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Since its inception, endoscopy has evolved from a solely diagnostic procedure to an expanding therapeutic field within gastroenterology. The incorporation of robotics in gastroenterology initially addressed shortcomings of flexible endoscopes in natural orifice transluminal endoscopy. Developing therapeutic endoscopic robotic platforms now offer operators improved ergonomics, visualization, dexterity, precision, and control and the possibility of increasing proficiency and standardization of complex endoscopic procedures including endoscopic submucosal dissection, endoscopic full-thickness resection, and endoscopic suturing. The following review discusses the history, potential applications, and tools currently available and in development for robotics in therapeutic endoscopy. [Display omitted] [ABSTRACT FROM AUTHOR]

One of the difficulties in performing endoscopic submucosal dissection (ESD) is the lack of retraction during submucosal dissection. The development of the EndoMaster EASE System (EndoMaster Pte Ltd, Singapore) aims to enhance the safety and efficacy of ESD through 2 flexible robotic arms for tissue retraction and dissection. This is a preclinical animal study to evaluate the performance of colorectal ESD using the latest version of the EndoMaster EASE System. The latest version of the EndoMaster EASE System consists of an independently designed, flexible platform with a built-in endoscopic imaging system and 3 working channels, 2 for the passage of robotic arms and 1 for accessories. In this animal study, the outcome measures were operating time (from starting incision to finishing dissection), completeness of resection, procedure-related adverse events, and limitations of arm manipulation in a narrow working space as assessed by counting the frequency of blind cutting. Five ESD procedures were performed in a 66.7-kg porcine model with the animal under general anesthesia. The mean operative time was 73.8 minutes, and the mean size of the specimen resected was 1340 mm2. There was no perforation, although profuse bleeding was encountered during 1 robotic ESD procedure. The current preclinical study confirmed the feasibility of performing colorectal ESD using the latest version of the EndoMaster EASE System. The system was also tested for the ability to manage adverse events including bleeding and perforation. This study provided important preclinical experience for clinical trial. [ABSTRACT FROM AUTHOR]

EUS-guided gallbladder drainage (EUS-GBD) is a safe alternative to percutaneous cholecystostomy (PT-GBD) for acute cholecystitis. How the procedure compares with laparoscopic cholecystectomy (LC) is uncertain. The aim of the current study is to compare the outcomes of EUS-GBD with LC for acute cholecystitis. This was propensity score analysis of all patients admitted for acute cholecystitis between 2012 and 2018. Consecutive patients who received EUS-GBD or LC were included. Patients were matched for age, sex, and age-adjusted Charlson score. Outcome measurements included 30-day adverse events, mortality, recurrent cholecystitis, recurrent biliary events, reinterventions, and readmissions. During the study period, 60 patients were selected (30 EUS-GBD vs 30 LC) after propensity score matching. Technical success rates (100% vs 100%), clinical success rates (93.3% vs 100%, P = 1), lengths of hospital stay (6.8 [8.1] vs 5.5 [2.7], P = 1), 30-day adverse events (4 [13.3%] vs 4 [13.3%], P = 1), and mortality rates (2 [6.7%] vs 0 [0%], P =.492) were similar. The rates of recurrent biliary events (3 [10%] vs 3 [10%], P =.784), reinterventions (4 [13.3%] vs 3 [10%], P = 1), and unplanned readmissions (3 [10%] vs 3 [10%], P =.784) in 1 year were also similar. The outcomes of EUS-GBD for acute cholecystitis were comparable with LC with acceptable rates of recurrent acute cholecystitis. These results support the role of EUS-GBD as an alternative to LC in patients who may or may not be surgically fit to undergo definitive cholecystectomy. [ABSTRACT FROM AUTHOR]

Background and Aims The recent development of EUS-guided gallbladder drainage (EGBD) with a lumen-apposing stent has made endoscopic assessment and advanced gallbladder interventions via the stent possible. The aim of this study was to assess the feasibility and safety of per-oral cholecystoscopy and the types of gallbladder interventions that can be performed. Methods This was a retrospective review conducted in the Prince of Wales Hospital from June 2012 to March 2016. All patients who had acute cholecystitis with EGBD were included. Cholecystoscopy was performed 1 to 3 months after stent insertion. Patients’ demographic data, technical success, types of intervention, and adverse events were recorded. Results Twenty-nine cholecystoscopies were performed in 25 patients. Twenty-seven of 29 cholecystoscopies were successful (93.1%). Magnifying endoscopy was performed in 10 patients, confocal endomicroscopy and EUS in 1 patient, and endocytoscopy in another patient. Fourteen patients (56%) had spontaneous stone passage. Eleven patients (44%) had residual gallstones on cholecystoscopy, and removed in 8. Overall stone clearance rate was 88% after a mean (standard deviation) number of 1.25 (0.46) sessions of cholecystoscopy. Conclusions Per-oral cholecystoscopy and advanced gallbladder interventions were feasible and safe. This opens up exciting possibilities for endoscopic treatment of gallbladder pathologies. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aims to compare the pooled diagnostic accuracy of the currently available esophageal squamous cell carcinoma (ESCC) screening tests. A comprehensive literature search of Embase and Medline (up to October 31, 2020) was performed to identify eligible studies. We pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for ESCC screening tools using a bivariate random-effects model. The summary receiver operating characteristic curves with area under the curve (AUC) were plotted for each screening test. We included 161 studies conducted in 81 research articles involving 32,209 subjects. The pooled sensitivity, specificity, and AUC of the major screening tools were respectively as follows: endoscopy (peroral endoscopy):.94 (95% confidence interval [CI],.87-.97),.92 (95% CI,.87-.95), and.97 (95% CI,.96-.99); endoscopy (transnasal endoscopy):.85 (95% CI,.70-.93),.96 (95% CI,.91-.98), and.97 (95% CI,.95-.98); microRNA:.77 (95% CI,.75-.80),.78 (95% CI,.75-.80), and.85 (95% CI,.81-.87); autoantibody:.45 (95% CI,.36-.53),.91 (95% CI,.89-.93), and.84 (95% CI,.81-.87); and cytology:.82 (95% CI,.60-.93),.97 (95% CI,.88-.99), and.97 (95% CI,.95-.98). There was high heterogeneity. The diagnostic accuracy seemed to be comparable between cytology and endoscopy, whereas autoantibody and microRNAs bear potential as future noninvasive screening tools for ESCC. To reduce ESCC-related death in high-risk populations, it is important to develop a more accurate and less-invasive screening test. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer (EC) is highly prevalent in Eastern Asia (including China) with high rates of mortality. The metastatic tendency in EC is associated with a poor prognosis. Our previous studies have demonstrated the suppressive effects of Andrographis paniculata water extract (APW) on metastatic esophageal cancer in vitro and in tumor-bearing mice models, as well as illustrated the potential underlying mechanism by transcriptome analysis.Hypothesis: High expressions of several membrane protein tetraspanins were reported to lead to a high risk of metastasis in esophageal cancer in patients. We hypothesized that APW could downregulate the expression of tetraspanin CD81 in esophageal cancer cells and xenografts.Methods: Human esophageal cancer cells EC109 and KYSE520 were incubated with APW for 24 hours in cell culture, while mice bearing EC109 xenograft tumors were treated with APW for 21 days. The expressions of CD81 in cancer cells and in tumors from mice were evaluated. Molecular docking and microscale thermophoresis analyses were applied to identify the components in APW interacting with CD81. The influence of the identified components on CD81 expression was further evaluated in EC109 cells.Results: APW could significantly suppress the expressions of CD81 in both EC109 and KYSE520 cells in a concentration-dependent manner. Treatment of APW in xenograft-bearing mice reduces the metastasis in lungs, livers, and lymph nodes. The expression of CD81 in xenograft tumors of APW-treated mice was significantly lower than those of untreated control mice. The binding of andrographolide, bisandrographolide A, and bisandrographolide C with CD81 were elucidated by microscale thermophoresis. The suppressive effects of these compounds on the motility of EC109 cells, as well as CD81 protein and mRNA expressions, were further confirmed.Conclusion: This is the first time to demonstrate that andrographolide, bisandrographolide A, and bisandrographolide C, which are present in APW, bind to CD81 and suppress its function. These compounds are likely to be responsible for the anti-metastatic activities of APW in esophageal cancer. [ABSTRACT FROM AUTHOR]

Despite the significant advances made in the diagnosis and treatment of Barrett's esophagus (BE), there is still a need for standardized definitions, appropriate recognition of endoscopic landmarks, and consistent use of classification systems. Current controversies in basic definitions of BE and the relative lack of anatomic knowledge are significant barriers to uniform documentation. We aimed to provide consensus-driven recommendations for uniform reporting and global application. The World Endoscopy Organization Barrett's Esophagus Committee appointed leaders to develop an evidence-based Delphi study. A working group of 6 members identified and formulated 23 statements, and 30 internationally recognized experts from 18 countries participated in 3 rounds of voting. We defined consensus as agreement by ≥80% of experts for each statement and used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool to assess the quality of evidence and the strength of recommendations. After 3 rounds of voting, experts achieved consensus on 6 endoscopic landmarks (palisade vessels, gastroesophageal junction, squamocolumnar junction, lesion location, extraluminal compressions, and quadrant orientation), 13 definitions (BE, hiatus hernia, squamous islands, columnar islands, Barrett's endoscopic therapy, endoscopic resection, endoscopic ablation, systematic inspection, complete eradication of intestinal metaplasia, complete eradication of dysplasia, residual disease, recurrent disease, and failure of endoscopic therapy), and 4 classification systems (Prague, Los Angeles, Paris, and Barrett's International NBI Group). In round 1, 18 statements (78%) reached consensus, with 12 (67%) receiving strong agreement from more than half of the experts. In round 2, 4 of the remaining statements (80%) reached consensus, with 1 statement receiving strong agreement from 50% of the experts. In the third round, a consensus was reached on the remaining statement. We developed evidence-based, consensus-driven statements on endoscopic landmarks, definitions, and classifications of BE. These recommendations may facilitate global uniform reporting in BE. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancers are among the commonest cancers worldwide. Treatment of these cancers at an early stage will result in a significantly better prognosis. Endoscopic submucosal dissection (ESD) is a new method of endoscopic resection that can achieve higher rates of en bloc resection for early gastrointestinal neoplasia. Three retrospective case-control studies showed that ESD achieved significantly higher en bloc resection with lower recurrence rates than endoscopic mucosal resection for treatment of early gastric cancers. Most of the reports on clinical outcomes of ESD were from countries with a high incidence of gastric cancers, including Japan and Korea. The development of ESD has been slow for countries outside Japan and Korea because ESD requires a high level of endoscopic skills, and the dissection was performed single-handedly without assistance. A newly developed robotic endoscopic platform will enhance the performance of ESD through the use of 2 robotic arms: one arm for retraction of the mucosa and the other arm for dissection. [Copyright &y& Elsevier]

Background: Peroral endoscopic myotomy (POEM) is a novel approach to performing esophageal myotomy through a long submucosal tunnel. Objective: This study aimed to investigate the feasibility and safety of POEM for treatment of achalasia. Design: Preclinical animal study and prospective clinical study. Patients: Consecutive patients diagnosed with achalasia with high-resolution manometry. Interventions: POEM was standardized for preclinical and clinical studies. After submucosal injection, a mucosal incision was made 15 cm above the gastroesophageal junction (GEJ). A long submucosal tunnel was created to extend below the GEJ. The endoscopic myotomy started 10 cm above and extended 2 cm below the GEJ. We first conducted a preclinical animal study to confirm the safety of POEM. POEM was then performed for the treatment of achalasia in humans. Main Outcome Measurements: Relief from dysphagia assessed by the dysphagia score and Eckhardt score. High-resolution manometry and pH monitoring were performed to evaluate the posttreatment effects and esophageal acid exposure. Results: Seven 30-kg porcine models underwent POEM in the survival study. All of the pigs survived except 1, which sustained pneumomediastinum. POEM was performed for the treatment of achalasia in 16 patients. The mean operating time was 117.0 ± 34.1 minutes. All patients tolerated food on day 2, with a contrast study confirming no leakage. The median follow-up was 176.5 days (range 98-230 days). The postoperative basal lower esophageal sphincter pressure was significantly reduced (mean reduction, 13.9 ± 14.5 mm Hg; P = .005) and 4-second integrated relaxation pressure of the GEJ (mean reduction, 10.1 ± 7.4 mm Hg; P = .001). Of these patients, 58.3% had a normalized 4-second integrated relaxation pressure, whereas 20% had excessive esophageal acid exposure after the procedure. There was a significant improvement in quality of life 6 months after POEM measured by the Short Form-36 questionnaire. Limitation: Small sample size. Conclusions: POEM is a feasible, safe, and effective treatment for achalasia. (Clinical trial registration number: NCT01525732.) [ABSTRACT FROM AUTHOR]

Background: Gastrojejunal anastomosis is commonly performed for palliative management of malignant gastric outlet obstruction and bariatric surgery. Natural orifice transluminal endoscopic surgery revolutionized the surgical approach to intra-abdominal surgery. This study explored the possibility of performing gastrojejunostomy (GJ) by using a hybrid natural orifice transluminal endoscopic surgery approach. Objective: To develop a surgical technique for the performance of transgastric endoscopic GJ (TGEJ) in a porcine model. Design: Prospective series of animal experiments. Setting: University hospital animal laboratory. Animals: Thirteen female domestic pigs. Interventions: With the animals under general anesthesia, the endoscope is passed through the gastrotomy and a segment of small bowel is retrieved into the stomach. An enterotomy is then created, and an EndoGIA stapler is introduced through an intragastric port and passed between the small bowel and stomach wall. A GJ is formed after firing of the EndoGIA stapler. The pigs are allowed to resume their diet 1 day after the operation and are allowed to survive for 2 weeks before they are euthanized. The patency of the GJ is confirmed with a repeat endoscopy, contrast study, and postmortem examination. Results: A total of 13 TEGJs were performed, 11 of which were successful. The mean operative time was 53.6 ± 45.7 minutes. The mean time for gastrotomy was 4.7 minutes, and that for GJ was 42.5 minutes. One TEGJ was converted to open surgery because of malpositioning of the intragastric port, and the other failed because the enterotomy was too extensive. Ten of 11 pigs survived for 2 weeks, and endoscopic examination with contrast study confirmed that all the gastrojejunostomies were patent. On postmortem examination, the average size of the GJ was 30 mm. Limitations: The length between duodenojejunal flexure and the site chosen to perform the GJ could not be determined. Conclusions: TEGJ is technically feasible with a patent and sizable anastomosis. [Copyright &y& Elsevier]

Peroral endoscopic myotomy (POEM) has become the mainstay for the treatment of achalasia at many institutions around the world since its inception in 2008. POEM can be performed using either the anterior or posterior approach. The primary aim of this study was to compare the efficacy of the anterior and posterior approaches at 1 year after POEM. This is a single-blinded, randomized, noninferiority international clinical trial. Eligible participants were adult patients with a confirmed diagnosis of achalasia via high-resolution esophageal manometry. Patients were randomly allocated with a 1:1 ratio to receive POEM with anterior or posterior approach. The primary aim was to compare the rate of clinical success (Eckardt score <3) of anterior and posterior approaches at 1 year. One hundred fifty patients were randomized to receive either anterior (n = 73) or posterior (n = 77) POEM. One hundred forty-eight patients received the POEM treatment, and 138 patients completed the 1-year follow-up and were included in the primary efficacy analysis. Technical success was achieved in 71 patients (97.3%) in the anterior group versus 77 patients (100%) in the posterior group (P =.23). The median (interquartile range) length of hospital stay after the procedure was 2 (1-3) days for both groups. Adverse events occurred in 15 patients (10%), 8 patients (11%) in the anterior group and 7 patients (9%) in the posterior group (P =.703). Clinical success was achieved in 90% of patients in the anterior group and 89% of patients in the posterior group. Abnormal esophageal acid exposure was detected in 29 of 59 patients (49%) and 25 of 60 patients (42%) in the anterior and posterior groups, respectively (P =.67). GERD questionnaire scores were also not significantly different between the study groups. In both groups, quality of life improved after POEM for all 36-Item Short-Form Health Survey measures and was similar between both groups. Posterior myotomy during POEM was not inferior to anterior myotomy in terms of efficacy and safety in the treatment of patients with achalasia. (Clinical trial registration number: NCT02454335.) [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer (EC) is a malignant gastrointestinal cancer with high morbidity worldwide and is the fourth leading cause of cancer-related deaths in China. Even though surgery and/or chemotherapy/chemoradiation might achieve good therapeutic response, recurrence rate is high due to cancer metastasis. Hence, the use of alternative adjuvant treatments, such as herbal medicines, for metastatic EC remains a great desire of the patients. Our previous studies have demonstrated the anti-metastatic efficacy of hot water extract of Andrographis paniculata (APW) in human esophageal cancer cells and tumor-bearing nude mice.Purpose: In the present study, the immunomodulatory activities of APW were further evaluated in human peripheral blood mononuclear cells (PBMCs) and in a carcinogen-induced esophageal tumorigenesis model using immune-competent C57BL/6 mice. Besides, the inhibitory effects of APW on esophageal cancer cell line-based xenografts and patient-derived xenografts (PDX) were examined so as to illustrate the potential multi-targeted efficacies of APW in esophageal cancer in pre-clinical models.Results: In vitro results showed that APW could stimulate proliferation of PBMCs, as well as TNF-α and IFN-γproductions. In mice with 4-nitroquinoline 1-oxide-induced tumorigenesis, 21-day oral treatment with APW (1600 mg/kg) decreased the level of dysplasia in esophagus and significantly modulated the population of regulatory T cells. The cytokines productions by spleen lymphocytes of APW-treated mice were shifted towards normal resting state (i.e. unchallenged with carcinogen). Furthermore, APW treatment suppressed the growth of cell line-based xenografts by significantly increasing apoptosis in tumors, without causing severe body weight loss as chemotherapeutics did. Most importantly, the inhibitory effects of APW treatment on esophageal patient-derived xenografts growth were demonstrated for the first time. Besides, several diterpenes were detected in the plasma after oral administration of APW in mice, suggesting that multi-components of APW were bioavailable and might have contributed towards the varied pharmacological activities demonstrated in our studies.Conclusion: APW was shown to possess anti-tumor, anti-metastatic and immunomodulatory activities in esophageal cancer cell-based and animal models, including immunocompromised mice model and clinically relevant PDX model. Our findings illustrated the potential multi-targeted efficacies of APW in esophageal cancer management. [ABSTRACT FROM AUTHOR]

Background and Aims Per-oral endoscopic myotomy (POEM) has shown promising safety and efficacy in short-term studies. However, long-term follow-up data are very limited. The aims of this study were to assess (1) clinical outcome of patients with a minimum post-POEM follow-up of 2 years and (2) factors associated with long-term clinical failure after POEM. Methods A retrospective chart review was performed that included all consecutive patients with achalasia who underwent POEM with a minimum follow-up of 2 years at 10 tertiary-care centers. Clinical response was defined by a decrease in Eckardt score to 3 or lower. Results A total of 205 patients (45.8% men; mean age, 49 years) were followed for a median of 31 months (interquartile range, 26-38 months). Of these, 81 patients (39.5%) had received previous treatment for achalasia before POEM. Clinical success was achieved in 98% (185/189), 98% (142/144), and 91% (187/205) of patients with follow-up within 6 months, at 12 months, and ≥24 months, respectively. Of 185 patients with clinical response at 6 months, 11 (6%) experienced recurrent symptoms at 2 years. History of previous pneumatic dilation was associated with long-term treatment failure (odds ratio, 3.41; 95% confidence interval, 1.25-9.23). Procedure-related adverse events occurred in 8.2% of patients and only 1 patient required surgical intervention. Abnormal esophageal acid exposure and reflux esophagitis were documented in 37.5% and 18% of patients, respectively. However, these rates are simply a reference number among a very selective group of patients. Conclusions POEM is safe and provides high initial clinical success and excellent long-term outcomes. Among patients with confirmed clinical response within 6 months, 6% had recurrent symptoms by 2 years. [ABSTRACT FROM AUTHOR]

Background & Aims: Limited endoscopic sphincterotomy with large balloon dilation (ESBD) is an alternative to endoscopic sphincterotomy (ES) for removing bile duct stones, but it is not clear which procedure is most effective. We compared the 2 techniques in removal of bile duct stones. Methods: Between September 2005 and September 2011, 156 consecutive patients with suspected of having, or known to have, common bile duct stones were randomly assigned to groups that underwent ES or ESBD. Patients in the ESBD group underwent limited sphincterotomy (up to half of the sphincter) followed by balloon dilation to the size of the common bile duct or 15 mm, and patients in the ES group underwent complete sphincterotomy alone. Stones were then removed using standard techniques. The primary outcome was percentage of stones cleared, and secondary outcomes included procedural time, method of stone extraction, number of procedures required for stone clearance, morbidities and mortality within 30 days, and direct cost. Results: There was no significant difference between groups in percentage of stones cleared (ES vs ESBD: 88.5% vs 89.0%). More patients in the ES group (46.2%) than the ESBD group (28.8%) required mechanical lithotripsy (P = .028), particularly for stones ≥15 mm (90.9% vs 58.1%; P = .002). Morbidities developed in 10.3% of patients in the ES group and 6.8% of patients in the ESBD group (P = .46). The cost of the hospitalization was also significantly lower in the ESBD group (P = .034). Conclusions: ESBD and ES clear bile stones with equal efficacy. However, ESBD reduces the need for mechanical lithotripsy and is less expensive; ClinicalTrials.gov number, NCT00164853. [Copyright &y& Elsevier]

Snake-like flexible manipulators are widely used in minimally invasive surgery (MIS), which require adequate dexterity in confined workspace. Typically, the design mechanisms of these manipulators include tendon-driven mechanism and concentric tube mechanism. Though, the workspace and dexterity of these designs are limited due to the lack of control in either the length of the bending section or the curvature of the bending section at the distal end. In this paper, we present a novel constrained wire-driven flexible mechanism (CWFM), in which both the length and the curvature of the bending section are controllable. The idea is to employ an active constraint to control the length of the bending section and use the wires to control the curvature of the bending section. Compared to the existing designs based on wire-driven flexible mechanism (WFM), CWFM has expanded workspace and enhanced dexterity while its size is not sacrificed. Additional benefits include much reduced sweeping area and controllable stiffness. Based on the computer simulation, on average, CWFM with the same size as WFM can improve the dexterity by 4.69 times and reduce the sweeping area to 20.5%. [ABSTRACT FROM AUTHOR]

Helix-based structures have been popularly used in flexible surgical tool designs due to their large bending range. However, the helix structures also have low compressional and torsional stiffness, which results in a limited payload. In this paper, we addressed these limitations by presenting a novel helix-based structure that mimicks the DNA double helix structure. This DNA-inspired helical continuum manipulator (DHCM) contains a helix structure and a constraint structure (a slender shaft or reinforced rings) that mimicks the base pairs of the DNA structure. Simulation results revealed that the stiffness of the helix structure is improved with the constraints. At the same bending stiffness, compared to the simple helix structure, the compressional and torsional stiffness of DHCM with the shaft constraint were improved by 12.3 times and 3.2 times, respectively. The kinematics of the DHCM were derived to predicate the deformation of the DHCM based on the piecewise constant curvature assumption. The model predicted deformation of the DHCM with a mean error of 4.16 mm (6.9%). The equivalent stiffness model of the DHCM was proposed and used to derive the statics of the DHCM. The mean error of distal end between statics predictions and experiment results was 1.01 mm (1.7%). • A novel helix-based continuum manipulator with constraints was proposed. • It has high torsional and axial stiffness while preserving low bending stiffness. • Kinematic model is derived and validated by experiments. • Equivalent stiffness is derived and validated by FEA. • With the Cosserat rod theory, the static model is developed and validated. [ABSTRACT FROM AUTHOR]