Underwater EMR versus conventional EMR for superficial non-ampullary duodenal epithelial tumors in the Western setting.

BACKGROUND AND AIMS: Conventional endoscopic mucosal resection (C-EMR) is established as the primary treatment modality for superficial non-ampullary duodenal epithelial tumors (SNADETs) but recently underwater EMR (U-EMR) emerged as a potential alternative. The majority of previous studies focused on Asian populations and small lesions (≤20 mm). We aimed to compare the efficacy and outcomes of U-EMR versus C-EMR for SNADETs in a Western setting. METHODS: This was a retrospective multinational study from 10 European centers that performed both C-EMR and U-EMR between January 2013 and July 2023. The main outcomes were the technical success, procedure-related adverse events (AEs), and the residual/recurrent adenoma (RRA) rate, evaluated on a per-lesion basis. We assessed the association between the type of EMR and the occurrence of AEs or RRA using mixed-effects logistic regression models (propensity scores). Sensitivity analyses were performed for lesions ≤ or >20 mm. RESULTS: A total of 290 SNADETs submitted to endoscopic resection during the study period met the inclusion criteria and were analyzed (C-EMR n=201, 69.3%; U-EMR n=89, 30.7%). Overall technical success rate was 95.5% and comparable between groups. In logistic regression models, compared with U-EMR, C-EMR was associated with a significantly higher frequency of overall delayed AEs (OR 4.95; 95%CI=2.87-8.53), post-procedural bleeding (OR=7.92; 95%CI=3.95-15.89) and RRA (OR=3.66; 95%CI=2.49-5.37). Sensitivity analyses confirmed these results when solely considering either small (≤20 mm) or large (>20 mm) lesions. CONCLUSION: Compared with C-EMR, U-EMR was associated with a lower rate of overall AEs and RRA, regardless of lesion size. Our results confirm the possible role of U-EMR as an effective and safe technique in the management of SNADETs.

Investigating Predictive Factors of Suicidal Re-attempts in Adolescents and Young Adults After a First Suicide Attempt, a Prospective Cohort Study. Study Protocol of the SURAYA Project.

Introduction: Suicide is the fourth leading cause of death in youth. Previous suicide attempts are among the strongest predictors of future suicide re-attempt. However, the lack of data and understanding of suicidal re-attempt behaviors in this population makes suicide risk assessment complex and challenging in clinical practice. The primary objective of this study is to determine the rate of suicide re-attempts in youth admitted to the emergency department after a first suicide attempt. The secondary objectives are to explore the clinical, socio-demographic, and biological risk factors that may be associated with re-attempted suicide in adolescents and young adults. Methods: We have developed a single-center prospective and naturalistic study that will follow a cohort of 200 young people aged 16 to 25 years admitted for a first suicide attempt to the emergency department of Lyon, France. The primary outcome measure will be the incidence rate of new suicide attempts during 3 months of follow-up. Secondary outcomes to investigate predictors of suicide attempts will include several socio-demographic, clinical and biological assessments: blood and hair cortisol levels, plasma pro- and mature Brain-Derived Neurotrophic Factor (BDNF) isoforms proportion, previous infection with toxoplasma gondii, and C-Reactive Protein (CRP), orosomucoid, fibrinogen, interleukin (IL)-6 inflammatory markers. Discussion: To our knowledge, the present study is the first prospective study specifically designed to assess the risk of re-attempting suicide and to investigate the multidimensional predictive factors associated with re-attempting suicide in youth after a first suicide attempt. The results of this study will provide a unique opportunity to better understand whether youth are an at-risk group for suicide re-attempts, and will help us identify predictive factors of suicide re-attempt risk that could be translated into clinical settings to improve psychiatric care in this population. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03538197, first registered on 05/29/2018. The first patient was enrolled 05/22/2018.

Zenker's peroral endoscopic myotomy, or flexible or rigid septotomy for Zenker's diverticulum: a multicenter retrospective comparison.

BACKGROUND: Treatment of Zenker's diverticulum has evolved from open surgery to endoscopic techniques, including flexible and rigid endoscopic septotomy, and more recently, peroral endoscopic myotomy (Z-POEM). This study compared the effectiveness of flexible and rigid endoscopic septotomy with that of Z-POEM. METHODS: Consecutive patients who underwent endoscopic septotomy (flexible/rigid) or Z-POEM for Zenker's diverticulum between 1/2016 and 9/2019 were included. Primary outcomes were clinical success (decrease in Dakkak and Bennett dysphagia score to ≤ 1), clinical failure, and clinical recurrence. Secondary outcomes included technical success and rate/severity of adverse events. RESULTS: 245 patients (110 females, mean age 72.63 years, standard deviation [SD] 12.37 years) from 12 centers were included. Z-POEM was the most common management modality (n = 119), followed by flexible (n = 86) and rigid (n = 40) endoscopic septotomy. Clinical success was 92.7 % for Z-POEM, 89.2 % for rigid septotomy, and 86.7 % for flexible septotomy (P = 0.26). Symptoms recurred in 24 patients (15 Z-POEM during a mean follow-up of 282.04 [SD 300.48] days, 6 flexible, 3 rigid [P = 0.47]). Adverse events occurred in 30.0 % rigid septotomy patients, 16.8 % Z-POEM patients, and 2.3 % flexible septotomy patients (P < 0.05). CONCLUSIONS: There was no difference in outcomes between the three treatment approaches for symptomatic Zenker's diverticulum. Rigid endoscopic septotomy was associated with the highest rate of complications, while flexible endoscopic septotomy appeared to be the safest. Recurrence following Z-POEM was similar to flexible and rigid endoscopic septotomy. Prospective studies with long-term follow-up are required.

Safety and effectiveness of peroral endoscopic myotomy in patients on antiplatelet or anticoagulant therapy: an international multicenter case-control study.

BACKGROUND AND AIMS: The risk of bleeding and thromboembolic events in patients undergoing peroral endoscopic myotomy (POEM) who are receiving antithrombotic therapy is unknown. Our primary aim was to assess the safety of POEM in this patient subset. Secondary outcomes were rates of clinical success, GERD, and procedure-related outcomes. METHODS: This was an international, 1:1, case-control study performed at 10 centers using prospectively maintained databases. All consecutive patients who underwent POEM before November 2019 were considered for inclusion. Cases were patients on antiplatelet and/or anticoagulant therapy. Controls not receiving antithrombotics were matched for age and esophageal motility disorder. Primary outcomes were major bleeding and thromboembolic events on postprocedural day 30. RESULTS: Of 2895 patients who underwent POEM, 126 cases (103 on antiplatelets, 35 anticoagulants, 12 both) and 126 controls were enrolled. The rate of major bleeding was higher for the antithrombotics users (5.6% vs 0.8%, P = .03). Anticoagulants and clopidogrel were temporarily interrupted in all cases. Aspirin was continued in 40.5% of users without increasing the bleeding risk. One thromboembolic event occurred in each group (0.79%; P = 1.00). No POEM-related deaths were noted. Rates of clinical success (91.7% vs 96% in controls, P = .20), postprocedural GERD, and technical-related outcomes were similar in both groups. Antithrombotic management was heterogeneous, and guidelines were not adhered to in 23.8% of cases. CONCLUSIONS: POEM is safe and effective in patients receiving antithrombotic therapy although it is associated with a greater risk of major bleeding.

Surgical robotic applications in otolaryngology.

OBJECTIVES: To explore the feasibility of performing endo-robotic neck surgery in a porcine model and to compare the results of robotically enhanced endoscopic surgery with those from a conventional endoscopic technique. STUDY DESIGN: Prospective, nonrandomized experimental investigation in a porcine model. METHODS: We performed a consecutive series of endoscopic neck surgeries using the daVinci surgical system (Intuitive Surgical Inc.). The length of time required to establish the operative pocket and to assemble the robotic components, as well as the total duration of each operation, was recorded. The animals were continuously monitored for heart rate, blood pressure, and end-tidal CO(2) pressure, and evaluation for presence of pneumothorax and subcutaneous emphysema was undertaken postoperatively. The specimens were examined histologically. RESULTS: Four different types of neck surgery were successfully performed on both sides of the neck of four animals using the daVinci surgical system. Creation of the operative pocket took, on average (+/-SD), 18.1 +/- 11.9 minutes, and assembly of the robot required 12.5 +/- 9.9 minutes, resulting in a mean preparation time for all procedures of 30.6 +/- 21.0 minutes. The mean operative time for submandibular resection (n = 3) was 19.0 +/- 6.6 minutes, with a total procedure time of 39.0 +/- 10.2 minutes. Selective neck dissections (n = 3) required a mean operative time of 66.0 +/- 18.5 minutes and a total procedure time of 85.7 +/- 16.7 minutes. One partial parotidectomy and one thymectomy were also performed. The median estimated blood loss was 0 mL (range, 0-10 mL). The end-tidal CO(2) pressure fell from the start to the end of the procedures by a mean of 4.4 +/- 7.9 mm Hg. The blood pressure fell by a mean of 1.9 +/- 7.5 mm Hg. There was one case of modest subcutaneous emphysema, and there were no cases of pneumothorax or air embolism. No conversions to open resection were necessary. CONCLUSIONS: Robotically enhanced endoscopic surgery in the neck is feasible and offers a number of compelling advantages over conventional endoscopic neck surgery. Clinical trials will be necessary to determine whether these advantages can be achieved in clinical practice.

Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells.

Fibulin-1 is an extracellular matrix protein induced by estradiol in estrogen receptor (ER) positive ovarian cancer cell lines. Alternative splicing of fibulin-1 mRNA results in four different variants named A, B, C and D that may have distinct biological functions. We studied the relative expression of fibulin-1 mRNA variants and their estrogen regulation in human ovarian cancer cells. In ovarian tissues and cancer cell lines, fibulin-1C and -1D are the predominant forms, whereas fibulin-1A and -1B are weakly expressed. We developed a competitive PCR assay based on coamplification of fibulin-1C and -1D to study the relative expression of these fibulin-1 variants in human ovarian samples. In ovarian cancer cell lines and ovarian cancer samples, there was a marked increase in the fibulin-1C:1D and fibulin-1C:HPRT mRNA ratios as compared to normal ovaries. In the BG1 estrogen receptor positive ovarian cancer cell line, fibulin-1C mRNA was induced by estradiol in a dose- and time-dependent manner. Since others and we have previously shown an increased expression of ERalpha as compared to ERbeta in ovarian cancer cells, we investigated whether ERalpha or ERbeta is involved in this induction. For this aim, MDA-MB-231 breast cancer cell line, which expresses both low basal levels of ERs and fibulin-1, was infected with recombinant ERalpha or ERbeta encoding adenovirus and treated with estradiol. Fibulin-1C was induced by estradiol in ERalpha- but not ERbeta-infected cells, suggesting that fibulin-1C induction is mediated through ERalpha. In ovarian tumors, a trend towards a correlation between fibulin-1C and ERalpha expression levels was noted. In conclusion, this study showed an increased fibulin-1C:-1D mRNA ratio in ovarian cancer cells as compared to normal ovaries. This finding suggests that the C variant may be involved in ovarian carcinogenesis. Fibulin-1C overexpression may thus be a clue for the understanding of a putative role of estrogens in ERalpha promoted ovarian tumor progression.