Establishment of standards for the referral of large nonpedunculated colorectal polyps: an international expert consensus using a modified Delphi process.

BACKGROUND AND AIMS: Resection of colorectal polyps has been shown to decrease the incidence and mortality of colorectal cancer. Large nonpedunculated colorectal polyps are often referred to expert centers for endoscopic resection, which requires relevant information to be conveyed to the therapeutic endoscopist to allow for triage and planning of resection technique. The primary objective of this study was to establish minimum expected standards for the referral of large nonpedunculated colonic polyps for potential endoscopic resection. METHODS: A Delphi method was used to establish consensus on minimum expected standards for the referral of large colorectal polyps among a panel of international endoscopy experts. The expert panel was recruited through purposive sampling, and 3 rounds of surveys were conducted to achieve consensus. Quantitative and qualitative data were analyzed for each round. RESULTS: A total of 24 international experts from diverse continents participated in the Delphi study, resulting in consensus on 19 statements related to the referral of large colorectal polyps. The identified factors, including patient demographic characteristics, relevant medications, lesion factors, photodocumentation, and the presence of a tattoo, were deemed important for conveying the necessary information to therapeutic endoscopists. The mean scores for the statements, which were scored on a scale of 1 to 10, ranged from 7.04 to 9.29, with high percentages of experts considering most statements as a very high priority. Subgroup analysis according to continent revealed some variations in consensus rates among experts from different regions. CONCLUSIONS: The identified consensus statements can aid in improving the triage and planning of resection techniques for large colorectal polyps, ultimately contributing to the reduction of colorectal cancer incidence and mortality.

EUS-Guided Choledocho-duodenostomy Using Lumen Apposing Stent Versus ERCP With Covered Metallic Stents in Patients With Unresectable Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Trial (DRA-MBO Trial).

BACKGROUND & AIMS: Several studies have compared primary endoscopic ultrasound (EUS)-guided biliary drainage to endoscopic retrograde cholangiopancreatography (ERCP) with insertion of metal stents in unresectable malignant distal biliary obstruction (MDBO) and the results were conflicting. The aim of the current study was to compare the outcomes of the procedures in a large-scale study. METHODS: This was a multicenter international randomized controlled study. Consecutive patients admitted for obstructive jaundice due to unresectable MDBO were recruited. Patients were randomly allocated to receive EUS-guided choledocho-duodenostomy (ECDS) or ERCP for drainage. The primary outcome was the 1-year stent patency rate. Other outcomes included technical success, clinical success, adverse events, time to stent dysfunction, reintervention rates, and overall survival. RESULTS: Between January 2017 and February 2021, 155 patients were recruited (ECDS 79, ERCP 76). There were no significant differences in 1-year stent patency rates (ECDS 91.1% vs ERCP 88.1%, P = .52). The ECDS group had significantly higher technical success (ECDS 96.2% vs ERCP 76.3%, P < .001), whereas clinical success was similar (ECDS 93.7% vs ERCP 90.8%, P = .559). The median (interquartile range) procedural time was significantly shorter in the ECDS group (ECDS 10 [5.75-18] vs ERCP 25 [14-40] minutes, P < .001). The rate of 30-day adverse events (P = 1) and 30-day mortality (P = .53) were similar. CONCLUSION: Both procedures could be options for primary biliary drainage in unresectable MDBO. ECDS was associated with higher technical success and shorter procedural time then ERCP. Primary ECDS may be preferred when difficult ERCPs are anticipated. This study was registered to Clinicaltrials.gov NCT03000855.

Locoregional delivery of CAR-T cells in the clinic.

Cellular therapies utilizing T cells expressing chimeric antigen receptors (CARs) have garnered significant interest due to their clinical success in hematological malignancies. Unfortunately, this success has not been replicated in solid tumors, with only a small fraction of patients achieving complete responses. A number of obstacles to effective CAR-T cell therapy in solid tumors have been identified including tumor antigen heterogeneity, poor T cell fitness and persistence, inefficient trafficking and inability to penetrate into the tumor, immune-related adverse events due to on-target/off-tumor toxicity, and the immunosuppressive tumor microenvironment. Many preclinical studies have focused on improvements to CAR design to try to overcome some of these hurdles. However, a growing body of work has also focused on the use of local and/or regional delivery of CAR-T cells as a means to overcome poor T cell trafficking and inefficient T cell penetration into tumors. Most trials that incorporate locoregional delivery of CAR-T cells have targeted tumors of the central nervous system - repurposing an Ommaya/Rickham reservoir for repeated delivery of cells directly to the tumor cavity or ventricles. Hepatic artery infusion is another technique used for locoregional delivery to hepatic tumors. Locoregional delivery theoretically permits increased numbers of CAR-T cells within the tumor while reducing the risk of immune-related systemic toxicity. Studies to date have been almost exclusively phase I. The growing body of evidence indicates that locoregional delivery of CAR-T cells is both safe and feasible. This review focuses specifically on the use of locoregional delivery of CAR-T cells in clinical trials.

Narrow band imaging versus white light for detecting sessile serrated lesion: A prospective randomized multicenter study.

Objectives: Colonoscopy is the gold standard diagnostic test used to detect early colorectal lesions and prevent colorectal carcinoma. Narrow band imaging (NBI) is an imaging technique that provides improved image resolution of the mucosa during endoscopy. Whether NBI improves the detection of sessile serrated lesion (SSL) is controversial-our aim was to assess this during routine colonoscopy. Methods: We conducted a multicenter, prospective, randomized, controlled trial. Patients underwent colonoscopy for screening, surveillance, or symptoms. They were randomized to either high-definition white light (HD-WL) or NBI in a 1:1 ratio. The primary outcome was SSL detection rate. Secondary outcomes were adenoma detection rate (ADR) and polyp detection rate (PDR). Results: A total of 400 patients were randomized to NBI (N = 200) or HD-WL (N = 200). The total colonoscopy time was slightly longer in the NBI group compared to HD-WL (median time 14 vs. 12 min, p = 0.033). There were no statistically significant differences in SSL detection rate (7.5% NBI vs. 8.0% HD-WL; p = 0.852), ADR (41.0% NBI vs. 37.5% HD-WL; p = 0.531), or PDR (61.0% NBI vs. 54.0% HD-WL; p = 0.157) between the two groups. No significant predictors of SSL detection were found on univariable or multivariable analysis. Increasing age and increased withdrawal time were an independent predictors of polyp detection and increasing age was also an independent predictor of adenoma detection on multivariable analysis. Conclusion: In the hands of experienced colonoscopists, NBI does not improve SSL detection compared to HD-WL. Withdrawal time and patient age remain important factors for polyp and adenoma detection.

The next wave of cellular immunotherapies in pancreatic cancer.

Pancreatic cancer is an aggressive disease that is predicted to become the second leading cause of cancer-related death worldwide by 2030. The overall 5-year survival rate is around 10%. Pancreatic cancer typically presents late with locally advanced or metastatic disease, and there are limited effective treatments available. Cellular immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has had significant success in treating hematological malignancies. However, CAR T cell therapy efficacy in pancreatic cancer has been limited. This review provides an overview of current and ongoing CAR T cell clinical studies of pancreatic cancer and the major challenges and strategies to improve CAR T cell efficacy. These strategies include arming CAR T cells; developing off-the-shelf allogeneic CAR T cells; using other immune CAR cells, like natural killer cells and tumor-infiltrating lymphocytes; and combination therapy. Careful incorporation of preclinical models will enhance management of affected individuals, assisting incorporation of cellular immunotherapies. A multifaceted, personalized approach involving cellular immunotherapy treatment is required to improve pancreatic cancer outcomes.

Exploring the Clinical Utility of Pancreatic Cancer Circulating Tumor Cells.

Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type, characterized by a dismal prognosis due to late diagnosis, frequent metastases, and limited therapeutic response to standard chemotherapy. Circulating tumor cells (CTCs) are a rare subset of tumor cells found in the blood of cancer patients. CTCs has the potential utility for screening, early and definitive diagnosis, prognostic and predictive assessment, and offers the potential for personalized management. However, a gold-standard CTC detection and enrichment method remains elusive, hindering comprehensive comparisons between studies. In this review, we summarize data regarding the utility of CTCs at different stages of PDAC from early to metastatic disease and discuss the molecular profiling and culture of CTCs. The characterization of CTCs brings us closer to defining the specific CTC subpopulation responsible for metastasis with the potential to uncover new therapies and more effective management options for PDAC.

Endoscopic ultrasound-guided gallbladder and bile duct drainage with lumen apposing metal stent: A large multicenter cohort (with videos).

BACKGROUND AND AIM: Cholecystectomy and endoscopic retrograde cholangiopancreatography are the gold standard for managing acute cholecystitis and malignant biliary obstruction, respectively. Recent advances in therapeutic endoscopic ultrasound (EUS) have provided alternatives for managing patients in whom these approaches fail, namely, EUS-guided gallbladder drainage (EUS-GB) and EUS-guided bile duct drainage (EUS-BD). We aimed to assess the technical and clinical success of these techniques in the largest multicenter cohort published to date. METHODS: A retrospective, multicenter, observational study involving 17 centers across Australia and New Zealand was conducted. All patients who had EUS-GB or EUS-BD performed in a participating center using a lumen apposing metal stent between 2016 and 2020 were included. Primary outcome was technical success, defined as intra-procedural successful drainage. Secondary outcomes included clinical success and 30-day mortality. RESULTS: One hundred and fifteen patients underwent EUS-GB (n = 49) or EUS-BD (n = 66). EUS-GB was technically successful in 47 (95.9%) while EUS-BD was successful in 60 (90.9%). All failed cases were due to maldeployment of the distal flange outside of the targeted lumen. Clinical success of EUS-GB was achieved in 39 (79.6%). No patients required subsequent cholecystectomy. Clinical success of EUS-BD was achieved in 52 (78.8 %). Thirty-day mortality was 14.3% for EUS-GB and 12.1% for EUS-BD. CONCLUSIONS: EUS-guided gallbladder drainage and EUS-BD are promising alternatives for managing nonsurgical candidates with cholecystitis and malignant biliary obstruction following failed endoscopic retrograde pancreatography. Both techniques delivered high technical success with acceptable clinical success. Further research is needed to investigate the gap between technical and clinical success.

Endoscopic bariatric therapies for obesity: a review.

▪ Obesity is reaching pandemic proportions globally, with overweight or obesity affecting at least two-thirds of Australian adults. ▪ Bariatric surgery is an effective weight loss strategy but is constrained by high resource requirements and low patient acceptance. ▪ Multiple endoscopic bariatric therapies have matured, with well established and favourable safety and efficacy profiles in multiple randomised controlled trials (RCTs), and are best used within a multidisciplinary setting as an adjuvant to lifestyle intervention. ▪ Three types of intragastric balloon are currently in use in Australia offering average total weight loss ranging from 10% to 18%, with others available internationally. ▪ Endoscopic sleeve gastroplasty produces average total weight loss of 15-20% with low rates of severe complications, with RCT data anticipated in December 2021. ▪Bariatric and metabolic endoscopy is rapidly evolving, with many novel, promising therapies currently under investigation.

SAGES guidelines for the use of peroral endoscopic myotomy (POEM) for the treatment of achalasia.

BACKGROUND: Peroral endoscopic myotomy (POEM) is increasingly used as primary treatment for esophageal achalasia, in place of the options such as Heller myotomy (HM) and pneumatic dilatation (PD) OBJECTIVE: These evidence-based guidelines from the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) intend to support clinicians, patients and others in decisions about the use of POEM for treatment of achalasia. RESULTS: The panel agreed on 4 recommendations for adults and children with achalasia. CONCLUSIONS: Strong recommendation for the use of POEM over PD was issued unless the concern of continued postoperative PPI use remains a key decision-making concern to the patient. Conditional recommendations included the option of using either POEM or HM with fundoplication to treat achalasia, and favored POEM over HM for achalasia subtype III.

To evaluate the minimum number of renal scans required to follow pediatric patient postpyeloplasty.

The aim of the study is to evaluate the minimum number of renal scans required to follow pediatric patients postpyeloplasty. We prospectively reviewed the renal scans of 145 children with unilateral pelvi-ureteric junction obstruction who underwent dismembered pyeloplasty. Patients were then divided into four groups based on preoperative split renal function. All patients were followed with renal scan and ultrasound for minimum of 4 years. Renal scan and ultrasound were done after stent removal at 3, 6, and 12 months and then yearly after surgery. Drainage pattern (T1/2) was seen in all groups, except in patients where there was no comment on drainage pattern. Statistical analysis was performed using the Friedman ANOVA and Wilcoxon signed-ranks test as a post hoc test with Bonferroni correction and Kruskal-Wallis test with Mann-Whitney U-test as a post hoc test with Bonferroni correction. On comparison of the pattern of drainage with time in Groups 1-4, it was found that there was no significant difference with time in Group 1. Then, further, using Wilcoxon signed-rank test as post hoc test for Friedman ANOVA, Group 2 showed statistically significant difference in drainage pattern in scans between 6 months and 1 year, Group 3 showed statistically significant difference in drainage pattern in scans between 3 months and 1 year, and Group 4 showed statistically significant difference in drainage pattern in scans done between 3 and 6 months (P < 0.05). Minimum of three renal scans were required for paediatric patients post pyeloplasty at 3 months, 6 months and 1 year in the follow up period.

A Rare Case of Duodenal Adenocarcinoma Presenting as a Subepithelial Lesion in a Patient Undergoing Investigation for Iron Deficiency Anaemia.

INTRODUCTION: Adenocarcinomas account for approximately 40% of small bowel cancers. They are typically mucosal lesions with distinctive features on endoscopy. We describe a rare case of duodenal adenocarcinoma presenting as a subepithelial lesion which posed a diagnostic challenge. CASE: An 85-year-old male patient presented for investigation of iron deficiency anaemia. Initial upper endoscopy found a subepithelial duodenal lesion with central depression but otherwise normal appearing mucosa. Superficial biopsies of the duodenal lesion were unremarkable. Subsequent antegrade single balloon enteroscopy revealed active bleeding from the lesion which was refractory to endoscopic treatment. A complete local excision of the lesion via laparotomy was necessary to achieve haemostasis. Histopathology from the lesion showed a moderately differentiated duodenal adenocarcinoma with invasion into the submucosa but no evidence of lymphovascular spread. CONCLUSION: Duodenal adenocarcinomas are rare gastrointestinal tumours associated with a poor prognosis. This case report outlines a rare presentation of duodenal adenocarcinoma and highlights the importance of judicious assessment of lesions found on endoscopy. Advances in endoscopic diagnostic modalities could facilitate early diagnosis and improve therapeutic outcomes.

An international, multi-institution survey of the use of EUS in the diagnosis of pancreatic cystic lesions.

BACKGROUND AND OBJECTIVES: Currently, pancreatic cystic lesions (PCLs) are recognized with increasing frequency and have become a more common finding in clinical practice. EUS is challenging in the diagnosis of PCLs and evidence-based decisions are lacking in its application. This study aimed to develop strong recommendations for the use of EUS in the diagnosis of PCLs, based on the experience of experts in the field. METHODS: A survey regarding the practice of EUS in the evaluation of PCLs was drafted by the committee member of the International Society of EUS Task Force (ISEUS-TF). It was disseminated to experts of EUS who were also members of the ISEUS-TF. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized. RESULTS: Fifteen questions were extracted and disseminated among 60 experts for the survey. Fifty-three experts completed the survey within the specified time frame. The average volume of EUS cases at the experts' institutions is 988.5 cases per year. CONCLUSION: Despite the limitations of EUS alone in the morphologic diagnosis of PCLs, the results of the survey indicate that EUS-guided fine-needle aspiration is widely expected to become a more valuable method.

Stylet slow-pull versus standard suction for endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic lesions: a multicenter randomized trial.

BACKGROUND AND STUDY AIM: Standard endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) procedures involve use of no-suction or suction aspiration techniques. A new aspiration method, the stylet slow-pull technique, involves slow withdrawal of the needle stylet to create minimum negative pressure. The aim of this study was to compare the sensitivity of EUS-FNA using stylet slow-pull or suction techniques for malignant solid pancreatic lesions using a standard 22-gauge needle. PATIENTS AND METHODS: Consecutive patients presenting for EUS-FNA of pancreatic mass lesions were randomized to the stylet slow-pull or suction techniques using a 22-gauge needle. Both techniques were standardized for each pass until an adequate specimen was obtained, as determined by rapid on-site cytology examination. Patients were crossed over to the alternative technique after four nondiagnostic passes. RESULTS: Of 147 patients screened, 121 (mean age 64 ±â€Š13.8 years) met inclusion criteria and were randomized to the stylet slow-pull technique (n = 61) or the suction technique (n = 60). Technical success rates were 96.7 % and 98.3 % in the slow-pull and suction groups, respectively (P > 0.99). The sensitivity for malignancy of EUS-FNA was 82 % in the slow-pull group and 69 % in the suction group (P = 0.10). The first-pass diagnostic rate (42.6 % vs. 38.3 %; P = 0.71), acquisition of core tissue (60.6 % vs. 46.7 %; P = 0.14), and the median (range) number of passes to diagnosis (2 1 2 3 vs. 1 1 2; P = 0.71) were similar in the slow-pull and suction groups, respectively. CONCLUSIONS: The stylet slow-pull and suction techniques both offered high and comparable diagnostic sensitivity with a mean of 2 passes required for diagnosis of solid pancreatic lesions. The endosonographer may choose either technique during FNA.

Peroral endoscopic myotomy as salvation technique post-Heller: International experience.

BACKGROUND: Treatment for achalasia has traditionally been Heller myotomy (HM). Despite its excellent efficacy rate, a number of patients remain symptomatic post-procedure. Limited data exist as to the best management for recurrence of symptoms post-HM. We present an international, multicenter experience evaluating the efficacy and safety of post-HM peroral endoscopic myotomy (POEM). METHODS: Patients who underwent POEM post-HM from 13 centers from January 2012 to January 2017 were included as part of a prospective registry. Technical success was defined as successful completion of the myotomy. Clinical success was defined as an Eckardt score of ≤3 on 12-month follow up. Adverse events (AE) including anesthesia-related, operative, and postoperative complications were recorded. RESULTS: Fifty-one patients were included in the study (mean age 54.2, 47% male). Technical success was achieved in 100% of patients. Clinical success on long-term follow up was achieved in 48 patients (94%), with a mean change in Eckardt score of 6.25. Seven patients (13%) had AE: six experienced periprocedural mucosal defect treated endoscopically and two patients developed mediastinitis treated conservatively. CONCLUSION: For patients with persistent symptoms after HM, POEM is a safe salvation technique with good short-term efficacy. As a result of the challenge associated with repeat HM, POEM might become the preferred technique in this patient population. Further studies with longer follow up are needed.

Practice guidelines for endoscopic ultrasound-guided celiac plexus neurolysis.

OBJECTIVES: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN). METHODS: Six important clinical questions were determined regarding EUS-CPN. Following a detailed literature review, 6 statements were proposed attempting to answer those questions. A group of expert endosonographers convened in Chicago, United States (May 2016), where the statements were presented and feedback provided. Subsequently a consensus group of 35 expert endosonographers voted based on their individual level of agreement. A strong recommendation required 80% voter agreement. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence. RESULTS: Eighty percent agreement was reached on 5 of 6 consensus statements, 79.4% agreement was reached on the remaining one. CONCLUSIONS: EUS-CPN is efficacious, should be integrated into the management of pancreas cancer pain, and can be considered early at the time of diagnosis of inoperable disease. Techniques may still vary based on operator experience. Serious complications exist, but are rare.

Double-balloon enteroscopy-assisted dilatation avoids surgery for small bowel strictures: A systematic review.

AIM: To evaluate the therapeutic role of double-balloon enteroscopy (DBE) in small bowel strictures and to propose a standard approach to small bowel strictures. METHODS: Systematic review of studies involving DBE in patients with small bowel strictures. Only studies limited to small bowel strictures were included and those with ileo-colonic strictures were excluded. RESULTS: In total 13 studies were included, in which 310 patients were dilated. The average follow-up time was 31.8 mo per patient. The complication rate was 4.8% per patient and 2.6% per dilatation. Surgery was avoided in 80% of patients. After the first dilatation, 46% were treated with re-dilatation and only 17% required surgery. CONCLUSION: DBE-assisted dilatation avoids surgery in 80% of patients with small bowel strictures and is safe and effective. We propose a standardized approach to small bowel strictures.

Efficacy and Safety of Peroral Endoscopic Myotomy for Treatment of Achalasia After Failed Heller Myotomy.

BACKGROUND & AIMS: In patients with persistent symptoms after Heller myotomy (HM), treatment options include repeat HM, pneumatic dilation, or peroral endoscopic myotomy (POEM). We evaluated the efficacy and safety of POEM in patients with achalasia with prior HM vs without prior HM. METHODS: We conducted a retrospective cohort study of 180 patients with achalasia who underwent POEM at 13 tertiary centers worldwide, from December 2009 through September 2015. Patients were divided into 2 groups: those with prior HM (HM group, exposure; n = 90) and those without prior HM (non-HM group; n = 90). Clinical response was defined by a decrease in Eckardt scores to 3 or less. Adverse events were graded according to criteria set by the American Society for Gastrointestinal Endoscopy. Technical success, clinical success, and rates of adverse events were compared between groups. Patients were followed up for a median of 8.5 months. RESULTS: POEM was technically successful in 98% of patients in the HM group and in 100% of patients in the non-HM group (P = .49). A significantly lower proportion of patients in the HM group had a clinical response to POEM (81%) than in the non-HM group (94%; P = .01). There were no significant differences in rates of adverse events between the groups (8% in the HM group vs 13% in the non-HM group; P = .23). Symptomatic reflux and reflux esophagitis after POEM were comparable between groups. CONCLUSIONS: POEM is safe and effective for patients with achalasia who were not treated successfully by prior HM. Although the rate of clinical success in patients with prior HM is lower than in those without prior HM, the safety profile of POEM is comparable between groups.