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1.  ERCP-related perforations in the new millennium: A large tertiary referral center 10-year experience 
Endoscopic retrograde cholangiopancreatography (ERCP) is an important diagnostic and therapeutic modality for pancreatic and biliary disorders. Perforation is one of the most dreaded complications of ERCP. Since it is uncommon, there has been little study of incidence, risk factors, and outcomes of management.
We aim to assess the incidence of ERCP-related perforations and outcomes at a large tertiary referral center.
We undertook a review of an ERCP database for all perforations from 2002 to December 2012.
The cumulative incidence of ERCP-related perforations was 0.14% (12 out of 8264), and sphincterotomy-related perforations constituted the most common cause. The mean age of these 12 patients was 58.6 years and majority were female (83.3%). The most common indications for ERCP were: suspected sphincter of Oddi dysfunction (SOD) 41%, and common bile duct stones (CBD stones) 41%. Nine of the 12 patients (75%) had a leak and were managed medically, and four who had a perforation had surgical repair (25%).
In our study, leaks were much more common than perforations and the majority of patients were successfully managed with conservative therapy alone. We report a very low perforation rate and most perforations can be managed conservatively with a good outcome.
PMCID: PMC4315685  PMID: 25653856
ERCP perforation; ERCP complication; ERCP perforation management; ERCP leak
2.  Poor agreement between endoscopists and gastrointestinal pathologists for the interpretation of probe-based confocal laser endomicroscopy findings 
World Journal of Gastroenterology : WJG  2014;20(47):17993-18000.
AIM: To compare the interpretation of probe-based confocal laser endomicroscopy (pCLE) findings between endoscopists and gastrointestinal (GI)-pathologists.
METHODS: All pCLE procedures were undertaken and the endoscopist rendered assessment. The same pCLE videos were then viewed offline by an expert GI pathologist. Histopathology was considered the gold standard for definitive diagnosis. The sensitivity, specificity and accuracy for diagnosis of dysplastic/ neoplastic GI lesions and interobserver agreement between endoscopists and experienced gastrointestinal pathologist for pCLE findings were analyzed.
RESULTS: Of the 66 included patients, 40 (60.6%) had lesions in the esophagus, 7 (10.6%) in the stomach, 15 (22.7%) in the biliary tract, 3 (4.5%) in the ampulla and 1 (1.5%) in the colon. The overall sensitivity, specificity and accuracy for diagnosing dysplastic/neoplastic lesions using pCLE were higher for endoscopists than pathologist at 87.0% vs 69.6%, 80.0% vs 40.0% and 84.8% vs 60.6% (P = 0.0003), respectively. Area under the ROC curve (AUC) was greater for endoscopists than the pathologist (0.83 vs 0.55, P = 0.0001). Overall agreement between endoscopists and pathologist was moderate for all GI lesions (K = 0.43; 95%CI: 0.26-0.61), luminal lesions (K = 0.40; 95%CI: 0.20-0.60) and those of dysplastic/neoplastic pathology (K = 0.55; 95%CI: 0.37-0.72), the agreement was poor for benign (K = 0.13; 95%CI: -0.097-0.36) and pancreaticobiliary lesions (K = 0.19; 95%CI: -0.26-0.63).
CONCLUSION: There is a wide discrepancy in the interpretation of pCLE findings between endoscopists and pathologist, particularly for benign and malignant pancreaticobiliary lesions. Further studies are needed to identify the cause of this poor agreement.
PMCID: PMC4273151  PMID: 25548499
Confocal endomicroscopy; Gastointestinal; Interobserver variation
3.  Using balloon-overtube-assisted enteroscopy for postoperative endoscopic retrograde cholangiopancreatography 
Endoscopic retrograde cholangiopancreatography (ERCP) is technically more challenging in patients with postsurgical anatomy such as Roux-en-Y anastomosis, frequently mandating an operative intervention. Although limited, there is growing evidence that ERCP can be performed using the balloon-overtube-assisted enteroscopy (BOAE) in patients with complex postoperative anatomy. We present the technical aspects of performing ERCP with the BOAE in patients presenting with complex postsurgical anatomy having biliary problems. ERCP using the BOAE is feasible in patients with complex postsurgical anatomy, permitting diagnostic and therapeutic interventions in 80% of patients.
PMCID: PMC4212471  PMID: 25364385
cholangiography; double balloon enteroscopy; hepaticojejunostomy; overtube-assisted enteroscopy; Roux-en-Y anastomosis; single balloon enteroscopy
4.  Safety and Yield of Diagnostic ERCP in Liver Transplant Patients with Abnormal Liver Function Tests 
Background. Abnormal liver enzymes postorthotopic liver transplant (OLT) may indicate significant biliary pathology or organ rejection. There is very little known in the literature regarding the current role of diagnostic ERCP in this scenario. Aim. To review the utility of diagnostic ERCP in patients presenting with abnormal liver function tests in the setting of OLT. Methods. A retrospective review of diagnostic ERCPs in patients with OLT from 2002 to 2013 from a prospectively maintained, IRB approved database. Results. Of the 474 ERCPs performed in OLT patients, 210 (44.3%; 95% CI 39.8–48.8) were performed for abnormal liver function tests during the study period. Majority of patients were Caucasian (83.8%), male (62.4%) with median age of 55 years (IQR 48–62 years). Biliary cannulation was successful in 99.6% of cases and findings included stricture in 45 (21.4 %); biliary stones/sludge in 23 (11%); biliary dilation alone in 31 (14.8%); and normal in 91 (43.3%). Three (1.4%) patients developed mild, self-limiting pancreatitis; one patient (0.5%) developed cholangitis and two (1%) had postsphincterotomy bleeding. Multivariate analyses showed significant association between dilated ducts on imaging with a therapeutic outcome. Conclusion. Diagnostic ERCP in OLT patients presenting with liver function test abnormalities is safe and frequently therapeutic.
PMCID: PMC4119651  PMID: 25110455
5.  Silencing of MGMT expression by promoter hypermethylation in the metaplasia–dysplasia–carcinoma sequence of Barrett’s esophagus 
Cancer letters  2008;275(1):117-126.
To determine the relevance of MGMT in Barrett’s carcinogenesis, we analyzed promotor hypermethylation and expression of MGMT in Barrett’s adenocarcinomas and its paired precursor lesions from 133 patients using a methylation-specific PCR, real-time RT-PCR and immunohistochemistry. Hypermethylation was detected in 78.9% of esophageal adenocarcinomas, in 100% of Barrett’s intraepithelial neoplasia, in 88.9% of Barrett’s metaplasia, but only in 21.4% of normal esophageal mucosa samples (P < 0.001) and correlated significantly with downregulation of MGMT transcripts (P = 0.048) and protein expression (P = 0.02). Decrease of protein expression was significantly correlated with progressed stage of disease, lymph node invasion and tumor size. We conclude, that aberrant promoter methylation of MGMT is a frequent and early event during tumorigenesis of Barrett’s esophagus. High prevalence of MGMT hypermethylation may represent a candidate marker for improved diagnosis and targeted therapy in Barrett’s adenocarcinoma.
PMCID: PMC4028828  PMID: 19027227
O6-methylguanine-DNA methyltransferase (MGMT); Hypermethylation; Carcinogenesis; Barrett’s metaplasia; Barrett’s adenocarcinoma
6.  Small Bowel Stent-in-Stent Placement for Malignant Small Bowel Obstruction Using a Balloon-Assisted Overtube Technique 
Clinical Endoscopy  2014;47(1):108-111.
Self-expanding metal stents are a useful therapy to palliate malignant and benign luminal gastrointestinal obstruction. Self-expanding metal stents has been widely reported for colonic, esophageal, and gastric obstruction. However, endoscopic delivery and placement to the small bowel is more challenging and difficult. This case illustrates the usefulness and technical advantages of the balloon-overtube and enteroscopy technique for the palliative treatment of neoplastic stenosis affecting the small intestine.
PMCID: PMC3928482  PMID: 24570892
Balloon-assisted enteroscopy; Overtube; Metal stent; Small bowel obstruction; Double-balloon enteroscopy
7.  Endoscopic closure of a gastrocolic fistula using the over-the-scope-clip-system 
Gastrointestinal (GI) defects such as fistulas and leaks can be potentially closed endoscopically using hemoclips and loops. However, hemoclips may not allow for closure of large defects and they do not exert enough tensile force to keep fibrotic defects larger than 5 mm approximated. Herein we present a case of successful endoscopic closure of a gastrocolic fistula in a severely malnourished patient with complex post-surgical upper GI anatomy. We strongly believe that this device is a major breakthrough for the management of various types of discontinuity defects or fistulas. In addition, we show the usefulness of placing a direct jejunostomy using the double balloon enteroscopy (DBE) technique during the same procedure. The concept of providing direct jejunal feedings while allowing for upper gastrointestinal bowel rest to promote the healing of the minimally invasive endoscopic operation is novel. Thus, our case is unique and exemplifies the utility of minimally invasive endoscopic endoluminal surgery.
PMCID: PMC3742706  PMID: 23951396
Over-the-scope-clip; Bear claw; Fistula; Endoscopic closure; Gastrocolic fistula; Over the scope clip; Clip
8.  Emergency double balloon enteroscopy: a feasible and promising diagnostic as well as possible therapeutic option in recurrent midgut bleeding 
BMJ Case Reports  2011;2011:bcr0620103068.
Gastrointestinal (GI) tract bleeding, in particular originating within the long segment of the small intestine, remains a diagnostic and therapeutic challenge. The authors describe the potential utility of emergency double balloon enteroscopy (DBE) for small bowel bleeding. An elderly woman was admitted because of a hypertensive crisis to the medical department of a regional hospital. Her medical history was significant for non-steroidal anti-inflammatory drug (NSAID) abuse. While in hospital she had massive obscure GI bleeding. Upper GI endoscopy and colonoscopy for recurrent bleeding showed only thrombotic residuals in two sigmoid diverticuli, which led to segmental resection of the sigmoid colon. However, postoperatively, bleeding recurred leading to transfer to our university hospital. Immediate angiography only revealed a vascular malformation at the upper jejunum but no ongoing bleeding. Subsequent emergency DBE detected an oozing jejunal ulcer, which was coagulated using a argon beamer. Because of recurrent falls in haemoglobin with the need for repeated transfusion, the patient underwent surgical reintervention including segmental resection of the ulcerated upper jejunum with subsequent end-to-end anastomosis. Histopathology revealed NSAID-induced ulcerous jejunopathy. Postoperatively, there was no further bleeding and the patient was discharged home in a stable condition. In conclusion, this is one of the first reports of successful emergency use of DBE in a case of recurrent and occult bleeding within the small bowel which successfully located the source of bleeding and facilitated successful superficial ulcer coagulation with an argon beamer to prevent further bleeding.
PMCID: PMC3070338  PMID: 22700075
9.  GERD assessment including pH metry predicts a high response rate to PPI standard therapy 
BMC Gastroenterology  2013;13:12.
Inadequate response to proton pump inhibitor (PPI) therapy in patients with gastroesophageal reflux disease (GERD) is reported in up to 40%. Patients with non erosive reflux disease (NERD) have lower response rates compared to patients with erosive reflux disease (ERD); pH metry contributes to GERD diagnosis and is critical for proper diagnosis of NERD.
Aim of the study was to assess the need for doubling esomeprazole standard dose (40 mg) for 4 weeks in PPI naive patients with typical reflux symptoms and diagnosis of GERD based on endoscopy and 48 hours, wireless pH metry.
All patients underwent upper GI endoscopy. Symptoms were recorded with a structured questionnaire (RDQ) and acid exposure was determined by 48 hours, wireless pH monitoring (BRAVO). In case of abnormal acid exposure, patients received a short term treatment with esomeprazole 40 mg q.d. for 4 weeks. If symptoms persisted, patients underwent a second pH metry on PPI and the dose was increased to 40 mg b.i.d.
31 consecutive patients with typical reflux symptoms underwent 48 hours pH monitoring. 22 patients (71%) had abnormal acid exposure, 9 patients had normal pH metry (29%). Of the 9 patients with normal pH metry, 2 were found with erosive esophagitis and 7 without endoscopic abnormalities.
24 patients with documented GERD received esomeprazole treatment. 21 patients achieved complete symptom resolution with 40 mg q.d. after 4 weeks (88%). Only 2 patients required doubling the dose of esomeprazole for complete symptom resolution, 1 patient remained with symptoms.
Patients with typical reflux symptoms and abnormal acid exposure have a high response rate to standard dose esomeprazole regardless of whether they have ERD or NERD.
PMCID: PMC3562521  PMID: 23324360
GERD; NERD; PPI; Esomeprazole; Treatment; ph metry; Diagnosis; Therapy
10.  Role of tight junction proteins in gastroesophageal reflux disease 
BMC Gastroenterology  2012;12:128.
Gastroesophageal reflux disease (GERD) is associated with impaired epithelial barrier function that is regulated by cell-cell contacts. The aim of the study was to investigate the expression pattern of selected components involved in the formation of tight junctions in relation to GERD.
Eighty-four patients with GERD-related symptoms with endoscopic signs (erosive: n = 47) or without them (non-erosive: n = 37) as well as 26 patients lacking GERD-specific symptoms as controls were included. Endoscopic and histological characterization of esophagitis was performed according to the Los Angeles and adapted Ismeil-Beigi criteria, respectively. Mucosal biopsies from distal esophagus were taken for analysis by histopathology, immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (RT-PCR) of five genes encoding tight junction components [Occludin, Claudin-1, -2, Zona occludens (ZO-1, -2)].
Histopathology confirmed GERD-specific alterations as dilated intercellular spaces in the esophageal mucosa of patients with GERD compared to controls (P < 0.05). Claudin-1 and −2 were 2- to 6-fold upregulation on transcript (P < 0.01) and in part on protein level (P < 0.015) in GERD, while subgroup analysis of revealed this upregulation for ERD only. In both erosive and non-erosive reflux disease, expression levels of Occludin and ZO-1,-2 were not significantly affected. Notably, the induced expression of both claudins did not correlate with histopathological parameters (basal cell hyperplasia, dilated intercellular spaces) in patients with GERD.
Taken together, the missing correlation between the expression of tight junction-related components and histomorphological GERD-specific alterations does not support a major role of the five proteins studied in the pathogenesis of GERD.
PMCID: PMC3503771  PMID: 22994974
Gastroesophageal reflux disease; Tight junction; Claudins; Esophagitis; Inflammation
11.  Difficult colon polypectomy 
Colorectal cancer (CRC) is one of the leading causes of death from cancer in the world. We now know that 90% of CRC develop from adenomatous polyps. Polypectomy of colon adenomas leads to a significant reduction in the incidence of CRC. At present most of the polyps are removed endoscopically. The vast majority of colorectal polyps identified at colonoscopy are small and do not pose a significant challenge for resection to an appropriately trained and skilled endoscopist. Advanced polypectomy techniques are intended for the removal of difficult colon polyps. We have defined a “difficult polyp” as any lesion that due to its size, shape or location represents a challenge for the colonoscopist to remove. Although many “difficult polyps” will be an easy target for the advanced endoscopist, polyps that are larger than 15 mm, have a large pedicle, are flat and extended, are difficult to see or are located in the cecum or any angulated portion of the colon should be always considered difficult. Although very successful, advanced resection techniques can potentially cause serious, even life-threatening complications. Moreover, post polypectomy complications are more common in the presence of difficult polyps. Therefore, any endoscopist attempting advanced polypectomy techniques should be adequately supervised by an expert or have an excellent training in interventional endoscopy. This review describes several useful tips and tricks to deal with difficult polyps.
PMCID: PMC3399004  PMID: 22816006
Colonoscopy; Polypectomy; Mucosectomy; Colon polyp; Polyp; Endoscopic mucosal resection; Mucosectomy; Endoscopic submucosal dissection
12.  Advanced Endoscopic Imaging for Diagnosis of Crohn's Disease 
Endoscopy in IBD has tremendous importance to diagnose inflammatory activity, to evaluate therapeutic success and for the surveillance of colitis associated cancer. Thus it becomes obvious that there is a need for new and more advanced endoscopic imaging techniques for better characterization of mucosal inflammation and early neoplasia detection in IBD. This paper describes the concept of advanced endoscopic imaging for the diagnosis and characterization of Crohn's disease, including magnification endoscopy, chromoendoscopy, balloon-assisted enteroscopy, capsule endoscopy, confocal laser endomicroscopy, and endocytoscopy.
PMCID: PMC3226328  PMID: 22144998
13.  Endoscopic and retrograde cholangiographic appearance of hepaticojejunostomy strictures: A practical classification 
AIM: To study the endoscopic and radiological characteristics of patients with hepaticojejunostomy (HJ) and propose a practical HJ stricture classification.
METHODS: In a retrospective observational study, a balloon-assisted enteroscopy (BAE)-endoscopic retrograde cholangiography was performed 44 times in 32 patients with surgically-altered gastrointestinal (GI) anatomy. BAE-endoscopic retrograde cholangio pancreatography (ERCP) was performed 23 times in 18 patients with HJ. The HJ was carefully studied with the endoscope and using cholangiography.
RESULTS: The authors observed that the hepaticojejunostomies have characteristics that may allow these to be classified based on endoscopic and cholangiographic appearances: the HJ orifice aspect may appear as small (type A) or large (type B) and the stricture may be short (type 1), long (type 2) and type 3, intrahepatic biliary strictures not associated with anastomotic stenosis. In total, 7 patients had type A1, 4 patients A2, one patient had B1, one patient had B (large orifice without stenosis) and one patient had type B3.
CONCLUSION: This practical classification allows for an accurate initial assessment of the HJ, thus potentially allowing for adequate therapeutic planning, as the shape, length and complexity of the HJ and biliary tree choice may mandate the type of diagnostic and therapeutic accessories to be used. Of additional importance, a standardized classification may allow for better comparison of studies of patients undergoing BAE-ERCP in the setting of altered upper GI anatomy.
PMCID: PMC3221953  PMID: 22110837
Endoscopic retrograde cholangio pancreatography; Roux en Y anastomosis; Hepaticojejunostomy; Biliary strictures; Bile duct strictures; Double balloon enteroscopy
15.  Drug treatment of functional dyspepsia 
Symptomatic improvement of patients with functional dyspepsia after drug therapy is often incomplete and obtained in not more than 60% of patients. This is likely because functional dyspepsia is a heterogeneous disease. Although great advance has been achieved with the consensus definitions of the Rome I and II criteria, there are still some aspects about the definition of functional dyspepsia that require clarification. The Rome criteria explicitly recognise that epigastric pain or discomfort must be the predominant complaint in patients labelled as suffering from functional dyspepsia. However, this strict definition can create problems in the daily primary care clinical practice, where the patient with functional dyspepsia presents with multiple symptoms. Before starting drug therapy it is recommended to provide the patient with an explanation of the disease process and reassurance. A thorough physical examination and judicious use of laboratory data and endoscopy are also indicated. In general, the approach to treat patients with functional dyspepsia based on their main symptom is practical and effective. Generally, patients should be treated with acid suppressive therapy using proton-pump inhibitors if the predominant symptoms are epigastric pain or gastroesophageal reflux symptoms. Although the role of Helicobacter pylori (H pylori) in functional dyspepsia continues to be a matter of debate, recent data indicate that there is modest but clear benefit of eradication of H pylori in patients with functional dyspepsia. In addition, H pylori is a gastric carcinogen and if found it should be eliminated. Although there are no specific diets for patients with FD, it may be helpful to guide the patients on healthy exercise and eating habits.
PMCID: PMC4130977  PMID: 16718755
Functional dyspepsia; Drug treatment; Helicobacter pylori; Predominant symptoms
16.  Echo-enhanced ultrasound with pulse inversion imaging: A new imaging modality for the differentiation of cystic pancreatic tumours 
AIM: To describe and discuss echo-enhanced sonography in the differential diagnosis of cystic pancreatic lesions.
METHODS: The pulse inversion technique (with intravenous injection of 2.4 mL SonoVue®) or the power-Doppler mode under the conditions of the 2nd harmonic imaging (with intravenous injection of 4 g Levovist®) was used for echo-enhanced sonography.
RESULTS: Cystadenomas frequently showed many vessels along fibrotic strands. On the other hand, cystadenocarcinomas were poorly and chaotically vascularized. ”Young pseudocysts” were frequently found to have a highly vascularised wall. However, the wall of the ”old pseudocysts” was poorly vascularized. Data from prospective studies demonstrated that based on these imaging criteria the sensitivities and specificities of echo-enhanced sonography in the differentiation of cystic pancreatic masses were > 90%.
CONCLUSION: Cystic pancreatic masses have a different vascularization pattern at echo-enhanced sonography. These characteristics are useful for their differential diagnosis, but histology is still the gold standard.
PMCID: PMC4087647  PMID: 16610022
Cystic pancreatic lesions; Differential diagnosis; Echo-enhanced sonography

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