Reem Z. Sharaiha

Human bile contains MicroRNA‐laden extracellular vesicles that can be used for cholangiocarcinoma diagnosis

Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Primary sclerosing cholangitis (PSC) patients pose a particularly difficult clinical dilemma because they harbor chronic biliary strictures that are difficult to distinguish from CCA. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither extracellular vesicles (EVs) nor miRs within EVs have been investigated in human bile. We aimed to comprehensively characterize human biliary EVs, including their miR content. We have established the presence of extracellular vesicles in human bile. In addition, we have demonstrated that human biliary EVs contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers, and size distribution of human biliary EVs. Utilizing multivariate organization of combinatorial alterations (MOCA), we defined a novel biliary vesicle miR‐based panel for CCA diagnosis that demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. Conclusion: These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR‐based disease markers in bile. Finally, we report on the development of a novel bile‐based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility. (Hepatology 2014;60:896–907)

Dating the Rise of Esophageal Adenocarcinoma: Analysis of Connecticut Tumor Registry Data, 1940–2007

Background: The timing of onset of the rise in incidence of esophageal adenocarcinoma (EAC) has not been clearly defined, and doing so may provide clues with regard to exposures associated with the changed epidemiology of this malignancy. We therefore aimed to investigate historical trends in the incidence of EAC and other upper gastrointestinal malignancies. Methods: We did a population-based study using Connecticut Tumor Registry (1940–2007) and Surveillance, Epidemiology, and End Results (SEER; 1973–2007) data. Age-adjusted incidence rates (per 100,000 person-years) were calculated for EAC and other upper gastrointestinal malignancies. Results: The incidence of EAC remained relatively constant until 1965–69, and then rose from 0.41 (95%CI, 0.26–0.56) to 1.31 (95%CI 1.07–1.54) in 1978–82 and 5.31 (95%CI 4.89–5.73) in 2003–07. The incidence of gastric cardia cancer began to rise in the 1950s and plateaued in the 1990s. The incidence of esophageal squamous cell carcinoma began to decrease around 1980. The trends from Connecticut Tumor Registry data closely mirrored those from SEER data. Conclusions: The incidence of EAC began to rise in the late 1960s, predating the rise in obesity by a decade. Reduced infection rates of Helicobacter pylori, changes in microbiome, or other exposures may have contributed to the changed epidemiology of this malignancy. Impact: Analysis of historical data of trends in EAC incidence implicate a change in environmental factors from the mid-20th century as primarily responsible for the initial rise in EAC incidence, predating the rise in obesity prevalence in the United States by over a decade. Cancer Epidemiol Biomarkers Prev; 20(1); 183–6. ©2011 AACR.

Initial experience with endoscopic sleeve gastroplasty: technical success and reproducibility in the bariatric population.

BACKGROUND AND AIMS Novel endoscopic techniques have been developed as effective treatments for obesity. Recently, reduction of gastric volume via endoscopic placement of full-thickness sutures, termed endoscopic sleeve gastroplasty (ESG), has been described. Our aim was to evaluate the safety, technical feasibility, and clinical outcomes for ESG. PATIENT AND METHODS Between August 2013 and May 2014, ESG was performed on 10 patients using an endoscopic suturing device. Their weight loss, waist circumference, and clinical outcomes were assessed. RESULTS Mean patient age was 43.7 years and mean body mass index (BMI) was 45.2 kg/m(2). There were no significant adverse events noted. After 1 month, 3 months, and 6 months, excess weight loss of 18 %, 26 %, and 30 %, and mean weight loss of 11.5 kg, 19.4 kg, and 33.0 kg, respectively, were observed. The differences observed in mean BMI and waist circumference were 4.9 kg/m(2) (P = 0.0004) and 21.7 cm (P = 0.003), respectively. CONCLUSIONS ESG is effective in achieving weight loss with minimal adverse events. This approach may provide a cost-effective outpatient procedure to add to the steadily growing armamentarium available for treatment of this significant epidemic.

Comparative analysis of traditional and coiled fiducials implanted during EUS for pancreatic cancer patients receiving stereotactic body radiation therapy.

BACKGROUND EUS-guided fiducial placement facilitates image-guided radiation therapy (IGRT). OBJECTIVE To compare 2 types of commercially available fiducials for technical success, complications, visibility, and migration. DESIGN Retrospective, single-center, comparative study. SETTING Tertiary-care medical center. INTERVENTIONS Traditional fiducials (TFs) (5-mm length, 0.8-mm diameter) and Visicoil fiducials (VFs) (10-mm length, 0.35-mm diameter) were compared. Fiducials were placed using linear 19-gauge (for TFs) or 22-gauge (for VFs) needles. A subjective visualization scoring system (0-2; 0 = not visible, 1 = barely visible, 2 = clearly visible) was used to assess visibility on CT. Fiducial migration was calculated as a change in interfiducial distance. MAIN OUTCOME MEASUREMENTS Technical success, complications, visibility, and migration of 2 types of fiducials. RESULTS Thirty-nine patients with locally advanced pancreatic cancer underwent EUS-guided placement of 103 fiducials (77 TFs, 26 VFs). The mean number of fiducials placed per patient was 2.66 (standard deviation 0.67) for the 19-gauge needle and 2.60 (standard deviation 0.70) for the 22-gauge needle (P = .83). No intra- or postprocedural complications were encountered. The median visibility score for TFs was significantly better than that for VFs, both when scores of 0 were and were not included (2.00, interquartile range [IQR] 2.00-2.00 vs 1.75, IQR 1.50-2.00, P = .009 and 2.00, IQR 2.00-2.00 vs 2.00, IQR 1.50-2.00, P < .0001, respectively). The mean migration was not significantly different between the 2 types of fiducials (0.8 mm [IQR 0.4-1.6 mm] for TFs vs 1.3 mm [IQR 0.6-1.5 mm] for VFs; P = .72). LIMITATIONS Retrospective, nonrandomized design. CONCLUSIONS Visibility was significantly better for TFs compared with VFs. The degree of fiducial migration was not significantly different for TFs and VFs. There was no significant difference in the mean number of fiducials placed, indicating a similar degree of technical difficulty for TF and VF deployment.

EUS-directed transgastric ERCP for Roux-en-Y gastric bypass anatomy: a minimally invasive approach

BACKGROUND ERCP is challenging in patients with Roux-en-Y gastric bypass. Using EUS to gain access to the excluded stomach and subsequently performing transcutaneous ERCP was described recently. OBJECTIVE We describe our initial experience with an internal EUS-directed transgastric ERCP (EDGE) procedure by using a lumen-apposing metal stent (LAMS). DESIGN Single-center case series. SETTING Tertiary center with expertise in EUS-guided procedures. PATIENTS Five patients with Roux-en-Y gastric bypass underwent EDGE via a LAMS. INTERVENTIONS A linear echoendoscope was used to access the excluded stomach. A LAMS was deployed over a wire to create a gastrogastric or jejunogastric fistula. A duodenoscope was then passed through the LAMS and conventional ERCP was performed. MAIN OUTCOME MEASUREMENTS Technical and clinical success rates as well as adverse events. RESULTS EUS-guided creation of a gastrogastric or jejunogastric fistula via placement of a LAMS was successful in all cases (100%). The ability to perform ERCP through the fashioned fistula during the index procedure was successful in 3 of 5 cases (60%). Two LAMS dislodgments requiring restenting were observed. No major adverse events were observed. No weight regain occurred. The median procedure time was 68.0 minutes. LIMITATIONS Small sample, single-institution experience. CONCLUSION The internal EDGE procedure may offer a cost-effective, minimally invasive option for a common problem in a growing patient demographic. Further refinement of the technique is required to minimize adverse events. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01522573.).

Management of pancreatic fluid collections: A comprehensive review of the literature

Pancreatic fluid collections (PFCs) are a frequent complication of pancreatitis. It is important to classify PFCs to guide management. The revised Atlanta criteria classifies PFCs as acute or chronic, with chronic fluid collections subdivided into pseudocysts and walled-off pancreatic necrosis (WOPN). Establishing adequate nutritional support is an essential step in the management of PFCs. Early attempts at oral feeding can be trialed in patients with mild pancreatitis. Enteral feeding should be implemented in patients with moderate to severe pancreatitis. Jejunal feeding remains the preferred route of enteral nutrition. Symptomatic PFCs require drainage; options include surgical, percutaneous, or endoscopic approaches. With the advent of newer and more advanced endoscopic tools and expertise, and an associated reduction in health care costs, minimally invasive endoscopic drainage has become the preferable approach. An endoscopic ultrasonography-guided approach using a seldinger technique is the preferred endoscopic approach. Both plastic stents and metal stents are efficacious and safe; however, metal stents may offer an advantage, especially in infected pseudocysts and in WOPN. Direct endoscopic necrosectomy is often required in WOPN. Lumen apposing metal stents that allow for direct endoscopic necrosectomy and debridement through the stent lumen are preferred in these patients. Endoscopic retrograde cholangio pancreatography with pancreatic duct (PD) exploration should be performed concurrent to PFC drainage. PD disruption is associated with an increased severity of pancreatitis, an increased risk of recurrent attacks of pancreatitis and long-term complications, and a decreased rate of PFC resolution after drainage. Any pancreatic ductal disruption should be bridged with endoscopic stenting.

Increasing incidence of enteropathy-associated T-cell lymphoma in the United States, 1973-2008.

Enteropathy‐associated T‐cell lymphoma (EATL) is a rare lymphoma subtype that is strongly associated with celiac disease (CD), an autoimmune disease triggered by the ingestion of gluten. Because CD rates are increasing in the United States, the authors sought to determine whether the incidence rates of EATL also are increasing.

A Large Multicenter Experience With Endoscopic Suturing for Management of Gastrointestinal Defects and Stent Anchorage in 122 Patients: A Retrospective Review.

Goals:To describe a multicenter experience using an endoscopic suturing device for management of gastrointestinal (GI) defects and stent anchorage. Background:Endoscopic closure of GI defects including perforations, fistulas, and anastomotic leaks as well as stent anchorage has improved with technological advances. An endoscopic suturing device (OverStitch; Apollo Endosurgery Inc.) has been used. Study:Retrospective study of consecutive patients who underwent endoscopic suturing for management of GI defects and/or stent anchorage were enrolled between March 2012 and January 2014 at multiple academic medical centers. Data regarding demographic information and outcomes including long-term success were collected. Results:One hundred and twenty-two patients (mean age, 52.6 y; 64.2% females) underwent endoscopic suturing at 8 centers for stent anchorage (n=47; 38.5%), fistulas (n=40; 32.7%), leaks (n=15; 12.3%), and perforations (n=20; 16.4%). A total of 44.2% underwent prior therapy and 97.5% achieved technical success. Immediate clinical success was achieved in 79.5%. Long-term clinical success was noted in 78.8% with mean follow-up of 68 days. Clinical success was 91.4% in stent anchorage, 93% in perforations, 80% in fistulas, but only 27% in anastomotic leak closure. Conclusions:Endoscopic suturing for management of GI defects and stent anchoring is safe and efficacious. Stent migration after stent anchoring was reduced compared with published data. Long-term success without further intervention was achieved in the majority of patients. The role of endoscopic suturing for repair of anastomotic leaks remains unclear given limited success in this retrospective study.

Endoscopic Ultrasound (EUS)-Directed Transgastric Endoscopic Retrograde Cholangiopancreatography or EUS: Mid-Term Analysis of an Emerging Procedure

Background/Aims Performing endoscopic retrograde cholangiopancreatography (ERCP) in patients who have undergone Rouxen-Y gastric bypass (RYGB) is challenging. Standard ERCP and enteroscopy-assisted ERCP are associated with limited success rates. Laparoscopy- or laparotomy-assisted ERCP yields improved efficacy rates, but with higher complication rates and costs. We present the first multicenter experience regarding the efficacy and safety of endoscopic ultrasound (EUS)-directed transgastric ERCP (EDGE) or EUS. Methods All patients who underwent EDGE at two academic centers were included. Clinical success was defined as successful ERCP and/or EUS through the use of lumen-apposing metal stents (LAMS). Adverse events related to EDGE were separated from ERCP- or EUS-related complications and were defined as bleeding, stent migration, perforation, and infection. Results Sixteen patients were included in the study. Technical success was 100%. Clinical success was 90% (n=10); five patients were awaiting maturation of the fistula tract prior to ERCP or EUS, and one patient had an aborted ERCP due to perforation. One perforation occurred, which was managed endoscopically. Three patients experienced stent dislodgement; all stents were successfully repositioned or bridged with a second stent. Ten patients (62.5%) had their LAMS removed. The average weight change from LAMS insertion to removal was negative 2.85 kg. Conclusions EDGE is an effective, minimally invasive, single-team solution to the difficulties associated with ERCP in patients with RYGB.

Endoscopic Sleeve Gastroplasty Significantly Reduces Body Mass Index and Metabolic Complications in Obese Patients

BACKGROUND & AIMS Endoscopic sleeve gastroplasty (ESG) is an incisionless, minimally invasive bariatric procedure that reduces the length and width of the gastric cavity to facilitate weight loss. We performed a prospective study to evaluate the effects of ESG on total body weight loss and obesity‐related comorbidities. METHODS We collected data from 91 consecutive patients (mean age, 43.86 ± 11.26 years; 68% female) undergoing ESG from August 2013 through March 2016. All patients had a body mass index (BMI) greater than 30 kg/m2 and had failed noninvasive weight‐loss measures or had a BMI greater than 40 kg/m2 and were not considered as surgical candidates or refused surgery. All procedures were performed with a cap‐based flexible endoscopic suturing system to facilitate a triangular pattern of sutures to imbricate the greater curvature of the stomach. Patients were evaluated after 6 months (n = 73), 12 months (n = 53), and 24 months (n = 12) for anthropometric features (BMI, weight, waist circumference, blood pressure) and underwent serologic (hemoglobin A1c), lipid panel, serum triglycerides, and liver function tests. The primary outcomes were total body weight loss at 6, 12, and 24 months. Secondary outcomes were the effects of ESG on metabolic factors (blood pressure, diabetes, hyperlipidemia, steatohepatitis) and safety. RESULTS The patients’ mean BMI before the procedure was 40.7 ± 7.0 kg/m2. Patients had lost 14.4% of their total body weight at 6 months (80% follow‐up rate), 17.6% at 12 months (76% follow‐up rate), and 20.9% at 24 months (66% follow‐up rate) after ESG. At 12 months after ESG, patients had statistically significant reductions in levels of hemoglobin A1c (P = .01), systolic blood pressure (P = .02), waist circumference (P < .001), alanine aminotransferase (P < .001), and serum triglycerides (P = .02). However, there was no significant change in low‐density lipoprotein after vs before ESG (P = .79). There was one serious adverse event (1.1%) (perigastric leak) that occurred that was managed non‐operatively. CONCLUSIONS ESG is a minimally invasive and effective endoscopic weight loss intervention. In addition to sustained total body weight loss up to 24 months, ESG reduced markers of hypertension, diabetes, and hypertriglyceridemia.