic pathological data inclusion. Material and methods We locally adapted a reporting system for colonoscopy by adding and structuring in a dedicated tab selected key QI. Endoscopic data from a reporting system and pathological results were extracted and merged in a separate database. During the initial period of use, performing physicians were encouraged to complete the dedicated tab on a voluntary basis. In a second stage, completing of the tab was made mandatory. The completeness of QI recording was evaluated across both periods. Performance measures for all endoscopists were compared to global results for the department and published targets. Results During the second semester of 2017, a total of 1827 colonoscopies were performed with a QI tab completed in 100 % of cases. Among key QI, the cecal intubation rate was 93.8 %, the rate of colonoscopies with adequate preparation was 90.7 %, and the adenoma detection rate was 29.8 % considering all colonoscopies, irrespective of indication; 28.8 % considering screening procedures; and 36.6 % in colonoscopies performed in people older than age 50 years. Conclusion This study shows that quality monitoring for colonoscopy can be easily implemented with limited human resources by adapting a reporting system and linking it to a pathology database.

Background Crohn’s disease (CD) can involve the upper gastrointestinal (GI) tract as well as the small and large bowel. PillCam colon capsule endoscopy (PCCE-2) enables observation of the whole GI tract, but its diagnostic yield for CD lesions in the whole GI tract remains unknown. Aim To elucidate the diagnostic yield of PCCE-2 in patients with CD. Methods Patients with CD who underwent PCCE-2 and double-balloon endoscopy (DBE) using oral and anal approaches were evaluated for CD lesions in the whole GI tract. We divided the small bowel into three segments (jejunum, ileum, and terminal ileum), and the large bowel into four segments (right colon, transverse colon, left colon, rectum). Detection of ulcer scars, erosion, ulcers, bamboo joint-like appearance, and notch-like appearance was assessed in each segment. The diagnostic yield of PCCE-2 was analyzed based on the DBE results as the gold standard. Results Of the total 124 segments, the sensitivities of PCCE-2 for ulcer scars, erosion, and ulcers were 83.3%, 93.8%, and 88.5%, respectively, and the specificities were 76.0%, 78.3%, and 81.6%, respectively. For the 60 small bowel segments, the sensitivities were 84.2%, 95.5%, and 90.0%, respectively, and the specificities were 63.4%, 86.8%, and 87.5%, respectively. For the 64 large bowel segments, the sensitivities were 80.0%, 90.0%, and 83.3%, respectively, and the specificities were 84.7%, 72.2%, and 77.6%, respectively. Conclusion PCCE-2 provides a high diagnostic yield for lesions in the whole GI tract of patients with CD. Thus, we recommend its use as a pan-enteric tool in clinical settings.

ObjectiveTo investigate the changes in gut microbiota after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhotic patients with mild hepatic encephalopathy (MHE) in different prognosis groups. MethodsA total of 28 MHE cirrhotic patients who were hospitalized and underwent TIPS in Xijing Hospital of Digestive Diseases from July 2016 to July 2017 were enrolled. Fecal samples and related clinical data were collected on days 1-3 before surgery and at 1 month after surgery. According to the prognosis after surgery, the patients were divided into none-hepatic encephalopathy (HE) group with 8 patients, MHE group with 12 patients, and overt hepatic encephalopathy (OHE) group with 8 patients. Fecal samples were analyzed by 16S rRNA sequencing to obtain the relative abundance of gut microbiota, and SPSS and R packages were used to analyze the biodiversity, postoperative changes, and differences in such changes of gut microbiota at the genus level between groups. The chi-square test was used for comparison of categorical data between groups; the Kruskal-Wallis H test was used for comparison of continuous data between three groups; the Bonferroni method was used for multiple comparisons of multiple samples; the Wilcoxon signed-rank test was used for comparison before and after surgery within each group. For microbiome beta-diversity analyses, a principal coordinate analysis (PCoA) was performed based on Bray-Curtis distance matrix, and the Adonis method (PerMANOVA) was used for comparison between groups. ResultsPCoA based on Bray-Curtis distance matrix showed that only the MHE group had a significant change in beta diversity after surgery (F=2.71, P=0.049). After surgery, the non-HE group had significant increases in the abundance of the native flora Dialister, Coprococcus, Ruminococcaceae_uncultured, Flavonifractor, and Clostridium_sensu_stricto_1 (Z=2.521, 2.1, 2.1, 2.1, and 1.96, all P＜0.05); the MHE group had significant reductions in the abundance of the harmful flora Granulicatella（Z=2.521,P=0.012）, Enterococcus（Z=2.51,P=0.012）, Streptococcus（Z=2.432,P=0.015）, and Rothia（Z=2.001,P=0.045） and significant increases in the abundance of Veillonella（Z=2.353,P=0.019） and Megasphaera（Z=1.955,P=0.05）; the OHE group only had a significant increase in the abundance of Veillonella after surgery (Z=2.38, P=0.017). There was a significant difference in the change in gut microbiota (postoperative abundance/preoperative abundance) between the non-HE group, the MHE group, and the OHE group ［2.00 (1.11-91.61) vs 1.21 (0.26-679) vs 0.09 (0.01-0.92), χ2=6.249, P=0.043］. ConclusionThere is a significant difference in the change in gut microbiota after TIPS between patients with different prognoses, and the increase in the abundance of native flora may have a certain influence on the remission of MHE.

Despite scant evidence, current guidelines indicate that esophageal varices are a relative contraindication to transesophageal echocardiography (TEE). The aim of this study is to compare the risk of gastrointestinal bleeding following TEE among cirrhotic patients with and without endoscopically-documented esophageal varices. This is a retrospective analysis of patients with cirrhosis who underwent upper endoscopy within 4 years of TEE at five institutions between January 2000 and March 2020. Primary outcome was overt gastrointestinal bleeding. Secondary outcomes were hemoglobin decline by at least 2 g/dL or blood transfusion within 48 hours following TEE. Of the 191 patients, 79 (41.4%) had esophageal varices (30.4% large). No patient experienced a primary outcome. Secondary outcomes occurred in 52 (27.2%): 28 (35.4%) with esophageal varices and 24 (21.4%) without varices. After propensity-score covariate adjustment, the odds ratio for a secondary outcome in patients with esophageal varices was 1.49 (95% confidence interval 0.74-2.99). Restricting analysis to those who underwent endoscopy within 1 year of TEE did not significantly alter results. The risk of a secondary outcome was identical between patients who had upper endoscopy prior (27.5%) versus subsequent (26.7%; P = 1.00) to TEE. Conclusions: Among patients with cirrhosis, there was no overt gastrointestinal bleeding after TEE. The likelihood of a 2 g/dL decline in hemoglobin or blood transfusion within 48 hours following TEE was not significantly higher in patients with esophageal varices after controlling for confounders. Patients who underwent upper endoscopy before TEE did not manifest a lower risk of secondary outcomes versus those who had endoscopy after TEE, suggesting that routine preprocedural endoscopy is of marginal utility.

Background and study aims In borderline resectable/locally advanced pancreatic ductal adenocarcinoma (PDAC), stereotactic body radiation therapy (SBRT) is an emerging neoadjuvant treatment option. Endoscopic ultrasound (EUS)-guided insertion of fiducial markers being a prerequisite, our aim was to assess its feasibility and safety and also to evaluate its success, from both the endoscopist’s and radiotherapist’s perspectives. Patients and methods We prospectively collected data concerning PDAC patients submitted to EUS-guided fiducial placement, from February 2018 to November 2019. Technical success was defined as at least one marker presumed inside the tumor. Quality success was assessed at pre-SBRT computed tomography, accordingly to the number of markers inside or, info:eu-repo/semantics/published

ObjectiveTo investigate the effect of the Yap1 gene and tanshinone ⅡA on the proliferation, migration, and invasion abilities of Huh-7 hepatoma cells. MethodsA total of 10 pairs of human hepatocellular carcinoma (HCC) samples and adjacent tissue samples were collected in Zhongnan Hospital of Wuhan University from June 1 to December 1, 2019. Quantitative real-time PCR and Western blotting were used to measure the expression of the Yap1 gene and phenotype-related molecules. MTT cell proliferation detection reagent was used to measure the inhibition rate of cell proliferation after the treatment with different concentrations of tanshinone ⅡA. Western blotting was used to measure the changes in the expression of apoptosis-and migration-related markers after different interventions. Flow cytometry and Transwell assay were used to measure apoptosis and cell migration and invasion abilities. The data of 375 cases of liver cancer and 50 cases of relatively normal liver tissue samples were downloaded from The Cancer Genome Atlas, including clinicopathological information. The t-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. ResultsIn 8 of the 10 pairs of HCC samples and adjacent tissue samples, HCC samples had significantly higher expression of Yap1 than the adjacent tissue samples. Compared with the normal human liver epithelial cells L02, the Huh-7 and HCCL-M3 hepatoma cells had a significant increase in the expression of Yap1. The silencing efficiency of si-Yap1-3 transfection reached 87.004% at the protein level. MTT results showed that tanshinone ⅡA effectively inhibited the proliferation of Huh-7 cells, with a half inhibitory concentration of 8.683 μmol/L. After the cells were treated with si-Yap1-3 and tanshinone ⅡA, there was an increase in the expression of the downstream marker for proliferation and migration E-cadherin and a reduction in the expression of vimentin, and the results of Transwell assay showed that compared with the si-NC group, the tanshinone ⅡA+si-Yap1-3 group had significant reductions in the migration and invasion abilities of Huh-7 cells (migration: 43.19±2.88 vs 132.20±10.03, t=8.527, P=0.001; invasion: 53.95±4.20 vs 179.10±11.11, t=4.484, P=0.011). The group treated with si-Yap1-3 and tanshinone ⅡA had an increase in the expression of the apoptosis-related marker Bax and a reduction in the expression of Bcl-2, as well as a significantly higher early apoptosis rate than the si-NC group (2598% vs 9.21%, χ2=4.078, P＜0.05). ConclusionOncogene Yap1 silencing combined with tanshinone ⅡA can promote the apoptosis of Huh-7 hepatoma cells and inhibit their migration and invasion, which can provide certain guiding significance for clinical medication.

Background Laparoscopic splenectomy (LS) being used after Transjugular intrahepatic portosystemic shunt (TIPS) has not been reported. This report aims to explore the feasibility, safety, and potential efficacy of LS after TIPS hypersplenism secondary to portal hypertension (PHT). Methods We retrospectively reviewed a series of six patients who underwent LS after TIPS for hypersplenism secondary to PHT between 2014 and 2020. The perioperative data and patients’ clinical outcomes were recorded. Results LS was successfully performed in all patients. Hypersplenism was corrected after LS in all six patients. Postoperative prothrombin time, prothrombin activity, international normalized ratio, and total bilirubin showed a trend toward improvement. The preoperative and 1-month postoperative albumin and activated partial thromboplastin levels showed no significant difference. Plasma ammonia level and thromboelastography indicators were ameliorated in two limited recorded patients. No postoperative complications such as subphrenic abscess, portal vein thrombosis, variceal bleeding, hepatic encephalopathy, and liver failure occurred during the 1-month follow-up period. Conclusion LS following TIPS is feasible, safe, and beneficial for patients with hypersplenism secondary to PHT. The following LS not only corrects the hypersplenism, but also has the potential to improve liver function.

ObjectiveTo investigate the efficacy and safety of Fuzheng Huayu tablets (FZHY) combined with entecavir (ETV) in the treatment of chronic hepatitis B (CHB) liver fibrosis. MethodsA total of 52 patients with CHB liver fibrosis with an Ishak stage of ≥F3 who were treated in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from April 2011 to January 2013 were enrolled and divided into FZHY combined with ETV group (combination group) and placebo combined with ETV group (control group), with 26 patients in each group, and the course of treatment was 48 weeks for both groups. Liver biopsy was performed before and after these treatment; clinical outcome was determined based on the reversal rate of Ishak stage for liver fibrosis and the improvement rate of histological activity index (HAI) for inflammation grade, and safety was evaluated based on electrocardiographic findings. Three datasets (full analysis set, per-protocol set, and safety dataset) were identified for analysis; the t-test or the Wilcoxon test was used for comparison of continuous data between two groups, and the CMH chi-square test, the chi-square test, or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsOf all 52 patients, 46 underwent the two liver biopsies before and after treatment, with 22 in the combination group and 24 in the control group. At week 48 of treatment, there was a significant difference in the proportion of patients with Ishak stage reduced by ≥1 stage between the combination group and the control group (81.8% vs 54.2%, χ2=5.297, P=0.021). There was also a significant difference in the improvement rate of HAI grade between the combination group and the control group were (59.1% vs 25.0%, χ2=6.822, P=0.009). There were no significant differences between the two groups in the incidence rates of adverse events and serious adverse events, the safety analysis of vital signs, and laboratory safety indicators (all P＞0.05). ConclusionFZHY combined with ETV has significant advantages over ETV alone in improving liver fibrosis and inflammation, and antiviral therapy combined with anti-fibrosis therapy can bring better hepatic histological improvement for CHB patients. FZHY combined with ETV has good safety in the treatment of patients with CHB liver fibrosis.

Background The application of measurement instruments is a strategy to evaluate the patient's knowledge about the disease. This study aims to build an instrument that evaluates the patient's knowledge about liver cirrhosis. Method This study includes three phases. The first one was the construction of the instrument based on a literature review. In the second phase, five experts were participated in the evaluation of the instrument, to check the validity of the content. Quantitative and qualitative analyzes were made. The tool used was the CVI (Content Validity Index) and it was used the semantic study of the questions. The third phase was the process of the restructuring the instrument. Results The final version of the instrument consisted of 36 questions. The instrument was evaluated in 91.7 by the average CVI and 94.4% by the universal CVI. Conclusions The questions are properly structured and clear, therefore, understandable. Thus, the final instrument presented satisfactory content validity, so that, it reached the aim of this study.

Ibrahim G Alghamdi,1 Majid Almadi,2,3 Fahad Alsohaibani,4 Mahmoud Mosli,5 Edward B De Vol,6 Faisal Abaalkhail,7,8 Faisal A AlSaif,9 Waleed K Al-hamoudi,10 Nasser Al-Sanea,11– 13 Mazen Hassanain,9,14 Saleh A Alqahtani6,15,16 1Public Health Department, College of Applied Medical Sciences, University of Al-Baha, Al-Baha, Saudi Arabia; 2Division of Gastroenterology, Department of Medicine, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia; 3Division of Gastroenterology, McGill University Health Center, Montreal General Hospital, McGill University, Montreal, Canada; 4Department of Medicine, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia; 5Division of Gastroenterology, Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 6Biostatistics, Epidemiology, and Scientific Computing Department, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia; 7Gastroenterology Section, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia; 8College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 9Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 10Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 11Health Affairs, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; 12Department of Surgery, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; 13Department of Surgery, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia; 14Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; 15Liver Transplant Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia; 16Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USACorrespondence: Saleh A AlqahtaniLiver Transplant Center, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi ArabiaEmail salalqahtani@kfshrc.edu.saPurpose: Over the last decades, the incidence of pancreatic cancer has increased, particularly in countries with a higher socioeconomic status. The present work aimed to provide detailed epidemiological data on the incidence of pancreatic cancer in Saudi Arabia.Patients and Methods: In this retrospective descriptive study, the epidemiological data on pancreatic cancer cases diagnosed in 13 administrative regions of Saudi Arabia between January 2004 and December 2015 were extracted from the Saudi Cancer Registry. The frequency, the crude incidence rate (CIR), and the age-standardized incidence rate (ASIR), stratified by geographical region, gender, and the year of diagnosis, were analyzed.Results: From January 2004 to December 2015, a total of 2338 cases of pancreatic cancer were registered, including 1443 males and 895 females. The overall CIR was 1.28/100,000 among males and 0.80/100,000 in females, with an overall ASIR of 2.26 and 1.41/100,000 for males and females, respectively. Higher ASIR and CIR were observed among males than females (ratio 1.6). In both genders, the ASIR of pancreatic cancer increased with increasing age, with the highest incidence in patients aged 70 years or more. The ASIR in the Eastern Region (3.2/100,000) and the regions of Riyadh (3.0/100,000) and Tabuk (2.6/100,000) proved to be significantly higher than in the other regions of the country. Among women, the ASIR was significantly higher in Riyadh (2.3/100,000), the northern region (2.2/100,000), and Tabuk (2.0/100,000).Conclusion: This study revealed a slight increase of the CIR and ASIR of pancreatic cancer among males and females of the Saudi population. Eastern region, Riyadh, and Tabuk had the highest overall ASIRs of pancreatic cancer among males, Riyadh, Northern region, and Tabuk among Saudi females. The area least affected by pancreatic cancer was observed in Jazan among male and female Saudis. The rates of pancreatic cancer in Saudi Arabia were significantly higher among males compared with female Saudis. Further analytical studies are needed to identify the potential risk factors for pancreatic cancer among the Saudi population.Keywords: pancreatic cancer, epidemiology, Saudi Arabia, incidence, Middle-East

Background Upper gastrointestinal (GI) bleeding is the most important presentation of an aorto-duodenal fistula (ADF). Early diagnosis is difficult, and the disease is associated with high mortality. The present study aimed to examine the clinical and the endoscopic characteristics of ADF in eight patients who presented to our hospital. We also sought to clarify the diagnostic approach towards the disease. Methods The present study examined the clinical and the endoscopic/computed tomography (CT) characteristics of ADF in eight patients who were definitively diagnosed with this condition in a 12-year period at our hospital. Results The patients comprised of five men and three women, with a mean age of 69.8 years. Upper gastrointestinal bleeding was the chief complaint for all the patients. Out of these, two patients presented with shock. The patients’ mean haemoglobin at presentation was 7.09 g/dL, and the mean number of blood transfusions was 7.5. All patients had undergone intervention to manage an aortic pathology in the past. As the first investigation, an upper GI endoscopy in 5 and a CT scan in 3 patients were performed. In cases where CT scan was performed first, no definitive diagnosis was obtained, and the diagnosis was confirmed by performing an upper GI endoscopy. In cases where endoscopy was performed first, definitive diagnosis was made in only one case, and the other cases were confirmed by the CT scan. In some cases, tip attachments, converting to long endoscopes, and marking clips were found useful. Conclusions In patients who have undergone intervention to manage an aortic pathology and have episodes of upper gastrointestinal bleeding, ADF cannot be definitively diagnosed with only one investigation. In addition, when performing upper GI endoscopy in cases where an ADF is suspected, tip attachment, converting to a long endoscope, and using marking clips can be helpful.

The aim of this study was to determine the dominant species of bacteria found in blood cultures collected from patients under treatment in the tertiary inflammatory bowel disease (IBD) center in Poland. The dominant pathogen isolated from blood in patients with IBD was Staphylococcus epidermidis MRCNS (MRCNS—methicillin-resistant coagulase-negative Staphylococcus), a strain resistant to all beta-lactam antibiotics (penicillins, penicillins with B-lactamase inhibitor, cephalosporins and carbapenems). The second most commonly isolated pathogen found in the blood samples was Escherichia coli. Blood cultures were found to be positive for these pathogens more frequently in male patients (90.0%). An increased risk of bacteremia in IBD patients was associated with prolonged hospitalization.

Background Studies have indicated that underdiagnosis and diagnostic delay are common in celiac disease. Therefore, it is important to increase our knowledge of what symptoms and biomarkers could identify undiagnosed cases of celiac disease. Methods We screened for celiac disease antibodies in stored blood samples from 16,776 participants in eight population-based studies examined during 1976–2012. Undiagnosed celiac seropositivity was defined as celiac disease antibody positivity (IgG-deamidated gliadin peptide above 10.0 U/mL and/or IgA-tissue transglutaminase (TTG) or IgG-TTG above 7.0 U/mL) without a known diagnosis of celiac disease in the National Patient Register. In all studies general health symptoms were recorded by participant-completed questionnaire, including self-perceived health, tiredness, headache and gastrointestinal symptoms. Furthermore, blood samples were drawn for analyses of biomarkers e.g. hemoglobin, blood glucose, cholesterol, liver parameters and vitamins. The participants with undiagnosed celiac seropositivity were matched by sex, age and study with four controls among the celiac disease antibody negative participants. Results We excluded, five participants with known celiac disease, resulting in a population of 16,771 participants. In this population 1% (169/16,771) had undiagnosed celiac seropositivity. There were no statistically significant differences in symptoms between cases and controls. Undiagnosed celiac seropositivity was associated with low blood cholesterol ( Conclusion In this general population study, undiagnosed cases of celiac seropositivity did not have more symptoms than controls, confirming the diagnostic difficulties of celiac disease and the low prognostic value of symptoms for a diagnosis of celiac disease. Furthermore, decreased levels of cholesterol and/or hemoglobin in the blood were associated with undiagnosed celiac seropositivity.

Background and study aims In 2015, the American Society for Gastrointestinal Endoscopy (ASGE) and American College of Gastroenterology (ACG) Task Force on Quality in Endoscopy deemed adenoma detection rate (ADR) the most important quality measure for colonoscopy. There has been much interest in factors that can increase ADR. To date, however, few studies have looked at what intra-procedural endoscopist practices are associated with improving ADR. We conducted a retrospective review of colonoscopy videos to evaluate intra-procedural practices that could be associated with ADR.Methods Videos were recorded of colonoscopies performed between September and December 2017 at the Palo Alto Veterans Affairs Health Care System. Colonoscopies for screening and surveillance were included for video review. Factors assessed included withdrawal time, intra-procedural cleaning, inspection technique, and other variables (colon distention, removal of equivocal/hyperplastic polyps). A series of multiple regression analyses was conducted on variables of interest before running a final model of significant predictors.Results A total of 130 videos were reviewed from nine endoscopists whose ADRs ranged between 37.5 % and 73.7 %. The final regression model was significant (F = 15.35, df = 2, P = 0.0044), R2 = 0.8365) with close inspection of behind folds and quality of cecal inspection being the factors highly correlated with predicting ADR. Withdrawal and inspection times, colonic wall distention, removal of equivocal/hyperplastic polyps, quality of rectal inspection, suctioning, and washing were factors moderately correlated with predicting ADR.Conclusions We found that behind-fold inspection and a meticulous cecal inspection technique were predictive of a high ADR.

ObjectiveTo investigate the effect of hypoxia-inducible factor-1α (HIF-1α) on the stemness and epirubicin sensitivity of hepatoma cells. MethodsHepatoma cells were selected for experiment. HepG2 hepatoma cells transfected with HIF-1α overexpression plasmid were selected as experimental group, and those transfected with pcDNA3.1 empty plasmid were selected as control group; HepG2 cells alone were selected as HepG2 group. Quantitative real-time PCR was used to measure the mRNA expression of HIF-1α; Western blot was used to measure the protein expression of HIF-1α; flow cytometry was used to measure the expression of CD133 on the surface of hepatoma cells. The three groups of cells were treated with epirubicin at different concentrations (0, 6.25, 12.5, 25, and 50 μmol/L) for 24 hours; MTT assay was used to measure cell viability, and flow cytometry was used to measure apoptosis after treatment with epirubicin (50 μmol/L). A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the t-test was used for further comparison between two groups. ResultsCompared with the HepG2 group and the control group, the experimental group had a significant increase in the mRNA expression of HIF-1α (both P＜0.001), and Western blot showed high expression of HIF-1α in the experimental group. The percentage of CD133 cells was 0.040%±0.003% in the HepG2 group, 0.030%±0.010% in the control group, and 20.110%±0.600% in the experimental group, and the experimental group had a significantly higher positive rate of CD133+ than the HepG2 group and the control group (both P＜0.001). At an epirubicin concentration of 25 and 50 μmol/L, the HepG2 group and the control group had significantly inhibited cell viability and a significantly lower cell viability than the experimental group (both P＜005). After the treatment with 50 μmol/L epirubicin for 48 hours, the experimental group had a significantly lower cell apoptosis rate than the HepG2 group (67.9%±2.5% vs 93.6%±1.5%, P＜0.001) and the control group (67.9%±2.5% vs 93.0%±1.2%, P＜0001). ConclusionHepG2 cells are successfully transfected with HIF-1α overexpression plasmid, and HIF-1α can increase the percentage of liver cancer stem cells and improve their resistance to epirubicin.

Refractory ascites is characterized by severe circulatory dysfunction and increased sensitivity to renal impairment by non‐selective beta‐blockers (NSBB). A novel serum microRNA signature, identified in the secretome of human cirrhotic hepatocytes, allows for the molecular characterization of patients with decompensated cirrhosis more prone to develop significant cardiac impairment after NSBB, as well as those more likely to respond to NSBB in terms of HVPG reduction., Noninvasive staging of decompensated cirrhosis is an unmet clinical need. The aims of this study were to characterize and validate a novel microRNA (miRNA) signature to stage decompensated cirrhosis and predict the portal pressure and systolic cardiac response to nonselective beta‐blockers (NSBBs). Serum samples from patients with decompensated cirrhosis (n = 36) and healthy controls (n = 36) were tested for a novel signature of five miRNAs (miR‐452‐5p, miR‐429, miR‐885‐5p, miR‐181b‐5p, and miR‐122‐5p) identified in the secretome of primary human hepatocytes and for three miRNAs (miR‐192‐5p, miR‐34a‐5p, and miR‐29a‐5p) previously discovered as biomarkers of chronic liver disease. All patients had ascites, which was refractory in 18 (50%), and were placed on NSBBs for variceal bleeding prophylaxis. In all patients, serum miRNAs, hepatic venous pressure gradient, and an echocardiogram study were performed before and 1 month after NSBBs. Patients with cirrhosis had lower serum levels of miR‐429, miR‐885‐5p, miR‐181b‐5p, miR‐122‐5p, miR‐192‐5p, and miR‐29a‐5p (P

The incidence of press-through pack (PTP) ingestion has been increasing. In many cases, the ingested PTP is lodged in the esophagus. Here, we report a case of endoscopic removal of a PTP from the anal canal. An 89-year-old man with mild dementia presented with a 3-day history of anal pain. On digital rectal examination, we felt a hard and sharp object, which could not be manually removed due to its shape. Therefore, it was removed endoscopically. We inserted an endoscope with a large-caliber soft oblique cap and observed the PTP in the anal canal. It was successfully removed using grasping forceps. The patient was stable, with only mild anal fissures, and no serious complications such as perforation and bleeding were observed. It is generally recognized that a PTP that reaches the large intestine is naturally expelled. Even if a PTP could pass through the pylorus or the small intestine, it could still be difficult to discharge naturally from the anus without discomfort or pain, as in this case.

ObjectiveTo investigate the virologic response to direct-acting antiviral (DAA) therapy and the changes in liver stiffness measurement (LSM), fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) after treatment in chronic hepatitis C (CHC) patients with different alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at baseline in a real-world setting. MethodsCHC patients who attended the outpatient service of Department of Infectious Diseases, Peking University First Hospital, from December 2017 to May 2020 were enrolled, and virologic response rate was calculated. The Wilcoxon rank-sum test was used to compare LSM, FIB-4, and APRI between groups at baseline and at 12 weeks after treatment, and the chi-square test was used for comparison of categorical data between groups. ResultsA total of 48 CHC patients were enrolled, among whom 33.3% had abnormal ALT or AST at baseline. Among these patients, the virologic response rate was 85.4% at week 4 of treatment and 100% at the end of treatment and at 12, 24, and 48 weeks after treatment, and there were significant changes from baseline to 12 weeks after treatment in LSM ［6.1 (51-12.4) kPa vs 8.6 (5.7-16.9) kPa, Z=-1.676, P=0.043］ and APRI ［0.24(0.19-0.48) vs 0.42(0.23-1.17), Z=-2.050, P=0027］. From baseline to 12 weeks after treatment, the patients with abnormal ALT or AST at baseline had significant changes in LSM ［89(5.6-13.1) kPa vs 14.4(8.0-28.2) kPa, Z=-1.679, P=0.047］ and APRI ［0.44(0.25-0.50) vs 1.29(0.99-2.09), Z=-3.427, P=0.001］. ConclusionCHC patients achieve a high sustained virologic response rate after DAA therapy, and the patients with abnormal ALT or AST at baseline tend to have more significant improvements in LSM and APRI than those without such abnormality.

Major international guidelines have not yet reached a consensus on the definition of the immune tolerance stage of chronic hepatitis B virus infection; however, almost all guidelines do not recommend starting treatment for patients in the immune tolerance stage of chronic hepatitis B. This article discusses the latest evidence for the treatment of such patients to prevent liver cirrhosis and hepatocellular carcinoma.

Background and study aims Storage of full-length endoscopic procedures is becoming increasingly popular. To facilitate large-scale machine learning (ML) focused on clinical outcomes, these videos must be merged with the patient-level data in the electronic health record (EHR). Our aim was to present a method of accurately linking patient-level EHR data with cloud stored colonoscopy videos. Methods This study was conducted at a single academic medical center. Most procedure videos are automatically uploaded to the cloud server but are identified only by procedure time and procedure room. We developed and then tested an algorithm to match recorded videos with corresponding exams in the EHR based upon procedure time and room and subsequently extract frames of interest. Results Among 28,611 total colonoscopies performed over the study period, 21,170 colonoscopy videos in 20,420 unique patients (54.2 % male, median age 58) were matched to EHR data. Of 100 randomly sampled videos, appropriate matching was manually confirmed in all. In total, these videos represented 489,721 minutes of colonoscopy performed by 50 endoscopists (median 214 colonoscopies per endoscopist). The most common procedure indications were polyp screening (47.3 %), surveillance (28.9 %) and inflammatory bowel disease (9.4 %). From these videos, we extracted procedure highlights (identified by image capture; mean 8.5 per colonoscopy) and surrounding frames. Conclusions We report the successful merging of a large database of endoscopy videos stored with limited identifiers to rich patient-level data in a highly accurate manner. This technique facilitates the development of ML algorithms based upon relevant patient outcomes.

International audience; Abstract Background Shewanella xiamenensis has been reported in water environment and in patients and can act as the originator of oxacillinase in gram-negative bacteria. In order to assess genome plasticity and its functional properties related diarrhea symptoms in pilgrim, comparisons of draft genome sequences of the two isolates were conducted with other closely related genomes. Results We isolated S. xiamenensis 111B and 111D strains from a pilgrim before travels to the Hajj and during travels with diarrhea symptom, respectively. Whole-genome sequencing showed that draft genome size of 111B strain was 5,008,191 bp, containing 49 kb of a putative plasmid. The genome size of 111D was 4,964,295 bp containing 225 kb of a putative plasmid that shared the backbone sequences with the hospital wastewater strain T17. Comparatively, two Hajj strains are identical at 97.3% identity and 98.7% coverage. They are closely related to river water strain, AS58 by SNPs analysis. Notably, a novel bla OXA-48 allele bla OXA-547 was identified in 111D, sharing 99.5% identity with bla OXA-546 and bla OXA-894 . Multiple copies of virulence specific genes, such as capsular polysaccharide biosynthesis, O-antigen and lasB (vibriolysin related gene) have been identified specifically in 111D, but absent in 111B strain. Conclusions The whole genome sequences of S. xiamenensis strain 111B and 111D, including comparative genomic analysis, highlight here the potential for virulence factors that might be related to the cause of diarrhea in humans and also indicate the possible acquisition of pathogenic bacteria, including antibiotic resistance genes or plasmids during the Hajj.

Background and study aims Conscious sedation is routinely administered for colonoscopy but is associated with risks and inconveniences. We sought to determine whether virtual reality (VR) may be a feasible alternative. Patients and methods Twenty-seven individuals scheduled for screening/surveillance colonoscopy participated. The VR device was activated throughout the colonoscopy, but subjects could opt out and request standard medications. Questionnaires were administered, and variables were assessed on a scale of 1 to 10. Results Cecal intubation was achieved in all cases without adverse events (AEs). Study colonoscopies were completed without pharmacological rescue in 26 of 27 patients (96.3 %) and procedure times were comparable to baseline. Subjects reported minimal pain, high satisfaction, and willingness to use VR for future colonoscopies to avoid narcotics and resume normal activities including driving. Conclusion Replacing pharmacological sedation with VR did not impact colonoscopy completion rates, procedure time, or AEs. Satisfaction was high and only one subject (3.7 %) chose to suspend VR. VR can be an effective alternative for patients undergoing colonoscopy who prefer to avoid narcotics.

Gallbladder adenomyomatosis (GA) is a benign alteration of the gallbladder wall. There are three types involved: segmental, fundal, and diffuse pattern; the last type is very rare. Ultrasound is the imaging method of choice for diagnosing that shows Rokitansky-Aschoff sinuses with cholesterol deposition creating comet-tail artifacts. Asymptomatic GA does not require surgery in case there are no malignant lesions defined by imaging diagnosis. We present the rare case of a 51-year-old man who was admitted to hospital due to abdominal pain concomitant with inflammatory syndrome. Imaging and histological findings were appropriate to diagnose diffuse GA and complication of cholecystitis.

Pankaj Garg,1,2 Baljit Kaur,3 Konica Singla,2 Geetha R Menon,4 Vipul D Yagnik5 1Department of Colorectal Surgery, Indus International Hospital, Mohali, India; 2Department of Colorectal Surgery, Garg Fistula Research Institute (GFRI), Haryana, India; 3Department of Radiology, SSRD Imaging Centre, Chandigarh, India; 4Department of Biostatistics, Indian Council of Medical Research, New Delhi, India; 5Department of Surgical Gastroenterology, Nishtha Surgical Hospital and Research Centre, Patan, Gujarat, IndiaCorrespondence: Pankaj GargGarg Fistula Research Institute (GFRI), H.no- 1042, Sector-15, Panchkula, Haryana, 134113, IndiaFax +91 9501522000Email drgargpankaj@yahoo.comPurpose: In some anal fistulas, the internal/primary opening cannot be located even after examination and assessment on MRI or transrectal ultrasound. The efficacy of a simple new protocol to manage such therapeutically challenging fistulas was tested.Patients and Methods: All anal fistula patients operated consecutively over 7 years were included in the study. A simple two-step protocol was followed for fistulas in which the internal opening was not locatable after clinical examination and MRI assessment. First, the MRI was reassessed. The site where the fistula was closest to the internal sphincter was noted. It was assumed that the internal-opening was located at that position and the fistula was treated accordingly. Second, in horseshoe anal fistulas with no apparent internal opening, it was assumed that the internal opening was located in the midline. Low fistulas were treated by fistulotomy and high fistulas by a sphincter-sparing procedure. Incontinence was evaluated by objective incontinence scores (Vaizey scores).Results: A total of 757 patients were operated (median follow-up-33 months). Of these, 57 patients were excluded due to short or inadequate follow-up. In 154/700 (22%) patients, the internal opening could not be located while in 546/700 (78%), the internal opening was found. Both the groups were similar in all parameters. In the “internal-opening found” group, the fistula healed completely in 486/546 (89%) and in the ‘internal-opening not found group’, the fistula healed in 140/156 (90.9%) (p=1.01). The objective continence scores did not change significantly after surgery in both the groups.Conclusion: This new protocol seems effective as a high cure rate could be achieved in ‘internal-opening not found’ fistulas which was comparable to fistula healing in the ‘internal-opening found’ group.Keywords: anal fistula, internal opening, horseshoe, MRI, recurrence, fistula-in-ano

Background Clostridioides difficile infection (CDI) is a common hospital-associated diarrhea. Several antibiotics commonly associate with CDI; however, limited data are available on the duration of exposure prior to CDI. Moreover, studies on the characteristics of CDI patients in Saudi Arabia are limited. Therefore, this study aimed to characterize CDI patients identified over 10 years and assess antibiotic days of therapy (DOT) prior to CDI. Methods This was a retrospective descriptive analysis of CDI patients at a Saudi tertiary academic medical center between December 2007 and January 2018. Patients characteristics, prior exposure to known CDI risk factors, and DOT of antibiotics prior to CDI incidence were assessed. Results A total of 159 patients were included. Median age was 62 years. Most cases were hospital-acquired (71.1%), non-severe (44.7%), and admitted to medical wards (81.1%). Prior exposure to antibiotics and acid suppression therapy were reported with the majority (76.1 and 75.5%, respectively). The most frequently prescribed antibiotics were piperacillin/tazobactam, ceftriaxone, meropenem, and ciprofloxacin with median DOTs prior to CDI incidence of 14 days for the β-lactams and 26 days for ciprofloxacin. The distribution of DOT was significantly different for piperacillin/tazobactam in different units (P = 0.003) where its median DOT was the shortest in medical wards (11 days), and for ciprofloxacin among different severity groups (P = 0.013), where its median DOT was the shortest in severe CDI patients (11 days). Conclusion Most patients in this study had hospital-acquired non-severe CDI and were largely exposed to antibiotics and acid suppression therapy. Therefore, such therapies should be revised for necessity.

Autoimmune pancreatitis (AIP) is characterized by pancreatic manifestations of IgG4-related disease. Malignancies in patients with AIP have been reported, but carcinoma of the bile duct is extremely rare. We report a patient with IgG4-related AIP who developed cholangiocarcinoma after 8 years of steroid treatment. A 76-year-old male presented with fever (37.8°C) due to biliary obstruction and cholangitis. He had been treated with steroids for 8 years to control inflammation due to IgG4-related AIP. During 8 years of treatment, hepatobiliary enzyme levels were well controlled within their normal range, but serum IgG4 levels remained elevated. A computed tomography scan showed intrahepatic bile duct dilatation. Magnetic resonance cholangiopancreatography showed obstructive changes at the junction of the cystic and common ducts. To relieve biliary obstruction, endoscopic bile duct drainage using a nasobiliary tube was performed, and cytology was Class IV. Aorto-caval lymph node enlargement was found at laparotomy, intraoperatively diagnosed as adenocarcinoma, and resection was abandoned. He died 4 months postoperatively. We report a patient with IgG4-related AIP complicated by cholangiocarcinoma which developed after 8 years of steroid treatment. Even if hepatobiliary markers are well controlled, periodic follow-up with imaging studies may facilitate detection of an early cholangiocarcinoma.

Reactivation of hepatitis B virus (HBV) is known to occur frequently after hematopoietic stem cell transplantation (HSCT). The reactivation can be prevented by nucleos(t)ide analogue (NA), but it is unclear how long NA should be continued. Here, we report 3 cases of HBV reactivation with discontinuation of NA following the discontinuation of immunosuppressive therapies after HSCT. Three male patients aged 34, 59, and 54 years received allogeneic HSCT (allo-HSCT) for chronic myeloid leukemia, mixed phenotype acute leukemia, and myelodysplastic syndrome, respectively. Before HSCT, 2 patients were positive for hepatitis B surface antigen (HBsAg) and 1 patient was negative for HBsAg and positive for antibodies to hepatitis B core antigen. NA (lamivudine or entecavir) was started at the same time as HSCT and stopped after the discontinuation of immunosuppressive therapies. In all patients, the serum HBV DNA levels were increased after the discontinuation of NAs. Two of the three patients developed severe hepatitis with high levels of HBV DNA (7.5 and 7.4 log IU/mL, respectively). A patient without hepatitis was re-administered NA soon after the HBV DNA started to increase (3.3 log IU/mL). Interestingly, the 2 patients who developed hepatitis cleared HBsAg promptly after the recovery from hepatitis and they could stop NAs without the reversion of HBsAg. It was speculated that transplanted immune cells, which were naïve for HBV, react strongly with HBV antigens that were increased after the NA discontinuation. The discontinuation of NA after allo-HSCT is not recommended generally because strong hepatitis might be induced even after several years.

ObjectiveTo investigate the difference in protein expression between hepatocellular carcinoma (HCC) patients with recurrence and those with good prognosis, the differential expression and regulatory mechanism of miR-152-3p target proteins, and the role of miR-152-3p in the recurrence of HCC. MethodsTMT-labeled proteomic sequencing and RT-PCR were used to measure the expression of proteins and the expression of miR-152-3p in the HCC tissue of six patients with recurrence at 2 years after HCC resection and six patients with good prognosis at 5 years. Six databases were used to analyze the target genes of miR-152-3p, and Gene Ontology, DAVID, and REACTOME databases were used to perform target gene screening, enrichment annotation, and signal transduction pathway enrichment analysis. Gene mutation frequency and survival curve analysis were performed for the target genes of miR-152-3p to verify the role of miR-152-3p target genes in patients with HCC recurrence. The independent samples t-test was used for comparison of continuous data between two groups, and a Kaplan-Meier analysis was performed to investigate the survival rates of liver-related genes. ResultsCompared with the patients with HCC recurrence, the patients with good prognosis after HCC resection had a significantly higher transcriptional expression level of miR-152-3p in HCC tissue (P＜0.05). The results of protein sequencing showed that there were 365 differentially expressed proteins in HCC tissue between the patients with good prognosis and the patients with recurrence, and the analysis of HCC recurrence databases showed that 17 proteins were regulated by miR-152-3p. Further analysis of the signaling pathways showed that the function of the 17 target genes regulated by miR-152-3p was enriched in the translation and regulation of mitochondria and ribosome, and multiple enrichment revealed that six target genes were closely associated with mitochondrial respiratory chain complex, i.e., AKAP1, FOXRED1, MRPL28, MRPL50, SHC1, and STAU1. Gene mutation frequency and survival curve analysis showed that the loss or weakening of the function of mitochondrial respiratory chain-related target proteins seriously affected the prognosis and survival rate of patients. ConclusionThere is a significant difference in the expression of miR-152-3p in HCC tissue between patients with good prognosis and those with recurrence after HCC resection, and miR-152-3p may lead to the recurrence of HCC by regulating the target genes AKAP1, FOXRED1, MRPL28, MRPL50, SHC1, and STAU1, acting on the mitochondrial respiratory chain, and affecting the oxidative respiratory function of cells.

Background Risk indices such as the pancreas donor risk index (PDRI) and pre-procurement pancreas allocation suitability score (P-PASS) are utilised in solid pancreas transplantation however no review has compared all derived and validated indices in this field. We systematically reviewed all risk indices in solid pancreas transplantation to compare their predictive ability for transplant outcomes. Methods Medline Plus, Embase and the Cochrane Library were searched for studies deriving and externally validating risk indices in solid pancreas transplantation for the outcomes of pancreas and patient survival and donor pancreas acceptance for transplantation. Results were analysed descriptively due to limited reporting of discrimination and calibration metrics required to assess model performance. Results From 25 included studies, discrimination and calibration metrics were only reported in 88% and 38% of derivation studies (n = 8) and in 25% and 25% of external validation studies (n = 12) respectively. 21 risk indices were derived with mild to moderate ability to predict risk (C-statistics 0.52–0.78). Donor age, donor body mass index (BMI) and donor gender were the commonest covariates within derived risk indices. Only PDRI and P-PASS were subsequently externally validated, with variable association with post-transplant outcomes. P-PASS was not associated with pancreas graft survival. Conclusion Most of the risk indices derived for use in solid pancreas transplantation were not externally validated (90%). PDRI and P-PASS are the only risk indices externally validated for solid pancreas transplantation, and when validated without reclassification measures, are associated with 1-year pancreas graft survival and donor pancreas acceptance respectively. Future risk indices incorporating recipient and other covariates alongside donor risk factors may have improved predictive ability for solid pancreas transplant outcomes.

Acute gastric dilatation is the radiological finding of a massively enlarged stomach as seen on plain film X-ray or a computerized tomography scan of the abdomen. It is a rare entity with high mortality if not treated promptly and is often not reported due to a lack of physician awareness. It can occur due to both mechanical obstruction of the gastric outflow tract, or due to nonmechanical causes, such as eating disorders and gastroparesis. Acute hyperglycemia without diagnosed gastroparesis, such as in patients with diabetic ketoacidosis, may also predispose to acute gastric dilatation. Prompt placement of a nasogastric tube can help deter its serious complications of gastric emphysema, ischemia, and/or perforation. We present our experience of 2 patients who presented with severe hyperglycemia and were found to have acute gastric dilation on imaging. Only one of the patients was treated with nasogastric tube placement for decompression and eventually made a full recovery.

Background Viral resistance-associated substitutions (RASs) can develop in the setting of DAAs therapy (i.e., emerging RASs). Long-term monitoring of fibrosis regression after achieving SVR to simiprevir (SMV)/sofosbuvir (SOF) is essential. The aim of this study was to determine the prevalence of baseline and emerging NS34A RASs in chronic HCV patients in Upper Egypt and to assess the impact of SMV/SOF therapy on liver stiffness. Results The enrolled 59 patients had HCV genotype 4a without any baseline RASs in the NS34A region. 96.6% (57/59) of patients achieved sustained virological response (SVR12). Of the two patients who failed to achieve SVR12, one of them developed emerging RASs Q80K in the NS34A region. Seventy-two weeks after SMV/SOF therapy, the percentage of patients with liver fibrosis stage (F2, F3, and F4) decreased from 75.4% before treatment to 42.1% after treatment. The combination of SOF and SMV appeared to be well tolerated. Conclusions All patients had HCV genotype 4a without any baseline RASs in the NS34A region. In addition, there was improvement of non-invasive measures of liver fibrosis in patients who achieved SVR, 72 weeks after SMV/SOF therapy.

ObjectiveTo screen out the mRNAs involved in the resistance of hepatoma cells to anlotinib using ceRNA microarray. MethodsHigh-dose shock combined with low-dose induction was used to culture hepatoma cells resistant to anlotinib, and CCK8 assay was used to verify the difference in the proliferation of drug-resistant hepatoma cells treated by anlotinib. The ceRNA microarray was used to screen out the differentially expressed genes between drug-resistant hepatoma cells and normal hepatoma cells, and real-time PCR was used to verify the differentially expressed genes detected by some microarrays. the independent samples t-test was used for comparison of continuous data between two groups, and the Kaplan-Meier method was used to analyze the overall survival of hepatoma cells samples, and the log-rank test was used to compare survival rates. Fisher’s exact test was used for chip screening. ResultsThere was a significant difference in gene expression between drug-resistant hepatoma cells and normal hepatoma cells, and 10 genes with the greatest difference were screened out for analysis by reducing the range. There were 4 genes associated with drug resistance and tumor growth, i.e., BIRC2, BIRC7, ABCC2, and MAPK8. There were significant reductions in the expression levels of BIRC2, ABCC2, and MAPK8 (P=0001 4, 0001 2, and 0.011 8), and there was a significant increase in the expression of BIRC7 (P＜0.001). The results of real-time PCR were consistent with those of microarray (t=10.74,32.65,18.34, and 2.80; P=0.000 4, 0.000 1, 0.000 1, and 0.044 8). The high expression of BIRC7 and the low expression of MAPK8 were associated with the significant reduction in survival time (P=0.022 0 and 0.005 6). ConclusionBIRC2, BIRC7, ABCC2, and MAPK8 are differentially expressed between anlotinib-resistant hepatoma cells and normal hepatoma cells and may be involved in the resistance of hepatoma cells to anlotinib.

Background/aims Application of polyglycolic acid (PGA) sheets using fibrin glue in post-endoscopic submucosal dissection (ESD) ulcers to prevent bleeding has been reported to be difficult with the conventional delivery method because of gravity. This study assessed the usefulness of the envelope-based delivery system with and against gravity in living pigs. Methods PGA sheets were applied on post-ESD ulcers with and against gravity six times each using the conventional and envelope methods, respectively. The PGA sheet delivery time and the endoscopic and histological findings of the treated ulcer floors were compared. Results With gravity, the median PGA sheet application time was 1.00 (0.68-1.30) min/cm2 and 0.32 (0.18-0.52) min/cm2 with the conventional and envelope techniques (p=0.002), respectively, and against gravity, it was 1.20 (1.13-1.63) min/cm2 and 0.50 (0.39-0.58) min/cm2 (p=0.002), respectively. Against gravity, the endoscopic and histological findings revealed that the conventional group had insufficient fixation of the PGA sheets, but the envelope groups had sufficient fixation. The results with gravity were similar between the groups. Conclusions The envelope method makes it possible to deliver PGA sheets to the stomach quickly and cover ulcers appropriately both with and against gravity in living pigs.

Whipple disease is a systemic chronic infection caused by Tropheryma whipplei. Although chronic diarrhea is a common gastrointestinal symptom, diagnosis is often difficult because there are no specific endoscopic findings, and the pathogen is not detectable by stool culture. We present a female patient with Whipple disease who developed chronic bloody diarrhea and growth retardation at the age of 4 years. Colonoscopy showed a mildly edematous terminal ileum and marked erythema without vascular patterns throughout the sigmoid colon and rectum. Subsequently, a primary diagnosis of ulcerative colitis was made. Histopathological analysis of the terminal ileum showed the presence of foamy macrophages filled with periodic acidSchiff-positive particles. Polymerase chain reaction using DNA from a terminal ileum biopsy sample amplified a fragment of 16S rRNA from T. whipplei. Antibiotic treatment relieved the patient’s symptoms. There was no evidence of immunodeficiency in the present case. Since Whipple disease worsens after anti-tumor necrosis factor inhibitor therapy, considering this infection in the differential diagnosis may be important in patients with inflammatory bowel disease, especially before initiation of immunotherapy.

Background/Aims: To determine if patients with a positive intraoperative cholangiogram (IOC) who undergo a subsequent endoscopic retrograde cholangiopancreatography (ERCP) have an increased risk of post-ERCP pancreatitis (PEP) compared to those who undergo ERCP directly for suspected common bile duct stones. Methods: A retrospective case-control study was performed from 2010 to 2016. Cases included inpatients with a positive IOC at cholecystectomy who underwent subsequent ERCP. The control group included age-sex matched cohorts who underwent ERCP for choledocholithiasis. Multivariate logistic regression was used to assess the association between PEP and positive IOC, adjusting for matching variables and additional potential confounders. Results: Of the 116 patients that met the inclusion criteria, there were 91 women (78%) in each group. Nine patients (7.8%) developed PEP in the IOC group, compared to 3 patients in the control group (2.6%). The use of pancreatic duct stents and rectal indomethacin was similar in both groups. After adjusting for age, sex, total bilirubin levels, and any stent placement, patients with a positive IOC had a significantly increased risk of PEP (odds ratio, 4.79; 95% confidence interval, 1.05-21.89; p

Picosulfate solution is widely used as a small volume bowel cleansing agent and is considered to be effective and relatively safe. A case of a 75-year-old woman ingested picosulfate powder and drank a small volume of water, subsequently experienced severe burning pain in the chest. Endoscopy was performed and showed a submucosal hemorrhage and exudative ulcers at the mid to lower esophagus. At 2 weeks, her symptoms improved with conservative treatment. However, liquid food dysphagia developed 11 weeks after ingestion. A follow-up endoscopy revealed multiple esophageal strictures, which were treated with a fully covered metal stent and esophageal balloon dilation. Consequently, the esophageal strictures improved after one year. As this case demonstrates, detailed information about picosulfate powder ingestion after dissolving it in more than 200 mL of water should be presented to patients to avoid esophageal injury. Clin Endosc 2021;54:122-126