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Background Anti-reflux mucosectomy (ARMS) is a novel endoscopic treatment for refractory gastroesophageal reflux disease (rGERD). Several studies have validated its safety and effectiveness, but postoperative dysphagia remains in concern. Since the influence of different resection ranges on efficacy and complications of ARMS has rarely been studied, this study aimed to compare outcomes of 180°ARMS and 270°ARMS in treatment of rGERD. Methods This study was conducted from August 2017 to September 2020. 39 eligible patients underwent either 180° ARMS or 270° ARMS and followed up at 6 months postoperation. Primary outcome measure was assessed by Gastroesophageal Reflux Disease Questionnaire (GERD-Q). Secondary outcomes included quality of life, PPI use, gastroesophageal flap valve grade, presence of reflux esophagitis, acid exposure time (AET), distal contractile integral (DCI), and integrated relaxation pressure (IRP) measured by high-resolution manometry (HRM) and complication rate. Per-protocol analysis was performed. Results Among 39 patients, 18 underwent 180° ARMS, while 21 underwent 270° ARMS. At postoperative 6 months follow-up period, primary outcome showed no significant difference between two groups (p = 0.34). Similarly, no significant difference was demonstrated between groups regarding most secondary outcomes except for fewer complaints of newly dysphagia in 180° ARMS group. No other serious complications were observed in both groups. Conclusion Although 180° ARMS and 270° ARMS could be equally effective for treatment of rGERD, 180° ARMS might be more recommended due to lower incidence of newly post-procedural dysphagia.

Although endoscopic retrograde cholangiopancreatography (ERCP) for large common bile duct (CBD) stones is facilitated by digital cholangioscopy-guided lithotripsy, it is performed by fluoroscopy guidance. Here, we report our experience of non-radiation ERCP for large CBD stones using digital cholangioscopy-guided laser lithotripsy. Sixteen patients with large CBD stones underwent non-radiation digital cholangioscopy-guided laser lithotripsy and lithotomy. Data relevant to procedure details, adverse events, and short-term follow-up were analyzed. Biliary access was achieved in all patients using standard guidewire-assisted cannulation, double-guidewire technique, and transpancreatic precut in twelve, two, and two patients, respectively. Balloons of 10 mm, 8 mm, and 6 mm in diameter were applied for EPBD in 8, 2, and 6 patients, respectively. Complete stone removal in one session was achieved in all patients. One round of laser lithotripsy was needed for stone ≤ 25 mm, and three-to-five rounds were needed for stones > 25 mm or multiple stones. One or two clips were used for endoscopic clipping. The time lengths of biliary access, digital cholangioscopy-assisted laser lithotripsy and stone extraction, and whole procedure were 3.5 ± 3.2 (0.5–12) minutes, 52.5 ± 30.6 (45–97) minutes, and 76 ± 23.3 (58–106) minutes, respectively. Asymptomatic hyperleukocytose, hyperamylasemia, and mild pancreatitis were present in 1, 2, and 1 patient(s), respectively. No other complications occurred. No cholangitis or recurrent CBD stones were observed. Non-radiation digital cholangioscopy-guided laser lithotripsy is technically feasible and can be safely performed for endoscopic management of large CBD stones.

Background Gastric intestinal metaplasia (GIM) is a significant risk factor for gastric cancer. Risk of gastric cancer/dysplasia between complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM) was controversial. Our study aimed to pool relative risk (RR) of cancer/dysplasia of IIM compared with CIM in GIM patients. Methods PubMed, EMBASE, Cochrane Library and Web of Science were searched for studies concerning cancer/dysplasia in GIM patients. Random-effects or fixed-effects model was utilized for pooling RR. Sensitivity and publication bias analyses were conducted. Stability of results would be evaluated in case of publication bias. Results 12 studies were included. Compared with CIM, pooled RR of cancer/dysplasia in IIM patients was 4.48 (95% CI 2.50–8.03), and the RR was 4.96 (95% CI 2.72–9.04) for cancer, and 4.82 (95% CI 1.45–16.0) for dysplasia. The pooled RR for cancer/dysplasia in type III IM was 6.27 (95% CI 1.89–20.77) compared with type II + I IM, while it was 5.55 (95% CI 2.07–14.92) compared with type II IM. Pooled RR between type II IM and type I IM was 1.62 (95% CI 1.16–2.27). Subgroup analyses showed that IIM was associated with a higher risk of gastric cancer/dysplasia in Western population (pooled RR = 4.65 95% CI 2.30–9.42), but not in East Asian population (pooled RR = 4.01 95% CI 0.82–19.61). Conclusions IIM was related to a higher risk of cancer/dysplasia compared with CIM. Risk of developing cancer/dysplasia from type I, II, and III intestinal metaplasia increased gradually.

Aim Although Clopidogrel is safe in healthy volunteers, it can induce recurrence of gastric ulcers in high-risk patients. Here, we investigated the protective effect of the natural product, stable gastric pentadecapeptide 157 (BPC 157) on Clopidogrel-induced gastric injury. Methods We used acetic acid to induce gastric ulcer in Sprague Dawley rats. Clopidogrel alone or in combination with BPC 157 or L-NAME (nitric oxide system blockade) were administered after healing of acetic acid-induced ulcer. One percent methylcellulose solution was used as control. Ulcer recurrence rate and the ulcer index were compared between these groups. Gastric mucosal apoptosis rate, microscopic inflammation activity and angiogenesis markers vascular endothelial growth factor A (VEGF-A) and CD34 were examined by TUNEL, histological evaluations (HE) and immunohistochemistry (IHC). Pathways involved, expressions of endoplasmic reticulum (ER) stress apoptosis marker CHOP, angiogenic markers VEGF-A and its receptor VEGFR1, and endothelial NO synthase (eNOS) were all analyzed by Western blot. Results This study indicated that Clopidogrel significantly induced the gastric ulcers recurrence, severe inflammation and ER stress related apoptosis of the gastric mucosa, suppressed the synthesis of angiogenic markers and eNOS. Furthermore, Clopidrogel intervention resulted in the activation of protein kinase B (AKT) and p38 mitogen-activated protein kinase (p38/MAPK). BPC 157 attenuated the gastric mucosal damage caused by Clopidogrel and reversed these molecular effects. However, NO blockade L-NAME weakened the protective effect and thus the molecular effects of BPC 157 on gastric mucosa. Conclusion In conclusion, these results suggest that BPC 157 inhibited Clopidogrel-induced gastric mucosa injury partially by inhibition of gastric mucosa cell ER stress-mediated apoptosis and inflammation, and promoting gastric mucosa angiogenesis via VEGF-A/VEGFR1 mediated-AKT/p38/MAPK signaling pathways.

Angiogenesis has an essential role in tumor growth and metastasis, and blocking this pathway has been a successfully utilized strategy in the clinical treatment of cancer. Anlotinib (AL3818) is a novel oral receptor tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 and 3, fibroblast growth factor 1-4, platelet-derived growth factor receptor α and β, c-Kit and Ret. Anlotinib exerts inhibitory effects on tumor growth and angiogenesis and received its first approval as a third-line treatment for refractory advanced non-small-cell lung cancer in May 2018 and its second approval as a second-line treatment for advanced soft-tissue sarcoma in June 2019 in the People's Republic of China. Anlotinib has encouraging efficacy and a manageable and tolerable safety profile in a broad range of malignancies, including medullary thyroid cancer, renal cell cancer, gastric cancer and esophageal squamous cell carcinoma. In the present review, the preclinical and clinical trials of anlotinib were summarized with a focus on safety evaluation and adverse event management.

Endoscopic sub-mucosal dismemberment (ESD) has become a settled strategy for treatment of shallow neoplasms in the gastrointestinal tract. In three local areas, ESD was introduced to overcome traditional endoscopic mucous resection (EMR) and inadequate resection of the EMR, combining mouth, stomach, and the colon, for early disruptive sores. ESD was grown first in Japan since that nation has the highest predominance of gastric malignant growth on the planet. Endoscopic sub-mucosal analyzation causes enormous fake ulcers with more severe dangers of intra-usable and deferred postoperative draining. However, there is no agreement in regards to the ideal peri-usable administration for the anticipation of free draining and the advancement of ulcer mending. The hugeness of this investigation is to locate a superior procedure to bring down the hazard post ESD draining and to plan to defeat the confinements of regular EMR (endoscopic mucosal resection) and fragmented resection for early malignant injuries in the three districts which incorporate throat, stomach, and colon. However, it has considered a standard in Eastern Asian nations and Japan because of the incredible importance of ESD. The EMR and ESD approaches are discussed in this report. Thus, the warning factors for early gastric neoplasms of PPB after ESD were established, and a superior technique was created to mitigate the danger of ESD dying. EMR was already widely used for treating early neoplastic sores in the gastrointestinal tract; colon adenoma and colorectal tumors are widely acknowledged.

Background and Purposes. Endoscopic resection has been worldwide recognized as a treatment strategy for early esophageal lesions. The occurrence of esophageal stricture after endoscopic resection will reduce the quality of life of patients. This study will evaluate the efficacy and safety of steroids in the prevention of esophageal stricture after endoscopic resection and the influence of different steroid administration methods.Methods. In the relevant literature database, literature from 2008 to 2018 is retrieved by using preset keywords, the search results are carefully screened, and the conclusion of the literature is synthesized to form arguments and draw conclusions.Results. 73 articles met our requirements. Oral steroid administration, not prophylactic endoscopic balloon dilation alone, was effective in preventing esophagostenosis after esophagoscopic treatment and reducing the number of repeated endoscopic balloon dilations even after extensive endoscopic resection. Local steroid injection is useful and economy for preventing esophageal stricture, even though it may raise the risk of perforation during dilations. A wider range of circumferential mucosal defects is an independent predictor for stricture formation for patents given preventive steroid injections after endoscopic submucosal dissection. For complete circular mucosal defect, the further researches are essential to investigate the role of local steroid injection. The effect of other methods such as steroid gel, intravenous infusion of steroid, and novel steroid filling methods require more confirmation.Conclusions. Therefore, steroids play an irreplaceable role in preventing esophageal stricture after endoscopic resection. Oral and local injections of steroids are the two most acceptable methods and more prospective studies are needed to compare the effectiveness and safety of these two methods.

Background The use of nonradiation endoscopic retrograde cholangiopancreatography (NR-ERCP) for choledocholithiasis is still limited. Hereby, we introduced our experience of digital cholangioscopy (DCS)-assisted NR-ERCP for retrieval of common bile duct stones. Methods Altogether, data of 132 patients who underwent DCS-assisted NR-ERCP for choledocholithiasis were collected. Procedure details, complications, and short-term follow-up were reviewed and analyzed and were compared with those of conventional endoscopic retrograde cholangiopancreatography (ERCP). Results Routine stone extraction and laser lithotripsy were planned in 116 and 16 patients, respectively. Biliary access was successfully achieved by standard biliary cannulation and by advanced techniques in 99 and 33 patients, respectively. Complete stone removal was achieved in a single session in all patients. Routine stone extraction was performed in 117 patients, and laser lithotripsy was applied in 15 patients, among whom 14 patients with planned lithotripsy and 1 unexpected impacted stone found during the procedure. Unexpected right localized intrahepatic stones and purulent cholecystitis were found in 1 and 3 patients, respectively. Three mild and 1 moderate pancreatitis, 5 cases of hyperamylasemia, and 2 cases of leukocytosis occurred as complications. Short-term follow-up revealed no stone residual. Procedure details, technical success, and complications were not statistically different than conventional ERCP. Conclusions DCS-assisted NR-ERCP is technically feasible, efficient, and safe for retrieval of common bile duct stones. This novel method is superior to conventional ERCP on detecting unexpected concomitant biliary diseases.

Studies have shown the value of subtypes and distribution of gastric intestinal metaplasia (GIM) for prediction of gastric cancer. We aim to combine GIM subtypes and distribution to form a new scoring system for GIM.This was a cross-sectional study. No GIM, type I, II, and III GIM of gastric antrum and corpus scored 0-3 points respectively. Then the severity of the whole stomach was calculated in two ways: 1. The gastric antrum and corpus scores were added together, with a score ranging from 0 to 6, which named "Subtype Distribution Score of Gastric Intestinal Metaplasia (SDSGIM)". 2. Direct classification according to a table corresponding to that of OLGIM. We compared the SDSGIM among benign lesions, dysplasia, and cancer and drew receiver operating characteristic (ROC) curve to determine the optimal cut-off value. According to the cut-off value and the classification from the table, the predictive ability of these two methods were calculated.227 patients were included. For SDSGIM, benign lesion group was significantly different from dysplasia or cancer group. Area under curve of ROC curve was 0.889 ± 0.023. The optimal cut-off value was 3. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SDSGIM for malignancy were 89.5%, 78.0%, 74.6%, 91.2% and 82.8%. And those for the second classification method were 84.2%, 82.6%, 77.7%, 87.9%, and 83.3% respectively.This study firstly combined GIM subtypes with its distribution forming a novel scoring system, which showed high prediction accuracy for malignant lesions.

Background Studies have shown the value of subtypes and distribution of gastric intestinal metaplasia (GIM) for prediction of gastric cancer. We aim to combine GIM subtypes and distribution to form a new scoring system for GIM. Methods This was a cross-sectional study. No GIM, type I, II, and III GIM of gastric antrum and corpus scored 0–3 points respectively. Then the severity of the whole stomach was calculated in two ways: 1. The gastric antrum and corpus scores were added together, with a score ranging from 0 to 6, which named “Subtype Distribution Score of Gastric Intestinal Metaplasia (SDSGIM)”. 2. Direct classification according to a table corresponding to that of OLGIM. We compared the SDSGIM among benign lesions, dysplasia, and cancer and drew receiver operating characteristic (ROC) curve to determine the optimal cut-off value. According to the cut-off value and the classification from the table, the predictive ability of these two methods were calculated. Results 227 patients were included. For SDSGIM, benign lesion group was significantly different from dysplasia or cancer group. Area under curve of ROC curve was 0.889 ± 0.023. The optimal cut-off value was 3. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SDSGIM for malignancy were 89.5%, 78.0%, 74.6%, 91.2% and 82.8%. And those for the second classification method were 84.2%, 82.6%, 77.7%, 87.9%, and 83.3% respectively. Conclusions This study firstly combined GIM subtypes with its distribution forming a novel scoring system, which showed high prediction accuracy for malignant lesions.

Immune checkpoint inhibitor (ICI) therapy may benefit patients with advanced esophageal squamous cell carcinoma (ESCC); however, novel biomarkers are needed to help predict the response of patients to treatment. Differentially expressed immune-related genes within The Cancer Genome Atlas ESCC dataset were selected using the weighted gene coexpression network and lasso Cox regression analyses. Based on these data, an immune-related gene prognostic index (IRGPI) was constructed. The molecular characteristics of the different IRGPI subgroups were assessed using mutation information and gene set enrichment analysis. Differences in immune cell infiltration and the response to ICI therapy and other drugs were also analyzed. Additionally, tumor and adjacent control tissues were collected from six patients with ESCC and the expression of these genes was verified using real-time quantitative polymerase chain reaction. IRGPI was designed based on CLDN1, HCAR3, FNBP1L, and BRCA2, the expression of which was confirmed in ESCC samples. The prognosis of patients in the high-IRGPI group was poor, as verified using publicly available expression data. KMT2D mutations were more common in the high-IRGPI group. Enrichment analysis revealed an active immune response, and immune infiltration assessment showed that the high-IRGPI group had an increased infiltration degree of CD8 T cells, which contributed to the improved response to ICI treatment. Collectively, these data demonstrate that IRGPI is a robust biomarker for predicting the prognosis and response to therapy of patients with ESCC.

Peroral endoscopic myotomy (POEM) is a rapidly evolving technique for the treatment of esophageal diverticulum. The aim of this study was to perform a systematic review and meta-analysis of the literature focusing on POEM for symptomatic esophageal diverticula, including an in-depth evaluation of its efficacy, safety, and limitations. A comprehensive literature search was completed to identify articles that examined the efficacy and safety of POEM for esophageal diverticula. Heterogeneity among studies was assessed using the I2 statistic. Meta-regression and sensitivity analyses were performed to explore the sources of heterogeneity and assess potentially important covariates influencing the main outcomes. Primary endpoints such as rates of success, adverse events, and recurrences were evaluated. P values of ≤0.05 were considered statistically significant. Nine studies with a total of 153 patients were enrolled. Pooled technical success, clinical success, adverse events, and recurrence rates were 99% [95% confidence interval (CI), 97-100%; I2 = 0%), 94% (95% CI, 89-97%; I2 = 24%), 2% (95% CI, 0-6%, I2 = 0%), and 0% (95% CI, 0-1%; I2 = 0%), respectively. The pooled perforation rate was 6% (95% CI, 1-11%; I2 = 0%). Meta-regression analysis indicated that esophageal diverticula types and motility disorders were not associated with the clinical success rate (P0.05). POEM is a feasible, safe, and effective treatment for symptomatic esophageal diverticula, with low adverse events and recurrence rates.

Refractory esophageal stricture is difficult to deal with. Some refractory stricture shows little response to now-existing endoscopic techniques. We assessed the efficacy of modified endoscopic radial incision and cutting method (M-RIC) for the treatment of refractory esophageal stricture. This was a retrospective study. Patients with refractory esophageal stricture who underwent M-RIC or dilation from June 2016 to June 2020 were included. Outcomes measured included technical and clinical success, restenosis rate, time to restenosis and complications. Risk factors for restenosis after M-RIC were assessed. 67 patients were enrolled (M-RIC group, n = 29; dilation group, n = 38). After propensity score matching, each group include 28 patients. There were no significant differences in technical success (96.4% vs 100%, p = 1.00) or clinical success (89.3% vs 100%, p = 0.23) between groups. Patients in M-RIC group had lower rates of restenosis (75% vs. 100%, p = 0.02) and longer time to restenosis (110 days vs 31.5 days, p = 0.00) compared with dilation group. 4 patients did not require any additional treatment after M-RIC and maintained food intake until the end of follow-up. Complications of M-RIC include perforation, fever and retrosternal pain, and no difference was found in total complication rate when compared with dilation group (25% vs 7.1%, p = 0.07). Although 3 out of 28 patients (10.7%) in M-RIC group had perforation, the perforation rate was not significantly different between groups (p = 0.11). Multivariate analyze suggested stricture length ≥ 5 cm (HR 7.25, p = 0.00) was a risk factor to restenosis while oral prednisone (HR 0.29, p = 0.02) was associated with preventing restenosis after M-RIC. M-RIC is a feasible and effective technique for refractory esophageal stricture with lower rate and longer time to restenosis. Stricture length ≥ 5 cm is a risk factor to restenosis while oral prednisone is helpful in remitting restenosis after M-RIC.

Background Few studies have evaluated digital cholangioscopy (DCS) assisted non-radiation endoscopic retrograde cholangiopancreatography (NR-ERCP) for choledocholithiasis. Here, we evaluated the application of DCS assisted NR-ERCP for endoscopic retrieval of common bile duct (CBD) stones.Methods Patients who underwent ERCP for choledocholithiasis and without prior ERCP were included. Data related to technical success and outcomes of DCS-assisted NR-ERCP and conventional ERCP were retrieved and compared. Procedure and technical details of DCS assisted NR-ERCP were collated and reviewed.Results In total, 304 and 53 patients who underwent conventional and DCS-assisted ERCP were recruited. Relatively larger stones (p p p p Conclusions DCS-based NR-ERCP is technically feasible and safe for retrieval of CBD stones. It provides an alternative to conventional ERCP for endoscopic treatment of simple choledocholithiasis.

The world is currently witnessing the spread of the deadly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19). In less than three months since the first cases were reported, the World Health Organization declared it a pandemic disease. Although several treatment and prevention strategies are currently under investigation, a continuous effort to investigate and develop effective cures is urgently needed. Thus, we performed molecular docking and structure-based virtual screening of libraries of approved drugs, antivirals, inhibitors of protein-protein interactions, and one million other small molecules to identify strong binders of the SARS-CoV-2 receptor-binding domain (RBD) that might interfere with the receptor recognition process, so as to inhibit the viral cellular entry. According to our screening and selection criteria, three approved antivirals (elbasvir, grazoprevir, and sovaprevir) and 4 other drugs (hesperidin, pamaqueside, diosmin, and sitogluside) were identified as potent binders of the RBD. The binding of these molecules involved several RBD residues required for the interaction of the virus with its cellular receptor. Furthermore, this study also discussed the pharmacological action of the 4 non-antiviral drugs on hematological and neurological disorders that, in addition to inhibiting the viral entry, could be beneficial against the neurological disorders identified in COVID-19 patients. Besides, six other small-molecules were identified, with no pharmacological description so far, exhibiting strong binding affinities to the RBD that we believe worth being investigated as inhibitors of the SARS-CoV-2-receptor interaction., Highlights • We aimed to identify strong binders of the SARS-CoV-2 RBD to be used as inhibitors of virus-receptor interaction. • Accordingly, 3 antivirals, 4 other approved drugs and 6 small-molecules have been identified as potential ligands of the RBD. • The binding of these selected compounds involves several RBD residues crucial for the virus-receptor interaction. • Besides RBD-binding, we discussed the possible effects of the selected drugs on the COVID-19- related neurological disorders.

Esophageal squamous cell carcinoma comprises the majority of esophageal carcinoma in the Eastern Asia. The need of early detection of precancerous neoplastic lesions and cancer has been necessitated due to the probability of progression to the advanced stage and its poor prognosis. In recent times, many endoscopic modalities have come into practice for early detection and treatment. Endoscopic radiofrequency ablation (RFA) has been recommended as an efficient therapy in treating the dysplastic mucosa in Barrett’s esophagus (BE). Its potential in reversing neoplastic lesions in squamous epithelium has been gradually explored. This article is aimed at reviewing the current evidence regarding the use of RFA on esophageal squamous cell neoplasia.

Glomus tumor (GT) is one of the rarest gastrointestinal soft tissue neoplasms. GT in the esophagus has been scarcely reported, and only less than ten cases have been reported. Herein, we report another case of asymptomatic esophageal GT. A 30-year-old male patient was admitted due to incidental finding of esophageal mass on gastroscopy examination. Gastroscopy examination revealed an esophageal mass of 2.0 cm × 1.8 cm. Endoscopic ultrasound (EUS) showed a heterogeneous, hypoechoic mass originated from the submucosal layer and was adjacent to the thoracic aorta. The final diagnosis was confirmed by immunohistochemistry of smooth muscle actin (SMA), vimentin, caldesmon and focal positive of desmin, synaptophysin. The patient underwent submucosal tunneling endoscopic resection (STER) which was effective and the patient was discharged from our hospital 6 days after surgery. Upon 1 year of follow-up, no metastasis was observed. Esophageal GTs lacked specific manifestations and immunohistochemistry was crucial in diagnosis. Endoscopic treatment such as STER is a safe and effective method of treatment.

Emergency endoscopic retrograde cholangiopancreatography (ERCP) for ascending acute cholangitis in patients with severe comorbidities is challenging. Here, we evaluated the efficacy and safety of one-stage ERCP in such patients by performing a retrospective study. We included all patients with ascending acute cholangitis and undergoing ERCP between January 2017 and March 2019. In total, we recruited 212 patients: 74 and 138 with and without severe comorbidities, respectively. We collected and analyzed data related to basal characteristics, ERCP, and clinical outcomes. Elderly age (76.20 ± 9.99 years vs. 66.52 ± 8.16 years, P = 0.000), higher levels of leukocyte count (15.86 ± 2.47 × 109/ml vs. 13.49 ± 1.65 × 109/ml, P = 0.000), and serum bilirubin (3.11 ± 1.29 mg/dl vs. 1.94 ± 0.90 mg/dl, P = 0.000) were present in patients with severe comorbidities. A significantly higher proportion of these patients were severe cases (32.4% vs. 6.5%, P = 0.000), American Society of Anesthesiologists (ASA) stage V status (37.8% vs. 10.1%, P = 0.000) and had undergone general anesthesia (56.8% vs. 18.8%, P = 0.000). Successful biliary cannulation and complete stone clearance in one session were achieved in 207 and 202 patients, respectively. Mean length of hospital stay was 8.02 ± 2.71 days. Forty-three patients required ICU stay with the mean length of 3.26 ± 3.51 days. In-hospital mortality occurred in seven patients; all these patients had severe comorbidities. ERCP details, including urgent and early ERCP, biliary cannulation, complete stone clearance in one session, stent insertion, and complications were not significantly different between the two groups. Patients with severe comorbidities had a longer in-hospital stay (9.39 ± 3.15 days vs. 7.29 ± 2.11 days, P = 0.000), a higher proportion of ICU admission (45.9% vs. 6.5%, P = 0.000), and a longer ICU stay length (4.88 ± 4.37 days vs. 1.44 ± 0.52 days, P = 0.000). Our data also revealed that early diagnosis is an important predictor associated with clinical outcomes. One-stage ERCP is safe and effective for ascending acute cholangitis caused by choledocholithiasis. Early diagnosis is a significant predictor of clinical outcomes.

Ilaprazole is a novel proton pump inhibitor that provides effective and long lasting inhibition of intragastric acid secretion. The objectives of this study were to investigate the pharmacokinetics, pharmacodynamics, and safety of intravenous ilaprazole after multiple administrations in healthy Chinese subjects. This was an open-label and multiple-dose clinical study. Ten healthy Chinese subjects received 10 mg ilaprazole infusion once daily for 5 days. Helicobacter pylori status was examined. Blood samples were collected and intragastric pH was recorded for 24 h. Safety was assessed throughout the study. There was no accumulation after multiple administrations. The mean steady-state half-life and clearance were comparable to those following single administration. Ilaprazole provided sustainable and significant intragastric pH control in terms of percentage time at pH >4, pH >6 within 24 h and mean 24-h pH values. The pH value within 24 h was affected by Helicobacter pylori infection in subjects with continuous infusion. Intravenous ilaprazole was safe and there were no serious adverse events. Intravenous ilaprazole provided stable pharmacokinetics and pharmacodynamics at a dose of 10 mg once daily for 5 days, and was well tolerated in healthy subjects.

1. Ilaprazole is a novel proton pump inhibitor and this is the first study to investigate the pharmacokinetics, pharmacodynamics and safety of intravenous ilaprazole in healthy volunteers. 2. In this open-label, single-dose, randomized and four-period crossover study, 16 healthy Chinese subjects received ilaprazole 5, 10 or 20 mg intravenously, or 10 mg orally. Serial blood and urine samples were collected and intragastric pH was recorded within 24 h. The percentage time of intragastric pH 6 was the major index. Safety was assessed throughout the study. 3. Plasma exposure of intravenous ilaprazole increased proportionally over the dose of 5-20 mg. Clearance and volume of distribution were independent of dose. Ilaprazole was not eliminated through urine and the absolute bioavailability was 55.2%. For the intravenous dose of 5, 10, 20 mg, and oral dose of 10 mg, the mean percentages time of intragastric pH 6 were 47.3%, 52.8%, 68.2% and 47.5%, respectively. 4. Ilaprazole showed linear pharmacokinetics over the dose of 5-20 mg. Intravenous ilaprazole provided rapid onset of action and the potency of effect were exhibited in a dose-dependent manner. Intravenous ilaprazole was safe and well tolerated except for elevated activated partial thromboplastin time (APTT) and prothrombin time (PT).

Prostate cancer is the most common cancer in men and it is estimated that 32,000 men in the US alone will die of this cancer in 2019. Androgen deprivation therapy (ADT) has been the mainstay of prostate cancer therapy. However, most of the patients will progress to castration resistance prostate cancer (CRPC) after several years of treatment. The current treatment of CRPC includes chemotherapeutic agents (docetaxel) and agents that target androgen signaling (abiraterone, enzalutamide and apalutamide). Ultimately, however, most patients develop resistance to the treatments. Two of the mechanisms of resistance involve the expression of constitutively active androgen receptor variant (AR-V7) and the increase in intra-tumoral biosynthesis of androgens. Several treatment strategies targeting AR-V7 have been reported. For the intra-tumoral biosynthesis of androgens, one of the enzymes, AKR1C3, plays a critical role in the development of CRPC and has been reported to be consistently elevated in CRPC patients who are resistant to abiraterone and enzalutamide. We have been involved in the development of agents to treat CRPC and overcome drug resistance of CRPC patients. We reported that niclosamide, an FDA-approved anthelminthic agent, could degrade AR-V7. We also reported that niclosamide, as well as an AKR1C3 inhibitor, indomethacin, were able to overcome enzalutamide and abiraterone resistance in several prostate cancer cell lines, suggesting that niclosamide is also an AKR1C3 inhibitor. By examining the reported structures of AKR1C3 inhibitors, niclosamide was found to contain the core scaffold of 4-Hydroxy-1-(4-methoxybenzyl)-N-(3-(trifluoromethyl) phenyl)-1H-1,2,3-triazole-5-carboxamide. Using this knowledge, we designed a series compounds with dual AR degrading and AKR1C3 inhibitory activities. Preliminary studies showed the compounds caused AR-V7 degradation and to a lesser extent AR full length degradation. The compounds also inhibited AKR1C3 and caused a dose dependent growth inhibition of several prostate cancer cell lines. Citation Format: Enming Xing, Xiaotian Kong, Wei Lou, Ruihua Shi, Xiaolin Cheng, Allen C. Gao, Pui Kai Li. Design, synthesis and study of small molecules with both AR degradation and AKR1C3 inhibitory activities [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5681.

Endoscopic submucosal tunnel dissection (ESTD) has been used for dissection of esophageal and gastric lesions. However, outcomes of ESTD for large lesions in the lesser gastric curvature had not been acknowledged because previous reports had the limitations of being single-center studies. We aimed to clarify the outcomes of ESTD for large lesser gastric curvature superficial neoplasms and provide our experience to accelerate its application. Between July 2014 and July 2016, 87 patients with early cancer in the lesser gastric curvature treated at six Chinese institutions were enrolled. Our primary outcome was dissection speed. Moreover, both efficacy and safety clinical data were collected and analyzed retrospectively. All of the 87 patients were found to successfully undergo ESTD or ESD. Of these, 32 underwent ESTD and 55 underwent endoscopic submucosal dissection (ESD). The ESTD group had a higher dissection speed (18.0 mm2/min vs. 7.8 mm2/min, p

Aims. To retrospectively analyze the clinical outcomes for a large number of endoscopic submucosal dissections (ESDs) in early esophageal squamous cell neoplasms (ESCNs) at the First Affiliated Hospital of Nanjing Medical University.Patients and Methods. From January 2010 to February 2014, 296 patients (mean age 61.4 years, range 31–85 years; 202 men) with 307 early ESCNs (79 intramucosal invasive esophageal squamous cell carcinomas (ESCCs) and 228 high-grade intraepithelial neoplasia (HGIN) cases) were included from a total of 519 consecutive patients who were treated by esophageal ESD at our hospital. The primary end points of the study were rates of en bloc resection and complete resection. Secondary end points were complications, residual and recurrence rates, and mortality during follow-up.Results. The en bloc resection rate and complete resection rate were 93.5% and 78.2%, respectively. Complications included strictures (8.4%), perforations (1.0%), and bleedings (0.7%). Twenty-seven (9.1%) patients experienced residual and 18 (6.1%) patients experienced recurrence during a mean follow-up period of 30 months. Thirteen patients died from causes unrelated to ESCC, and no cancer-related death was observed.Conclusions. Our study showed that ESD is a successful and relatively safe treatment for intramucosal invasive ESCC and HGIN, fulfilling the criteria of lymph node negative tumors. This should encourage clinicians to select ESD performed by experienced operators as a potential or even preferred treatment option for lesions amenable to endoscopic treatment.

Jingjing Zhang,1,* Qing Ji,2,* Chunhua Jiao,3,* Lihua Ren,4 Ye Zhao,4 Yanfang Chen,4 Ruihua Shi,4 Yadong Feng4 1State Key Laboratory of Reproductive Medicine, Department of Prenatal Diagnosis, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 2Department of Emergency, Jingjiang People’s Hospital, Jingjiang, 3Department of Gastroenterology, First Affiliated Hospital with Nanjing Medical University, 4Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China *These authors contributed equally tothis work Background: The clinical significance of insulin-like growth factor-II mRNA-binding protein-3 (IGF2BP3) in esophageal high-grade intraepithelial neoplasia (HGIN) is not clear. This study was designed to characterize the expression of IGF2BP3 in HGIN. Patients and methods: IGF2BP3 expression was evaluated by Western blot analyses in 12cases and by immunohistochemistry (IHC) in 112 cases. The associations between IGF2BP3 expression in HGIN and the clinicopathological parameters were examined. Results: Moderate to strong IGF2BP3 expression was present in HGIN samples. Using IHC, itwas found that IGF2BP3 was positive in 68 (60.71%) cases. Intense IHC of IGF2BP3 in HGIN was associated with a deeper lesion depth, and the lesion depth was the only predictor of the positive expression of IGF2BP3. Conclusion: Our results suggested that IGF2BP3 may be a supplementary tissue marker for preoperative diagnosis of HGIN. Keywords: esophageal squamous cell carcinoma, precancerous lesion, immunohistochemistry detection, early diagnosis

The efficacy and safety of polaprezinc combined with triple therapy was compared with triple therapy alone in the eradication of Helicobacter pylori. A randomized, parallel-group, open-label, controlled, prospective multicenter study was conducted in 11 cities in China. Treatment-naive patients with H. pylori–associated gastritis were randomly assigned to one of three arms for a 14-day treatment: Arm A triple therapy (omeprazole 20 mg, amoxicillin 1 g, and clarithromycin 500 mg, each twice daily) plus polaprezinc 75 mg twice daily; Arm B triple therapy plus polaprezinc 150 mg twice daily, or Arm C triple therapy alone. The rate of H. pylori eradication was the primary endpoint. Secondary endpoints were symptom improvement and lower incidence of adverse events. 303 patients completed the study– 106, 96, and 101 patients in Arms A, B, and C, respectively. Intention-to-treat (ITT) analysis showed that the rate of H. pylori eradication was significantly higher for Arms A (77.0%) and B (75.9%) compared to Arm C (58.6%) (P < 0.01), whereas there was no difference between Arms A and B (P = 0.90). Per-protocol (PP) analysis showed that the rate of H. pylori eradication was significantly higher for Arms A (81.1%) and B (83.3%) compared to Arm C (61.4%) (P < 0.01), whereas there was no significant difference between Arms A and B (P = 0.62). All three groups reported significant symptom improvement at 7, 14, and 28 days after treatment, compared to baseline (P < 0.0001). The adverse event rate for Arm B (5.1%) was higher than for Arms A (2.8%) (P = 0.04) and C (1.9%) (P = 0.02). There were no serious adverse events in any group. It appears that standard dose polaprezinc combined with triple therapy can significantly improve the H. pylori eradication rate, without an increase in toxicity.

Summary Objective: To use a meta-analysis approach to evaluate the efficacy and safety of purine analogues, azathioprine (AZA) and 6-mercaptopurine (6-MP), in the prevention of postoperative recurrence of Crohn’s disease (CD), as compared with mesalamine or 5-aminosalicylic acid (5-ASA). Methods: The Pubmed, Cochrane Library, and Embase literature databases were searched for relevant studies with the key words “azathioprine”, “6-mercaptopurine”, “purine analogue”, “mesalamine”, or “5-ASA”. The efficacy and safety of purine analogues in the retrieved randomized controlled trials (RCTs) were evaluated with RevMan 5.0.25 (The Cochrane Collaboration, Oxford, England) and STATA 12.0 (Stata Corporation, College Station, TX, USA). The outcome measures of AZA and 6-MP, compared to mesalamine and 5-ASA (control arms), were: clinical recurrence, endoscopic recurrence, and adverse event rates. Results: Five RCTs, comprised of 429 patients, were analyzed. The effect of purine analogues for preventing clinical recurrence for year 1 and 2 were similar to controls (year 1: n = 390; recurrence rate: 18.6% vs. 20.9%; RR: 0.88, 95% CI: 0.60–1.30, p = 0.53; year 2: n = 270; recurrence rate: 29.9% vs. 38.2%; RR: 0.76, 95% CI: 0.55–1.05, p = 0.10). In contrast, purine analogues were more effective than controls in preventing severe endoscopic recurrence (i2–4) for year 1 (n = 289; 32.4% vs. 46.1%; RR: 0.71, 95% CI: 0.53–0.94, p = 0.02). However, purine analogues were associated with more adverse events leading to drug withdrawal than the controls (20.1% vs. 7.9%; RR: 2.57, 95% CI: 1.47–4.51, p = 0.0010). Conclusion: Purine analogues are more effective than controls in preventing endoscopic postoperative recurrence in CD, but are associated with more adverse events.

Background: Bismuthyl ecabet is a combination of sulfodehydroabietic acid and bismuth, which forms a new type of salt that is useful in treating peptic ulcers and gastritis. Objective: This study was designed to assess the safety and tolerability of bismuthyl ecabet suspension in healthy Chinese subjects. Methods: For the study 77 volunteers were randomized into single- or multiple-dose groups for oral administration of bismuthyl ecabet 200–1600 mg once daily or 1200 mg twice daily for 7 days. Safety and tolerability were assessed by adverse events, physical examination and serum biochemistry. Results: In both the single- and multiple-dose studies, no severe adverse events were observed in any of the volunteers. The main adverse events caused by the drug in single-dose groups were an increase in serum alanine transaminase (ALT), γ-glutamyl transpeptidase, blood urea nitrogen, total bilirubin and skin rash. The numbers of adverse events judged to be possibly related to the drug were 2/18 in the 400 mg, 2/18 in the 800 mg, 1/8 in the 1200 mg, and none in the 200 or 1600 mg dose groups. In the multiple-dose studies, an increased serum ALT and aspartate transaminase (AST) was found in one subject after 7 days of administration of the drug. All serum biochemistry returned to normal levels and skin rash resolved after 7 days without any special treatment. Conclusion: Bismuthyl ecabet was shown to be safe and well tolerated in healthy Chinese subjects. The oral dosing regimen selected for subsequent phase II/III clinical trials was 800 mg twice daily.

Background and Aims: Uncoupling protein-2 (UCP-2) is a negative regulator of reactive oxygen species (ROS) production. We investigated the effect of UCP-2 on disease progression in a murine dextran sodium sulfate (DSS)-induced colitis model, and the expression and distribution of tight junction (TJ) proteins, such as occludin, zonula-1 (ZO-1), claudin-4, and junctional adhesion molecule-1 (JAM-1). Methods: Male UCP-2−/− mice and wild-type littermates were divided into four groups: groups I and II, which comprised each type of mouse, were administered 2.5% DSS dissolved in drinking water to create a colitis model. The control groups (groups III and IV, which comprised each type of mouse) were given normal drinking water. Disease progression was evaluated according to colon length and the disease activity index. The distribution of TJ proteins was detected by immunohistochemical analysis. Results: Compared with wild-type littermates, UCP-2−/− mice treated with DSS developed more severe diarrhea, body weight loss (P

Background and Aim: To study the low-molecular-weight metabolites in blood plasma of patients with the progressive disease, gastric cancer, and to characterize different stages from chronic superficial gastritis (CSG) to chronic atrophic gastritis (CAG), intestinal metaplasia (IM), gastric dysplasia (DYS) and finally gastric cancer (GC). Methods: We applied gas chromatography time-of-flight mass spectrometry (GC/TOF-MS) to determine metabolites levels in plasma obtained from 80 patients including 19 with CSG, 13 with CAG, 10 with IM, 15 with DYS and 22 with GC (nine preoperation and 13 postoperation). Principal component analysis (PCA) and statistics were used to differentiate the stages and to identify the markers of gastric cancer. Results: Totally, 223 peaks were detected in GC/TOF-MS and 72 compounds were authentically identified. CSG showed distinct difference from the other groups of CAG, IM, DYS and GC, whose plots clustered closely. IM clustered closely to GC, suggesting similar metabolic patterns of them. Fifteen identified metabolites contributed most to the differentiating between CSG and GC, and characterized different stages of GC. Statistics revealed elevated levels of 2-Hydroxybutyrate, pyroglutamate, glutamate, asparagine, azelaic acid, ornithine, urate, 11-eicosenoic acid, 1-monohexadecanoylglycerol and γ-tocopherol, while downregulation of creatinine, threonate in GC group, indicating that GC patients were obviously involved in oxidative stress, and perturbed metabolism of amino acids and fatty acids. Conclusion: The metabolic phenotype of CSG is significantly different from GC, while that of IM is similar to it. The discriminatory metabolites characterizing progressive stages from CSG to GC might be the potential markers to indicate a risk of GC.

Background: For proven gastro-oesophageal reflux disease, partial fundoplication is considered as effective as Nissen, but with fewer side effects. The aim of this meta-analysis was to compare the effect of laparoscopic partial fundoplication (LPF) with laparoscopic Nissen fundoplication (LNF). Methods: Extensive medical literature searches of the PubMed, Medline and Embase databases were performed up to April 2010 for all randomized clinical trials that compared LPF versus LNF. The effect variables analysed were the incidence of post-operative dysphagia, heartburn, inability to belch, outcome or satisfaction and Visick score. Meta-analyses were carried out using odds ratios (ORs) with 95% confidence interval. Results: Thirteen randomized trials were considered suitable for the meta-analysis. A total of 1374 patients underwent LPF or LNF. There was a significant reduction of the incidence of post-operative dysphagia (OR = 0.44, P < 0.0001) and inability to belch (OR = 0.41, P < 0.005) for the LPF compared to that of the LNF group. Compared with LPF, LNF resulted in a significant reduction of the incidence of post-operative heartburn (OR = 1.94, P < 0.01). The outcome or satisfaction of patients and Visick I and II scores were comparable between the two groups. Conclusion: Both LPF and LNF are effective for the treatment of proven gastro-oesophageal reflux disease. LPF enables a decreased post-operative dysphagia and gas-related side effects, while LNF is more successful in controlling reflux symptoms, particularly heartburn, than LPF. A balance should be found between anti-reflux and side effects.

To explore the effect of cytochrome P450 2C19 (CYP2C19) polymorphisms on the relationship between the pharmacokinetics and pharmacodynamics of omeprazole administered by intravenous successive infusions in Chinese healthy volunteers.A total of 21 subjects [7 homozygous extensive metabolizers (homEMs), 9 heterozygous extensive metabolizers (hetEMs), 5 poor metabolizers (PMs)] received a 5-day course of omeprazole (40 mg) administered as a single dose daily during a 30-min period. Plasma concentrations were monitored by sampling at very short intervals for the first 8.5 h post-omeprazole administration and at 24 h post-administration, and intragastric pH was recorded on days 1 and 5.After a single dose, both the area under the plasma concentration-time curve (AUC) and peak concentration (C(max)) were higher in PMs than in EMs. Both the mean half-life (t((1/2))) and total clearance in PMs were significantly higher and lower than those in homEMs and EMs, respectively. Mean AUC and C(max) ratios in homEMs, hetEMs, and PMs were 1.0:1.1:1.4 and 1.0:1.0:1.1, respectively. Relative to the values determined after a single dose in EMs, after repeated doses, the intragastric pH, AUC, C(max), and t((1/2)) had increased significantly, while the total clearance had decreased significantly. Mean AUC and C(max) ratios in homEMs, hetEMs, and PMs were 1.4:1.4:1.5 and 1.2:1.2:1.3, respectively, compared to those of a single dose. The mean intragastric pH was significantly higher in PMs than in EMs after the fifth dose.There is a relationship between the pharmacokinetics and pharmacodynamics of omeprazole, with the latter depending in part on the duration of administration as evidenced by a higher AUC or C(max) and intragastric pH resulting from repeated dosing.

Background: Some studies have reported that Toll-like receptor 4 (TLR4) D299G and T399I polymorphisms are associated with increased Crohn’s disease (CD) and ulcerative colitis (UC) risk in the Caucasian population. However, the results have been inconsistent. Methods: A systemic review of the published data (16 studies with 8,387 cases and 7,013 controls for D299G; 8 studies with 3,881 cases and 1,861 controls for T399I) was undertaken and a meta-analysis was performed to test whether TLR4 D299G and T399I polymorphisms were associated with CD or UC susceptibility and whether 299Gly carriage was associated with phenotypes of CD patients. Results: The TLR4 299Gly allele showed a significant association with CD and UC in the Caucasian population (OR 1.29, 95% CI 1.08–1.54, and OR 1.28, 95% CI 1.08–1.51, respectively). Similar association was detected between the T399I polymorphism and susceptibility to CD and UC (OR 1.37, 95% CI 1.12–1.68, and OR 1.46, 95% CI 1.13–1.88, respectively). However, no significant association was identified between CD phenotypes and 299Gly carriage. Conclusion: The meta-analysis showed that TLR4 D299G and T399I confer a significant risk for developing CD and UC in Caucasians. Additional well-powered studies of the association between TLR4 variants and UC are needed.

The aim of the study was to investigate the effects of rebamipide on symptom, histology, endogenous prostaglandin, and mucosal oxygen free radicals in chronic erosive gastritis (CEG) patients by using sucralfate as a control. The trial also examined whether Helicobacter pylori infection would affect rebamipide-induced protection. A total of 453 endoscopy-confirmed CEG patients from 11 hospitals in China were enrolled in the study. They randomly received either rebamipide (100 mg t.i.d) or sucralfate (1.0 t.i.d) for 8 weeks with a ratio of 3:1. Per-protocol analysis (n = 415) showed the accumulated symptom score in the rebamipide group dropped from 5.54 +/- 0.97 to 0.80 +/- 0.47 after 8 weeks (P < 0.001 versus control). The endoscopic inflammation score in rebamipide group also decreased from 2.65 +/- 0.09 to 0.60 +/- 0.10, which showed better effects than sucralfate. It was shown a significant improvement (P < 0.01) in prostaglandin E2 (PGE(2)) contents in rebamipide-treated subjects mucosa (225.4 +/- 18.3 pg/g versus 266.7 +/- 14.7 pg/g) compared with that in sucralfate group after 8 weeks of treatment. Malondialdehyde (MDA) contents were significantly depressed both in the trial and control group. When Helicobacter pylori infection was considered, no statistically difference was found in the effect of rebamipide on either symptom or inflammation scores. In conclusion, Rebamipide demonstrated a stronger suppressive effect on the mucosal inflammation in chronic erosive gastritis than sucralfate. The gastroprotection induced by rebamipide is not influenced by H. pylori infection, which indicates its usage in the treatment of H. pylori-associated CEG.

Aims. This study was to compare the degradation, complications, and tissue reactions of two segmented biodegradable esophageal stents in a porcine model.Methods. Uncovered biodegradable segmented stents and fully covered biodegradable segmented stents (FCBDS) were transplanted into the porcine esophagus lumen. Data on biodegradation, complications, and tissue reactions were collected and compared.Results. All animals kept good general conditions. No severe complications and stents migration occurred. Stents degradation commenced at week 3. Compared with uncovered stents, stents structure breakage and complete stents absorption in FCBDS were postponed for 1-2 weeks. Hyperplasia was prominent at early stage and ameliorated at late stage after stents insertion. Tissue reactions in FCBDS were milder than those in uncovered stents in the early stage. A longer degradation period was present in FCBDS than in uncovered stents, while FCBDS induced tissue reaction at late stage was mild.Conclusions. Biodegradable esophageal stents with a segmented trunk may be further evaluated in refractory benign esophagus strictures. This FCBDS may be advantageous compared with uncovered stents for a longer degradation period.

Background and Aims: Dysregulation of microRNAs (miRNAs) is associated with a variety of diseases, including Crohn’s disease (CD), but the essential biological functions and crucial targets of miRNAs remain largely unknown. The present study investigated the aberrant colonic mucosal miRNAs in active CD patients. Methods: miRNA levels were assayed in inflamed colon of active CD patients by quantitative real-time polymerase chain reaction. The influence of differential expressed miR-124 on its putative target, the aryl hydrocarbon receptor (AHR), was investigated in CD patients, intestinal epithelial cells (IECs) and 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis mice. The role of miR-124 was further studied in experimental colitis mice by intracolonic administration of miR-124 inhibitors or precursors. Results: We found an inverse correlation between miR-124 and AHR protein levels in colon tissues and IECs of active CD patients. Further results demonstrated that miR-124 suppressed AHR expression by directly targeting the AHR 3ʹ-untranslated region (3ʹ-UTR) in Caco-2 cells and HT-29 cells. MiR-124 mediated the inflammatory response in lipopolysaccharide-stimulated cells through retroregulation of AHR in vitro . Downregulation or upregulation of miR-124 in TNBS-induced colitic colon alleviated or aggravated experimental colitis, respectively. Conclusions: These findings suggest that miR-124 induces intestinal inflammation by inhibiting AHR to modulate pro-inflammatory cytokine production and thereby promotes the pathogenesis of CD.

This study retrospectively reviewed 48 cases of gastric submucosal tumors (SMTs) treated by endolumenal endoscopic full-thickness resection (EFR) microsurgery in our gastrointestinal endoscopy center.From November 2009 to October 2012, 48 cases underwent endolumenal EFR for resection of muscularis propria-originating gastric SMTs. Characteristics of the 48 patients, clinical efficacy, safety of EFR, and post-EFR pathological diagnoses were evaluated retrospectively.EFR was successfully performed in 48 cases with 52 lesions. The median operation time was 59.72 minutes (range, 30-270 minutes; standard deviation, 39.72 minutes). The mean tumor size was 1.59 cm (range, 0.50-4.80 cm; standard deviation, 1.01 cm). During the EFR process, dual-channel gastroscopy was applied in 20 cases of SMTs, and paracentesis during the EFR process was applied in 9 cases. EFR for larger SMTs and gastric corpus-originating SMTs had longer operative times. Pathological diagnosis included 43 gastrointestinal stromal tumors, 4 leiomyomas, and 1 schwannoma. A larger tumor size was associated with higher risk of malignancy. No severe postoperative complications were observed. No tumor recurrences were confirmed in follow-up gastroscopy.The endolumenal EFR technique proved to be feasible and minimally invasive, even for the resection of large gastric tumors originating from the muscularis propria. However, more data on EFR must be obtained and analyzed.

Interleukin-17(IL-17)-producing T helper(Th)17 cells are considered as a new subset of cells critical to the development of inflammatory bowel disease (IBD). We aimed to investigate the distribution of Th17 cells, the expressions of Th17-related cytokines (IL-17, IL-21 and IL-22) and their association with disease activity in IBD patients.We collected intestinal tissue biopsies from 40 patients with active ulcerative colitis (UC), 20 patients with active Crohn's disease (CD) and 20 healthy controls. The distribution of Th17 cells and expressions of Th17-related cytokines in colonic tissues were evaluated by a standard immunohistochemical procedure. Serum IL-17, IL-21 and IL-22 levels were determined by ELISA. Pearson's and Spearman's correlation analyses were performed to analyze the correlation between the number of Th17 cells, the expressions of Th17-related cytokines and disease activity index, endoscopic and histological grading, and CRP and PLT levels, respectively.Compared with healthy controls, the number of Th17 cells and the expressions of IL-17, IL-21 and IL-22 were significantly increased in active IBD patients (P 0.05). In addition, Pearson's and Spearman's correlation analyses showed that the number of Th17 cells and the expressions of Th17-related cytokines were correlated with disease activity index, endoscopic and histological grading, CRP and PLT levels (P 0.05).Th17 cells and Th17-related cytokines (IL-17, IL-21 and IL-22) were increased in the intestinal mucosa in active IBD patients and may play an important role in disease activity and mucosal damage.

Interleukin-17A and interleukin-17F (IL-17A and IL-17F) are candidate genes for chronic inflammatory disease. We investigated the association between IL17A/F gene polymorphisms and susceptibility to and clinical features of inflammatory bowel disease (IBD).A total of 270 ulcerative colitis (UC) patients, 82 Crohn's disease (CD) patients and 268 healthy controls were recruited in this study. Genomic DNA was extracted and analyzed for IL17A/F gene polymorphisms using ligase detection reaction allelic technology.Compared to the controls, the mutant allele C for IL17F rs763780 was significantly more common in CD patients [14.0 vs 8.4 %, P = 0.033, odds ratio (OR) 1.18, 95 % confidence interval (CI) 1.41-3.04] and was associated with the disease lesion location. This variant of IL17F rs763780 also had a weak correlation with the age of UC onset (P = 0.05, OR 0.97, 95 % CI 0.94-1.00). The IL17A (rs2275913, G-197A) variant had a weak association with the severity of disease: patients with the mutant allele A tended to suffer mild active UC. The haplotype (GGTT) of IL17A formed with four single nucleotide polymorphisms (rs2275913, rs8193037, rs8193038, and rs3804513) was associated with an increased risk of UC (P = 0.034, OR 4.58, 95 % CI 1.54-13.64).The IL17F (rs763780, 7488T/C) variant was associated with an increased risk for the development of CD, and affected some clinical features of UC and CD. The IL17A (rs2275913, G-197A) variant had a weak association with the severity of UC. There was a risk haplotype in IL17A which could increase the risk of UC.

Aims To compare the efficacy and the adverse effects of levofloxacin-containing triple therapy, standard sequential therapy, and levofloxacin-containing sequential therapy as first-line treatment for Helicobacter pylori eradication. Methods Three hundred and forty-five naive H. pylori-positive patients were randomized to receive levofloxacin-containing 7-day triple therapy (Levo triple, i.e., esomeprazole, 20 mg, twice daily, amoxicillin, 1 g, twice daily, and levofloxacin, 500 mg, once daily for 7 days, n = 114), standard sequential therapy (SST-10, 5-day esomeprazole, 20 mg, twice daily and amoxicillin, 1 g, twice daily followed by 5-day esomeprazole, 20 mg, twice daily, clarithromycin, 500 mg, twice daily and tinidazole, 500 mg, twice daily for 5 days, n = 115) or levofloxacin-containing sequential therapy (Levo-ST-10, 5-day esomeprazole, 20 mg, twice daily and amoxicillin, 1 g, twice daily for 5 days followed by 5-day esomeprazole, 20 mg, twice daily, levofloxacin, 500 mg, once daily and tinidazole, 500 mg, twice daily, n = 116). Eradication was confirmed by a 13C-urea breath test 4 weeks after completion of treatment. Results Intention to treat (ITT) eradication rates were 78.1% (95% CI: 69.4, 85.3%), 78.3% (95% CI: 69.6, 85.4%), and 82.8% (95% CI: 74.6, 89.1%) for Levo triple, SST-10, Levo-ST-10, respectively (p = .599). Per protocol (PP) eradication rates were 80.9% (95% CI: 72.3, 87.8%), 82.6% (95% CI: 74.1, 89.2%), and 86.5% (95% CI: 78.7, 92.2%), respectively, for the three therapies (p = .513). Overall, 3.8% experienced mild to moderate adverse events; the rates were 1.75, 4.35, and 5.17%, respectively, in the three groups (p = .325). Conclusions Standard sequential therapy and 7-day levofloxacin triple therapy produced unacceptably therapeutic efficacy in China. Only levofloxacin-containing sequential therapy achieved borderline acceptable result. None of the regimens tested reliably achieved 90% or greater therapeutic efficacy in China.

To investigate the pharmacokinetics and pharmacodynamics of rabeprazole (RPZ) given as successive intravenous infusion to healthy Chinese volunteers.A total of 63 subjects (33 males and 30 females) were recruited at four research centers and given a 5-day therapeutic course of RPZ (10, 20, or 40 mg) administered as single daily doses during a 30-min period. Plasma concentrations were monitored by sampling at very short intervals for the first 330, 360, or 420 min post-RPZ administration. Intragastric pH was recorded 24 h post-RPZ administration on day 1 and day 5.After receiving a single and repeated doses of RPZ, the area under the plasma concentration-time curve (AUC(0-τ)) was 51.9 ± 22.1, 96.7 ± 27.6, and 188.4 ± 65.8 mg·min/L on day 1 and 59.3 ± 23.9, 106.7 ± 27.8, and 200.3 ± 79.0 mg·min/L on day 5 for the low-, middle-, and high-dose groups, respectively. The corresponding peak concentrations (C(max)) were 0.64 ± 0.11, 1.30 ± 0.26, and 2.6 ± 0.54 μg/mL on day 1 and 0.76 ± 0.15, 1.39 ± 0.25, and 2.91 ± 0.53 μg/mL on day 5, respectively. Although the mean AUC and C(max) values increased from a single dose to repeated doses in the three groups, the difference was not significant. The mean AUC((0, τ)) and C(max) ratios of repeated dose to single dose were 1.14, 1.10, and 1.06 on day 1 and 1.19, 1.07, and 1.12 on day 5 for the low-, middle-, and high-dose groups, respectively. After administration of a single dose, the 24-h pH value was significantly higher in the high-dose group than in the low-dose group. After repeated doses, significant increases in pH were observed in the low-, middle-, and high-dose groups; however, the between-group differences were not statistically significant.There is a relationship between the pharmacokinetics and pharmacodynamics of RPZ, with the latter depending in part on the duration of administration, as evidenced by a higher AUC or C(max) and intragastric pH from repeated dosing.

AIM: To compare neoadjuvant chemoradiotherapy and surgery with surgery alone for resectable esophageal carcinoma. METHODS: We used MEDLINE and EMBASE databases to identify eligible studies and manual searches were done to ensure no studies were missed. Trial validity assessment was performed and a trial quality score was assigned. RESULTS: Eleven randomized controlled trials (RCTs) including 1308 patients were selected. Neoadjuvant chemoradiotherapy significantly improved the overall survival compared with surgery alone. Odds ratio (OR) [95% confidence interval (CI), P value], expressed as neoadjuvant chemoradiotherapy and surgery vs surgery alone, was 1.28 (1.01-1.64, P = 0.05) for 1-year survival, 1.78 (1.20-2.66, P = 0.004) for 3-year survival, and 1.46 (1.07-1.99, P = 0.02) for 5-year survival. Postoperative mortality increased in patients treated by neoadjuvant chemoradiotherapy (OR: 1.68, 95% CI: 1.03-2.73, P = 0.04), but incidence of postoperative complications was similar in two groups (OR: 1.14, 95% CI: 0.88-1.49, P = 0.32). Neoadjuvant chemoradiotherapy lowered the local-regional cancer recurrence (OR: 0.64, 95% CI: 0.41-0.99, P = 0.04), but incidence of distant cancer recurrence was similar (OR: 0.94, 95% CI: 0.68-1.31, P = 0.73). Histological subgroup analysis indicated that esophageal squamous cell carcinoma did not benefit from neoadjuvant chemoradiotherapy, OR (95% CI, P value) was 1.16 (0.85-1.57, P = 0.34) for 1-year survival, 1.34 (0.98-1.82, P = 0.07) for 3-year survival and 1.41 (0.98-2.02, P = 0.06) for 5-year survival. CONCLUSION: Neoadjuvant chemoradiotherapy can raise the survival rate of patients with esophageal adenocarcinoma.