Flexible endoscopic treatment for Zenker's diverticulum: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Flexible endoscopic septum division (FESD) is a rapidly evolving technique for the treatment of Zenker's diverticulum (ZD). The aim was to perform a systematic review and meta-analysis of the literature focusing on FESD for ZD, including an in-depth evaluation of its efficacy, safety, and limitations. METHODS: A comprehensive literature search was completed to identify papers that examined the efficacy and safety of FESD for ZD. Demographic, clinical, and technical information was retrieved. Main outcomes were extracted, pooled, and analyzed. Heterogeneity among studies was assessed using the I(2) statistic. A random effect model was used as the pooling method in cases of high heterogeneity; otherwise the fixed effect model was applied. Meta-regression was also performed. Main outcomes such as rates of success, adverse events, and recurrences were evaluated. RESULTS: Twenty studies with a total of 813 patients were selected. The pooled success, adverse events, and recurrence rates were 91% (95% confidence interval [CI], 86%-95%; I(2) = 69.5%), 11.3% (95% CI, 8%-16%; I(2) = 64%), and 11% (95% CI, 8%-15%; I(2) = 38.4%), respectively. Substantial heterogeneity across studies was found. However, for success rates, excluding 3 studies reduced heterogeneity to non-significant rates [I(2) = 25.6%; P = .154]. Adverse event rates decreased with larger samples (coefficient, -0.0123; 95% CI, -0.03 to -0.003; P = .017), whereas recurrence rates increased (coefficient, 0.006; 95% CI, -0.0010 to 0.0125; P = .093). Year of publication was negatively associated with success rate, whereas the opposite pattern was found for recurrence rates. CONCLUSIONS: FESD is a feasible, safe, and effective treatment for symptomatic ZD, with low adverse event and recurrence rates.

Adherence to WCRF/AICR lifestyle recommendations for cancer prevention and the risk of Barrett's esophagus onset and evolution to esophageal adenocarcinoma: results from a pilot study in a high-risk population.

PURPOSE: While adherence to the World Cancer Research Fund (WCRF) guidelines on lifestyle and cancer was recently proven to be associated with an increased risk of esophageal cancer, no investigation has yet been carried out on its role on Barrett's esophagus (BE) development and its progression to esophageal adenocarcinoma (EAC). The primary aim of this study was to evaluate the role of adherence to WCRF lifestyle recommendations in BE onset and progression. The secondary aim was to investigate the association between disease progression and specific aspects of diet and lifestyle. METHODS: Established risk factors for BE and EAC development and adherence to WCRF guidelines were assessed in 107 consecutive patients undergoing an upper gastrointestinal endoscopy for symptoms suggesting gastroesophageal reflux (GERD) and a suspected diagnosis of BE/dysplasia on BE. Patients were divided according to histology: those with GERD without metaplasia, with non-dysplastic BE, with low-grade dysplasia, with high-grade dysplasia or with early EAC. The four groups were expressed as an ordered categorical variable of disease progression. An ordered logit model was estimated to identify the independent predictors of disease progression. RESULTS: Adherence to WCRF guidelines was identified as independent protective factor (OR 0.51, 95 % CI 0.37-0.67) of disease progression. Disease progression was associated with reduced adherence to guidelines on physical activity (from 48.2 to 5.3 %, p = 0.001), sedentary habits (from 33.3 to 0 %, p = 0.03), fruit consumption (from 37.0 to 5.6 %, p = 0.02) and processed meat consumption (from 51.9 to 10.5 %, p = 0.002). CONCLUSION: Adherence to WCRF guidelines has a protective factor in BE onset and its evolution to EAC.

The role of flexible endotherapy for the treatment of recurrent Zenker's diverticula after surgery and endoscopic stapling.

BACKGROUND: Currently there are three main treatment options for Zenker's diverticulum (ZD): surgery, rigid endoscopy and flexible endoscopy. After primary success, recurrence can be as high as 19 % for surgery, 12.8 % for rigid endoscopy and 20 % for flexible endoscopy. Flexible endoscopy may represent an ideal treatment option for recurring ZD. The aims of this paper are to evaluate the efficacy and safety of flexible endotherapy for recurring ZD after surgery and/or endoscopic stapling and to compare the treatment outcome between naive and recurring patients. METHODS: Data on patients that underwent flexible endotherapy for ZD between January 2010 and January 2015 were collected. Patients were divided into those with recurrences after surgery and/or endoscopic stapling and those who did not have previous treatments. Dysphagia, regurgitation, and respiratory symptom severity before the procedure were graded. The outcome parameters were: complications, symptom improvement after the first treatment, number of treatment sessions, rate of complete remission and relapses. These parameters were then compared between patients groups. RESULTS: Twenty-five recurring patients were included. Treatment was carried out successfully in all patients. Two adverse events occurred; they were successfully managed conservatively. After the first treatment, there was a significant reduction in dysphagia, regurgitation and respiratory symptoms scores. The median number of treatments was 1 (IQR 0.25, range 1-3): symptom remission was achieved in 84 % patients and partial improvement in 16 %. Relapsing symptoms occurred in 20 % patients; they were successfully managed with an additional treatment session. Results were compared with data on 34 consecutive naive patients treated within the same time span; no differences of the outcome parameters were revealed. CONCLUSIONS: Flexible endotherapy for ZD recurrences after surgery and endoscopic stapling appears to be safe and effective, and its efficacy and safety profile seems to be comparable between recurring and naive patients.

Feasibility, efficacy and safety of stent insertion as a palliative treatment for malignant strictures in the cervical segment of the esophagus and the hypopharynx.

BACKGROUND: 50% of esophageal cancers are inoperable at the time of diagnosis, and around 15% involve the cervical esophagus. The hypopharynx is often involved by these malignancies as well. Palliation of cervical esophageal malignancies through stent insertion is considered limited due to technical challenges, poor patient tolerance and high complication rate. The aim of this study is to review our experience with stent insertion in the cervical segment of the esophagus and to evaluate outcome differences between stent insertions involving or sparing the hypopharynx. METHODS: We retrospectively reviewed data on 69 consecutive patients that underwent stent insertion for malignant strictures in the cervical esophagus at our Department. Patients were divided according to involvement or sparing of the lower hypopharynx. Dysphagia severity was measured with the Mellow-Pinkas scale before the procedure and on monthly follow-ups. Any complication and its management were recorded. The main outcome parameters were as follows: dysphagia improvement, rate of successful dysphagia palliation (i.e., a reduction of the score to 0 or 1 after stent insertion) and complication rate. Multivariable analysis was carried out to assess the influence of patient- and procedure-related factors on the outcome of the procedure. RESULTS: Stent insertion was achieved in 100% patients. At 4 weeks, dysphagia score improved from a median of 3-0 (p < 0.001), and a successful palliation was achieved in 76.8% patients. The 30-day mortality rate was 14.5%. Successful palliation throughout the follow-up was achieved in 72.9% of the surviving patients. Complications occurred in 31.9% patients. Dilation before stent insertion was associated with a less efficient short-term dysphagia palliation (OR 6.77, 95% CI 1.46-31.29, p = 0.02). CONCLUSIONS: Stent insertion is a safe and effective palliative treatment for malignant cervical esophageal strictures. Results are consistent even in patients with hypopharyngeal lesions. Dilation should be avoided before stent insertion.

Flexible endoscopic treatment for Zenker's diverticulum with the SB Knife. Preliminary results from a single-center experience.

BACKGROUND AND AIM: Flexible endoscopic septum division is becoming a prominent treatment option for Zenker's diverticulum (ZD). Over the years, various techniques have been developed and many cutting tools have been tested with varying results. We report our experience with a recently designed, monopolar, rotating, scissor-shaped device (SB Knife). METHODS: Data on 31 consecutive patients that underwent flexible endoscopic treatment for ZD with the use of the SB Knife were retrieved. Dysphagia, regurgitation, and respiratory symptom severity before the procedure were graded. Procedure duration, rate of complications, symptom changes after the procedure and rate of relapsing patients during follow up were recorded. RESULTS: The procedure was carried out successfully in all patients. Median procedure time was 14 min. One case of late-onset bleeding developed 1 week after the procedure, and was managed endoscopically. A significant symptom improvement was achieved (dysphagia: median score <3, median score >0, P < 0.001; regurgitation: median score <2, median score >0, P < 0.001; respiratory symptoms: median score <2, median score >0, P = 0.009). Two patients had mild relapsing symptoms, respectively, after 4 and 9 months from the procedure but refused further treatment. CONCLUSIONS: Endoscopic treatment of ZD using this new device is safe and efficient at short term follow up. No perforations were observed and there was a substantial reduction of symptoms after the treatment. Larger studies are needed to fully assess advantages of this new device for endoscopic treatment of ZD.

Insulin promotes HER2 signaling activation during Barrett's Esophagus carcinogenesis.

BACKGROUND: Insulin-resistance and hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion Barrett's Esophagus (BE). HER2 activation has also a pivotal role in EAC carcinogenesis but no data correlate these two phenomena in this disease context. AIMS: To investigate the role of hyperinsulinemia in BE-dysplasia-adenocarcinoma sequence and the possible relationship between insulin-mediated and HER2 signaling in EAC development. METHODS: Serum insulin, C-peptide, IGF1, glucagon, IL-6, TNF-alpha, leptin, adiponectin and Insulin-Resistance-index were analyzed in 19 patients with gastro-esophageal reflux disease, 51 with BE, 24 with dysplastic-BE and 14 with EAC. Insulin/IGF1/HER2 pathways were analyzed in esophageal biopsies using Luminex® Technology. Insulin effect was also evaluated in EAC-derived OE19 cells. Data were analyzed by Fisher's exact test, Kruskal-Wallis test, Mann-Whitney U-test, Cuzick's test and Spearman correlation coefficient calculation. RESULTS: Insulin-Resistance-index, insulin and C-peptide levels increased along with disease progression (p=0.019, p=0.002, p<0.0001, respectively) and correlated with HER2 expression and with downstream mediators phospho-Akt and phospho-mTOR in esophageal tissue. In vitro, insulin was also able to induce cell proliferation through HER2 activation. CONCLUSIONS: Our data pinpoint a possible role of hyperinsulinemia in the Barrett's Esophagus metaplasia-dysplasia-adenocarcinoma sequence through HER2 activation in esophageal epithelial cells.

Spontaneous bleeding or thrombosis in cirrhosis: What should be feared the most?

The more modern and accurate concept of a rebalanced hemostatic status in cirrhosis is slowly replacing the traditional belief of patients with cirrhosis being "auto-anticoagulated", prone only to bleeding complications, and protected from thrombotic events. With greater attention to clinical thrombotic events, their impact on the natural history of cirrhosis, and with the emergence and increased use of point-of-care and global assays, it is now understood that cirrhosis results in profound hemostatic alterations that can lead to thrombosis as well as to bleeding complications. Although many clinical decisions are still based on traditional coagulation parameters such as prothrombin (PT), PT, and international normalized ratio, it is increasingly recognized that these tests do not adequately predict the risk of bleeding, nor they should guide pre-emptive interventions. Moreover, altered coagulation tests should not be considered as a contraindication to the use of anticoagulation, although this therapeutic or prophylactic approach is not at present routinely undertaken. Gastroesophageal variceal bleeding continues to be one of the most feared and deadly complications of cirrhosis and portal hypertension, but great progresses have been made in prevention and treatment strategies. Other bleeding sites that are frequently part of end-stage liver disease are similar to clinical manifestations of thrombocytopenia, with gum bleeding and epistaxis being very common but fortunately only rarely a cause of life-threatening bleeding. On the contrary, manifestations of coagulation factor deficiencies like soft tissue bleeding and hemartrosis are rare in patients with cirrhosis. As far as thrombotic complications are concerned, portal vein thrombosis is the most common event in patients with cirrhosis, but venous thromboembolism is not infrequent, and results in important morbidity and mortality in patients with cirrhosis, especially those with decompensated disease. Future studies and the more widespread use of point-of-care tests in evaluating hemostasis will aid the clinician in decision making when facing the patient with bleeding or with thrombotic complications, with both ends of a continuum being potentially fatal.

Solvent structuring and its effect on the polymer structure and processability: the case of water-acetone poly-ε-caprolactone mixtures.

One of the most common processes to produce polymer nanoparticles is the solvent-displacement method, in which the polymer is dissolved in a "good" solvent and the solution is then mixed with an "anti-solvent". The polymer processability is therefore determined by its structural and transport properties in solutions of the pure solvents and at the intermediate compositions. In this work, we focus on poly-ε-caprolactone (PCL) which is a biocompatible polymer that finds widespread application in the pharmaceutical and biomedical fields, performing full atomistic molecular dynamics simulations of one PCL chain of different molecular weight in a solution of pure acetone (good solvent), of pure water (antisolvent), and their mixtures. Our simulations reveal that the nanostructuring of one of the solvents in the mixture leads to an unexpected identical polymer structure irrespectively of the concentration of the two solvents. In particular, although in pure solvents the behavior of the polymer is, as expected, very different, at intermediate compositions, the PCL chain shows properties very similar to those found in pure acetone as a result of the clustering of the acetone molecules in the vicinity of the polymer chain. We derive an analytical expression to predict the polymer structural properties in solution at different solvent compositions and show that the solvent clustering affects in an unpredictable way the polymer diffusion coefficient. These findings have important consequences on the optimization of the nanoparticle production process and in the implementation of continuum modeling techniques to model it.