Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

Pre-transjugular-intrahepatic-portosystemic-shunt measurement of hepatic venous pressure gradient and its clinical application: A comparison study.

BACKGROUND: It is controversial whether transjugular intrahepatic portosystemic shunt (TIPS) placement can improve long-term survival. AIM: To assess whether TIPS placement improves survival in patients with hepatic-venous-pressure-gradient (HVPG) ≥ 16 mmHg, based on HVPG-related risk stratification. METHODS: Consecutive variceal bleeding patients treated with endoscopic therapy + nonselective ß-blockers (NSBBs) or covered TIPS placement were retrospectively enrolled between January 2013 and December 2019. HVPG measurements were performed before therapy. The primary outcome was transplant-free survival; secondary endpoints were rebleeding and overt hepatic encephalopathy (OHE). RESULTS: A total of 184 patients were analyzed (mean age, 55.27 years ± 13.86, 107 males; 102 in the EVL+NSBB group, 82 in the covered TIPS group). Based on the HVPG-guided risk stratification, 70 patients had HVPG < 16 mmHg, and 114 patients had HVPG ≥ 16 mmHg. The median follow-up time of the cohort was 49.5 mo. There was no significant difference in transplant-free survival between the two treatment groups overall (hazard ratio [HR], 0.61; 95% confidence interval [CI]: 0.35-1.05; P = 0.07). In the high-HVPG tier, transplant-free survival was higher in the TIPS group (HR, 0.44; 95%CI: 0.23-0.85; P = 0.004). In the low-HVPG tier, transplant-free survival after the two treatments was similar (HR, 0.86; 95%CI: 0.33-0.23; P = 0.74). Covered TIPS placement decreased the rate of rebleeding independent of the HVPG tier (P < 0.001). The difference in OHE between the two groups was not statistically significant (P = 0.09; P = 0.48). CONCLUSION: TIPS placement can effectively improve transplant-free survival when the HVPG is greater than 16 mmHg.

A comprehensive analysis of partial peristalsis recovery after peroral endoscopic myotomy in patients with achalasia.

OBJECTIVE: To determine whether peroral endoscopic myotomy (POEM) improves esophageal peristalsis and to investigate the association between recovery of esophageal peristalsis after POEM and clinical features of the patients. METHODS: In this single-center retrospective study, data were collected from medical records of the patients with achalasia who underwent POEM between January 2014 and May 2016. Demographics data, high-resolution esophageal manometry parameters, Eckardt score, and gastroesophageal reflux disease questionnaire (GERD-Q) score were collected. Weak and fragmented contraction was defined as partial recovery of esophageal peristalsis based on the Chicago classification version 3.0. Logistic regression analysis was used to identify variables associated with the partial recovery of peristalsis after POEM. RESULTS: A total of 103 patients were enrolled. Esophageal contractile activity was observed in the distal two-thirds of the esophagus in 24 patients. The Eckardt score, integrated relaxation pressure, and lower esophageal sphincter (LES) resting pressure were significantly decreased after POEM. Multivariate analysis revealed that preprocedural LES resting pressure (P = 0.013) and preprocedural Eckardt score (P = 0.002) were related to the partial recovery of peristalsis after POEM. Symptoms of gastroesophageal reflux and reflux esophagitis after POEM were less frequent in those with partial recovery of peristalsis (both P < 0.05). CONCLUSIONS: Normalization of esophagogastric junction relaxation pressure achieved by POEM is associated with the partial recovery of esophageal peristalsis in patients with achalasia. Preprocedural LES resting pressure and the Eckardt score are predictive of the recovery of esophageal peristalsis.

Safety and efficacy of endoscopic ultrasound-guided gastroenterostomy for gastric outlet obstruction in different sites: A single-center retrospective study.

OBJECTIVES: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has recently been employed as a novel treatment for gastric outlet obstruction (GOO). The aim of this study was to evaluate the safety and efficacy of EUS-GE for GOO at different sites. METHODS: Consecutive hospitalized patients who underwent EUS-GE for GOO at the Department of Gastroenterology, Nanjing Drum Tower Hospital from March 2017 to April 2020 were recruited in this retrospective study. Patients were divided into three groups depending on the obstruction site. The primary outcomes included technical success and clinical success. The secondary outcomes were operation time, post-procedure length of stay (LOS), hospitalization cost, and complications such as peritonitis, bleeding, pneumoperitoneum, abdominal pain, and infection. RESULTS: A total of 51 patients were included. Technical success achieved in 100% patients with proximal GOO and in 88.9% with distal GOO (P = 0.176). Clinical success declined from the oral side to the anal side (P = 0.510). Operation time, hospitalization costs, and post-procedural LOS were similar among groups (P = 0.532, 0.520, and 0.144, respectively). Complications were observed in 28 (54.9%) patients. In approaching the mature phase of the endosopist, clinical success improved, while the secondary outcomes showed no statistically significant difference compared with the initial phase. CONCLUSIONS: EUS-GE may be challenging for distal GOO; however, it is safe and effective when carried out by experienced endoscopists. A complete preoperative evaluation to assess the difficulty of the procedure is necessary. Prospective studies with large sample size are needed to further validate our findings.

Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer.

BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).

Evaluation of Minimal Change Lesions Using Linked Color Imaging in Patients With Nonerosive Reflux Esophagitis.

BACKGROUND AND AIMS: High prevalence of minimal change lesion (MCL) in nonerosive reflux esophagitis (NERD) patients is commonly recognized by many endoscopists. However, it is difficult to detect MCL with conventional white-light imaging (WLI) endoscopy. Linked color imaging (LCI), a novel image-enhanced endoscopy technology with strong, unique color enhancement, is used for easy recognition of early gastric cancer and detection of Helicobacter pylori infection. The aim of the study was to compare the efficacy of LCI and WLI endoscopy in evaluating MCL in patients with NER. MATERIALS AND METHODS: Forty-one patients with NERD and 38 subjects with nongastroesophageal reflux disease (non-GERD) were recruited in this study between August 2017 and July 2018. During upper gastrointestinal endoscopy, the distal 5 cm of the esophageal mucosal morphology at the squamocolumnar junction was visualized using WLI followed by LCI. MCL was defined as areas of erythema, blurring of the Z-line, friability, decreased vascularity, white turbid discoloration, and edema or accentuation of the mucosal folds. Three experienced endoscopists evaluated the color patterns for MCL on WLI images and on WLI combined with LCI images in both groups. A biopsy was taken 2 cm above the esophagogastric junction. Histologic slides were scored by a pathologist in a blinded manner. RESULTS: The proportion of MCL was higher in the patients with NERD (70.7%, 29/41) than in patients with non-GERD (39.5%, 15/38) using WLI combined with LCI. In 12 patients with NERD, both WLI and LCI showed normal mucosa. The MCL detection rate was significantly higher when using WLI combined with LCI than when using WLI (70.7% vs. 51.2%, P=0.039) in patients with NERD. The histopathologic score of MCL (+) was significantly higher than that of MCL (-) patients in both the NERD group (4.59±0.32 vs. 2.36±0.34, P<0.01) and the non-GERD group (3.47±0.50 vs. 2.00±0.28, P<0.01). The intraobserver reproducibility levels and interobserver agreement were better with LCI than with WLI alone. CONCLUSIONS: Frequency of MCL was higher in patients with NERD than in those with non-GERD. MCL can be identified by using WLI combined with LCI in patients with NERD. By enhancing endoscopic images, LCI is more sensitive in detecting MCL compared with WLI.

Risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) abdominal pain in patients without post-ERCP pancreatitis.

BACKGROUND: Abdominal pain is often observed after endoscopic retrograde cholangiopancreatography (ERCP). Few studies have focused on the risk factors of post-ERCP abdominal pain without post-ERCP pancreatitis (PEP). This study aimed to identify risk factors of post-ERCP abdominal pain without PEP and investigate characteristics of the abdominal pain in non-PEP patients. METHODS: Data from patients who underwent ERCP from August 2019 to January 2020 were retrospectively collected. Characteristics of the abdominal pain after ERCP were recorded and compared between PEP and non-PEP patients. Multivariate analysis was conducted to identify risk factors of non-PEP abdominal pain. RESULTS: A total of 1295 ERCP procedures were investigated in this study, among which 100 (7.72%) patients presented post-ERCP abdominal pain without PEP and 63 (4.86%) patients with PEP. Multivariate analysis found 9 risk factors of non-PEP abdominal pain: age ≤ 65 years [odds ratio (OR): 1.971], primary ERCP (OR: 2.442), dilated extrahepatic bile duct (OR: 1.803), no papilla opening (OR: 2.095), pancreatic guidewire passages (OR: 2.258), white blood cells (WBC) ≤ 6.0 × 109/L (OR: 1.689), platelet (PLT) ≤ 250 × 109/L (OR: 2.505), serum γ-glutamyl transferase (γ - GT) ≤ 35 U/L (OR: 2.190), and albumin ≥ 40 g/L (OR: 1.762). The PEP group had later pain onset, higher pain frequency and longer hospital stay than those of the non-PEP pain group (P < 0.05). There were no significant differences in the pain duration, visual analogue scale score and mortality between the PEP group and non-PEP pain group (P > 0.05). CONCLUSIONS: This study indicated that age ≤ 65 years, primary ERCP, dilated extrahepatic bile duct, no papilla opening, pancreatic guidewire passages, lower WBC, lower PLT, normal γ - GT and elevated albumin were independent risk factors for post-ERCP abdominal pain without PEP. The pain occurred earlier in non-PEP patients than in PEP patients.

Isoacteoside attenuates acute kidney injury induced by severe acute pancreatitis.

Severe acute pancreatitis (SAP) is a common acute abdominal disease accompanied by systemic inflammatory response syndrome, which may be complicated by acute kidney injury (AKI). Isoacteoside (ISO) is the active ingredient of Monochasma savatieri Franch. ex Maxim and has been reported to have anti­inflammatory activities. The present study detected the effects of ISO on AKI induced by SAP in rat models, and the underlying mechanism. The optimum dose of ISO for treatment of AKI induced by SAP was determined. The serum levels of TNF­α and IL­6 were estimated using an ELISA. Kidney injury was evaluated by histopathological examination, and the expression levels of nitric oxide were also detected. The expression levels of Toll­like receptor 4 (TLR4) and NF­κB p65 were measured by immunohistochemistry and western blotting. The results revealed that ISO may serve a critical role in ameliorating AKI induced by SAP. These effects may be associated with the TLR4/NF­κB signaling pathway.

Unraveling the identity of gastric cardiac cancer.

The classification of gastric cardiac carcinoma (GCC) is controversial. It is currently grouped with esophageal adenocarcinoma (EAC) as an adenocarcinoma of the gastroesophageal junction (GEJ). Recently, diagnostic criteria for adenocarcinoma in the GEJ were established and GCC was separated from EAC. We viewed published evidence to clarify the GCC entity for better patient management. GCC arises in the cardiac mucosa located from 3 cm below and 2 cm above the GEJ line. Compared with EAC, GCC is more like gastric cancer and affects a higher proportion of female patients, younger patients, those with a lower propensity for reflux disease, a wider histopathologic spectrum, and more complex genomic profiles. Although GCC pathogenesis mechanisms remain unknown, the two-etiology proposal is appealing: in high-risk regions, the Correa pathway with Helicobacter pylori infection, chronic inflammation, low acid and intestinal metaplasia, dysplasia and carcinoma may apply, while in low-risk regions the sequence from reflux toxin-induced mucosal injury and high acid, to intestinal metaplasia, dysplasia and carcinoma may occur. In early GCC a minimal risk of nodal metastasis argues for a role of endoscopic therapy, whereas in advanced GCC, gastric cancer staging rules and treatment strategy appear to be more appropriate than the esophageal cancer staging scheme and therapy for better prognosis stratification and treatment. In this brief review we share recent insights into the epidemiology, histopathology and genetics of GCC and hope that this will stimulate further investigations in order to improve the clinical management of patients with GCC.

Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis.

BACKGROUND: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. METHODS: Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. RESULTS: COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. CONCLUSIONS: Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.

R-spondin2 Suppresses the Progression of Hepatocellular Carcinoma via MAPK Signaling Pathway.

The R-spondin family plays important roles in embryonic development, including in humans. However, information on the relationship between R-spondin2 and hepatocellular carcinoma (HCC) is lacking. This study aimed was to explore the mechanisms of R-spondin2 action in the progression of HCC. By analyzing R-spondin2 expression levels in HCC tissues by IHC and database, we identified that HCC tissues had lower expression levels of R-spondin2, correlated with a poor prognosis. We also established R-spondin2-overexpressing and knockdown cell lines and measured their viabilities and invasion abilities in vitro and their oncogenic capacity in vivo. Human mRNA microarray analysis was performed to screen for mRNAs that were differentially expressed between R-spondin2-overexpressing and control HCC cells. Microarray and Western blot analyses showed significant changes in the MAPK signaling pathway after transfection. Furthermore, in vivo experiments indicated that R-spondin2 knockdown increased the tumorigenicity of HCC cells after subcutaneous implantation in mice. Altogether, our results indicate that the R-spondin2, which might be a novel tumor suppressor gene, were responsible for inhibiting the proliferation and invasion of HCC via the MAPK signaling pathway. IMPLICATIONS: R-spondin2 gene might be a novel tumor suppressor gene providing new clues to clarify the biological behavior of HCC and thus reduce patient mortality and prolong survival.

Factors affecting the accuracy of endoscopic ultrasound-guided fine needle aspiration for the diagnosis of small (≤20 mm) pancreatic lesions.

To explore the diagnostic value of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for small, solid or semi-solid pancreatic lesions (≤20 mm) and the factors affecting its accuracy. METHODS: Altogether 92 patients with small, solid or semi-solid pancreatic lesions who underwent EUS-FNA at the Nanjing Drum Tower Hospital from November 2009 to January 2019 were retrospectively analyzed. Univariate and multivariate analyses were used to determine the factors affecting the accuracy of EUS-FNA for detecting these lesions. RESULTS: Among the 92 cases, 56 (60.9%) were diagnosed as having malignant lesions and 36 (39.1%) as benign lesions, respectively. The overall sensitivity, specificity and accuracy of EUS-FNA for the diagnosis of small, solid or semi-solid pancreatic lesions were 71.4%, 100% and 82.6%, respectively. When considering the impact of the presence of a tissue core on the diagnosis, the sensitivity, specificity, and accuracy of EUS-FNA with tissue core compared with those based on cytology alone were 77.3% vs 50.0%; 100% vs 100%; and 86.8% vs 62.5%, respectively. The multivariate analysis showed that larger tumor size (>15-20 mm) (odds ratio [OR] 4.200, 95% confidence interval [CI] 1.21-14.53, P = 0.023) and histologic diagnosis based on tissue core (OR 4.593, 95% CI 1.03-20.47, P = 0.046) were related to a higher accuracy of EUS-FNA. Adverse events were observed in three patients, all were treated conservatively and recovered within 3 days. CONCLUSIONS: EUS-FNA is effective and safe for diagnosing small pancreatic lesions. Tumor size and presence of tissue core are related to higher accuracy of the EUS-FNA.

Marked thickening of muscularis mucosae and submucosa in the gastric cardia: A histopathological study of 110 surgical resection cases.

OBJECTIVE: To investigate histopathologic changes of muscularis mucosae (MM) and submucosa in the gastric cardia. METHODS: We performed a histopathology study of 50 distal esophagectomies with proximal gastrectomies for esophageal squamous cell carcinoma as the study (non-cancerous cardiac) group and 60 gastrectomies for early gastric cardiac carcinoma as the cancer group. The gastroesophageal junction was defined as the distal end of squamous epithelium, multilayered epithelium, or deep esophageal glands or ducts. Gastric cardia (n = 110) was defined as the presence of cardiac and cardio-oxyntic mucosae distal to the gastroesophageal junction. RESULTS: The average thickness of MM and submucosa in the cardia was 1.04 and 1.41 mm, respectively, which was significantly thicker than that in distal stomach (n = 34) (0.22 and 0.99 mm) or distal esophagus (n = 92) (0.60 and 1.15 mm). In the cardia, thickened MM displayed frayed muscle fibers (93.3%) with a significantly higher prevalence of entrapped glands, cysts, and lymphoid follicles than in the distal stomach or distal esophagus. In the submucosa fatty changes, cysts, and abnormal arteries were significantly more common in the cardia than in the distal stomach or distal esophagus. Compared with the study group, the cardia in the cancer group showed significantly thicker MM (average 1.31 vs 0.72 mm) and submucosa (average 1.61 vs 1.16 mm), more frequent frayed MM (93.3% vs 60.0%), prolapse-like changes (50.0% vs 2.0%), and cysts (26.7% vs 4.0%). CONCLUSION: MM and submucosa of the cardia were significantly thickened, especially in early gastric cardiac carcinomas.

Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study.

BACKGROUND: Chemoprevention of colorectal adenoma and colorectal cancer remains an important public health goal. The present study aimed to investigate the clinical potential and safety of berberine for prevention of colorectal adenoma recurrence. METHODS: This double-blind, randomised, placebo-controlled trial was done in seven hospital centres across six provinces in China. Individuals aged 18-75 years who had at least one but no more than six histologically confirmed colorectal adenomas that had undergone complete polypectomy within the 6 months before recruitment were recruited and randomly assigned (1:1) to receive berberine (0·3 g twice daily) or placebo tablets via block randomisation (block size of six). Participants were to undergo a first follow-up colonoscopy 1 year after enrolment, and if no colorectal adenomas were detected, a second follow-up colonoscopy at 2 years was planned. The study continued until the last enrolled participant reached the 2-year follow-up point. All participants, investigators, endoscopists, and pathologists were blinded to treatment assignment. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. Analysis was based on modified intention-to-treat, with the full analysis set including all randomised participants who received at least one dose of study medication and who had available efficacy data. The study is registered with ClinicalTrials.gov, number NCT02226185; the trial has ended and this report represents the final analysis. FINDINGS: Between Nov 14, 2014, and Dec 30, 2016, 553 participants were randomly assigned to the berberine group and 555 to the placebo group. The full analysis set consisted of 429 participants in the berberine group and 462 in the placebo group. 155 (36%) participants in the berberine group and 216 (47%) in the placebo group were found to have recurrent adenoma during follow-up (unadjusted relative risk ratio for recurrence 0·77, 95% CI 0·66-0·91; p=0·001). No colorectal cancers were detected during follow-up. The most common adverse event was constipation (six [1%] of 446 patients in the berberine group vs one [<0·5%] of 478 in the placebo group). No serious adverse events were reported. INTERPRETATION: Berberine 0·3 g twice daily was safe and effective in reducing the risk of recurrence of colorectal adenoma and could be an option for chemoprevention after polypectomy. FUNDING: National Natural Science Foundation of China.

Survey of nocturnal reflux in patients with gastroesophageal reflux disease in China.

To evaluate current diagnosis and treatment of patients with nocturnal gastroesophageal reflux (nGER). METHODS: This multicenter observational study was conducted in 44 hospitals in China from May 2017 to February 2018. Outpatients with nGER were recruited and their relevant data were collected using a questionnaire, including age, gender, body mass index, history of smoking and alcohol consumption, comorbid diseases, lifestyle, self-reported health status, medical history, nGER symptoms and severity, Hospital Anxiety Depression Scale, Pittsburgh Sleep Quality Index, diagnosis and treatment choices. The study was registered on the Chinese Clinical Trial Registry (no. ChiCTR1800017525). RESULTS: The study included 4978 individuals, with valid questionnaires collected from 4448 patients (89.4%). The symptoms of heartburn and regurgitation were more severe at night than during the day (P < 0.05). Age and body mass index were positively correlated with reflux severity at night and during the day (P < 0.05). The severity of nGER was positively associated with lifestyle factors such as smoking, a high-fat diet, carbonated beverage consumption, late supper (later than 9 pm), and snoring (all P < 0.05). Night-time heartburn and regurgitation were related with sleep disorder. CONCLUSIONS: Lifestyle factors are associated with nGER severity, and nGER affects sleep quality. It will be beneficial to popularize and strengthen the diagnosis and treatment of nGER.

Artesunate exerts protective effects against ulcerative colitis via suppressing Toll­like receptor 4 and its downstream nuclear factor­κB signaling pathways.

Artesunate (ART) is a semi­synthetic derivative of artemisinin used in the treatment of patients with malaria, which has also been reported to have immunoregulatory, anticancer and anti­inflammatory properties. The aim of the present study was to investigate the possible beneficial effects of ART on ulcerative colitis (UC) rats and to detect the possible mechanisms underlying these effects. A UC rat model was established using dextran sulfate sodium (DSS). Rats were randomly divided into the following groups: Normal control, UC model group, UC rats treated with a low, medium or high dose of ART (10, 30 and 50 mg/kg/day, respectively), and the positive control group (50 mg/kg/day 5­aminosalicylic acid). The damage status of colonic mucosal epithelial tissue was investigated by hematoxylin and eosin staining, and then the weight, colon length and disease activity index (DAI) were measured. Western blotting and reverse transcription­quantitative polymerase chain reaction analysis were used to detect the levels of cytokines associated with UC and proteins associated with Toll­like receptor 4 (TLR4)­nuclear factor (NF)­κB pathway. ELISA was also performed to measure the levels of inflammatory cytokines. In addition, the viability and infiltration of RAW264.7 cells were examined using Cell Counting Kit­8 and Transwell assays. The results demonstrated that treatment with ART significantly alleviated the UC symptoms induced by DSS in the rat model, lowered the DAI, ameliorated pathological changes, attenuated colon shortening, inhibited the levels of pro­inflammatory mediators and myeloperoxidase activity, and increased hemoglobin expression. Additionally, inflammatory and apoptotic markers were found to be significantly downregulated following treatment with ART in UC rats and RAW264.7 cells. To the best of our knowledge, the present study is the first to demonstrate that ART exerts anti­inflammatory effects via regulating the TLR4­NF­κB signaling pathway in UC.

Big-data analysis: A clinical pathway on endoscopic retrograde cholangiopancreatography for common bile duct stones.

BACKGROUND: A clinical pathway (CP) is a standardized approach for disease management. However, big data-based evidence is rarely involved in CP for related common bile duct (CBD) stones, let alone outcome comparisons before and after CP implementation. AIM: To investigate the value of CP implementation in patients with CBD stones undergoing endoscopic retrograde cholangiopancreatography (ERCP). METHODS: This retrospective study was conducted at Nanjing Drum Tower Hospital in patients with CBD stones undergoing ERCP from January 2007 to December 2017. The data and outcomes were compared by using univariate and multivariable regression/linear models between the patients who received conventional care (non-pathway group, n = 467) and CP care (pathway group, n = 2196). RESULTS: At baseline, the main differences observed between the two groups were the percentage of patients with multiple stones (P < 0.001) and incidence of cholangitis complication (P < 0.05). The percentage of antibiotic use and complications in the CP group were significantly less than those in the non-pathway group [adjusted odds ratio (OR) = 0.72, 95% confidence interval (CI): 0.55-0.93, P = 0.012, adjusted OR = 0.44, 95%CI: 0.33-0.59, P < 0.001, respectively]. Patients spent lower costs on hospitalization, operation, nursing, medication, and medical consumable materials (P < 0.001 for all), and even experienced shorter length of hospital stay (LOHS) (P < 0.001) after the CP implementation. No significant differences in clinical outcomes, readmission rate, or secondary surgery rate were presented between the patients in the non-pathway and CP groups. CONCLUSION: Implementing a CP for patients with CBD stones is a safe mode to reduce the LOHS, hospital costs, antibiotic use, and complication rate.

The impact of endoscopic ultrasound in preoperative evaluation for ampullary adenomas.

OBJECTIVE: We aimed to evaluate the efficacy of endoscopic ultrasonography (EUS) in assessing locoregionally and determining therapeutic options for ampullary adenomas and the related factors. METHODS: Patients undergoing EUS and surgical or endoscopic resection for biopsy-proven ampullary adenomas between 2009 and 2016 were retrospectively analyzed. The depth of tumor invasion, intraductal extension, and regional lymph node staging evaluated by EUS were compared with post-treatment pathological findings. RESULTS: Altogether 120 patients were enrolled in this study. The overall accuracy for EUS in T staging was 81.7%. The sensitivity and specificity of EUS for T staging were 93.9%, 45.5% for adenoma and T1, 50.0% and 96.5% for T2, 66.7% and 97.4% for T3, 50.0% and 97.5% for T4 lesions, respectively. The sensitivity, specificity, and accuracy of EUS for the diagnosis of any intraductal extension were 89.5%, 86.1%, and 86.7%, respectively. The overall accuracy of EUS for regional lymph node staging was 75.0%. The sensitivity and specificity of EUS for diagnosing N1 were 62.5% and 87.5%. By multivariate analysis no factors were found to be independently associated with EUS accuracy for tumor invasive depth. However, small lesion size (≤15 mm) and dilated duct were associated with an overestimation in intraductal extension. CONCLUSION: EUS may be a useful diagnostic tool for selecting endoscopic or surgical treatment for ampullary adenomas.

The coexistence of a Wilms' tumor and renal cell carcinoma in children: a case report and review of the literature.

A combination of a Wilms' tumor (WT) and renal cell carcinoma (RCC) is an extremely rare pediatric renal neoplasm. Its prognosis and clinicopathological features remain unclarified. Herein, we describe a case of the coexistence of a WT and an RCC in a male child aged 5 years and 10 months. The child had symptoms of hematuria for more than 1 month. Although his irises were clear, medical imaging revealed a potential malignant tumor in the left kidney. The patient underwent resection of the left kidney. The pathological diagnosis was the coexistence of a WT and papillary RCC. Negative surgical margins were examined. One month following the resection, chemotherapy with vincristine plus dactinomycin (EE-4A regimen) was commenced. At the 69-month follow-up, there was no recurrence or metastasis. The coexistence of a WT and an RCC in the pediatric population is considered a rare pathological event. At present, there is no standard treatment for these renal neoplasms. In this study, the RCC treatment, which was the same as that applied in cases of WTs, was reasonable.