Endoscopic Submucosal Dissection (ESD) Offers a Safer and More Cost-effective Alternative to Transanal Endoscopic Microsurgery (TEM): An International Collaborative Study.

BACKGROUND: Endoscopic submucosal dissection (ESD) and transanal endoscopic microsurgery (TEM) are minimally invasive procedures that treat early rectal cancer (ERC). Both are effective treatments, yet there are very few studies comparing them. The aim of our study was to identify ideal candidates for each procedure. MATERIALS AND METHODS: Between January 2016 and November 2019, 204 ERC patients were managed with either ESD (n=101) or TEM (n=103) at 7 international centers. Data analyzed included clinical success, tumor characteristics, procedure info, and recurrence rates. RESULTS: Median tumor size was 40 mm±23.9 in the ESD group and 56 mm±27.9 in the TEM group, significantly larger in the latter ( P <0.00001). Average procedure time was 131.5±67.9 minutes in ESD group and 104.9±28.4 minutes in TEM group ( P =0.000347). Average hospital stay was 3.3±2.6 days in the ESD group and 4.7±0.7 days in the TEM group ( P <0.00001). Adverse event rate was 6.8% in the ESD group and 24% in the TEM group. There were no significant difference in the rate of en bloc resection, technical success, tumor location, necessity of additional procedures, and tumor recurrence rates. CONCLUSION: Compared with TEM, ESD is a safer procedure with shorter hospital stay and should be offered for patients who have ERC.

Endoscopic retrograde cholangiopancreatography outcomes in inflammatory bowel disease patients: a 12-year analysis of a national database.

BACKGROUND: Despite inflammatory bowel disease's (IBD) association with hepatobiliary disorders and the use of endoscopic retrograde cholangiopancreatography (ERCP) for both diagnostic and therapeutic evaluation of these diseases, it remains a poorly studied area within the literature. The purpose of this study is to examine the effect of IBD on the occurrence of adverse events (AE) pertaining to ERCP. METHODS: This project utilized the National Inpatient Sample (NIS) database, the largest inpatient database in the USA. All patients 18 years or older with and without IBD undergoing ERCP were identified from 2008 to 2019. Post-ERCP AEs were analyzed using multivariate logistic or linear regression controlling for age, race, and existing comorbidities using the Charlson comorbidity index (CCI). RESULTS: There was no difference in post-ERCP pancreatitis (PEP) or mortality. IBD patients were also found to have a lower risk of bleeding and decreased length of stay (LOS) despite adjustment for comorbidities. They also underwent less sphincterotomies when compared to the non-IBD cohort. Subgroup analysis between ulcerative colitis (UC) and Crohn's disease (CD) did not find any significant differences in outcomes. CONCLUSION: To our knowledge, this is the largest study to date evaluating ERCP outcomes in IBD patients. After adjustment of co-variates, there was no difference in the occurrence of PEP, infections, and perforation. IBD patients were less likely to experience post-ERCP bleeding and mortality and had shorter LOS which may be due to the decreased frequency of sphincterotomy in this population.

Gastrointestinal Symptoms Predict the Outcomes From COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) has taken hundreds of thousands of lives globally. Besides the respiratory tract, the virus can affect the gastrointestinal (GI) tract. Data regarding the significance of GI symptoms in the COVID-19 course are limited. In this largest US study to date, the authors reviewed electronic encounters of 1003 consecutive patients who were tested positive for the virus between March 12 and April 3, 2020. Initial GI symptoms were present in up to 22.4% of patients and were associated with worse outcomes after adjustment for demographics, comorbidities, and other clinical symptoms. COVID-19 with GI involvement may define a more severe phenotype.

EUS-guided fine-needle liver biopsy in pediatric patients using a modified technique with one-pass, one-actuation wet suction.

BACKGROUND AND AIMS: Liver biopsy (LB) can be a valuable tool to determine the etiology of pediatric liver disease. There is limited data of the role of EUS-LB in children. This study evaluated the efficacy and the safety of a modified technique (M)LB in cases at high risk of bleeding or obese children. In addition, the tissue yield of EUS-(M)LB and percutaneous (PC) approach were compared. METHODS: A retrospective analysis was performed, comparing EUS-(M)LB and PC-LB in children at a tertiary referral center. All consecutive children referred for PC-LB and EUS-LB who had an unexplained liver test abnormality after exclusion of biliary disorders from March-2017 to August-2018 were included. EUS-(M)LB consisted of a one pass wet suction technique using a 19-gauche core needle. A comparison was performed between total specimen length (TSL) and the number of complete portal triads (CPTs). RESULTS: The cohort included 28 EUS-(M)LB and 28 PC-LB pediatric cases. The median (IQR) age was 14.5 years (13.4-16). The median TSL was 8.6 (5.8-9.6) in EUS-(M)LB cases and 7 cm (7-9) in PC-LB cases (P =0.788). The maximum intact specimen was 2.8 cm (EUS-(M)LB) and 1.6 cm (PC-LB) (P =0.009). The mean (SD) number of CPTs per sample was 28.2 (7.3) and 11.6 (2.1), respectively (P =0.001). Adverse events included once case of self-limited abdominal pain in the PC-LB group. CONCLUSION: EUS-(M)LB has the potential to be a safe and effective alternative diagnostic modality when compared to PC-LB, to evaluate children with unexplained liver test abnormalities who undergo EUS to evaluate biliary disorders.

Symptom resolution of bile reflux gastritis after transoral gastric outlet reduction in a patient with Billroth II anastomosis.

Endoscopic transoral outlet reduction (TORe) utilizing a full thickness endoscopic suturing device is a minimally invasive therapeutic option in bariatric surgery patients who have experienced weight gain, but also can be used in patients who underwent Billroth II (B-II) procedure with biliary reflux symptoms.

Revisional endoscopic sleeve gastroplasty of laparoscopic sleeve gastrectomy: an international, multicenter study.

BACKGROUND AND AIMS: Laparoscopic sleeve gastrectomy (LSG) facilitates significant and durable weight loss; however, weight recidivism and need for revisional surgery occur in a subset of patients. Reduction of a dilated LSG using the revisional endoscopic sleeve gastroplasty (R-ESG) approach is an appealing and minimally invasive alternative to surgical revision that is congruent with obesity as a chronic relapsing disease model. In this study, we examine the safety and efficacy of the technique in a large multicenter international cohort. METHODS: Prospectively collected data from 9 centers for 82 consecutive adults who underwent R-ESG for weight regain after LSG using the OverStitch device (Apollo Endosurgery, Austin, Tex, USA) from March 2014 to November 2019 were reviewed. Total body weight loss (TBWL) and adverse events were reported up to 12 months. Univariable logistic regression was used to identify predictors of response at 12 months. RESULTS: Eighty-two adults (92.7% female) experienced 27.9 ± 20.7 kg weight regain from post-LSG nadir weight, prompting R-ESG (mean age, 42.8 ± 10.4 years) at a mean weight of 128.2 ± 57.5 kg. Mean R-ESG procedure duration was 48.3 ± 20.5 minutes, and the median number of sutures used was 4 (interquartile range, 3-4). After R-ESG, TBWL (follow-up %) was 6.6% ± 3.2% at 1 month (81.7%), 10.6% ± 4.4% at 3 months (74.4%), 13.2% ± 10.1% at 6 months (63.4%), and 15.7% ± 7.6% at 12 months (51.2%). In a per-protocol analysis, ≥10% TBWL was achieved by 37 of 51 patients (72.5%) at 6 months and 34 of 42 patients (81.0%) at 12 months; ≥15% TBWL was achieved by 20 of 46 patients (43.5%) at 6 months and 22 of 42 patients (52.4%) at 12 months. Only 1 moderate adverse event occurred in the form of a narrowed gastroesophageal junction, which resolved after a single endoscopic dilation. CONCLUSIONS: R-ESG is a safe and effective means of facilitating weight loss for weight recidivism after LSG, with sustained results at 1 year. R-ESG should be considered before pursuing more-invasive surgical revisional options.

Impact of prior treatment on feasibility and outcomes of Zenker's peroral endoscopic myotomy (Z-POEM).

BACKGROUND: Zenker's peroral endoscopic myotomy (Z-POEM) is a novel procedure for the management of symptomatic Zenker's diverticulum. This study aims to report the technical feasibility and outcomes of Z-POEM in the management of Zenker's diverticulum after prior failed interventions. METHODS: Patients with persistent or recurrent symptoms after prior endoscopic and/or surgical intervention for Zenker's diverticulum were retrospectively included. The primary outcome was clinical success, defined as complete or near complete resolution of dysphagia (dysphagia score of 0 or 1) without the need for repeat endoscopic or surgical intervention during follow-up. RESULTS: Z-POEM was technically successful in 30/32 patients (93.8 %). Clinical success was achieved in 29/30 patients (96.7 %), and Z-POEM significantly reduced the median (interquartile range [IQR]) dysphagia score of patients from 2 (1 - 2) to 0 (0) (P < 0.001) over a median duration of follow up of 166 days (IQR 39 - 566). Four patients (12.5 %) had adverse events (two inadvertent mucosotomies and two leaks found on post-procedural esophagrams). CONCLUSION: Z-POEM is feasible, safe, and effective in the majority of patients with recurrent symptoms after prior surgical or endoscopic interventions.

Gastric per-oral endoscopic myotomy versus pyloromyotomy for gastroparesis: An international comparative study.

BACKGROUND AND AIM: Gastroparesis is a potentially debilitating gastric motility disorder with limited treatment options. Highest efficacy treatments include gastric per-oral endoscopic myotomy (GPOEM) and surgical pyloromyotomy. This study compares the efficacy and safety of GPOEM versus laparoscopic pyloromyotomy for refractory gastroparesis. METHODS: Patients who underwent GPOEM or laparoscopic pyloromyotomy for refractory gastroparesis from four centers across the USA and Latin America were included in a dedicated registry. Data collected included patient demographics, imaging, laboratory values, clinical success, gastroparesis cardinal symptom index, procedure time, pre-op and post-op gastric emptying times, adverse events, and hospital length of stay. RESULTS: A total of 102 patients were included (mean age 47; 32.4% male): GPOEM n = 39, surgical pyloromyotomy n = 63.Technical success was 100% in both groups. Clinical success was 92.3% in the GPOEM group and 82.5% in the surgery group (P = 0.164). The GPOEM group had a significantly higher post-op GSCI score reduction by 1.3 units (P < 0.00001), post-op retention reduction at 2 h by 18% (P < 0.00001), post-op retention reduction at 4 h by 25% (P < 0.00001) and a lower procedure time by 20 min (P < 0.00001) as compared with surgery. GPOEM also had a lower hospital length of stay by 2.8 days (P < 0.00001). Adverse events were significantly fewer in the GPOEM group (13%) compared with surgery group (33.3%; P = 0.021). Mean blood loss in the GPOEM group was only 3.6 mL compared with 866 mL in the surgery group. CONCLUSIONS: The GPOEM may be a less invasive, safer, and more efficacious procedural treatment for refractory gastroparesis as compared with surgical pyloromyotomy.

Mammary-like Carcinoma of the vulva: A diagnostic challenge.

Mammary-like carcinoma of the vulva is incredibly rare with less than 30 cases published since 1935, and the similarities of such pathology between breast cancer metastases, squamous adenocarcinoma, Bartholin gland carcinomas, etc, make an accurate diagnosis challenging. A diagnosis can be made utilizing immunohistochemical staining and patient history to rule out more likely causes such as metastases to ensure a correct diagnosis.

Helicobacter pylori Infection and Complications of Cirrhosis.

INTRODUCTION: Helicobacter pylori is a significant contributor to conditions such as peptic ulcer disease, gastric cancer, gastric mucosa-associated lymphoid tissue lymphoma, and colorectal cancer. Recent studies have suggested a potential link between H. pylori and cirrhosis. However, the impact of H. pylori on cirrhosis-related mortality, inpatient outcomes, and decompensating events remains unclear. Considering the widespread availability of H. pylori testing and effective treatment options, there is a potential rationale for eradicating H. pylori in cirrhotic patients to mitigate the morbidity and mortality associated with cirrhosis. This study aims to investigate the association between H. pylori and inpatient outcomes and complications related to cirrhosis. METHODS: The National Inpatient Sample (NIS) database, a part of the Healthcare Cost & Utilization Project, was utilized for this study. Inpatient data from the years 2016 through 2019 were extracted for patients with a primary discharge diagnosis of cirrhosis and a concurrent diagnosis of H. pylori infection. The primary outcomes included inpatient mortality, length of stay, and cost of care. Secondary outcomes involved cirrhosis-related complications during hospitalization, such as gastrointestinal bleeding, hepatic encephalopathy, and hepatorenal syndrome. RESULTS: Over the years 2016 to 2019, 416,410 patients received a primary discharge diagnosis of cirrhosis. Among them, 990 patients (0.2%) had a secondary diagnosis of H. pylori infection. Those with both cirrhosis and H. pylori tended to be younger on average (mean age 54.25 vs. 57.18 years, p=0.01) and more frequently fell within the age range of 18-49 (33.84% vs. 24.71%, P=0.01). H. pylori-infected patients were also more likely to be male (70.71% vs. 63.11%, P<0.028), of Hispanic race (36.4% vs. 18.6%, p< 0.1), and of Black race (20.2% vs. 8.1%, p< 0.1). While H. pylori-exposed patients had lower in-hospital mortality (0.51% vs. 4.44%, p=0.007), their mean length of stay was higher (6.97 days vs. 5.75, p=0.002). The overall cost of care was comparable between the H. pylori-exposed and non-exposed groups (mean USD18,106.18 vs. $16,543.49, P=0.160). H. pylori-exposed patients had a higher overall rate of cirrhosis-related complications (84.85% vs. 67.59%, p< 0.001), gastrointestinal bleeding (48.48% vs. 27.34%, p< 0.001), and hepatorenal syndrome (70.71% vs. 46.99%, p< 0.001), and these differences persisted in multivariable analysis. Initially, rates of hepatic encephalopathy were higher in H. pylori non-exposed patients (21.57% vs. 15.66%, p=0.04), but this discrepancy was corrected after adjusting for potential confounders. CONCLUSION: While patients in this study were diagnosed with both H. pylori and cirrhosis by discharge, it cannot be definitively concluded that H. pylori was the direct cause of cirrhosis complications. Recognizing this uncertainty, further studies are needed better to understand the associations between cirrhosis and H. pylori complications. Distinguishing the causes of cirrhosis and its relationship with H. pylori may offer deeper insights into whether H. pylori is a causative factor or merely correlated in its effects on patients with cirrhosis.

Endoscopic Management of Gastric Band Erosion: a Systematic Review and Meta-Analysis.

BACKGROUND: Gastric band erosion may be seen in up to 3% of patients. Endoscopic intervention has become increasingly utilized due to its minimally invasive nature. The purpose of this study was to perform a systematic review and meta-analysis to examine the role of endoscopic removal for eroded gastric bands. METHODS: Individualized search strategies were developed for PubMed, EMBASE, Web of Science, and Cochrane Library databases in accordance with PRISMA and MOOSE guidelines. Outcomes included technical success, clinical success, procedure duration, adverse events, and surgical conversion. Pooled proportions were analyzed using random effects models. Heterogeneity and publication bias was assessed with I2 statistics and funnel plot asymmetry using Egger and Begg tests. Meta-regression was also performed comparing outcomes by endoscopic tools. RESULTS: Ten studies (n=282 patients) were included in this meta-analysis. Mean age was 40.68±7.25 years with average duration of band placement of 38.49±19.88 months. Pre-operative BMI was 42.76±1.06 kg/m2 with BMI of 33.06±3.81 kg/m2 at time of band erosion treatment. Endoscopic removal was attempted in 240/282 (85.11%) of cases. Pooled technical and clinical success of the endoscopic therapy was 86.08% (95% CI: 79.42-90.83; I2=28.62%) and 85.34% (95% CI: 88.70-90.62; I2=38.56%), respectively. Mean procedure time for endoscopic removal was 46.47±11.52 min with an intra-operative adverse event rate of 4.15% (95% CI: 1.98-8.51; I2=0.00%). Post-procedure-associated adverse events occurred in 7.24% (CI: 4.46-11.55; I2=0.00%) of patients. Conversion to laparotomy/laparoscopy occurred in 10.54% (95% CI: 6.12-17.54) of cases. CONCLUSION: Endoscopic intervention is a highly effective and safe modality for the treatment of gastric band erosion.

Ex vivo nonbiomaterial gel-based model for endoscopic training.

Video 1Use of artificial model for endoscopic training.

Antireflux band mucosectomy: a novel minimally invasive approach for the treatment of refractory gastroesophageal reflux disease.

Background and Aims: Endoscopic therapies in the treatment of refractory GERD have largely been regarded as inferior as surgical intervention. Procedures such as the transoral endoscopic incisionless fundoplication (TIF), Stretta, and antireflux mucosectomy (ARMS) are less invasive but produce outcomes that are middling to lackluster, with many patients having to continue proton pump therapy without resolution of symptoms. Antireflux band mucosectomy (ARBM), in which the cardia is banded, may provide more effective relief. We present 4 patients with refractory GERD who did not opt for surgical intervention and were successfully treated with the ARBM procedure. Methods: Four patients with GERD refractory to medical therapy underwent ARBM. Three patients had nonerosive esophagitis and 1 patient had erosive esophagitis. Two patients had hiatal hernias ≤2 cm. All underwent preprocedure and postprocedure pH bravo testing as well as follow-up EGD. Results: All cases were completed successfully. All patients underwent a decrease in DeMeester score and acid exposure time. Procedure time ranged from 6 to 15 minutes. There were no adverse events. All patients were taken off proton pump inhibitor (PPI) therapy by 4 weeks postprocedure. Conclusions: Four patients with refractory GERD who declined surgery underwent the ARBM procedure with technical success. All experienced significant decrease to complete resolution of symptoms. All patients were weaned off PPIs by 4 weeks postprocedure.

Opioid use as a potential risk factor for pancreatic cancer in the United States: An analysis of state and national level databases.

Pancreatic cancer (PC) rate is increasing in the U.S. The use of prescription and illicit opioids has continued to rise nationally in recent years as well. Opioids have been shown to have a deleterious effect on multiple types of cancer with recent data suggesting opium use as a risk factor for PC. Using national databases, we tested whether opioid usage pattern over time could explain the state and national-based variations in PC rates in the U.S. Opioid death rate (as a surrogate for prescription and illicit opioid use) was extracted from the CDCs Wonder online data through the Vital Statistics Cooperative Program. Incidence of pancreatic cancer was retrieved from the online CDCs data base gathered from the U.S. Cancer Statistics Working Group. Prevalence of obesity, tobacco and alcohol use was collected from Behavioral risk factor surveillance system. Mixed-effects regression models were used to test the association between levels of PC rate and opioid death/use rates during the years 1999-2016. A rise in PC was seen over time at the national and state levels. Similarly, the opioid death rates increased over time. Among other potential PC risk factors, only obesity prevalence showed an increase during the study period. A state's opioid death rate at 4 years prior significantly predicted initial incidence of PC (ß = 0.1848, p<0.0001) and had a significant effect on the estimated annual change in the rate of PC (ß = -.0193,p<0.0001). Opioid use may be an un-identified risk factor contributing to the increasing incidence of PC in the U.S. These novel findings need to be verified by population-based studies.

Successful removal of a giant esophageal lipoma with hybrid endoscopic submucosal dissection.

Video 1Endoscopic submucosal dissection of a giant esophageal lipoma.

EUS-guided fine-needle core liver biopsy with a modified one-pass, one-actuation wet suction technique comparing two types of EUS core needles.

Background and study aims We compared the diagnostic yield and specimen adequacy in EUS-guided parenchymal biopsies between two types of EUS 19 G core needles. Patients and methods This is a retrospective study of 420 patients at two tertiary medical centers in Florida with unexplained abnormal liver associated tests were referred for EUS evaluation of biliary obstruction and pancreatic pathology. EUS-guided liver biopsy (EUS-LB) was performed at the same session after biliary obstruction was excluded. We compared intact specimen length (ISL), total specimen length (TSL), complete portal triads (CPT) and adverse events (AE). Welch's T and Tukey tests were used for ISL, TSL and CPT. Results A total of 210 patients underwent EUS-LB using a Franseen needle, 210 patients using a fork-tip needle. Median patient age was 52 years (15.63) and 238 (56.7 %) were female. The fork-tip needle had a mean ISL of 2.7 (1.1 SD) cm, TSL of 6 cm (2.1 SD), and mean 19.5 CPT (8.5 SD) Abdominal pain occurred in 35 patients (17 %) post-procedure and was managed with supportive care. Two patients required intravenous (IV) narcotic administration. Subcapsular hematomas occurred in 1 (0.5 %) patients. The Franseen needle had a mean ISL of 3.1 cm (1.3 SD), TSL of 6.5 cm (2.6 SD), and mean of 24 CPT (8.8 SD). Abdominal pain occurred in four patients (2 %) post-procedure, which resolved in all patients after IV narcotic administration. Subcapsular hematomas occurred in 1 (0.5 %) and bile leak in 1(0.4 %) patients. Conclusions Use of the Franseen needle resulted in better liver core samples than that obtained with a fork-tip needle.

Detection of Protease Activity by Fluorescent Peptide Zymography.

The purpose of this method is to measure the proteolytic activity of complex biological samples. The samples are separated by molecular weight using electrophoresis through a resolving gel embedded with a degradable substrate. This method differs from traditional gel zymography in that a quenched fluorogenic peptide is covalently incorporated into the resolving gel instead of full length proteins, such as gelatin or casein. Use of the fluorogenic peptides enables direct detection of proteolytic activity without additional staining steps. Enzymes within the biological samples cleave the quenched fluorogenic peptide, resulting in an increase in fluorescence. The fluorescent signal in the gels is then imaged with a standard fluorescent gel scanner and quantified using densitometry. The use of peptides as the degradable substrate greatly expands the possible proteases detectable with zymographic techniques.

Matrix-metalloproteinase expression and gelatinase activity in the avian retina and their influence on Müller glia proliferation.

Gelatinases are a class of matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) to regulate intercellular signaling and cell migration. Gelatinase activity is tightly regulated via proteolytic activation and through the expression of tissue inhibitors of matrix metalloproteinases (TIMPs). Gelatinase activity has been implicated in retinal pathophysiology in different animal models and human disease. However, the role of gelatinases in retinal regeneration remains uncertain. In this study we investigated the dynamic changes in gelatinase activity in response to excitotoxic damage and how this enzymatic activity influenced the formation of Müller glia progenitor cells (MGPCs) in the avian retina. This study used hydrogels containing a gelatinase-degradable fluorescent peptide to measure gelatinase activity in vitro and dye quenched gelatin to localize enzymatic activity in situ. These data were corroborated by using single cell RNA sequencing (scRNA-seq). Gelatinase mRNA, specifically MMP2, was detected in oligodendrocytes and Non-Astrocytic Inner Retinal Glia (NIRG). Total retinal gelatinase activity was reduced following NMDA-treatment, and sustained inhibition of MMP2 prior to damage or growth factor treatment increased the formation of proliferating MGPCs and c-fos signaling. We observed that microglia, Müller glia (MG), and NIRG cells were involved in regulating changes in gelatinase activity through TIMP2 and TIMP3. Collectively, these findings implicate MMP2 in reprogramming of Muller glia into MGPCs.

MDM2 Derived from Dedifferentiated Liposarcoma Extracellular Vesicles Induces MMP2 Production from Preadipocytes.

Dedifferentiated liposarcoma (DDLPS) is frequently diagnosed late, and patients typically respond poorly to treatments. DDLPS is molecularly characterized by wild-type p53 and amplification of the MDM2 gene, which results in overexpression of MDM2 protein, a key oncogenic process in DDLPS. In this study, we demonstrate that extracellular vesicles derived from patients with DDLPS or from DDLPS cell lines are carriers of MDM2 DNA that can be transferred to preadipocytes, a major and ubiquitous cellular component of the DDLPS tumor microenvironment, leading to impaired p53 activity in preadipocytes and increased proliferation, migration, and production of matrix metalloproteinase 2; treatment with MDM2 inhibitors repressed these effects. Overall, these findings indicate that MDM2 plays a crucial role in DDLPS by enabling cross-talk between tumor cells and the surrounding microenvironment and that targeting vesicular MDM2 could represent a therapeutic option for treating DDLPS. SIGNIFICANCE: Extracellular vesicles derived from dedifferentiated liposarcoma cells induce oncogenic properties in preadipocytes.