An Update on Current Management Strategies for Achalasia and Future Perspectives.

The last decade has seen growing insight into the pathophysiology of achalasia, and current treatments decreasing the resting pressure in the lower esophageal sphincter by endoscopic (botulinum toxin injection, pneumatic dilation, peroral endoscopic myotomy) or surgical means (Heller myotomy). Manometry is considered the gold standard to confirm the diagnosis of achalasia. Pneumatic dilation and laparoscopic Heller myotomy have similar effectiveness and are both more successful in patients with type II achalasia. Laparoscopic myotomy when combined with partial fundoplication is an effective surgical technique and has been considered the operative procedure of choice until recently. Peroral endoscopic myotomy is an emerging therapy with promising results since it offers a minimally invasive and efficacious option especially in type III achalasia. However, it remains to be determined if peroral endoscopic myotomy offers long-term efficacy.

Do Statins Increase the Risk of Esophageal Conditions? Findings from Four Propensity Score-Matched Analyses.

BACKGROUND AND OBJECTIVE: Statins are commonly used medications. Whereas some observational studies suggested an association of statin use with Barrett's esophagus and some upper gastrointestinal symptoms, there is a dearth of data on the association of statins and common esophageal conditions such as gastroesophageal reflux disease and esophagitis. The aim of this study is to examine the association of statins with esophageal conditions. METHODS: This is a retrospective cohort study using regional military healthcare data (1 October, 2003 to 1 March, 2012). The primary analyses evaluated the odds of: esophagitis; symptoms of esophagitis; gastroesophageal reflux disease/dyspepsia; and esophageal complications of gastroesophageal reflux disease in four propensity score-matched cohorts of statin users and non-users (propensity score-overall, propensity score-healthy, propensity score-women, and propensity score-men cohorts). Secondary and sensitivity analyses were performed. RESULTS: In the propensity score-overall cohort (n = 12,684), statin users were more likely to be diagnosed with esophagitis (odds ratio 1.11, 95% confidence interval 1.01-1.22) and gastroesophageal reflux disease/dyspepsia (odds ratio 1.18, 95% confidence interval 1.10-1.27) compared with non-users. Similar findings were seen in the propensity score-healthy cohort and in the propensity score-men cohort. In the propensity score-women cohort, the odds of esophagitis was higher among statin users compared with non-users (odds ratio 1.16, 95% confidence interval 1.02-1.32) but other outcomes were not different. In sensitivity analyses, which excluded patients with obesity, statin use was not associated with an increased odds ratio of gastroesophageal reflux disease/dyspepsia. CONCLUSION: Statin therapy was associated with higher odds of being diagnosed with esophagitis and gastroesophageal reflux disease/dyspepsia. Further study is warranted to elucidate the potential role of statins in these commonly diagnosed esophageal conditions.

Biliary Tumor Ablation with Photodynamic Therapy and Radiofrequency Ablation.

Within the past two decades, major progress has been made in biliary endoscopy both with stenting and with ablative therapy. A primary goal in patients with malignant biliary lesions who are not candidates for surgery is to provide localized and efficient necrosis of the lesions. This article summarizes the current literature on biliary tumor ablation with photodynamic therapy and radiofrequency ablation. Prognosis, treatment technique, potential complications, treatment efficacy, and controversies are discussed.

Incidentally Identified Common Bile Duct Dilatation: A Systematic Review of Evaluation, Causes, and Outcome.

BACKGROUND: With the widespread use of abdominal imaging, an incidentally found dilated common bile duct (CBD) is a common radiographic finding. The significance of a dilated CBD as a predictor of underlying disease and long-term outcome have not been well elucidated. GOALS: A systematic review of studies on patients with dilated CBD was performed to identify etiologies and clinical factors that may predict which patients require further diagnostic testing and long-term outcomes. A PubMed search for relevant articles published between 2001 and 2014 was performed. RESULTS: The search yielded a total of 882 articles, and after careful individual review for eligibility and relevancy, 9 peer-reviewed studies were included. A cause of the CBD dilation was found on average in 33% of cases and the most common causes were: CBD stone, chronic pancreatitis, and periampullary diverticulum. The overall CBD diameter was not associated with finding a causative lesion. Coexisting CBD and intrahepatic bile duct dilation, age, and jaundice were found to be indicators of pathologic lesions. Dilation of both the CBD and pancreatic duct was suggestive of pancreatic disease, especially pancreatic malignancy in the setting of obstructive jaundice. Follow-up was reported in 6 studies ranging from 6 to 85 months, and generally there was no change in the diagnosis. CONCLUSIONS: Incidentally found biliary tract dilatation can be a manifestation of significant biliary tract disease including malignancy. Long-term outcome is not well defined and further prospective studies examining the most cost-effective approach to evaluation are needed.

Emerging Role of Endoscopic Ultrasound in the Diagnostic Evaluation of Idiopathic Pancreatitis.

BACKGROUND: "Idiopathic pancreatitis" is diagnosed when clinical, laboratory and conventional radiologic methods do not provide a clear etiology for the episode. Given its associated morbidity and mortality, it is important to determine the cause of pancreatitis to provide early treatment and prevent recurrence. METHODS: The aim of this systematic review was to evaluate the utility of endoscopic ultrasound (EUS) in determining an etiology in patients classified as having idiopathic pancreatitis and to assess how EUS performed compared with other modalities. A PubMed search for relevant articles (January 2000-November 2014) was performed using the search terms "(pancreatitis or idiopathic pancreatitis or unexplained pancreatitis) and (EUS or endoscopic ultrasound)." RESULTS: The search yielded a total of 963 articles, and 13 studies were included in the final review. In some studies, the yield of EUS was higher than magnetic resonance cholangiopancreatography in idiopathic pancreatitis. EUS more accurately detected biliary stones, whereas magnetic resonance cholangiopancreatography more often identified pancreatic duct abnormalities. The yield of EUS was lower in patients postcholecystectomy but was not influenced by gender, severity of pancreatitis, or recurrent disease. The most frequent diagnoses by EUS for those with idiopathic pancreatitis were biliary tract disease (41%). Overall, EUS identified additional diagnostic information in 61% of patients with idiopathic pancreatitis. CONCLUSIONS: Given the high incidence of microlithiasis and/or biliary sludge as a cause of idiopathic pancreatitis as well as the safety and high accuracy, EUS should be considered 1st for evaluation of idiopathic pancreatitis if conventional cross-sectional radiography fails to reveal a cause.

Endoscopic extra-cavitary drainage of pancreatic necrosis with fully covered self-expanding metal stents (fcSEMS) and staged lavage with a high-flow water jet system.

AIM: To present a novel, less-invasive method of endoscopic drainage (ED) for walled-off pancreatic necrosis (WON).We describe the feasibility, success rate, and complications of combined ED extra-cavitary lavage and debridement of WON using a biliary catheter and high-flow water jet system (water pump). PATIENTS AND METHODS: Endoscopic ultrasound (EUS)-guided drainage was performed with insertion of two 7-Fr, 4-cm double pigtail stents. Subsequently a fully covered self-expanding metal stent (fcSEMS) was placed. The key aspect of the debridement was the insertion of a 5-Fr biliary catheter through or along the fcSEMS into the cavity, with ensuing saline lavage using a high-flow water jet system. The patients were then brought back for repeated, planned endoscopic lavages of the WON. No endoscopic intra-cavitary exploration was performed. RESULTS: A total of 17 patients (15 men, 2 women; mean age 52.6, range 24 - 69; mean American Society of Anesthesiologists [ASA] score of 3) underwent ED of WON with this new method. The mean initial WON diameter was 9.5 cm, range 8 to 26 cm. The total number of ED was 84, range 2 to 13. The mean stenting period was 42.5 days. The mean follow-up was 51 days, range 3 to 370. A resolution of the WON was achieved in 14 patients (82.3 %). There were no major complications associated with this method. CONCLUSION: ED of complex WON with fcSEMS followed by repeated endoscopic extra-cavitary lavage and debridement using a biliary catheter and high-flow water jet system is a minimally invasive, feasible method with high technical and clinical success and minimal complications.

Impact of metabolic syndrome on the hospitalization rate of Crohn's disease patients seen at a tertiary care center: a retrospective cohort study.

BACKGROUND/AIMS: Recent studies suggest that markers of mesenteric inflammation, such as increased adipose tissue, may be associated with poor outcomes in Crohn's disease (CD). This study's hypothesis is that CD patients with metabolic syndrome (MetS) have more CD-related hospitalizations than CD patients without MetS. METHODS: We conducted a retrospective cohort study of CD patients seen from 2000 to 2012 at our tertiary care center. We analyzed crude and age-, sex- and duration of CD-adjusted incidence rate ratio (IRR) of CD-related hospitalization of those with MetS versus those without MetS. We also investigated possible associations between individual component conditions of MetS and rate of CD-related hospitalization. RESULTS: A total of 868 CD patients were included. There were 37 (4%) patients with MetS at initial observation. After multi-variable adjustment, patients with MetS had a CD-related hospitalization rate twice that of those who did not have MetS. High triglycerides (TG), low high density lipoprotein (HDL) cholesterol and diabetes mellitus (DM) were associated with increased risk of CD-related hospitalization. CONCLUSIONS: CD patients with MetS have a higher rate of CD-related hospitalization compared to those without MetS. Hypertriglyceridemia, low HDL cholesterol and DM may be good markers of local and systemic inflammation as seen in CD.

Probe-based confocal laser endomicroscopy for indeterminate biliary strictures: refinement of the image interpretation classification.

Background. Accurate diagnosis and clinical management of indeterminate biliary strictures are often a challenge. Tissue confirmation modalities during Endoscopic Retrograde Cholangiopancreatography (ERCP) suffer from low sensitivity and poor diagnostic accuracy. Probe-based confocal laser endomicroscopy (pCLE) has been shown to be sensitive for malignant strictures characterization (98%) but lacks specificity (67%) due to inflammatory conditions inducing false positives. Methods. Six pCLE experts validated the Paris Classification, designed for diagnosing inflammatory biliary strictures, using a set of 40 pCLE sequences obtained during the prospective registry (19 inflammatory, 6 benign, and 15 malignant). The 4 criteria used included (1) multiple thin white bands, (2) dark granular pattern with scales, (3) increased space between scales, and (4) thickened reticular structures. Interobserver agreement was further calculated on a separate set of 18 pCLE sequences. Results. Overall accuracy was 82.5% (n = 40 retrospectively diagnosed) versus 81% (n = 89 prospectively collected) for the registry, resulting in a sensitivity of 81.2% (versus 98% for the prospective study) and a specificity of 83.3% (versus 67% for the prospective study). The corresponding interobserver agreement for 18 pCLE clips was fair (k = 0.37). Conclusion. Specificity of pCLE using the Paris Classification for the characterization of indeterminate bile duct stricture was increased, without impacting the overall accuracy.

Endoscopic versus surgical therapy for Barrett's esophagus neoplasia.

Esophagectomy has been the traditional therapy for high-grade dysplasia and intramucosal cancer. Though surgery can completely resect the cancer and the affected lymph nodes, it carries significant morbidity and mortality (often exceeds 2%). New developments in endoscopy have provided less-invasive therapies that can also be used to stage tissue invasion of cancer; they include esophageal mucosal resection (EMR) and endoscopic submucosal dissection. Additional endoscopic therapies include photodynamic therapy, radiofrequency ablation (RFA) and argon plasma coagulation. Combining EMR that targets the cancer and RFA that targets the surrounding Barrett's esophagus offers an alternative to the operative approach when there is no lymph node metastasis. Arguments for surgical esophagectomy include concern for missed lymph node metastasis and incomplete endoscopic resection. Based on EMR's high neoplasia eradication rate and its fewer and more manageable complications, EMR, especially when combined with RFA, appears to be a viable alternative to surgery in early submucosal cancers, that is, sm1.

Safety of endoscopic retrograde cholangiopancreatography in pregnancy: Fluoroscopy time and fetal exposure, does it matter?

AIM: To estimate the fetal radiation exposure using thermoluminescent dosimeters (TLD's) in pregnant patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and assess its relevance. METHODS: Data on thirty-five therapeutic ERCPs conducted in pregnant patients from 2001 to 2009 were retrieved from a prospective database. Techniques to minimize fluoroscopy time were implemented and the fluoroscopy times captured. TLD's were placed on the mother to estimate the fetal radiation exposure and the results were compared to the maximum allowed dose of radiation to the fetus [0.005 gray (Gy)]. Obstetrics consultations were obtained and the fetus was monitored before and after the ERCP. Fluoroscopy was performed at 75 kVp. ERCP was performed with the patients supine by dedicated biliary endoscopists performing more than 500 cases a year. RESULTS: A total of 35 pregnant patients underwent ERCP and biliary sphincterotomy (14 in first trimester, 11 in second trimester, and 10 in third trimester). Mean maternal age was 25 years (range 16-37 years) and mean gestational age was 18.9 wk (range 4-35 wk). Mean fluoroscopy time was 0.15 min (range 0-1 min). For 23 women, the estimated fetal radiation exposure was almost negligible (< 0.0001 Gy) while for 8 women, it was within the 0.0001-0.0002 Gy range. Three women had an estimated fetal radiation exposure between 0.0002 and 0.0005 Gy and 1 woman had an estimated fetal radiation exposure greater than 0.0005 Gy. Complications included 2 post-sphincterotomy bleeds, 2 post-ERCP pancreatitis, and 1 fatal acute respiratory distress syndrome. One patient developed cholecystitis 2 d after ERCP. CONCLUSION: ERCP with modified techniques is safe during pregnancy, and estimating the fetal radiation exposure from the fluoroscopy time or measuring it via TLD's is unnecessary.

Chronic Recurrent Esophageal Diverticulitis - A Rare Entity.

In this report, we seek to shed light on a 44-year-old Caucasian male with a known history of an esophageal diverticulum, who was transferred to our facility after an upper endoscopy at an outside hospital suggested a purulent discharge emanating from the mouth of a mid-esophageal diverticulum. A barium swallow done at the outside institution had reportedly demonstrated an 8 cm long barium collection parallel to and anterolateral to the mid-and distal esophagus which terminated several centimeters proximal to the gastroesophageal junction. At our facility, antibiotics (piperacillin/tazobactam) were continued, and a double-contrast esophagram was performed. The presence of an unusual mid-esophageal diverticulum was confirmed. He clinically improved after a 3-day course of intravenous broad-spectrum antibiotics. No surgical or endoscopic repair was elected as the patient opted for continued medical management. While esophageal diverticula are not rare in humans, to our knowledge, this is the first report of development of esophageal diverticulitis in humans. We believe that antibiotic coverage in addition to dietary restriction is the logical mainstay of acute therapy. Optimal antibiotic coverage should likely include oral flora aerobes and anaerobes. Once symptoms resolve, diverticula may be managed expectantly.

Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) of the Pancreas in a Porcine Model.

Backgrounds. Limited effective palliative treatments exist for pancreatic cancer which includes surgery or chemotherapy. Radiofrequency ablation (RFA) uses high frequency alternating current to ablate diseased tissue and has been used to treat various tumors. In this study, we evaluated a prototype probe adjusted to the EUS-needle to perform EUS-RFA to permit coagulative necrosis in the pancreas. Methods. Five Yucatan pigs underwent EUS-guided radiofrequency ablation of the head of their pancreas. Using an EUS-needle, RFA was applied with 6 mm and then 10 mm of the probe exposed at specific wattage for preset durations. Results. Only one pig showed moderate levels of pancreatitis (20% proximal pancreatitis). The other animals showed much lower areas of tissue damage. In 3 of the 5 pigs, the proximal pancreas showed greater levels of tissue injury than the distal pancreas, consistent with the proximity of the tissue to the procedure site. In 1 pig, both proximal and distal pancreas showed minimal pancreatitis (1%). There was minimal evidence of fat necrosis in intra-pancreatic and/or extra-pancreatic adipose tissue. Conclusion. EUS-guided RFA of the pancreatic head with the monopolar probe through a 19-gauge needle was well tolerated in 5 Yucatan pigs and with minimal amount of pancreatitis.

Endoscopic retrograde cholangiopancreatography complications in the era of cholangioscopy: is there an increased risk?

BACKGROUND: Single-operator cholangioscopy allows direct visualization of the biliary tree and is being used in the diagnosis and treatment of various biliary conditions. To date, there are few data examining complications of single-operator cholangioscopy. METHODS: We evaluated all endoscopic retrograde cholangiopancreatography procedures over a two-year period and compared its complication rate to single-operator cholangioscopy in a tertiary care centre with extensive experience in single-operator cholangioscopy. A total of 2087 patients (55% men, mean age 57.4±16.4) had a therapeutic endoscopic retrograde cholangiopancreatography, out of which 169 also had single-operator cholangioscopy performed on them. RESULTS: 169 single-operator cholangioscopy procedures were performed (53% men) with a mean patient age of 60.7±15.2 years. Out of the 2087 patients, 160 complications occurred (7.7%), and included pancreatitis (n=47, 2.2%), infection (n=24, 1.1%), bleeding (n=44, 2.1%), perforation (n=16, 0.8%) and other (n=29, 1.4%). Univariate analysis on overall complications identified seven variables with a p value<0.2, which were included in the multivariate analysis. Biliary sphincterotomy, pancreatic duct stent placement, and ampullectomy were associated with increased complications. Single-operator cholangioscopy was not associated with increased complications on multivariate analysis. CONCLUSION: Single-operator cholangioscopy is not associated with an increased rate of complications when compared to endoscopic retrograde cholangiopancreatography. The types and frequencies of overall endoscopic retrograde cholangiopancreatography complications are similar to previously reported series.

A review on the use of confocal laser endomicroscopy in the bile duct.

Background. Current methods to diagnose malignant biliary strictures are of low sensitivity. Probe-based confocal laser endomicroscopy (pCLE) is a new approach that can be used to evaluate in vivo histopathology of the GI tract. This paper is of studies evidencing pCLE's application in the diagnosis of indeterminate biliary strictures. Methods. This paper examined peer-reviewed studies conducted between January 2000 and November 2011. A PubMed search for relevant articles was performed using the following keywords:"pCLE", "confocal", "endomicroscopy", "probe-based confocal laser endomicroscopy", "and "bile duct". Further individual review was done to assess the screened articles' relevance to the topic. Results. After individual review, 6 studies were included; with a cumulative sample size of 165, with 75 subjects identified as having a malignancy. These studies included tertiary care centers in Germany, France, and USA, including one multicenter trial. 3 studies assessed pCLE's specificity (range 67%-88%) ,sensitivity (range 83%-98), and accuracy (range 81%-86%). Conclusion. Confocal endomicroscopy is a novel and promising modality for the biliary tree. Further studies need to be conducted both to establish its usefulness for the diagnosis of indeterminate biliary strictures and to understand the histological meaning of the imaging patterns that are observed.

A kit for eus-guided access and drainage of pancreatic pseudocysts: efficacy in a porcine model.

OBJECTIVE: Transluminal pseudocyst drainage with currently available tools remains technically challenging, time consuming and limited to fluid collections adherent to the GI tract. Multiple tools and steps are still required to achieve pseudocyst drainage. We evaluated a novel kit to facilitate endoscopic ultrasonography (EUS)-guided access, drainage and rapid decompression in a porcine model. METHODS: The kit consists of the NAVIX access device and the AXIOS stent delivery system. The NAVIX contains an inner trocar for puncture and an outer dual balloon catheter for anchorage and dilation. The AXIOS stent is a fully covered dual flanged stent. Both are inserted through the working channel of a curved linear array echoendoscope. In a porcine model, a gallbladder was used as a proxy for a pseudocyst. RESULTS: Six Yorkshire pigs underwent this procedure successfully without complication and 3 of them were kept alive. After a 4-week implantation period, the AXIOS stents were removed easily using a snare and the 3 animals were observed for an additional 4 weeks. The stents were well-tolerated by the stomach and gallbladder tissues, as confirmed by weekly endoscopic inspection, gross necropsy and histopathology. CONCLUSION: EUS-guided transluminal access and drainage of the porcine gallbladder was technical feasible using a novel kit. This kit has the potential to simplify, streamline, and improve the safety of pancreatic pseudocyst drainage.