Endoscopic Gallbladder Drainage: A Comprehensive Review on Indications, Techniques, and Future Perspectives.

In recent years, therapeutic endoscopy has become a fundamental tool in the management of gallbladder diseases in light of its minimal invasiveness, high clinical efficacy, and good safety profile. Both endoscopic transpapillary gallbladder drainage (TGBD) and endoscopic ultrasound (EUS)-guided gallbladder drainage (EUS-GBD) provide effective internal drainage in patients with acute cholecystitis unfit for cholecystectomy, avoiding the drawbacks of external percutaneous gallbladder drainage (PGBD). The availability of dedicated lumen-apposing metal stents (LAMS) for EUS-guided transluminal interventions contributed to the expansion of endoscopic therapies for acute cholecystitis, making endoscopic gallbladder drainage easier, faster, and hence more widely available. Moreover, EUS-GBD with LAMS opened the possibility of several cholecystoscopy-guided interventions, such as gallstone lithotripsy and clearance. Finally, EUS-GBD has also been proposed as a rescue drainage modality in malignant biliary obstruction after failure of standard techniques, with encouraging results. In this review, we will describe the TBGD and EUS-GBD techniques, and we will discuss the available data on clinical efficacy in different settings in comparison with PGBD. Finally, we will comment on the future perspectives of EUS-GBD, discussing the areas of uncertainty in which new data are more strongly awaited.

Plastic pigtail vs lumen-apposing metal stents for drainage of walled-off necrosis (PROMETHEUS study): an open-label, multicenter randomized trial.

BACKGROUND: Lumen-apposing metal stents (LAMS) have displaced double-pigtail plastic stents (DPS) as the standard treatment for walled-off necrosis (WON),ß but evidence for exclusively using LAMS is limited. We aimed to assess whether the theoretical benefit of LAMS was superior to DPS. METHODS: This multicenter, open-label, randomized trial was carried out in 9 tertiary hospitals. Between June 2017, and Oct 2020, we screened 99 patients with symptomatic WON, of whom 64 were enrolled and randomly assigned to the DPS group (n = 31) or the LAMS group (n = 33). The primary outcome was short-term (4-weeks) clinical success determined by the reduction of collection. Secondary endpoints included long-term clinical success, hospitalization, procedure duration, recurrence, safety, and costs. Analyses were by intention-to-treat. CLINICALTRIALS: gov, NCT03100578. RESULTS: A similar clinical success rate in the short term (RR, 1.41; 95% CI 0.88-2.25; p = 0.218) and in the long term (RR, 1.2; 95% CI 0.92-1.58; p = 0.291) was observed between both groups. Procedure duration was significantly shorter in the LAMS group (35 vs. 45-min, p = 0.003). The hospital admission after the index procedure (median difference, - 10 [95% CI - 17.5, - 1]; p = 0.077) and global hospitalization (median difference - 4 [95% CI - 33, 25.51]; p = 0.82) were similar between both groups. Reported stent-related adverse events were similar for the two groups (36 vs.45% in LAMS vs. DPS), except for de novo fever, which was significantly 26% lower in LAMS (RR, 0.26 [0.08-0.83], p = 0.015). CONCLUSIONS: The clinical superiority of LAMS over DPS for WON therapy was not proved, with similar clinical success, hospital stay and similar safety profile between both groups, yet a significant reduction in procedure time was observed. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03100578.

Endoscopic management of pancreatic collections. Endoscopic Ultrasound Group from the Spanish Society of Digestive Endoscopy (GSEED-USE) Clinical Guidelines.

Acute pancreatitis is associated with significant morbidity and mortality. It can develop complications such as fluid collections and necrosis. Infection of necrosis occurs in about 20-40% of patients with severe acute pancreatitis, and is associated with organ failure and worse prognosis. In the past years, the treatment of pancreatic collections has shifted from open surgery to minimally invasive techniques, such as endoscopic ultrasound guided drainage. These guidelines from a selection of experts among the Endoscopic Ultrasound Group from the Spanish Society of Gastrointestinal Endoscopy (GSEED-USE) have the purpose to provide advice on the management of pancreatic collections based on a thorough review of the available scientific evidence. It also reflects the experience and clinical practice of the authors, who are advanced endoscopists or clinical pancreatologists with extensive experience in managing patients with acute pancreatitis.

Endoscopic ultrasonography-guided gastroenterostomy versus uncovered duodenal metal stenting for unresectable malignant gastric outlet obstruction (DRA-GOO): a multicentre randomised controlled trial.

BACKGROUND: Endoscopic ultrasonography-guided gastroenterostomy (EUS-GE) is a novel endoscopic method to palliate malignant gastric outlet obstruction. We aimed to assess whether the use of EUS-GE with a double balloon occluder for malignant gastric outlet obstruction could reduce the need for reintervention within 6 months compared with conventional duodenal stenting. METHODS: The was an international, multicentre, randomised, controlled trial conducted at seven sites in Hong Kong, Belgium, Brazil, India, Italy, and Spain. Consecutive patients (aged ≥18 years) with malignant gastric outlet obstruction due to unresectable primary gastroduodenal or pancreatobiliary malignancies, a gastric outlet obstruction score (GOOS) of 0 (indicating an inability in intake food or liquids orally), and an Eastern Cooperative Oncology Group performance status score of 3 or lower were included and randomly allocated (1:1) to receive either EUS-GE or duodenal stenting. The primary outcome was the 6-month reintervention rate, defined as the percentage of patients requiring additional endoscopic intervention due to stent dysfunction (ie, restenosis of the stent due to tumour ingrowth, tumour overgrowth, or food residue; stent migration; or stent fracture) within 6 months, analysed in the intention-to-treat population. Prespecified secondary outcomes were technical success (successful placement of a stent), clinical success (1-point improvement in gastric outlet obstruction score [GOOS] within 3 days), adverse events within 30 days, death within 30 days, duration of stent patency, GOOS at 1 month, and quality-of-life scores. This study is registered with ClinicalTrials.gov (NCT03823690) and is completed. FINDINGS: Between Dec 1, 2020, and Feb 28, 2022, 185 patients were screened and 97 (46 men and 51 women) were recruited and randomly allocated (48 to the EUS-GE group and 49 to the duodenal stent group). Mean age was 69·5 years (SD 12·6) in the EUS-GE group and 64·8 years (13·0) in the duodenal stent group. All randomly allocated patients completed follow-up and were analysed. Reintervention within 6 months was required in two (4%) patients in the EUS-GE group and 14 (29%) in the duodenal stent group [p=0·0020; risk ratio 0·15 [95% CI 0·04-0·61]). Stent patency was longer in the EUS-GE group (median not reached in either group; HR 0·13 [95% CI 0·08-0·22], log-rank p<0·0001). 1-month GOOS was significantly better in the EUS-GE group (mean 2·41 [SD 0·7]) than the duodenal stent group (1·91 [0·9], p=0·012). There were no statistically significant differences between the EUS-GE and duodenal stent groups in death within 30 days (ten [21%] vs six [12%] patients, respectively, p=0·286), technical success, clinical success, or quality-of-life scores at 1 month. Adverse events occurred 11 (23%) patients in the EUS-GE group and 12 (24%) in the duodenal stent group within 30 days (p=1·00); three cases of pneumonia (two in the EUS-GE group and one in the duodenal stent group) were considered to be procedure related. INTERPRETATION: In patients with malignant gastric outlet obstruction, EUS-GE can reduce the frequency of reintervention, improve stent patency, and result in better patient-reported eating habits compared with duodenal stenting, and the procedure should be used preferentially over duodenal stenting when expertise and required devices are available. FUNDING: Research Grants Council (Hong Kong Special Administrative Region, China) and Sociedad Española de Endoscopia Digestiva.

Double-Blind Multicenter Randomized Clinical Trial Comparing Glucagon vs Placebo in the Resolution of Alimentary Esophageal Impaction.

INTRODUCTION: The aim of this study was to compare the effectiveness of glucagon vs placebo in resolving esophageal foreign body impaction (EFBI), as well as the length of the procedure and adverse events. METHODS: This was a multicenter, randomized, double-blind trial involving consecutive patients diagnosed with alimentary EFBI. Participants were randomized to receive either 1 mg of intravenous glucagon or placebo. All patients underwent upper endoscopy, and adverse events were assessed through a protocolized telephonic interview 7 days later. RESULTS: The study included 72 subjects in the glucagon group and 68 in the placebo group. The foreign body was not identified in 23.6% of subjects in the glucagon group and 20.6% of subjects in the placebo group (difference 3%, 95% confidence interval -10.7% to 16.8%, P = 0.67). The median time required to remove the foreign body was similar in both groups 4 minutes (range 2-10) in the glucagon group and 3.5 minutes (range 2-7) in the placebo group (difference 0.5 minutes, 95% confidence interval -1.3 to 2.3; P = 0.59). The most common adverse event reported in both groups was mild pharyngeal pain. DISCUSSION: Glucagon is no more effective than placebo in resolving EFBI or shortening the time required to remove the foreign body (EUDRA-CT number 2019-004920-40).

Endoscopic ultrasound-guided gallbladder drainage with long-term lumen-apposing metal stent indwell: 1-year results from a prospective nationwide observational study.

BACKGROUND AND AIM: This study aimed to determine safety and risk factors for adverse events (AEs) of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) with long-term indwell of lumen-apposing metal stents (LAMS). METHODS: This study is a multicenter prospective observational study on consecutive high surgical-risk patients requiring gallbladder drainage who underwent EUS-GBD with LAMS over 12 months. Centralized telephone follow-up interviews were conducted every 3 months for 1 year. Patients were censored at LAMS removal, cholecystectomy, or death. AE-free survival was determined using log-rank tests. Cumulative risks were estimated using life-table analysis. RESULTS: Eighty-two patients were included (53.7% male, median [interquartile range] age of 84.6 [76.5-89.8] years, and 85.4% with acute cholecystitis). Technical success was achieved in 79 (96.3%), and clinical success in 73 (89%). No patient was lost to follow-up; 45 patients (54.9%) completed 1-year follow-up with in situ LAMS. Median (interquartile range) LAMS indwell time was 364 (47-367) days. Overall, 12 (14.6%) patients presented 14 AEs, including 5 (6.1%) recurrent biliary events (3 acute cholangitis, 1 mild acute pancreatitis, and 1 acute cholecystitis). Patients with pancreatobiliary malignancy had an increased risk of recurrent biliary events (33% vs 1.5%, P = 0.001). The overall 1-year cumulative risk of recurrent biliary events was 9.7% (4.1-21.8%). The 1-year risk of AEs and of severe AEs was 18.8% (11-31.2%) and 7.9% (3.3-18.2%), respectively. Pancreatobiliary malignancy was the single risk factor for recurrent biliary events; LAMS misdeployment was the strongest risk factor for AEs. CONCLUSIONS: Long-term LAMS indwell does not increase the risk of delayed AEs following EUS-GBD.

International Consensus Recommendations for Safe Use of LAMS for On- and Off-Label Indications Using a Modified Delphi Process.

INTRODUCTION: The study aimed to develop international consensus recommendations on the safe use of lumen-apposing metal stents (LAMSs) for on- and off-label indications. METHODS: Based on the available literature, statements were formulated and grouped into the following categories: general safety measures, peripancreatic fluid collections, endoscopic ultrasound (EUS)-biliary drainage, EUS-gallbladder drainage, EUS-gastroenterostomy, and gastric access temporary for endoscopy. The evidence level of each statement was determined using the Grading of Recommendations Assessment, Development, and Evaluation methodology.International LAMS experts were invited to participate in a modified Delphi process. When no 80% consensus was reached, the statement was modified based on expert feedback. Statements were rejected if no consensus was reached after the third Delphi round. RESULTS: Fifty-six (93.3%) of 60 formulated statements were accepted, of which 35 (58.3%) in the first round. Consensus was reached on the optimal learning path, preprocedural imaging, the need for airway protection and essential safety measures during the procedure, such as the use of Doppler, and measurement of the distance between the gastrointestinal lumen and the target structure. Specific consensus recommendations were generated for the different LAMS indications, covering, among others, careful patient selection, the preferred size of the LAMS, the need for antibiotics, the preferred anatomic location of the LAMS, the need for coaxial pigtail placement, and the appropriate management of LAMS-related adverse events. DISCUSSION: Through a modified international Delphi process, we developed general and indication-specific experience- and evidence-based recommendations on the safe use of LAMS.

What Is in a Simplicial Complex? A Metaplex-Based Approach to Its Structure and Dynamics.

Geometric realization of simplicial complexes makes them a unique representation of complex systems. The existence of local continuous spaces at the simplices level with global discrete connectivity between simplices makes the analysis of dynamical systems on simplicial complexes a challenging problem. In this work, we provide some examples of complex systems in which this representation would be a more appropriate model of real-world phenomena. Here, we generalize the concept of metaplexes to embrace that of geometric simplicial complexes, which also includes the definition of dynamical systems on them. A metaplex is formed by regions of a continuous space of any dimension interconnected by sinks and sources that works controlled by discrete (graph) operators. The definition of simplicial metaplexes given here allows the description of the diffusion dynamics of this system in a way that solves the existing problems with previous models. We make a detailed analysis of the generalities and possible extensions of this model beyond simplicial complexes, e.g., from polytopal and cell complexes to manifold complexes, and apply it to a real-world simplicial complex representing the visual cortex of a macaque.

Sleep disruption, use of sleep-promoting medication and circadian desynchronization in spaceflight crewmembers: Evidence in low-Earth orbit and concerns for future deep-space exploration missions.

Introduction: The spaceflight environment presents unique demands on human physiology; among those demands, is sleep. Sleep loss and circadian desynchronization is a major concern for future deep- exploration plans, including long-term crewed missions to the Moon and Mars. Aims: Analyze evidence of sleep disruption in crewmembers during low-Earth orbit missions, identify the use of sleep-promoting medication among crewmembers and deepen the comprehension of challenges to sleep physiology for future missions to the Moon and Mars. Results: Evidence consistently indicates a loss of sleep and circadian rhythm disruption during low-Earth orbit missions. Sleep duration is shortened especially the night before a critical operation and during circadian-misaligned sleep episodes. The prevalence of sleep-promoting medication ranges between 71% and 78%; medication is more frequently taken on circadian-misaligned sleep episodes. Regarding the Moon, Apollo astronauts had variable sleep duration. For some, sleep was restful while others had poor-quality sleep. Many reported fatigue and errors due to the lack of rest. A loss of the 24-h light/dark might be expected due to the Moon's complex illumination characteristics. Regarding Mars, one main challenge will consist in synchronizing the circadian clock to a Martian day (24.65 h).

Antimigration versus conventional fully covered metal stents in the endoscopic treatment of anastomotic biliary strictures after deceased-donor liver transplantation.

INTRODUCTION: Migration of fully covered metal stents (FCMS) remains a limitation of the endoscopic treatment of anastomotic biliary strictures (ABS) following orthotopic liver transplantation (OLT). The use of antimigration FCMS (A-FCMS) might enhance endoscopic treatment outcomes for ABS. METHODS: Single center retrospective study. Consecutive patients with ABS following OLT who underwent ERCP with FCMS placement between January 2005 and December 2020 were eligible. Subjects were grouped into conventional-FCMS (C-FCMS) and A-FCMS. The primary outcome was stent migration rates. Secondary outcomes were stricture resolution, adverse event, and recurrence rates. RESULTS: A total of 102 (40 C-FCMS; 62 A-FCMS) patients were included. Stent migration was identified at the first revision in 24 C-FCMS patients (63.2%) and in 21 A-FCMS patients (36.2%) (p = 0.01). The overall migration rate, including the first and subsequent endoscopic revisions, was 65.8% in C-FCMS and 37.3% in A-FCMS (p = 0.006). The stricture resolution rate at the first endoscopic revision was similar in both groups (60.0 vs 61.3%, p = 0.87). Final stricture resolution was achieved in 95 patients (93.1%), with no difference across groups (92.5 vs 93.5%; p = 0.84). Adverse events were identified in 13 patients (12.1%) with no difference across groups. At a median follow-up of 52 (IQR: 19-85.5) months after stricture resolution, 25 patients (24.5%) developed recurrences, with no difference across groups (C-FCMS 30% vs A-FCMS 21%; p = 0.28). CONCLUSIONS: The use of A-FCMS during ERCP for ABS following OLT results in significantly lower stent migration rates compared to C-FCMS. However, the clinical benefit of reduced stent migration is unclear. Larger studies focusing on stricture resolution and recurrence rates are needed.

Topologically induced suppression of explosive synchronization.

Nowadays, explosive synchronization is a well-documented phenomenon consisting in a first-order transition that may coexist with classical synchronization. Typically, explosive synchronization occurs when the network structure is represented by the classical graph Laplacian, and the node frequency and its degree are correlated. Here, we answer the question on whether this phenomenon can be observed in networks when the oscillators are coupled via degree-biased Laplacian operators. We not only observe that this is the case but also that this new representation naturally controls the transition from explosive to standard synchronization in a network. We prove analytically that explosive synchronization emerges when using this theoretical setting in star-like networks. As soon as this star-like network is topologically converted into a network containing cycles, the explosive synchronization gives rise to classical synchronization. Finally, we hypothesize that this mechanism may play a role in switching from normal to explosive states in the brain, where explosive synchronization has been proposed to be related to some pathologies like epilepsy and fibromyalgia.

Endoscopic removal of lumen-apposing metal stents - risk factors for stent embedment, complex removals, and adverse events: analysis from a multicenter prospective case series.

BACKGROUND: Removing lumen-apposing metal stents (LAMSs) may be difficult and even harmful, but these features have seldom been analyzed. We aimed to generate a comprehensive assessment of the feasibility and safety of LAMS retrieval procedures. METHODS: A prospective multicenter case series including all technically successfully deployed LAMSs between January 2019 and January 2020 that underwent endoscopic stent removal. All retrieval-related data were prospectively recorded using standardized telephone questionnaires as part of centralized follow-up that ended after stent removal had been performed. Multivariable logistic regression models assessed the potential risk factors for complex removal. RESULTS: For the 407 LAMSs included, removal was attempted in 158 (38.8 %) after an indwell time of 46.5 days (interquartile range [IQR] 31-70). The median (IQR) removal time was 2 (1-4) minutes. Removal was labelled as complex in 13 procedures (8.2 %), although advanced endoscopic maneuvers were required in only two (1.3 %). Complex removal risk factors were stent embedment (relative risk [RR] 5.84, 95 %CI 2.14-15.89; P = 0.001), over-the-wire deployment (RR 4.66, 95 %CI 1.60-13.56; P = 0.01), and longer indwell times (RR 1.14, 95 %CI 1.03-1.27; P = 0.01). Partial and complete embedment were observed in 14 (8.9 %) and five cases (3.2 %), respectively. The embedment rate during the first 6 weeks was 3.1 % (2/65), reaching 15.9 % (10/63) during the following 6 weeks (P = 0.02). The adverse event rate was 5.1 %, including seven gastrointestinal bleeds (5 mild, 2 moderate). CONCLUSIONS: LAMS removal is a safe procedure, mostly requiring basic endoscopic techniques attainable in conventional endoscopy rooms. Referral to advanced endoscopy units should be considered for stents with known embedment or long indwell times, which may require more technically demanding procedures.

Prospective multicenter assessment of the impact of EUS-guided gastroenterostomy on patient quality of life in unresectable malignant gastric outlet obstruction.

BACKGROUND AND AIMS: EUS-guided gastroenterostomy (EUS-GE) is increasingly used for malignant gastric outlet obstruction (GOO) in inoperable patients. However, the impact of EUS-GE on patient quality of life (QoL) has not been evaluated prospectively. METHODS: Consecutive patients with unresectable malignant GOO who underwent EUS-GE between August 2019 and May 2021 at 4 Spanish centers were prospectively assessed using the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 at baseline and 1 month after the procedure. Centralized follow-up by telephone calls was undertaken. The Gastric Outlet Obstruction Scoring System (GOOSS) was used to assess oral intake, defining clinical success as a GOOSS ≥2. Differences between baseline and 30-day QoL scores were assessed using a linear mixed model. RESULTS: Sixty-four patients were enrolled, 33 (51.6%) men, with a median age of 77.3 years (interquartile range, 65.5-86.5). The most common diagnoses were pancreatic (35.9%) and gastric (31.3%) adenocarcinoma. Thirty-seven patients (57.9%) presented a 2/3 baseline Eastern Cooperative Oncology Group performance status score. Oral intake was restarted within 48 hours in 61 patients (95.3%), and the median postprocedure hospital stay was 3.5 days (interquartile range, 2-5). The 30-day clinical success rate was 83.3%. A clinically significant increase of 21.6 points (95% confidence interval, 11.5-31.7) in the global health status scale was documented, with significant improvements in nausea and vomiting, pain, constipation, and appetite loss. CONCLUSIONS: EUS-GE relieves GOO symptoms in patients with unresectable malignancy, allowing rapid oral intake and hospital discharge. It also provides a clinically relevant increase in QoL scores at 30 days from baseline. (Clinical trial registration number: NCT04660695.).