Translational gastroenterology and hepatology最新文献

The liver is a functionally unique organ with an immunosuppressive microenvironment. The liver is the sixth most common site of primary cancer in humans and is a frequent site of metastasis from other solid tumors. The development of effective therapies for primary and metastatic liver cancer has been challenging due to the complex metabolic and immune microenvironment of the liver. The liver tumor microenvironment (TME) in primary and secondary (metastatic) liver cancers is heterogenous and consists of unique immune and stromal cell populations. Crosstalk between these cell populations and tumor cells creates an immunosuppressive microenvironment within the liver which potentiates cancer progression. Immune checkpoint inhibitors (ICIs) are now clinically approved for the management of primary and secondary liver cancer and can partially overcome liver immune tolerance, but their efficacy is limited. In this review, we describe the liver microenvironment and the use of immunotherapy in primary and secondary liver cancer. We discuss emerging combination strategies utilizing locoregional and systemic therapy approaches which may enhance efficacy of immunotherapy in primary and secondary liver cancer. A deeper understanding of the immunosuppressive microenvironment of the liver will inform novel therapies and therapeutic combinations in order to improve outcomes of patients with primary and secondary liver cancer.

Background: Recently, increasing literature has been reported on optimal therapies in patients with advanced hepatocellular carcinoma (HCC) and many therapeutic modalities have been proposed to improve the survival rate. However, the results are not consistent due to different research protocols, small sample sizes and different study endpoints and there is no standard treatment protocol has been defined. Therefore, it is very important to explore the optimal bonding mode and to evaluate the efficacy and safety of the optimal sequential therapy for those patients.

Methods: We searched available databases through January 2020 for relevant studies. The main outcome measure was 1-year overall survival (OS) and overall response rate (ORR); the secondary outcome measure was a composite of toxic effects retrieved grade 3 or 4 adverse events (AEs) from all included studies. Statistical analyses were conducted using STATA version 15 and GeMTC package in the R statistical software.

Results: After a detailed review, 8 randomized controlled trials (RCTs) and 20 retrospective studies involving 3,675 advanced HCC patients were included for network meta-analysis. Indirect comparisons showed that hepatic arterial infusion chemotherapy (HAIC) plus radiofrequency ablation (RFA) was highest probability of obtaining the best OS rate of 1 year [surface under the cumulative ranking (SUCRA), 0.95] and ORR (SUCRA, 0.86) when compared with other potential optimal therapies and which had ranked the first in all treatment regimens, followed by HAIC (SUCRA, 0.75). Direct and indirect comparison of 1-year OS and ORR with all treatment regimens each other showed that for all treatment regimens, patients showed significant clinical benefit when compared with transcatheter arterial chemoembolization (TACE) or sorafenib alone. However, the incidence of treatment-related AEs of grade 3 or 4 occurred in patients who have received targeted drug sorafenib therapy (SUCRA, 0.51) compared with other interesting regimens.

Conclusions: HAIC may be a valuable therapeutic strategy for advanced HCC patients to prevent recurrence and metastasis after RFA, as well as in improving patient prognosis and quality of life. Meanwhile, HAIC combined with RFA is a safe and effective treatment in patients with advanced HCC, and this combination therapy can significantly prolong 1-year survival rate when compared with other optimal sequential therapies.

Trial registration: This study is registered with PROSPERO, number CRD42020176149.

Background: Intravenous erythromycin prior to endoscopy for upper gastrointestinal bleeding (GIB) improves outcomes but requires immediate preparation delaying administration in emergency cases. Azithromycin is readily available and does not require prolonged preparation. The aim of the study was to assess the effect of azithromycin in improving the quality of endoscopic visualization in upper GIB compared to erythromycin.

Methods: Patients admitted with upper GIB who received erythromycin or azithromycin before urgent endoscopy were included. Primary outcome of the quality of visualization was assessed by two gastroenterologists, blinded to the choice of infusion, using a scoring system ranging from 0 to 8, with a maximum of 2 points assigned to the fundus, body, antrum and bulb.

Results: Sixty-six patients were included; 25 received azithromycin and 41 received erythromycin. Mean total visualization score was significantly higher with azithromycin compared to that with erythromycin (6.8±1.4 vs. 5.5±2.2, respectively; P=0.01) and remained significant after adjusting for confounders (Diff: 0.01, 1.88; P=0.05). Secondary outcomes analyses showed a shorter LOS when given azithromycin compared to erythromycin [6 (3 to 9) vs. 8 (7 to 16) days, respectively, 95% CI: 1.03, 3.89; P=0.04]. Time between initiating the infusion and endoscopy was longer with azithromycin (Diff: 40.64 min; 95% CI: 7.23, 74.05; P=0.02). Need for second look endoscopy, procedure time, blood transfusion requirements and procedure-related complications did not differ between the groups.

Conclusions: Azithromycin infusion before endoscopy for upper GIB was associated with better visualization than that of erythromycin. Randomized trials are needed to validate these findings.

[This corrects the article DOI: 10.21037/tgh-2020-07.].

Novel corona virus disease (COVID-19) is an ongoing pandemic that has spread across the globe. The virus primarily infects type-2 pneumocytes in alveoli and causes lung disease, with severity ranging from mild pneumonia to acute respiratory distress syndrome. The virus also invades gastrointestinal epithelial cells, hepatocytes, and biliary epithelial cells. Derangement of liver function tests is noted in about one third of patients and appears to correlate with more severe disease. There are multiple mechanisms by which the virus can cause liver injury; immune-mediated inflammation and direct viral cytotoxicity are believed to be the predominant mechanisms. Liver injury appears to be transient, usually recovering with resolution of illness. Limited available studies and experience from prior corona virus pandemics seem to suggest that immunosuppressed patients have similar outcomes compared to non-immunosuppressed patients. Age and comorbid conditions seem to influence outcome, irrespective of immune status. Additionally, patients with preexisting comorbid conditions are more prone to acquire infection and should strictly adhere to travel and social distancing advisories. Telemedicine should be utilized to provide uninterrupted care for patients with liver disease, and clinic or hospital visits should be advised only in sick patients with advanced liver disease. In conclusion, liver dysfunction is not uncommon in COVID-19, it generally improves with resolution of disease, and patients with chronic liver disease (CLD) need continued follow up, uninterrupted by the ongoing pandemic, preferably in virtual clinic settings.

Background: Flexible endoscopic cricopharyngeal myotomy and septotomy offer a minimally invasive transluminal option for the treatment of symptomatic Zenker's diverticulum (ZD). There is currently no consensus regarding postoperative follow-up imaging. We suggest a standardized computed tomography (CT) esophagram protocol for radiographic evaluation of postoperative findings.

Methods: Single center retrospective analysis of patients with symptomatic ZD who underwent flexible endoscopic diverticulotomy and postoperative imaging with CT esophagram from January 2015 to March 2020. An experienced radiologist blinded to the initial imaging reports prospectively interpreted all CT esophagram findings, in order to minimize bias.

Results: Twenty-one patients underwent CT esophagram following flexible endoscopic diverticulotomy for ZD. Diverticulotomy was technically successful in all patients. Most common findings on imaging included: atelectasis (13/21; 62%), persistent esophageal diverticulum (7/21; 33%), pneumomediastinum (3/21; 14%), aspiration (2/21; 10%), and extraluminal air and contrast extravasation consistent with focal esophageal perforation (1/21; 5%).

Conclusions: We describe a standardized, simple, and accessible CT esophagram protocol for postoperative imaging of patients with post-flexible endoscopic cricopharyngeal myotomy and septotomy for ZD. CT esophagram facilitates a definitive exclusion of focal esophageal perforation as a postoperative complication of flexible endoscopic diverticulotomy by ruling out extraluminal air and contrast extravasation.