A novel polyp retrieval bag reduces the polyp fragmentation rate in colon polypectomy: a single-blind randomized controlled study.

PURPOSE: The fragmentation of polyps affects complete resection confirmation. The primary aim of this study was to assess the feasibility of a novel polyp retrieval bag for reducing the fragmentation rate of colon polyps. METHODS: Patients with a 5-15 mm colon polyp were recruited and randomized into two groups at a 1:1 ratio. After polyp resection, polyps obtained from patients in the treatment group were extracted via a novel polyp retrieval bag without traversing the instrument channel, whereas polyps obtained from patients in the control group were collected through the instrument channel, attaching the polyp trap to the instrument channel port, and applying suction. RESULTS: From January to July 2022, 225 patients were assessed for eligibility. The study participants included 204 patients, and seven patients whose samples were not retrieved were excluded. Polyp fragmentation was significantly lower in the treatment group than in the control group (3.0% [3/100] vs. 17.5% [17/97], P = 0.001). The retrieval failure rates in the treatment group and control group were not significantly different (2.0% [2/102] vs. 4.9% [5/102], P = 0.442). There were fewer colonoscope insertions in the treatment group than in the control group (102 vs. 110), but a significant difference was not present (P = 0.065). No significant adverse events were observed during the follow-up. CONCLUSIONS: This study demonstrated that the polyp retrieval bag was safe and feasible for reducing the fragmentation rate of retrieved polyps. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT05189912, 1/12/2021).

Continuous suture technique increases the complete closure rate of colorectal mucosal defects after endoscopic resection: a single-blind, randomized controlled trial.

BACKGROUND: Complete closure of mucosal defects after colorectal endoscopic submucosal dissection (ESD)/piecemeal endoscopic mucosal resection (p-EMR) procedures reduces postoperative adverse events, but the complete closure rate of the traditional method using only hemostatic clips is not satisfactory. Therefore, we invented a continuous suture technique using a barbed suture and clips to increase the complete closure rate of colorectal mucosal defects. METHODS: Patients with a single large (≥ 2 cm) colorectal lesion were recruited. After completion of the ESD/p-EMR procedures, they were randomly allocated to the treatment group or control group. The mucosal defects of the treatment group were closed using barbed suture and clips, while the control group was closed using only clips. RESULTS: From January 18, 2022 to April 13, 2022, a total of 62 patients with colorectal lesions were enrolled, with 31 patients in each group. Complete closure was achieved in 29 patients (93.5%) in the treatment group and 18 patients (58.1%) in the control group (P = 0.001). The median closure time was 13 min in the treatment group and 19 min in the control group (P < 0.001). The median closure speed was 6.4 cm2/10 min in the treatment group and 3.5 cm2/10 min in the control group (P = 0.008). CONCLUSIONS: This study provided a clinically feasible continuous suture technique that was safe and effective for the complete closure of colorectal mucosal defects after endoscopic resection.

Balloon-occluded retrograde transvenous obliteration and simultaneous endoscopic cyanoacrylate injection for treating gastric varices draining through gastrorenal shunts.

BACKGROUND AND STUDY AIMS: Balloon-occluded retrograde transvenous obliteration-assisted endoscopic cyanoacrylate injection (E-BRTO) temporarily treats gastric fundic varices draining through gastrorenal shunts (GRS) occluding the GRS with a balloon, then endoscopically injecting cyanoacrylate. We retrospectively examined the safety, feasibility, and efficacy of E-BRTO. PATIENTS AND METHODS: We enrolled 85 patients with hepatic cirrhosis plus gastric fundic varices with GRS; 34 underwent E-BRTO. The 51 patients who refused all secondary prophylactic treatments served as controls. RESULTS: Finally, 33 of the 34 patients underwent successful E-BRTO without major adverse events. Gastric varices were eradicated from all 33 patients in the E-BRTO group; the average follow-up time was 161.0 (74.0) weeks (mean [SD]). Four end-point events (12%) were recorded during the follow-up period. In the control group, 33 patients (65%) suffered repeat variceal bleeding, resulting in seven deaths. The cumulative rebleeding rates of the E-BRTO group on the 6th, 24th, 48th, 96th, 144th, 192nd, 240th, and 288th week were 0%, 3%, 9%, 9%, 13%, 13%, 13%, and 13%, while the cumulative rebleeding rates of the control group in the same period were 10%, 20%, 35%, 46%, 55%, 65%, 76%, and 76%. CONCLUSIONS: E-BRTO was safe, feasible, and well tolerated by patients with hepatic cirrhosis plus gastric fundic varices with GRS. Over the long-term follow-up period, the E-BRTO group demonstrated a lower rate of repeat bleeding than the control group.

Osteopontin contributes to TGF-ß1 mediated hepatic stellate cell activation.

BACKGROUND AND PURPOSE: Liver fibrosis is characterized by accumulation of extracellular matrix. Our previous study found that osteopontin (OPN) increased in plasma of cirrhotic patients and indicative of cirrhosis staging. The present study was designed to investigate the expression of OPN in liver tissues and plasma of cirrhotic patients and further explore the role of OPN in human hepatic stellate cell (HSC) activation. METHODS: We used immunohistochemical staining and enzyme-linked immunosorbent assay to evaluate the expression level of OPN in liver tissues and plasma from cirrhotic patients, respectively. We produced lentivirus particles and infected target cell to manipulate OPN expression. Infection efficiency was determined by real-time RT-PCR and western blot. Cell proliferation was determined using CCK8 assay, and phenotypes of HSC activation were determined by real-time RT-PCR. OPN promoter activity was determined by dual luciferase reporter assay. RESULTS: We found that OPN expression in human cirrhotic liver tissues was upregulated compared to normal controls. In addition, its expression correlated with Child-Pugh classification, MELD score and the occurrence of complications. We further explored OPN level in patients' plasma and showed that its level correlated with transforming growth factor-ß1 (TGF-ß1). In human HSC cell line LX-2, we found that change of OPN expression level could not only affect the proliferation of cells but also the TGF-ß1 mediated HSC activation. Moreover, OPN was increased by TGF-ß1 stimulation and regulated by TGF-ß1 at transcription level. CONCLUSIONS: OPN is upregulated in liver tissues and plasma of cirrhotic patients and promotes TGF-ß1 mediated HSC activation.

Investigation report on endoscopic management of esophagogastric variceal bleeding by Chinese endoscopists.

BACKGROUND: Esophagogastric variceal bleeding (EGVB) is a potentially life-threatening complication of portal hypertension. Endoscopic treatment combined with pharmacotherapy remains the mainstay in the management of acute variceal bleeding. AIM: This article intends to highlight the potential differences in the endoscopic management of EGVB in China. METHODS: A cross-sectional descriptive study was conducted. Endoscopists from 85 hospitals in 62 cities from 26 provinces were contacted by email. The items in questionnaire involved academic experience, screening, esophagogastric varices (EGV) classification, emergency treatment, and primary and secondary prophylaxis of EGVB by endoscopists with different lengths of experience. RESULTS: A total of 85 questionnaires were collected. There was no statistical difference in the selection of items (P < .05 indicated statistical significance). The majority of endoscopists (95.29%) offered EGV screening for patients with liver cirrhosis. The location, diameter, and risk factor classification was selected by 82.35% of endoscopists. Endoscopy + medication was preferred (42.35%) for the primary prophylaxis of moderate-to-severe EGVs. There was no statistical difference in emergency intervention time for active EGVB (P > .05). The response "patients receive emergency endoscopic intervention within 12 hours" was selected by 61.2% of the endoscopists. The preferred emergency treatment for EGVB was combination treatment (40%). Tissue adhesive embolization was selected for the treatment of gastric variceal bleeding by 74.12% of endoscopists; transjugular intrahepatic portosystemic stent shunt/percutaneous transhepatic variceal embolization were selected as remedial measures by 48.23% to 52.94% of endoscopists. In addition, 67.06% of endoscopists elected to perform secondary prophylaxis and treatment within 1 week after hemostasis. Endoscopy and endoscopy + medication were selected by 44.71% and 49.41% of endoscopists, respectively, for secondary prophylaxis. The choice of laboratory indicators did not differ with length of experience. CONCLUSIONS: There was no statistical difference in the endoscopic management of EGVB among Chinese endoscopists. The selection of diagnosis/treatment schemes was mainly based on guidelines and physician experience.

Epidemiological and clinical differences of coronavirus disease 2019 patients with distinct viral exposure history.

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread from the early epicenter, Wuhan, to the rest of China, the virulence of SARS-CoV-2 might have evolved at different phases of the pandemic. We therefore compared the unique features among 62 coronavirus disease 2019 (COVID-19) inpatients who contracted SARS-CoV-2 in Wuhan (15 cases), exposed to the patients from Wuhan (26 cases), or acquired the disease without exposure to Wuhan patients (21 cases). Median incubation periods are 4.5 days (3-5) for Wuhan patients, 8 days (3-11) for those infected by Wuhan patients, and 12 days (7-13) for those without aforementioned experience. The disease onset dates are earliest for Wuhan patients and latest for those without exposure to Wuhan patients. Blood lymphocytes were lowest in Wuhan patients, lower in those affected by Wuhan patients, and modest reduced in remaining ones. Disease severity is worst for Wuhan patients, and modest for those without contact with Wuhan patients. Wuhan patients had longest (27 days, 18-28), those transmitted by Wuhan patients had intermediate (16 days, 8-23), and the rest of the patients had shortest (13 days, 8.5-22.5) hospital stay. Early viral exposure, older age, lymphocytopenia, and underlying conditions are risk factors which warrant aggressive intervention. Even though the virulence of SARS-CoV-2 appears decline over the course of serial transmissions, viral testing, contact tracing, social distancing, and face masking should be imposed on general public to contain viral dissemination from both symptomatic and asymptomatic patients with this highly contagious disease.

Characterization of uncommon portosystemic collateral circulations in patients with hepatic cirrhosis.

The purpose of the present study was to characterize uncommon portosystemic collateral circulation in hepatic cirrhosis. Portosystemic uncommon collateral circulation (UCC) was detected, characterized and evaluated by a combination of spiral computed tomography angiography, three-dimensional imaging angiography and electronic gastroscopy in patients diagnosed with hepatic cirrhosis. In total, 118 cases with UCC were detected from a pool of 700 hepatic cirrhosis patients with portal hypertension. The incidence was 16.86% and included cases with splenic-renal, gastro-renal, paravertebral, retroperitoneal, gastric-splenic and cardio-phrenic angle vein shunts. The occurrence rate of UCC formation increased with the Child-Pugh grade. Compared with common collateral circulations, the incidence of severe esophageal or gastric fundus varicose veins, severe portal hypertensive gastropathy and the incidence of a large quantity of ascites was much lower in the patients with UCC (P<0.01), whereas the incidence of hepatic encephalopathy and chronic elevated blood ammonia levels was significantly higher (P<0.01). The incidence of uncommon portosystemic collateral circulation is extremely common in patients with liver cirrhosis and is associated with the Child-Pugh grades of hepatic function. UCC can aid in the relief of the complications derived from portal hypertension, but it may increase the incidence of hepatic encephalopathy and chronic elevated blood ammonia levels.

[Immunoregulation of autologous peripheral blood stem cell transplantation in patients with hepatitis B-related end-stage liver disease].

OBJECTIVE: To investigate the immunoregulatory effect of autologous peripheral blood stem cells (PBSCs) transplantation on T lymphocytes and cytokines in patients with HBV-related end-stage liver disease. METHODS: Flow cytometry was used to measure the percentages of Th1, Th2 and regulatory T cells (Treg) in peripheral blood. Enzyme-linked immunosorbent assay (ELISA) was performed to analyze the levels of serum IFN-γ, IL-6 and IL-10. RESULTS: Patients with HBV-related end-stage liver disease displayed significantly improved liver function after PBSCs transplantation. Statistically, after PBSCs transplantation, the percentages of Th2 and Treg in peripheral blood markedly increased, but serum IL-6 and IL-10 declined significantly. No significant differences were observed in the changes of Th1 and its cytokine, IFN-γ after transplantation. CONCLUSION: Autologous PBSCs transplantation can depress inflammation in liver by regulating immune microenvironment, which at least in part delineates the mechanism of stem cells-mediated therapeutic benefit on end-stage liver disease.

Bone marrow-derived stem cells ameliorate hepatic fibrosis by down-regulating interleukin-17.

BACKGROUND: Accumulating evidences have identified the immunoregulatory features of stem cells. In this study, the immunoregulation of bone marrow-derived stem cells (BMSCs) transplanted into patients with HBV-related decompensated cirrhosis and mouse model of liver injury induced by carbon tetrachloride (CCl4) administration was observed. RESULTS: Compared with healthy controls, patients with HBV-related decompensated cirrhosis showed significantly higher levels of TNF-alpha, IL-12, TGF-beta1, IL-17, and IL-8. However, only IL-17 was markedly decreased after autologous BMSCs transplantation during their follow-up. The same results were found in the CCl4-treated mice. Furthermore, we found that exogenous IL-17 partly abolished the therapeutic effect of BMSCs whereas IL-17-specific antibody promoted improvement of liver injury in CCl4-treated mice, resembling the therapeutic effect of BMSCs transplantation. CONCLUSIONS: These data suggested that BMSCs transplantation induces a decrease of IL-17 level, which at least in part delineates the mechanisms of stem cells-mediated therapeutic benefit on liver disease.

Dynamic microRNA profiles of hepatic differentiated human umbilical cord lining-derived mesenchymal stem cells.

Despite the extensive hepatic differentiation potential of human umbilical cord lining-derived mesenchymal stem cells (hUC-MSC), little is known about the molecular mechanisms of hUC-MSC differentiation. At the post-transcriptional level, microRNAs are key players in the control of cell fate determination during differentiation. In this study, we aimed to identify microRNAs involved in the hepatic differentiation of hUC-MSCs. After successfully isolating hUC- MSCs, we induced hepatocyte formation in vitro with growth factors. After 26 days of induction, hUC-MSCs could express hepatocyte-specific genes, synthesize urea and glycogen and uptake low-density lipoprotein. Cellular total RNA from hUC-MSCs and hepatic differentiated hUC-MSCs was collected at 7 time points, including 2 days, 6 days, 10 days, 14 days, 22 days and 26 days, for microRNA microarray analysis. Dynamic microRNA profiles were identified that did not overlap or only partially overlapped with microRNAs reported to be involved in human liver development, hepatocyte regeneration or hepatic differentiation of liver-derived progenitor cells. A total of 61 microRNAs among 1205 human and 144 human viral microRNAs displayed consistent changes and were altered at least 2-fold between hUC-MSCs and hepatic differentiated hUC-MSCs. Among these microRNAs, 25 were over-expressed; this over-expression occurred either gradually or increased sharply and was maintained at a high level. A total of 36 microRNAs were under-expressed, with an expression pattern similar to that of the over-expressed microRNAs. The expression of the altered expressed microRNAs was also confirmed by quantitative reverse-transcription polymerase chain reaction. We also found that microRNAs involved in hepatic differentiation were not enriched in hepatocyte or hepatocellular carcinoma cells and can potentially target liver-enriched transcription factors and genes. The elucidation of the microRNA profile during the hepatic differentiation of hUC-MSCs provides the basis for clarifying the role of microRNAs in hUC-MSC hepatic differentiation and specific microRNA selection for the conversion of hUC-MSCs to hepatocytes.