Successful minimally invasive management of adverse events following EUS-guided gallbladder drainage in a suboptimal surgical patient.

Video 1Successful minimally invasive management of adverse events following EUS-guided gallbladder drainage in a suboptimal surgical patient.

Characterizing a CT esophagram protocol after flexible endoscopic diverticulotomy for Zenker's diverticulum: a retrospective series.

Background: Flexible endoscopic cricopharyngeal myotomy and septotomy offer a minimally invasive transluminal option for the treatment of symptomatic Zenker's diverticulum (ZD). There is currently no consensus regarding postoperative follow-up imaging. We suggest a standardized computed tomography (CT) esophagram protocol for radiographic evaluation of postoperative findings. Methods: Single center retrospective analysis of patients with symptomatic ZD who underwent flexible endoscopic diverticulotomy and postoperative imaging with CT esophagram from January 2015 to March 2020. An experienced radiologist blinded to the initial imaging reports prospectively interpreted all CT esophagram findings, in order to minimize bias. Results: Twenty-one patients underwent CT esophagram following flexible endoscopic diverticulotomy for ZD. Diverticulotomy was technically successful in all patients. Most common findings on imaging included: atelectasis (13/21; 62%), persistent esophageal diverticulum (7/21; 33%), pneumomediastinum (3/21; 14%), aspiration (2/21; 10%), and extraluminal air and contrast extravasation consistent with focal esophageal perforation (1/21; 5%). Conclusions: We describe a standardized, simple, and accessible CT esophagram protocol for postoperative imaging of patients with post-flexible endoscopic cricopharyngeal myotomy and septotomy for ZD. CT esophagram facilitates a definitive exclusion of focal esophageal perforation as a postoperative complication of flexible endoscopic diverticulotomy by ruling out extraluminal air and contrast extravasation.

CYP2C19 genotype variability in patients with refractory gastroesophageal reflux after per-oral endoscopic myotomy (POEM).

Background and study aims Symptomatic gastroesophageal reflux is a recognized potential adverse event following peroral endoscopic myotomy (POEM). Proton pump inhibitors (PPIs) are an effective first-line therapy; although their efficacy can be affected by genotype cytochrome P450 2C19 (CYP2C19) variability leading to enhanced clearance of PPIs. The aim of our study was to evaluate the incidence of CYP2C19 genotype variability in POEM patients with refractory gastroesophageal reflux symptoms. Patients and methods This was a single-center, prospective, cohort study of consecutive POEM cases during a 7-year study period (2013-2020). Reflux symptoms were assessed with the validated gastroesophageal reflux disease questionnaire (GerdQ) and objective pH testing after POEM. CYP2C19 genotype testing was obtained in all patients with refractory gastroesophageal reflux disease (GERD) symptoms, defined as an abnormal pH study and GerdQ score ≥ 8 while on PPIs twice daily. Results POEM was performed in 325 consecutive patients (48.3 % female; mean age 57 years) during the study period. Twenty patients (6.8 %) had PPI-refractory, post-POEM gastroesophageal reflux based on their GerdQ score (median 9, range 8-11) and abnormal pH studies. CYP2C19 genotype testing identified 55 % (11/20) of these patients as being rapid metabolizers. Out of these, 9 (82 %) had improvement in clinical GERD symptoms after changing to a PPI less affected by CYP2C19 pharmacogenetics. Conclusions Post-POEM, PPI-refractory GERD is rare. As shown in this study, rapid metabolizers commonly respond by changing to a PPI less affected by CYP2C19 pharmacogenetics, thereby reducing the risk of long-term consequences from GERD and unnecessary anti-reflux surgery.

Diagnostic yield of EUS-guided through-the-needle microforceps biopsy versus EUS-FNA of pancreatic cystic lesions: a systematic review and meta-analysis.

Background and study aims Accurate diagnosis and risk stratification of pancreatic cysts (PCs) is challenging. The aim of this study was to perform a systematic review and meta-analysis to assess the feasibility, safety, and diagnostic yield of endoscopic ultrasound-guided through-the-needle biopsy (TTNB) versus fine-needle aspiration (FNA) in PCs. Methods Comprehensive search of databases (PubMed, EMBASE, Cochrane, Web of Science) for relevant studies on TTNB of PCs (from inception to June 2019). The primary outcome was to compare the pooled diagnostic yield and concordance rate with surgical pathology of TTNB histology and FNA cytology of PCs. The secondary outcome was to estimate the safety profile of TTNB. Results: Eight studies (426 patients) were included. The diagnostic yield was significantly higher with TTNB over FNA for a specific cyst type (OR: 9.4; 95 % CI: [5.7-15.4]; I 2  = 48) or a mucinous cyst (MC) (OR: 3.9; 95 % CI: [2.0-7.4], I 2  = 72 %). The concordance rate with surgical pathology was significantly higher with TTNB over FNA for a specific cyst type (OR: 13.5; 95 % CI: [3.5-52.3]; I 2  = 48), for a MC (OR: 8.9; 95 % [CI: 1.9-40.8]; I 2  = 29), and for MC histologic severity (OR: 10.4; 95 % CI: [2.9-36.9]; I 2  = 0). The pooled sensitivity and specificity of TTNB for MCs were 90.1 % (95 % CI: [78.4-97.6]; I 2  = 36.5 %) and 94 % (95 % CI: [81.5-99.7]; I 2  = 0), respectively. The pooled adverse event rate was 7.0 % (95 % CI: [2.3-14.1]; I 2  = 82.9). Conclusions TTNB is safe, has a high sensitivity and specificity for MCs and may be superior to FNA cytology in risk-stratifying MCs and providing a specific cyst diagnosis.

Effect of referral pattern and histopathology grade on surgery for nonmalignant colorectal polyps.

BACKGROUND AND AIMS: The incidence of surgery for nonmalignant colorectal polyps is rising. The aims of this study were to evaluate referral patterns to surgery for nonmalignant polyps, to compare outcomes between surgery and endoscopic resection (ER), and to identify factors associated with surgery in a university-based, tertiary care center. METHODS: Patients referred to colorectal surgery (CRS) for nonmalignant colorectal polyps between 2014 and 2019 were selected from the institution's integrated data repository. Clinical characteristics were obtained through chart review. Multivariate analysis was performed to identify factors associated with surgery for nonmalignant polyps. RESULTS: Six hundred sixty-four patients with colorectal lesions were referred to CRS, of which 315 were for nonmalignant polyps. Most referrals (69%) came from gastroenterologists. Of the 315 cases, 136 underwent surgery and 117 were referred for attempt at ER. Complete ER was achieved in 87.2% (n = 102), with polyp recurrence in 27.2% at a median of 14 months (range, 0-72). When compared with surgery, ER was associated with a lower hospitalization rate (22.2% vs 95.6%; P < .0001), shorter hospital stay (mean, .5 ± .9 vs 2.23 ± 1 days; P < .0001), and fewer adverse events (5.9% vs 22.8%; P = .0002). Intramucosal adenocarcinoma on baseline pathology (odds ratio, 5.7; 95% confidence interval, 1.2-28.2) and referrals by academic gastroenterologists (odds ratio, 2.5; 95% confidence interval, 1.11-5.72) were associated with a higher likelihood of surgery on multivariate analysis. CONCLUSIONS: Gastroenterologists commonly refer nonmalignant colorectal polyps to surgery, even though ER is effective and associated with lower morbidity. Both referrals from academic gastroenterologists and baseline pathology of intramucosal adenocarcinoma were factors associated with surgery. All colorectal polyps should be evaluated in a multidisciplinary approach to identify lesions suitable for ER before embarking in surgery.

Safety and effectiveness of balloon cryoablation for treatment of Barrett's associated neoplasia: systematic review and meta-analysis.

Background and study aims Balloon cryoablation (BC) is a novel procedure for endoscopic ablation of Barrett's esophagus (BE- associated neoplasia. We performed a meta-analysis to assess the feasibility, effectiveness, and safety of BC for treatment of BE neoplasia. Patients and methods Several databases were searched for relevant articles (PubMed, Web of Science, Google Scholar, EMBASE) as well as abstracts of recent gastroenterology meetings. Data extraction was performed by two investigators using standardized forms, including age, gender, length of BE segment, prior treatments, procedural time and number ablation sessions, technical feasibility, adverse events, and eradication rates of intestinal metaplasia (CE-IM) and dysplasia (CE-D) at follow-up. Quality of the studies was assessed using a modified Newcastle Ottawa Scale. Results Seven studies met inclusion criteria for a total of 548 ablation sessions in 272 patients. The most common histopathology reported prior to BC was high-grade dysplasia (n = 131), followed by low-grade dysplasia (n = 75), and intramucosal adenocarcinoma (n = 52). The pooled rate for technical feasibility was 95.8 % (95 % CI: 93.6-97.5 %; I 2  = 13.2 %; P  = 0.3). Pooled rates of CE-IM and CE-D were 85.8 % (95 % CI: 77.8-92.2 %, I 2  = 55.5 %; p = 0.04) and 93.8 % (95 % CI: 85.5-98.7 %, I 2  = 74.2 %; P  = 0.001), respectively. The overall adverse event (AE) rate was 12.5 % (34 out of 272 patients), of which stricture formation was the most common (5.8 %), followed by mucosal laceration (0.7 %), perforation (0.4 %), and bleeding (0.4 %). All AEs were successfully managed endoscopically. Conclusion This meta-analysis suggests that BC is a safe and effective ablative technique for treatment of BE neoplasia; future prospective comparative trials are needed to corroborate these initial findings.

Discrepancy between self-reported and actual colonoscopy polypectomy practices for the removal of small polyps.

BACKGROUND AND AIMS: Cold snare polypectomy (CSP) is associated with higher rates of complete resection compared with cold biopsy forceps (CBF) for the removal of small polyps (4-9 mm). This study aimed to evaluate self-reported polypectomy preferences and actual practice patterns among endoscopists at an academic center and to identify factors associated with the use of CSP for small polyps. METHODS: In phase A, endoscopists completed a survey evaluating preferences for polypectomy techniques. In phase B, we performed a retrospective analysis of all consecutive colonoscopies with polypectomy (January 2016 to September 2018). Uni- and multivariate analysis were performed to identify factors associated with CSP for small polyps. RESULTS: Nineteen of 26 (73%) endoscopists completed the survey (phase A); 3 (15.8%) were interventional endoscopists. Most respondents indicated that they use CSP (89.5%) for small polyps and identified no reasons for choosing CBF over CSP (73.7%). In phase B, we identified 1118 colonoscopies with 2625 polypectomies for polyps ≤9 mm. Most diminutive polyps (≤3 mm) were removed with CBF (819 of 912; 90%). CBF (46.2%) was also preferentially used for removal of small polyps (n = 1713), followed by hot snare polypectomy (27.2%), and CSP (26.6%). On multivariate analysis, interventional endoscopists were associated with a higher likelihood of using CSP for small polyps (odds ratio, 1.38; 95% confidence interval, 1.07-1.79; P = .01). CONCLUSIONS: Significant discrepancy exists between self-reported preferences and actual polypectomy practices. CBF is still preferentially used over CSP for the removal of polyps sized 4-9 mm; further strategies are needed to monitor and implement adequate polypectomy techniques.

Effect of prophylactic clip placement following endoscopic mucosal resection of large colorectal lesions on delayed polypectomy bleeding: A meta-analysis.

BACKGROUND: The role of prophylactic clipping for the prevention of delayed polypectomy bleeding (DPB) remains unclear and conclusions from prior meta-analyses are limited due to the inclusion of variety of resection techniques and polyp sizes. AIM: To conduct a meta-analysis on the effect of clipping on DPB following endoscopic mucosal resection (EMR) of colorectal lesions ≥ 20 mm. METHODS: We performed a search of PubMed and the Cochrane library for studies comparing the effect of clipping vs no clipping on DPB following endoscopic resection. The Cochran Q test and I 2 were used to test for heterogeneity. Pooling was conducted using a random-effects model. RESULTS: Thirteen studies with a total of 7794 polyps were identified, of which data was available on 1701 cases of EMR of lesions ≥ 20 mm. Prophylactic clipping was associated with a lower rate of DPB (1.4%) when compared to no clipping (5.2%) (pooled OR: 0.24, 95%CI: 0.12-0.50, P < 0.001) following EMR of lesions ≥ 20 mm. There was no significant heterogeneity among the studies (I 2 = 0%, P = 0.67). CONLUSION: Prophylactic clipping may reduce DPB following EMR of large colorectal lesions. Future trials are needed to further identify risk factors and stratify high risk cases in order to implement a cost-effective preventive strategy.

Once Versus Twice-Daily Oral Proton Pump Inhibitor Therapy for Prevention of Peptic Ulcer Rebleeding: A Propensity Score-Matched Analysis.

BACKGROUND: After inpatient management of upper gastrointestinal bleeding (GIB) due to peptic ulcer disease (PUD), oral proton pump inhibitor (PPI) therapy is recommended at discharge to decrease rebleeding risk and improve ulcer healing. Our aim is to determine whether once-daily oral PPI dosing at hospital discharge is associated with inferior 30-day rebleeding outcomes as compared to twice-daily dosing. METHODS: We retrospectively identified 233 patients admitted with signs and symptoms of upper GIB found to be due to PUD on upper endoscopy. After inpatient management, patients discharged on once-daily oral PPI were compared to those discharged on twice-daily therapy. We utilized propensity score matching based on Rockall scores to ensure the two groups were closely matched in terms of their baseline rebleeding risk. Primary outcome was the incidence of rebleeding within 30 days. Secondary outcomes were all-cause mortality, blood transfusion requirement, requirement for interventional radiology or surgery. RESULTS: Overall, 49 patients were discharged on once-daily and 184 on twice-daily PPI. Recurrent bleeding occurred in 18 patients (7.7%) within 30 days. There was no statistically significant difference in recurrent bleeding rates between once-daily (n = 7, 14.3%) as compared to twice-daily PPI (n = 11, 6%) (P = 0.053). In a 1:1 propensity score matched analysis, there was no statistically significant difference in 30-day recurrent bleeding rate between groups (14% once-daily vs. 4% twice-daily, P = 0.159). There were no differences in secondary outcomes. CONCLUSIONS: Once-daily oral PPI dosing at hospital discharge was not associated with inferior outcomes compared to twice-daily dosing in patients hospitalized for upper GIB due to PUD.

Merkel Cell Carcinoma of the Hand: A Case Report and Review of the Literature.

Background: Merkel cell carcinoma (MCC) is a relatively rare and aggressive cutaneous neuroendocrine malignancy characterized by high incidence of local recurrence, distant metastases, regional nodal metastases, and high mortality. Clinically, MCC presents as a persistent asymptomatic red/pink shaped nodule, usually smaller than 2 cm with nontender intracutaneous swelling, with rapidly growing localized disease with lymph node metastases preceding distant metastases. Because of its rare nature and the lack of comprehensive understanding of the disease, management of MCC has been controversial. Methods: An 87-year-old retired Caucasian male with a history of tobacco use, chronic sun exposure, and multiple squamous and basal cell carcinomas presented with a 1.8 × 1.3 cm red, nontender nodule on the dorsum of the proximal phalanx of the left long finger first noticed 6 months prior to presentation. Biopsy was consistent with MCC after which he was treated with wide local excision, full-thickness skin grafting, and sentinel lymphadenectomy (1/4 nodes positive) followed by adjuvant radiation therapy. Results: He recovered appropriately and was clinically and radiographically disease free at 2.5-year follow-up. Conclusion: Although it remains rare, MCC has increased in incidence over the last several decades and has a predilection to occur over sun exposed areas. Highly aggressive, it has a high incidence of regional and distant metastasis as well as local recurrence. As a result, it is important that practitioners involved in the care of skin and hand lesions be aware of this condition and the need for a multidisciplinary treatment approach.

Oral delivery of bioencapsulated proteins across blood-brain and blood-retinal barriers.

Delivering neurotherapeutics to target brain-associated diseases is a major challenge. Therefore, we investigated oral delivery of green fluorescence protein (GFP) or myelin basic protein (MBP) fused with the transmucosal carrier cholera toxin B subunit (CTB), expressed in chloroplasts (bioencapsulated within plant cells) to the brain and retinae of triple transgenic Alzheimer's disease (3×TgAD) mice, across the blood-brain barriers (BBB) and blood-retinal barriers (BRB). Human neuroblastoma cells internalized GFP when incubated with CTB-GFP but not with GFP alone. Oral delivery of CTB-MBP in healthy and 3×TgAD mice shows increased MBP levels in different regions of the brain, crossing intact BBB. Thioflavin S-stained amyloid plaque intensity was reduced up to 60% by CTB-MBP incubation with human AD and 3×TgAD mice brain sections ex vivo. Amyloid loads were reduced in vivo by 70% in hippocampus and cortex brain regions of 3×TgAD mice fed with bioencapsulated CTB-MBP, along with reduction in the ratio of insoluble amyloid ß 42 (Aß42) to soluble fractions. CTB-MBP oral delivery reduced Aß42 accumulation in retinae and prevented loss of retinal ganglion cells in 3×TgAD mice. Lyophilization of leaves increased CTB-MBP concentration by 17-fold and stabilized it during long-term storage in capsules, facilitating low-cost oral delivery of therapeutic proteins across the BBB and BRB.