Exploring the casual association between gut microbiome, circulating inflammatory cytokines and chronic pancreatitis: A Mendelian randomization analysis.

It has been established that gut dysbiosis contributed to the pathogenesis of digestive disorders. We aimed to explore the causal relationships between intestinal microbiota, circulating inflammatory cytokines and chronic pancreatitis (CP). Summary statistics of genome-wide association studies (GWAS) of intestinal microbiome was retrieved from the MiBioGen study and the GWAS data of 91 circulating inflammatory cytokines and CP were obtained from the GWAS catalog. The 2-sample bidirectional Mendelian randomization (MR) analysis was performed between gut microbiota, circulating inflammatory cytokines and CP, in which the inverse variance weighted (IVW) method was regarded as the primary analysis approach. To prove the reliability of the causal estimations, multiple sensitivity analyses were utilized. IVW results revealed that genetically predicted 2 genera, including Sellimonas and Eubacteriumventriosumgroup, and plasm C-C motif chemokine 23 (CCL23) level were positively associated with CP risk, while genus Escherichia Shigella, Eubacteriumruminantiumgroup and Prevotella9, and plasma Caspase 8, Adenosine Deaminase (ADA), and SIR2-like protein 2 (SIRT2) level, demonstrated an ameliorative effect on CP. Leave-one-out analysis confirmed the robustness of the aforementioned causal effects and no significant horizontal pleiotropy or heterogeneity of the instrumental variables was detected. However, no association was found from the identified genera to the CP-related circulating inflammatory cytokines. Besides, the reverse MR analysis demonstrated no causal relationship from CP to the identified genera and circulating inflammatory cytokines. Taken together, our comprehensive analyses offer evidence in favor of the estimated causal connections from the 5 genus-level microbial taxa and 4 circulating inflammatory cytokines to CP risk, which may help to reveal the underlying pathogenesis of CP.

MYEF2: an immune infiltration-related prognostic factor in IDH-wild-type glioblastoma.

Glioblastoma (GBM) is the most malignant and prevalent primary brain tumor. In this study, weighted gene coexpression network analysis (WGCNA) was performed to analyze RNA binding protein (RBP) expression data from The Cancer Genome Atlas (TCGA) for the IDH-wild type GBM cohort. The CIBERSORT algorithm quantified the cellular composition of immune cells and was used to identify key modules associated with CD8+ T cell infiltration. Coexpression networks analysis and protein-protein interaction (PPI) network analysis was used to filter out central RBP genes. Eleven RBP genes, including MYEF2, MAPT, NOVA1, MAP2, TUBB2B, CDH10, TTYH1, PTPRZ1, SOX2, NOVA2 and SCG3, were identified as candidate CD8+ T cell infiltration-associated central genes. A Cox proportional hazards regression model and Kaplan-Meier analysis were applied to identify candidate biomarkers. MYEF2 was selected as a prognostic biomarker based on the results of prognostic analysis. Flow Cytometric Analysis indicated that MYEF2 expression was negatively correlated with dysfunctional CD8+ T cell markers. Kaplan-Meier survival analysis (based on IHC staining) revealed that GBM patients with elevated MYEF2 expression have a better prognosis. Knockdown of MYEF2 in GBM cells via in vitro assays was observed to promote cell proliferation and migration. Our study suggests that MYEF2 expression negatively correlates with T cell exhaustion and tumor progression, rendering it a potentially valuable prognostic biomarker for GBM.

Peroral endoscopic shorter versus longer myotomy for the treatment of achalasia: a comparative retrospective study.

INTRODUCTION: Peroral esophageal myotomy (POEM) is a novel endoscopic treatment for achalasia. It has gained popularity worldwide among surgeons and endoscopists, but no studies have compared peroral endoscopic short with long myotomy for achalasia. We aimed to compare the clinical efficacy and safety between peroral endoscopic shorter and longer myotomy. METHODS: The retrospective study enrolled 129 achalasia patients who underwent POEM from July 2011 to September 2017. Based on the myotomy length (ML), patients were divided into shorter myotomy (SM) group (ML ≤ 7 cm, n = 36) and longer myotomy (LM) group (ML > 7 cm, n = 74). Procedure-related parameters, symptom scores, adverse events and manometric data were compared between two groups. RESULTS: The mean ML was 6.0 ± 0.6 cm in SM group, and 11.5 ± 3.1 cm in LM group (p < 0.001). The mean operation time was significantly less in SM group than LM group (46.6 ± 18.5 min vs 62.1 ± 25.2 min, p = 0.001). During a mean follow-up period of 28.7 months, treatment success (Eckardt score ≤ 3) was achieved in 94.4% (34/36) of patients in SM group and 91.9% (68/74) in LM group (p = 0.926). There was no statistical difference in the incidence of intraoperative complications (8.4% vs 8.2%, p = 0.823) and reflux rate (8.3% vs. 14.9%, p = 0.510) between two groups. CONCLUSIONS: Peroral endoscopic shorter myotomy is comparable with longer myotomy for treating achalasia with regard to clinical efficacy and has the advantage of shorter procedure time.

Submucosal Tunnel Endoscopic Resection for Esophageal Submucosal Tumors: A Multicenter Study.

BACKGROUND: Submucosal tumors (SMTs) are primarily benign tumors, but some may have a malignant potential. Endoscopic submucosal dissection that has been used for removing esophageal SMTs could cause perforation. Submucosal tunnel endoscopic resection (STER) is an improved and an effective technique for treating esophageal SMTs. AIMS: This study was conducted to evaluate the efficacy and safety of STER for treating esophageal SMTs. METHODS: A retrospective study design was adopted to analyze the baseline characteristics, clinical outcomes, and follow-up data of patients with esophageal SMTs, which originated from the muscularis propria layer and were treated with STER from September 2011 to May 2018. RESULTS: A total of 119 lesions were included from 115 patients who were successfully treated with STER. The mean age of the patients was 49.7 ± 10.7 years. The lesions were primarily located in the middle and lower esophagus. The mean size of the lesions was 19.4 ± 10.0 mm. The mean operation duration was 46.7 ± 25.6 min, and the mean duration of hospitalization was 5.9 ± 2.8 days. The total en bloc resection rate and the complete resection rate were 97.5% and 100%, respectively. Regarding complications, there were 9 (7.8%) cases of perforation, 2 (1.7%) cases of pneumothorax, and 9 (7.8%) cases of subcutaneous emphysema. Histopathological results revealed 113 (95.0%) cases of leiomyoma, 5 (4.2%) cases of gastrointestinal stromal tumors, and 1 (0.8%) case of a granular cell tumor. During the mean 15-month follow-up, there were no cases of recurrence and distant metastasis. CONCLUSIONS: STER is a safe and feasible technique for treating esophageal SMTs originating from the muscularis propria layer.

Peroral endoscopic myotomy is safe and effective in achalasia patients aged older than 60 years compared with younger patients.

AIM: Peroral endoscopic myotomy (POEM) has been proven to be effective for treating achalasia, but there are limited data on POEM in elderly patients. We therefore aimed to assess the role of POEM for achalasia in patients aged ≥60 years. METHODS: All consecutive patients that underwent POEM between December 2011 and November 2015 at a single center were retrospectively reviewed. Patients aged ≥60 years were assigned to group A, whereas patients aged <60 years were assigned to group B. Demographic data, clinical data and treatment outcomes were compared between the two groups. RESULTS: During the study period, 113 patients (18 in group A, and 95 in group B) were enrolled. The mean age of patients in group A was 63 ± 3.9 years (range 60-74 years; 55.6% women), and that for patients in group B was 37.7 ± 11.6 years (range 18-59 years; 42.2% women). The procedural time in group A was similar to group B (66.3 ± 33.3 vs 59.8 ± 24.2 min, P = 0.332). There were also no significant differences in the incidence of intraoperative complications (P = 1.000) and gastroesophageal reflux rate (P = 0.906) between the two groups. During the mean follow-up period of 25.2 months, treatment success (Eckardt score ≤3) was achieved in 92.9% of patients in group A, and 89.9% in group B (P = 1.000). CONCLUSIONS: As well as in younger patients, POEM can be safely carried out in elderly patients, providing significant symptom relief. POEM might be recommended as the first therapeutic approach to elderly achalasia patients. Geriatr Gerontol Int 2017; 17: 2407-2413.

Endoscopic submucosal tunnel dissection of upper gastrointestinal submucosal tumors: A comparative study of hook knife vs hybrid knife.

AIM: To compare the efficacy and safety of a hook knife (HO) with a hybrid knife (HK) during endoscopic submucosal tunnel dissection (ESTD) procedure. METHODS: Between August 2012 and December 2015, the ESTD procedure was performed for 83 upper GI submucosal lesions, which originated from the muscularis propria layer identified by upper endoscopy and endoscopic ultrasonography. Of these, 34 lesions were treated by a HO, whereas 49 lesions were treated by a HK. Data regarding age, gender, presenting symptoms, tumor location and size, procedure time, complications, en bloc resection rate and others were analyzed and compared between the two groups. RESULTS: There were no significant differences in the age, gender, presenting symptoms and tumor location between the two groups. ESTD was successfully completed in all the patients, and no case was converted to laparoscopy. The mean procedure time was significantly shorter in the HK group than in the HO group (41.3 ± 20.3 min vs 57.2 ± 28.0 min, P = 0.004). The mean frequency of device exchange was 1.4 ± 0.6 in the HK group and significantly less than 3.3 ± 0.6 in the HO group (P < 0.001). The differences in tumor size and histopathological diagnoses were not significant between the two groups (P = 0.813, P = 0.363, respectively). Both groups had an equal en bloc resection rate and complete resection rate. Additionally, the complication rate was similar between the two groups (P = 0.901). During the follow-up, no recurrence occurred in either group. CONCLUSION: We demonstrate for the first time that HO and HK do not differ in efficacy or safety, but HK reduces the frequency of device exchange and procedure time.

Endoscopic Submucosal Tunnel Dissection for Upper Gastrointestinal Submucosal Tumors Originating from the Muscularis Propria Layer: A Single-Center Study.

BACKGROUND/AIMS: In recent years, endoscopic submucosal tunnel dissection (ESTD) has gained popularity worldwide. The aim of this study was to evaluate the safety and efficacy of ESTD in treating upper gastrointestinal submucosal tumors (SMTs) in a large-volume endoscopic center. METHODS: Patients with SMTs were enrolled in this study between January 2012 and January 2015. Demographic data, clinical data, and treatment outcome were collected and analyzed. RESULTS: Seventy SMTs originating from the muscularis propria (MP) layer were identified in 69 patients. All patients successfully underwent the ESTD procedure. The mean procedure time was 49.0±29.5 minutes, and the mean tumor size was 18.7±7.2 mm. Among all lesions, the majority (70.0%) were located in the esophagus, 12.9% in the cardia, and 17.1% in the stomach. Complete resection was achieved in 67 lesions (95.7%). Perforation occurred in three patients (4.3%), who were treated by endoclips. Pneumothorax occurred in two patients (2.9%) and was successfully managed by thoracic drainage. During a median follow-up of 18.1 months, patients were free of local recurrence or distant metastasis. CONCLUSIONS: Our results demonstrated the feasibility and safety of ESTD in treating upper gastrointestinal SMTs originating from the MP layer. Large-scale comparative studies with other treatment methods should be conducted in the future.