Background: Whereas the role of neoadjuvant radiotherapy in rectal cancer is well-established, the ability to discriminate between radioresistant and radiosensitive tumors before starting treatment is still a crucial unmet need. Here we aimed to develop an in vivo test to directly challenge living cancer cells to radiotherapy, using zebrafish xenografts. Methods: We generated zebrafish xenografts using colorectal cancer cell lines and patient biopsies without in vitro passaging, and developed a fast radiotherapy protocol consisting of a single dose of 25 Gy. As readouts of the impact of radiotherapy we analyzed proliferation, apoptosis, tumor size and DNA damage. Findings: By directly comparing isogenic cells that only differ in the KRAS G13D allele, we show that it is possible to distinguish radiosensitive from radioresistant tumors in zebrafish xenografts, even in polyclonal tumors, in just 4 days. Most importantly, we performed proof-of-concept experiments using primary rectum biopsies, where clinical response to neoadjuvant chemoradiotherapy correlates with induction of apoptosis in their matching zebrafish Patient-Derived Xenografts-Avatars. Interpretation: Our work opens the possibility to predict tumor responses to radiotherapy using the zebrafish Avatar model, sparing valuable therapeutic time and unnecessary toxicity.
BackgroundRefractory benign esophageal strictures (RBESs) have been treated with the temporary placement of different self-expanding stents with conflicting results. We compared the clinical effectiveness of 3 types of stents: self-expanding plastic stents (SEPSs), biodegradable stents, and fully covered self-expanding metal stents (FCSEMSs), for the treatment of RBES.MethodsThis study prospectively evaluated 3 groups of 30 consecutive patients with RBESs who underwent temporary placement of either SEPSs (12 weeks, n = 10), biodegradable stents (n = 10) or FCSEMSs (12 weeks, n = 10). Data were collected to analyze the technical success and clinical outcome of the stents as evaluated by recurrent dysphagia, complications and reinterventions.ResultsStent implantation was technically successful in all patients. Migration occurred in 11 patients: 6 (60%) in the SEPS group, 2 (20%) in the biodegradable group and 3 (30%) in the FCSEMS group (P = 0.16). A total of 8/30 patients (26.6%) were dysphagia-free after the end of follow-up: 1 (10%) in the SEPS group, 3 (30%) in the biodegradable group and 4 (40%) in the FCSEMS group (P = 0.27). More reinterventions were required in the SEPS group (n = 24) than in the biodegradable group (n = 13) or the FCSEMS group (n = 13) (P = 0.24). Multivariate analysis showed that stricture length was significantly associated with higher recurrence rates after temporary stent placement (HR = 1.37; 95% CI = 1.08-1.75; P = 0.011).ConclusionsTemporary placement of a biodegradable stent or of a FCSEMS in patients with RBES may lead to long-term relief of dysphagia in 30 and 40% of patients, respectively. The use of SEPSs seems least preferable, as they are associated with frequent stent migration, more reinterventions and few cases of long-term improvement. Additionally, longer strictures were associated with a higher risk of recurrence.
This large series of patients undergoing endoscopic pancreatic sphincterotomy provides further evidence that both patient characteristics and technical factors modify the risk profile for post-ERCP pancreatitis. In addition to providing further definition of which patients are at risk, it also suggests that pancreatic duct drainage is an independently significant protective maneuver.
Postcholecystectomy leaks may occur in 0.3–2.7% of patients. Bile leaks associated with laparoscopy are often more complex and difficult to treat than those occurring after open cholecystectomy. Furthermore, their incidence has remained unchanged despite improvements in laparoscopic training and technological developments. The management of biliary leaks has evolved from surgery into a minimally invasive endoscopic procedural approach, namely, endoscopic retrograde cholangiopancreatography (ERCP), which decreases or eliminates the pressure gradient between the bile duct and the duodenum, thus creating a preferential transpapillary bile flow and allowing the leak to seal. For simple leaks, the success rate of endotherapy is remarkably high. However, there are more severe and complex leaks that require multiple endoscopic interventions, and clear strategies for endoscopic treatment have not emerged. Therefore, there is still some debate regarding the optimal time point at which to intervene, which technique to use (sphincterotomy alone or in association with the placement of stents, whether metallic or plastic stents should be used, and, if plastic stents are used, whether they should be single or multiple), how long the stents should remain in place, and when to consider treatment failure. Here, we review the types and classification of postoperative biliary injuries, particularly leaks, as well as the evidence for endoscopic treatment of the latter.
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