Metal versus plastic stents in the management of benign biliary strictures: systematic review and meta-analysis of randomized controlled trials.

Benign biliary strictures (BBS) are usually treated with endoscopic retrograde cholangiopancreatography (ERCP) with the placement of multiple plastic stents (MPS) or a covered self-expandable metal stent (CSEMS). In this meta-analysis, we compared the efficacy and safety of MPS and CSEMS in the management of BBS. We reviewed several databases from inception to 28 April 2021 to identify RCTs that compared MPS with CSEMS in the management of BBS. Our outcomes of interest were stricture resolution, stricture recurrence, adverse events, stent migration and mean number of ERCPs to achieve stricture resolution. Data were analyzed using a random-effects model. We included eight RCTs with 524 patients. We found no significant difference in the rate of stricture resolution (risk ratio, 1.02; 95% CI, 0.96-1.10), stricture recurrence (risk ratio, 1.68; 95% CI, 0.72-3.88) or adverse events (risk ratio, 1.17; 95% CI, 0.73-1.87) between groups. Mean number of ERCPs was significantly lower in the CSEMS group (SMD, -1.99; 95% CI, -3.35 to -0.64). The rate of stent migration was significantly higher in the CSEMS group. CSEMS are comparable in efficacy and safety to MPS in the management of BBS but require fewer ERCPs to achieve stricture resolution.

Systematic review with meta-analysis: one-year outcomes of gastric peroral endoscopic myotomy for refractory gastroparesis.

BACKGROUND: Several studies have examined the efficacy of gastric peroral endoscopic myotomy (G-POEM) for gastroparesis. AIM: To evaluate the mid-term efficacy of G-POEM by meta-analysis of studies with a minimum 1 year of follow-up. METHODS: We reviewed several databases from inception to 10 June 2021 to identify studies that evaluated the efficacy of G-POEM in refractory gastroparesis, and had at least 1 year of follow-up. Our outcomes of interest were clinical success at 1 year, adverse events, difference in mean pre- and 1 year post-procedure Gastroparesis Cardinal Symptom Index (GCSI) score, and difference in mean pre- and post-procedure EndoFLIP measurements. We analysed data using a random-effects model and assessed heterogeneity by I2 statistic. RESULTS: We included 10 studies comprising 482 patients. Pooled rates (95% CI) of clinical success at 1 year and adverse events were 61% (49%, 71%) and 8% (6%, 11%), respectively. Mean GCSI at 1 year post-procedure was significantly lower than pre-procedure; mean difference (MD) (95% CI) -1.4 (-1.9, -0.9). Mean post-procedure distensibility index was significantly higher than pre-procedure in the clinical success group at 40 and 50 mL volume distension; standardised mean difference (95% CI) 0.82 (0.07, 1.64) and 0.91 (0.32, 1.49), respectively. In the clinical failure group, there was no significant difference between mean pre- and post-procedure EndoFLIP measurements. CONCLUSIONS: G-POEM is associated with modest clinical success at 1 year. Additional studies with longer follow-up are required to evaluate its longer-term efficacy.

Outcomes of Endoscopic Submucosal Dissection for Treatment of Superficial Pharyngeal Cancers: Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Studies evaluating the role of endoscopic submucosal dissection (ESD) in the management of superficial pharyngeal cancers have reported promising results. This meta-analysis evaluates the efficacy and safety of ESD in the management of superficial pharyngeal cancers. METHODS: We reviewed several databases from inception to September 03, 2020, to identify studies evaluating the efficacy and safety of ESD in the management of superficial pharyngeal cancers. Our outcomes of interest were en bloc resection rate, complete resection rate, adverse events, and rates of local recurrence. Pooled rates with 95% confidence intervals (CI) for all outcomes were calculated using random-effect model. Heterogeneity was assessed by I2 statistic. We assessed publication bias by using funnel plots and Egger's test. We conducted meta-regression analysis to explore heterogeneity in analyses. RESULTS: Ten studies were included in analyses. All studies were from Asia. Pooled rates (95% CI) for en bloc resection and complete resection were 94% (87%, 97%) and 72% (62%, 80%), respectively. The pooled rates (95% CI) for adverse events and local recurrence were 10% (5%, 17%) and 1.9% (0.9%, 4%), respectively. Most of the analyses were limited by substantial heterogeneity. On meta-regression analysis, the heterogeneity was explained by size of tumor and histology. Funnel plots and Egger's test showed no evidence of publication bias. CONCLUSIONS: This meta-analysis including studies from Asian countries demonstrated that ESD is an efficacious and safe option in the management of superficial pharyngeal cancers. More studies and studies from Western countries are needed to further validate these findings.

Efficacy of empiric esophageal dilation in patients with non-obstructive dysphagia: systematic review and meta-analysis.

BACKGROUND AND AIMS: Empiric esophageal dilation is frequently performed for non-obstructive dysphagia. Studies evaluating its efficacy have reported conflicting results. In this meta-analysis, we have evaluated the efficacy of esophageal dilation in the management of non-obstructive dysphagia. METHODS: We reviewed several databases from inception to 26 May 2021 to identify randomized controlled trials (RCTs) and observational studies that evaluated the role of empiric esophageal dilation for non-obstructive dysphagia. Our outcomes of interest were clinical success (improvement in dysphagia after dilation) and difference in post-operative dysphagia score between groups. For categorical variables, we calculated pooled odds ratios (OR) with 95% confidence intervals (CI); for continuous variables, we calculated standardized mean difference (SMD) with 95% CI. Data were analyzed using a random effects model. We used GRADE framework to ascertain the quality of evidence. RESULTS: We included 4 studies (3 RCTs and one observational) with 243 patients; there were 133 treated with empiric dilation and 110 controls. We found no significant difference in clinical success (OR (95% CI) 1.91 (0.89, 4.08)) or post-procedure dysphagia score between groups (SMD (95% CI) 0.38 (-0.37, 1.14)). Our findings remained consistent on subgroup analysis including RCTs only. Quality of evidence ranged from low to very low based on GRADE framework. CONCLUSIONS: Our meta-analysis does not support the use of empiric esophageal dilation in patients with non-obstructive dysphagia. More studies are required to confirm these findings.

Efficacy and safety of supplemental intravenous lidocaine for sedation in gastrointestinal endoscopic procedures: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Some studies have shown that intravenous (IV) lidocaine reduces the dose requirement of propofol in GI endoscopic procedures. We conducted this study to evaluate the efficacy and safety of the combination of IV lidocaine and propofol compared with propofol alone in GI endoscopic procedures. METHODS: We reviewed several databases from inception to October 13, 2020, to identify randomized controlled trials (RCTs) that compared the role of IV propofol and lidocaine with IV propofol plus placebo for sedation in endoscopic procedures. Our outcomes of interest were the differences in total dose of propofol administered, procedure time, and intraoperative adverse events. For categorical variables, we calculated pooled risk ratios with 95% confidence intervals (CI); for continuous variables, we calculated standardized mean difference (SMD) with 95% CI. Data were analyzed using a random effect model. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework to ascertain the quality of evidence. RESULTS: We included 5 randomized controlled trials with 318 patients. We found that the total dose of propofol administered was significantly lower in the lidocaine group than the control group (SMD, -0.76; 95% CI, -1.09 to -0.42). We found no significant difference in procedure time (SMD, 0.16; 95% CI, -0.26 to 0.57) or adverse events (risk ratio, 0.60; 95% CI, 0.35-1.03) between the groups. There was moderate to substantial heterogeneity in the data. Quality of evidence based on the GRADE framework ranged from low to moderate. CONCLUSIONS: Moderate quality of evidence suggests that IV lidocaine decreases the dose of propofol administered for GI endoscopic procedures.

Role of routine second-look endoscopy in patients with acute peptic ulcer bleeding: meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Studies evaluating the role of routine second-look endoscopy in patients with acute upper GI bleed because of peptic ulcer disease (PUD) have reported conflicting results. This meta-analysis evaluates the usefulness of routine second-look endoscopy in these patients. METHODS: We reviewed several databases from inception to September 15, 2020 to identify randomized controlled trials (RCTs) that compared routine second-look endoscopy with no planned second-look endoscopy in patients with acute upper GI bleed because of PUD. Our outcomes of interest were recurrent bleeding, mortality, need for surgery, and mean number of units of blood transfused. For categorical variables, we calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs); for continuous variables, we calculated standardized mean difference with 95% CIs. Data were analyzed using a random effects model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to ascertain the quality of evidence. RESULTS: We included 9 RTCs comprising 1452 patients; 726 patients underwent planned/routine second-look endoscopy and 726 did not. We found no significant difference in recurrent bleeding (RR, .79; 95% CI, .51-1.23), need for surgery (RR, .58; 95% CI, .29-1.15), mortality (RR, .69; 95% CI, .33-1.45), or mean number of units of blood transfused (standardized mean difference, -.06; 95% CI, -.19 to .07). Quality of evidence ranged from low to moderate based on the GRADE framework. CONCLUSIONS: Single endoscopy with complete endoscopic hemostasis is not inferior to routine second-look endoscopy in reducing the risk of recurrent bleeding, mortality, or need for surgery in patients with acute upper GI bleed because of PUD.

Efficacy and safety of tranexamic acid in acute upper gastrointestinal bleeding: meta-analysis of randomised controlled trials.

BACKGROUND: Studies evaluating the role of tranexamic acid in acute upper GI bleeding (UGIB) have reported conflicting results. In this systematic review, we have evaluated the efficacy and safety of tranexamic acid in UGIB. METHODS: We searched several databases from inception to June 6, 2020 to identify randomised controlled trials (RCTs) that compared tranexamic acid and placebo in UGIB. Our outcomes of interest were mortality, rebleeding, all thromboembolic events, venous thromboembolic events, need for transfusion, endoscopic intervention and surgery. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using fixed effect model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess the certainty of evidence. RESULTS: We included 12 RCTs comprising 14,100 patients. We found no significant difference in mortality, pooled RR (95% CI) 0.87 (0.74-1.01), rebleeding, pooled RR (95% CI) 0.90 (0.79-1.02), need for surgery, pooled RR (95% CI) 0.86 (0.73-1.02), need for transfusion, pooled RR (95% CI) 1.00 (0.99-1.01) or thromboembolic events, RR (95% CI) 1.16 (0.87-1.56) between treatments. We found an increased risk of venous thromboembolic events with tranexamic acid, pooled RR (95% CI) 1.94 (1.23-3.05). Certainty of evidence based on the GRADE framework for the different outcomes ranged from low to very low. CONCLUSIONS: Tranexamic acid does not improve outcomes in UGIB and may increase the risk of venous thromboembolic events.

Topical tacrolimus for the treatment of secondary lymphedema.

Secondary lymphedema, a life-long complication of cancer treatment, currently has no cure. Lymphedema patients have decreased quality of life and recurrent infections with treatments limited to palliative measures. Accumulating evidence indicates that T cells play a key role in the pathology of lymphedema by promoting tissue fibrosis and inhibiting lymphangiogenesis. Here using mouse models, we show that topical therapy with tacrolimus, an anti-T-cell immunosuppressive drug, is highly effective in preventing lymphedema development and treating established lymphedema. This intervention markedly decreases swelling, T-cell infiltration and tissue fibrosis while significantly increasing formation of lymphatic collaterals with minimal systemic absorption. Animals treated with tacrolimus have markedly improved lymphatic function with increased collecting vessel contraction frequency and decreased dermal backflow. These results have profound implications for lymphedema treatment as topical tacrolimus is FDA-approved for other chronic skin conditions and has an established record of safety and tolerability.

Inhibition of Inflammation and iNOS Improves Lymphatic Function in Obesity.

Although recent studies have shown that obesity decreases lymphatic function, the cellular mechanisms regulating this response remain unknown. In the current study, we show that obesity results in perilymphatic accumulation of inflammatory cells and that local inhibition of this response with topical tacrolimus, an inhibitor of T cell differentiation, increases lymphatic vessel density, decreases perilymphatic iNOS expression, increases lymphatic vessel pumping frequency, and restores lymphatic clearance of interstitial fluid to normal levels. Although treatment of obese mice with 1400W, a selective inhibitor of iNOS, also improved lymphatic collecting vessel contractile function, it did not completely reverse lymphatic defects. Mice deficient in CD4(+) cells fed a high fat diet also gained weight relative to controls but were protected from lymphatic dysfunction. Taken together, our findings suggest that obesity-mediated lymphatic dysfunction is regulated by perilymphatic accumulation of inflammatory cells and that T cell inflammatory responses are necessary to initiate this effect.

On-chip open microfluidic devices for chemotaxis studies.

Microfluidic devices can provide unique control over both the chemoattractant gradient and the migration environment of the cells. Our work incorporates laser-machined micro and nanofluidic channels into bulk fused silica and cover slip-sized silica wafers. We have designed "open" chemotaxis devices that produce passive chemoattractant gradients without an external micropipette system. Since the migration area is unobstructed, cells can be easily loaded and strategically placed into the devices with a standard micropipette. The reusable monolithic glass devices have integral ports that can generate multiple gradients in a single experiment. We also used cover slip microfluidics for chemotaxis assays. Passive gradients elicited from these cover slips could be readily adapted for high throughput chemotaxis assays.We have also demonstrated for the first time that cells can be recruited into cover slip ports eliciting passive chemoattractant gradients. This proves, in principle, that intravital cover slip configurations could deliver controlled amounts of drugs, chemicals, or pathogens as well as recruit cells for proteomic or histological analysis in living animals while under microscopic observation. Intravital cover slip fluidics will create a new paradigm for in vivo observation of biological processes.

Open access microfluidic device for the study of cell migration during chemotaxis.

Cells sense and interpret chemical gradients, and respond by localized responses that lead to directed migration. An open microfluidic device (OMD) was developed to provide quantitative information on both the gradient and morphological changes that occurred as cells crawled through various microfabricated channels. This device overcame problems that many current devices have been plagued with, such as complicated cell loading, media evaporation and channel blockage by air bubbles. We used a micropipette to set up stable gradients formed by passive diffusion and thus avoided confounding cellular responses produced by shear forces. Two versions of the OMD are reported here: one device that has channels with widths of 6, 8, 10 and 12 µm, while the other has two large 100 µm channels to minimize cellular interaction with lateral walls. These experiments compared the migration rates and qualitative behavior of Dictyostelium discoideum cells responding to measurable cAMP and folic acid gradients in small and large channels. We report on the influence that polarity has on a cell's ability to migrate when confined in a channel. Polarized cells that migrated to cAMP were significantly faster than the unpolarized cells that crawled toward folic acid. Unpolarized cells in wide channels often strayed off course, yet migrated faster than unpolarized cells in confined channels. Cells in channels farthest from the micropipette migrated through the channels at rates similar to cells in channels with higher concentrations, suggesting that cell speed was independent of mean concentration. Lastly, it was found that the polarized cells could easily change migration direction even when only the leading edge of the cell was exposed to a lateral gradient.