Bone morphogenetic protein 4 (BMP4) signaling is involved in the development of Barrett's esophagus (BE), a precursor of esophageal adenocarcinoma (EAC). In various cancers, BMP4 has been found to ...induce epithelial-mesenchymal transition (EMT) but its function in the development of EAC is currently unclear.
To investigate the expression of BMP4 and several members of the BMP4 pathway in EAC. Additionally, to determine the effect of BMP4 signaling in a human Barrett's esophagus (BAR-T) and adenocarcinoma (OE33) cell line.
Expression of BMP4, its downstream target ID2 and members of the BMP4 pathway were determined by Q-RT-PCR, immunohistochemistry and Western blot analysis using biopsy samples from EAC patients. BAR-T and OE33 cells were incubated with BMP4 or the BMP4 antagonist, Noggin, and cell viability and migration assays were performed. In addition, expression of factors associated with EMT (SNAIL2, CDH1, CDH2 and Vimentin) was evaluated by Q-RT-PCR and Western blot analysis.
Compared to squamous epithelium (SQ), BMP4 expression was significantly upregulated in EAC and BE. In addition, the expression of ID2 was significantly upregulated in EAC and BE compared to SQ. Western blot analysis confirmed our results, showing an upregulated expression of BMP4 and ID2 in both BE and EAC. In addition, more phosphorylation of SMAD1/5/8 was observed. BMP4 incubation inhibited cell viability, but induced cell migration in both BAR-T and OE33 cells. Upon BMP4 incubation, SNAIL2 expression was significantly upregulated in BAR-T and OE33 cells while CDH1 expression was significantly downregulated. These results were confirmed by Western blot analysis.
Our results indicate active BMP4 signaling in BE and EAC and suggest that this results in an invasive phenotype by inducing an EMT-like response through upregulation of SNAIL2 and subsequent downregulation of CDH1.
•Long-term oncologic outcomes seem similar when emergency surgery is compared to stent placement.•Permanent stoma rate is lower when patients are initially treated with SEMS as bridge to ...surgery.•Sensitivity analysis shows opposite outcomes, with a trend towards worse survival in the SEMS group when only RCTs are taken into account.•Adequate experience with SEMS placement seems of importance for long-term oncologic outcomes.
This meta-analysis aims to determine the long-term oncological outcomes of SEMS as bridge to surgery (BTS) versus emergency surgery (ES). A systematic search without restrictions was conducted, and all studies comparing SEMS with ES reporting on long-term outcomes were included. Methodological quality was assessed using the appropriate tools. Twenty-one comparative studies were selected, reporting on 1919 patients. Meta-analysis showed no significant difference regarding three- and five-year overall survival (OR = 0·85 (0·68-1·08) and OR = 1·04 (0·68-1·57), respectively), disease-free survival (OR = 0·96 (0·73-1·26) and OR = 0·86 (0·54-1·36), respectively) and local recurrence rate (OR = 1·32 (0·78-2·23)). Permanent stomas were significantly lower in the SEMS group (OR 0·49 (0·32-0·74)). Sensitivity analysis on three-year survival showed opposite outcomes, with a trend towards worse survival in the SEMS group when only RCTs are taken into account. In conclusion, when in experienced hands, SEMS placement as BTS seems oncologically safe.
With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. ...We aimed to explore the evolution of IBD-related costs over two years of follow-up.
In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of €7,835 in CD and €3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02-3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61-13.86)).
BD-related costs remained stable over two years. However, the proportion of anti-TNF-related healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC.
Background and study aims:
A novel large-diameter, lumen-apposing, self-expanding metal stent with bilateral flanges was recently developed for endoscopic ultrasound (EUS)-guided transmural drainage ...of symptomatic pancreatic fluid collections (PFCs). The aim of this study was to evaluate the efficacy and safety of this stent in a large cohort.
Patients and methods:
Patients with a PFC undergoing EUS-guided drainage with this novel stent were prospectively enrolled in this multicenter cohort study.
Results:
There were 61 patients: 46 patients (75 %) with walled-off necrosis (WON) and 15 (25 %) with a pancreatic pseudocyst. Stent placement was technically successful in 60 patients (98 %, 95 %CI 95 % – 100 %). Clinical success, defined as resolution of clinical symptoms in combination with a decrease in the PFC size to ≤ 2 cm on imaging, was achieved in 93 % of patients with a pancreatic pseudocyst (95 %CI 77 % – 100 %) and in 81 % of patients with WON (95 %CI 69 % – 94 %). Treatment failure occurred in nine patients (16 %, 95 %CI 6 % – 26 %), including four patients who required surgical intervention. Stent removal was performed in 82 % of patients after a median of 32 days (range 2 – 178) and was rated as easy in all but one patient. In 10 patients, endoscopic stent removal was not performed because of stent migration (n = 3), stent dislodgement during necrosectomy (n = 3), stent removal during surgery (n = 2), or refusal by the patient (n = 2). In total, five major complications were reported (9 %, 95 %CI 2 % – 16 %), including PFC infection (n = 4) and perforation (n = 1).
Conclusion:
EUS-guided drainage using this novel stent is feasible and the clinical results obtained are promising with a low major complication rate.
IMPORTANCE: Bridge to elective surgery using self-expandable metal stent (SEMS) placement is a debated alternative to emergency resection for patients with left-sided obstructive colon cancer because ...of oncologic concerns. A decompressing stoma (DS) might be a valid alternative, but relevant studies are scarce. OBJECTIVE: To compare DS with SEMS as a bridge to surgery for nonlocally advanced left-sided obstructive colon cancer using propensity score matching. DESIGN, SETTING, AND PARTICIPANTS: This national, population-based cohort study was performed at 75 of 77 hospitals in the Netherlands. A total of 4216 patients with left-sided obstructive colon cancer treated from January 1, 2009, to December 31, 2016, were identified from the Dutch Colorectal Audit and 3153 patients were studied. Additional procedural and intermediate-term outcome data were retrospectively collected from individual patient files, resulting in a median follow-up of 32 months (interquartile range, 15-57 months). Data were analyzed from April 7 to October 28, 2019. EXPOSURES: Decompressing stoma vs SEMS as a bridge to surgery. MAIN OUTCOMES AND MEASURES: Primary anastomosis rate, postresection presence of a stoma, complications, additional interventions, permanent stoma, locoregional recurrence, disease-free survival, and overall survival. Propensity score matching was performed according to age, sex, body mass index, American Society of Anesthesiologists score, prior abdominal surgery, tumor location, pN stage, cM stage, length of stenosis, and year of resection. RESULTS: A total of 3153 of the eligible 4216 patients were included in the study (mean SD age, 69.7 11.8 years; 1741 55.2% male); after exclusions, 443 patients underwent bridge to surgery (240 undergoing DS and 203 undergoing SEMS). Propensity score matching led to 2 groups of 121 patients each. Patients undergoing SEMS had more primary anastomoses (104 of 121 86.0% vs 90 of 120 75.0%, P = .02), more postresection stomas (81 of 121 66.9% vs 34 of 117 29.1%, P < .001), fewer major complications (7 of 121 5.8% vs 18 of 118 15.3%, P = .02), and more subsequent interventions, including stoma reversal (65 of 113 57.5% vs 33 of 117 28.2%, P < .001). After DS and SEMS, the 3-year locoregional recurrence rates were 11.7% for DS and 18.8% for SEMS (hazard ratio HR, 0.62; 95% CI, 0.30-1.28; P = .20), the 3-year disease-free survival rates were 64.0% for DS and 56.9% for SEMS (HR, 0.90; 95% CI, 0.61-1.33; P = .60), and the 3-year overall survival rates were 78.0% for DS and 71.8% for SEMS (HR, 0.77; 95% CI, 0.48-1.22; P = .26). CONCLUSIONS AND RELEVANCE: The findings suggest that DS as bridge to resection of left-sided obstructive colon cancer is associated with advantages and disadvantages compared with SEMS, with similar intermediate-term oncologic outcomes. The existing equipoise indicates the need for a randomized clinical trial that compares the 2 bridging techniques.
Definitive chemoradiation is the recommended treatment for locally advanced, irresectable oesophageal cancer and a valid alternative to neoadjuvant chemoradiotherapy (CRT) with surgery in oesophageal ...squamous cell cancer (OSCC) patients. In case of locoregional recurrence, salvage treatment can be considered in fit and resectable patients. Salvage surgery is a valid option but associated with significant morbidity. Therefore, for tumors confined to the mucosa or submucosal layers endoscopic resection is a good and less-invasive alternative. Over the last decade several case-series have demonstrated a high technical success rate of endoscopic treatment after definitive CRT. In this review we summarize the clinical outcomes and challenges of endoscopic treatment of early recurrence after definitive CRT in oesophageal cancer.
Abstract Background and Aims There is little evidence that structures targeted during EUS-guided celiac ganglia neurolysis (EUS-CGN) are celiac ganglia and that selective ethanol injection into ...ganglia is feasible. We aimed to visualize celiac ganglia, confirm that these structures are ganglia, and visualize ethanol spread after EUS-CGN and EUS-guided celiac plexus neurolysis (EUS-CPN). Methods First, celiac ganglia were sought during 97 consecutive EUS procedures. Second, ganglia were identified in a prosected human cadaver by placing a linear echo-endoscope next to the celiac trunk and the underlying tissue was removed for histology. Finally, various EUS-CGN and EUS-CPN techniques were performed in human cadavers; EUS-CGN was performed with 1 mL ethanol in one ganglion, 1 mL per ganglion (both “low volume”), and 4 mL per ganglion (“high volume”). EUS-CPN was performed with a central (20 mL) and a bilateral (2*10 mL) approach. Transverse sections (75 μm) were obtained and photographed to visualize the spread of ethanol. Results 204 ganglia were detected in 83 patients. Mean size of the long axis was 8.1 (±7.4) mm. Histology of the removed region in the cadaver showed only nerve cell bodies. After low volume EUS-CGN in cadavers, ethanol spread well beyond the targeted ganglion. After high-volume EUS-CGN in cadavers, a larger ethanol spread was seen, which also reached unidentified ganglia; the spread was comparable with spread after EUS-CPN. Conclusions Specific EUS-CGN is not feasible because ethanol spreads well beyond the targeted ganglion. Unidentified celiac ganglia are better reached with high-volume EUS-CGN, and this would likely result in a more thorough neurolysis. High-volume EUS-CGN should be preferred to low-volume EUS-CGN.
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