Using single-operator cholangioscopy for endoscopic evaluation of indeterminate biliary strictures: results from a large multinational registry.

BACKGROUND: Peroral cholangioscopy (POCS) of indeterminate biliary strictures aims to achieve a diagnosis through visual examination and/or by obtaining targeted biopsies under direct visualization. In this large, prospective, multinational, real-life experience of POCS-guided evaluation of indeterminate biliary strictures, we evaluated the performance of POCS in this difficult-to-manage patient population. METHODS: This prospective registry enrolled patients, with indeterminate biliary strictures across 20 centers in Asia, the Middle East, and Africa. The primary end points were the ability to visualize the lesion, obtain histological sampling when intended, and an assessment of the diagnostic accuracy of POCS for malignant strictures. Patients were followed for 6 months after POCS or until a definitive malignant diagnosis was made, whichever occurred first. RESULTS: 289 patients underwent 290 POCS procedures with intent to biopsy in 182 cases. The stricture/filling defect was successfully visualized in 286/290 (98.6 %), providing a visual diagnostic impression in 253/290 (87.2 %) and obtaining adequate biopsies in 169/182 (92.9 %). Procedure-related adverse events occurred in 5/289 patients (1.7 %). POCS influenced patient management principally by elucidating filling defects or the causes of bile duct stricture or dilation. The visual impression of malignancy showed 86.7 % sensitivity, 71.2 % specificity, 65.8 % positive and 89.4 % negative predictive value, and 77.2 % overall accuracy compared with final diagnosis. Histological POCS-guided samples showed 75.3 % sensitivity, 100 % specificity, 100 % positive and 77.1 % negative predictive value, and 86.5 % overall accuracy. CONCLUSION: In this large, real-life, prospective series, POCS was demonstrated to be an effective and safe intervention guiding the management of patients with indeterminate biliary strictures.

Cholangioscopy-guided lithotripsy for difficult bile duct stone clearance in a single session of ERCP: results from a large multinational registry demonstrate high success rates.

BACKGROUND: Peroral cholangioscopy (POCS) can be useful for difficult bile duct stone clearance. Large prospective multinational data on POCS-guided lithotripsy for clearing difficult bile duct stones in a single session of endoscopic retrograde cholangiopancreatography (ERCP) are missing. METHODS: Patients with difficult bile duct stones (defined as one or more of: largest stone diameter ≥ 15 mm, failed prior attempt at stone clearance, impacted, multiple, hepatic duct location, or located above a stricture) were enrolled at 17 centers in 10 countries. The principal endpoint was stone clearance in a single ERCP procedure using POCS. RESULTS : 156 patients underwent 174 sessions of POCS-guided electrohydraulic or laser lithotripsy. Stone clearance had failed in a previous ERCP using traditional techniques in 124/156 patients (80 %), while 32 /156 patients (21 %) were referred directly to POCS-guided therapy based on preprocedural assessment of the difficulty of stone clearance. In 101/156 patients (65 %), there were impacted stones. POCS-guided stone clearance was achieved in a single POCS procedure in 125 /156 patients (80 %, 95 % confidence interval [CI] 73 % - 86 %), and was significantly more likely for stones ≤ 30 mm compared with > 30 mm (odds ratio 7.9, 95 %CI 2.4 - 26.2; P = 0.002). Serious adverse events occurred in 3/156 patients (1.9 %, 95 %CI 0.4 % - 5.5 %), and included pancreatitis, perforation due to laser lithotripsy, and cholangitis (n = 1 each), all resolved within 1 week. CONCLUSION: POCS-guided lithotripsy is highly effective for clearance of difficult bile duct stones in a single procedure and successfully salvages most prior treatment failures. It may also be considered first-line therapy for patients with difficult choledocholithiasis to avoid serial procedures.

Simethicone use during gastrointestinal endoscopy: Position statement of the Gastroenterological Society of Australia.

Concern has been raised regarding the use of simethicone, a de-foaming agent, during endoscopic procedures. Following reports of simethicone residue in endoscope channels despite high level disinfection, an endoscope manufacturer recommended that it not be used due to concerns of biofilm formation and a possible increased risk of microorganism transmission. However, a detailed mucosal assessment is essential in performing high-standard endoscopic procedures. This is impaired by bubbles within the gastrointestinal lumen. The Gastroenterological Society of Australia's Infection Control in Endoscopy Guidelines (ICEG) Committee conducted a literature search utilizing the MEDLINE database. Further references were sourced from published paper bibliographies. Following a review of the available evidence, and drawing on extensive clinical experience, the multidisciplinary ICEG committee considered the risks and benefits of simethicone use in formulating four recommendations. Published reports have documented residual liquid or crystalline simethicone in endoscope channels after high level disinfection. There are no data confirming that simethicone can be cleared from channels by brushing. Multiple series report benefits of simethicone use during gastroscopy and colonoscopy in improving mucosal assessment, adenoma detection rate, and reducing procedure time. There are no published reports of adverse events related specifically to the use of simethicone, delivered either orally or via any endoscope channel. An assessment of the risks and benefits supports the continued use of simethicone during endoscopic procedures. Strict adherence to instrument reprocessing protocols is essential.

Australian infection control in endoscopy consensus statements on carbapenemase-producing Enterobacteriaceae.

Outbreaks of carbapenemase-producing Enterobacteriaceae clinical infections related to endoscopic transmission are well documented. The high morbidity and mortality associated with these infections emphasizes the need to reassess endoscopic reprocessing protocols. The Gastroenterological Society of Australia established a multi-society committee to formulate evidence-based consensus statements on the prevention and management of endoscopic transmission of carbapenemase-producing Enterobacteriaceae. A literature search was undertaken utilizing the MEDLINE database. Further references were sourced from published paper bibliographies. Nine statements were formulated. Using the Delphi methodology, the statements were initially reviewed electronically by the committee members and subsequently at a face-to-face meeting in Melbourne, Australia. After further discussion, four additional sub-statements were added resulting in a total of 13 statements. Each statement was assessed for level of evidence, recommendation grade and the voting on recommendation was recorded. For a statement to be accepted, five out of six committee members had to "accept completely" or "accept with some reservation." All 13 statements achieved consensus agreement. Eleven statements achieved 100% "accepted completely." Two statements were 83% "accepted completely" and 17% "accepted with some reservation." Of particular significance, automated flexible endoscope reprocessors were mandated for high-level disinfection, and the use of forced-air drying cabinets was mandated for endoscope storage. These evidence-based statements encourage preventative strategies with the aim of ensuring the highest possible standards in flexible endoscope reprocessing thereby optimizing patient safety. They must be considered in addition to the broader published guidelines on infection control in endoscopy.

Comparison of secretin-stimulated magnetic resonance pancreatography and manometry results in patients with suspected sphincter of oddi dysfunction.

RATIONALE AND OBJECTIVES: To measure main pancreatic duct diameter (PDD) with magnetic resonance pancreatography (MRP) before and after secretin injection in patients with suspected sphincter of Oddi dysfunction (SOD) and to determine if the diameter change is predictive of sphincter of Oddi manometry (SOM) results. MATERIALS AND METHODS: We identified all patients during the study period referred for SOM for clinically suspected SOD; patients with an intact sphincter and without contraindication to MRP examination were considered for study entry. Consenting patients underwent MRP, including dynamic imaging of the pancreatic duct after intravenous administration of porcine secretin followed by SOM during endoscopic retrograde cholangiopancreatography. MRP was defined as abnormal when PDD remained increased by > or = 1.0 mm from baseline 15 minutes after secretin injection. SOM was abnormal when basal sphincter pressure (SP) was > or = 40 mm Hg. Mean PDD before and after secretin administration was compared within normal and abnormal SP groups with two-tailed unpaired t-test; the mean difference between baseline and peak PDD and duration of > or = 0.5 mm increase in PDD was compared between groups with two-tailed t-test. P < .05 was considered significant. RESULTS: Of 70 patients referred for SOM, 30 met all entry criteria, gave consent to participate, and underwent both MRP and SOM. Ten of 30 patients (33%) had normal SP; 20 (67%) were abnormal. PDD increased significantly after secretin injection (normal SP, 1.62 +/- 0.73 to 2.78 +/- 0.77 mm, P < .01; abnormal SP, 1.45 +/- 0.26 to 2.32 +/- 0.75 mm, P < .01). There was no difference between normal and abnormal SP groups in amount of PDD increase (1.15 +/- 0.75 vs. 0.88 +/- 0.72 mm; P = .33) or duration of > or = 0.5 mm increase in PDD (5.28 +/- 8.76 vs. 13.60 +/- 13.00 minutes; P = 0.07). CONCLUSIONS: In patients with suspected sphincter of Oddi dysfunction, magnetic resonance pancreatography demonstrated PDD increase following secretin injection but did not predict the results of manometry.

Comparison of endoscopic ultrasound and computed tomography for the preoperative evaluation of pancreatic cancer: a systematic review.

BACKGROUND & AIMS: It is uncertain whether computed tomography (CT) or endoscopic ultrasound (EUS) is superior for the detection, staging, and resectability of pancreatic cancer. We therefore performed a systematic literature review to determine which test is more accurate. METHODS: We identified relevant studies from MEDLINE (1986-2004) and evaluated study quality, which was measured on the basis of guidelines for assessing studies of diagnostic tests. Quantitative outcomes data were abstracted from the studies. RESULTS: Eleven studies with 678 patients satisfied inclusion criteria. Nine studies assessed tumor detection, all of which concluded that the sensitivity of EUS was superior to CT. Four of 5 studies that assessed tumor staging accuracy and 5 of 8 that assessed nodal staging accuracy concluded that EUS was superior to CT. Among the 4 studies that assessed resectability, 2 showed no difference between EUS and CT, and 1 favored each modality. Three of 11 studies met all but one of the quality criteria. The most important and frequent study limitations were lack of a consecutive series of patients and biased patient selection for surgery. Quantitative comparisons among studies were precluded by differences in tumor staging classifications, surgical selection, CT and EUS techniques, and reporting of operating characteristics. CONCLUSIONS: The published literature comparing EUS and CT for preoperative assessment of pancreatic cancer is heterogeneous in study design, quality, and results. All studies have methodologic limitations that potentially affect validity. Prospective studies with state-of-the-art imaging are needed to further define the role of each test.

Endoscopic ultrasound in non-small cell lung cancer and negative mediastinum on computed tomography.

Despite technical advances in staging non-small cell lung cancer (NSCLC), accurate staging remains a challenge. Endoscopic ultrasound is useful in staging NSCLC when lymphadenopathy is present on a computed tomography (CT), but its role in the absence of lymphadenopathy on CT has not been well defined. Therefore, we sought to determine the clinical impact of endoscopic ultrasound (EUS) in staging NSCLC in absence of mediastinal lymphadenopathy on CT. Seventy-six patients with NSCLC with absence of mediastinal lymphadenopathy on CT were enrolled and followed prospectively. EUS-guided fine-needle aspiration was performed on sites that were suspicious for metastases. Surgical pathology after thoracotomy was used as the reference standard for assessing accuracy. Sixty-two (86%) patients underwent surgery, and 10 (13%) did not. EUS precluded surgery in 9 patients (12%) and influenced management in 18 (25%) of all patients in this study. EUS detected malignant mediastinal lymphadenopathy more frequently in patients with lower lobe and hilar cancers combined compared with upper lobe cancers (p = 0.004). EUS played a significant role in identifying patients with unresectable (N3) NSCLC when adenopathy was not present on CT imaging and appears to be more sensitive in detecting lymph node metastases in lower lobe and hilar NSCLC compared with upper lobe NSCLC.

Sphincter of Oddi (pancreatic) hypertension and recurrent pancreatitis.

Major papilla pancreatic sphincter dysfunction, a variant of sphincter of Oddi dysfunction, causes pancreatitis and pancreatic-type pain. The gold standard for diagnosis is sphincter of Oddi manometry, most commonly performed at endoscopic retrograde cholangiopancreatography (ERCP). Noninvasive testing, such as secretin-stimulated transabdominal or endoscopic ultrasound assessment of pancreatic duct diameter, is less reliable and has relatively low sensitivity. Two thirds of patients with biliary sphincter of Oddi dysfunction have elevated pancreatic basal sphincter pressure. To maximize the diagnostic yield of sphincter of Oddi dysfunction, both the biliary and pancreatic sphincter pressures should be measured. Patients with sphincter of Oddi dysfunction may respond to biliary sphincterotomy alone, but evaluation of their pancreatic sphincter is warranted if symptoms persist after biliary therapy alone. Whether both biliary and pancreatic sphincters should be treated at the first ERCP session is controversial. Biliary and pancreatic endoscopic sphincterotomies are associated with two- to fourfold increased incidence of pancreatitis following the procedure in patients with pancreatic sphincter hypertension. Prophylactic pancreatic duct stenting reduces the frequency and severity of complications by greater than 50%.

Facilitation of pancreatic duct cannulation using a new synthetic porcine secretin.

OBJECTIVES: Cannulation of the pancreatic duct at ERCP can represent a technical challenge, even to experienced pancreaticobiliary endoscopists. Secretin is a polypeptide hormone that increases the volume and bicarbonate content of pancreatic secretions. We report our single center experience in the use of a new synthetic porcine secretin (sPS) for the facilitation of cannulation of either the major or minor pancreatic orifice during ERCP. METHODS: Patients presenting for a variety of indications were enrolled. If identification or cannulation of the desired pancreatic duct was difficult, 0.2 microg/kg of sPS was administered i.v. Cannulation success or failure was recorded. RESULTS: Between March, 1999, and May, 2000, a total of 25 patients (seven men and 18 women) were enrolled. The most frequent indication (15 of 25 cases) was facilitation of dorsal pancreatic duct cannulation in patients with pancreas divisum. The overall rate of successful cannulation secretin administration was 24 of 25 cases (96%). No adverse events directly attributable to secretin were observed. CONCLUSIONS: The results of this study show that sPS is safe and efficacious in faciliting cannulation of either the major or minor pancreatic orifice at ERCP in the subset of patients who represent cannulation difficulties. Once commercially available, sPS can be added to the armamentarium of techniques to facilitate ERP.

Clinical utility of stent cytology for the diagnosis of pancreaticobiliary neoplasms.

OBJECTIVE: ERCP is frequently the technique of choice for the diagnosis and palliative treatment of pancreaticobiliary neoplasms. The sensitivity of tissue sampling techniques has been disappointing. Two small series have reported a high diagnostic yield from cytological examination of cellular debris from removed biliary stents. The aim of this study was to determine the clinical utility of stent cytology for the diagnosis of biliary and pancreatic neoplasia. METHODS: Patients who had biliary or pancreatic stents removed at ERCP and evaluated cytologically were the subjects of this study. Stents were scraped and washed, and the cellular debris was examined cytologically and recorded as positive, atypical, or negative. Patient demographics, ductal stricture, and stent characteristics were recorded. RESULTS: Between January, 1994 and January, 2001 a total of 126 biliary stents from 101 patients (61 male, 40 female, mean age 62 yr) and 29 pancreatic stents from 19 patients (seven male, 12 female, mean age 58 yr) were examined. The sensitivity, specificity, positive predictive value, and negative predictive value of biliary and pancreatic stents for the diagnosis of neoplasia were: 11%, 100%, 100%, 53%, and 25%, 100%, 100%, 77.8%, respectively. The sensitivity improved slightly if all degrees of atypia were considered positive for neoplasia. The mean duration of stent placement was 93.6 days for biliary stents and 43.5 days for pancreatic stents. CONCLUSIONS: Biliary and pancreatic stent cytology has limited clinical utility in the diagnosis of pancreaticobiliary neoplasia, owing to poor sensitivity. In addition, the time lag between stent placement and removal for cytologic examination further limits its contribution to patient management.

Clinical utility of EUS-guided fine-needle aspiration of mediastinal masses in the absence of known pulmonary malignancy.

BACKGROUND: Mediastinal masses represent a diagnostic challenge because of their proximity to numerous critical structures, difficulty of access for tissue sampling, and myriad potential pathologic etiologies. A large, single-center experience with EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis of non-lung cancer-related mediastinal masses is presented. METHODS: An EUS database was reviewed and all cases of mediastinal mass or lymphadenopathy encountered between 1994 and 1999 were included. Final diagnoses were determined by EUS-FNA cytology and clinical follow-up. RESULTS: Forty-nine patients were identified (27 women, 22 men; mean age 58.1 years, range 30-89 years). A malignant process was diagnosed in 22 cases (45%) and a benign process in 24 (49%). The EUS-FNA specimen was nondiagnostic in 3 cases (6%). An accurate diagnosis was made in 46 of the 49 patients (94%). No complication was noted. CONCLUSIONS: EUS-FNA is a minimally invasive technique that facilitates detection and tissue sampling of mediastinal masses. It is a safe procedure that can be performed with the patient under conscious sedation in an outpatient setting.

A new synthetic porcine secretin for facilitation of cannulation of the dorsal pancreatic duct at ERCP in patients with pancreas divisum: a multicenter, randomized, double-blind comparative study.

BACKGROUND: Secretin, a 27 amino acid polypeptide released in response to duodenal luminal acidification, stimulates secretion of water and bicarbonate from pancreatic ductal cells. To date the only secretin available for clinical use has been a biologically derived compound extracted from porcine duodenums. Although used to facilitate pancreatic duct cannulation, secretin has not been approved for this indication. In this study, a new synthetic porcine secretin with an identical amino acid composition was compared with saline solution for the facilitation of minor papilla cannulation in patients with pancreas divisum. METHODS: A multicenter, prospective, randomized, placebo-controlled, double-blind, comparative trial was conducted at 4 centers with expertise in pancreaticobiliary endoscopy. Patients with pancreas divisum in whom minor papilla cannulation initially was unsuccessful were enrolled. Either saline solution (placebo) or synthetic porcine secretin was administered. If the minor papilla orifice and/or pancreatic juice flow was noted, cannulation was attempted and success or failure was documented (phase 1), as well as the time taken for successful cannulation. If cannulation was unsuccessful, no juice flow was noted, or the orifice was not seen, the alternate agent was administered (phase 2). RESULTS: Twenty-nine patients (7 men, 22 women; mean age 51 years, range 21-76 years) were enrolled. In phase 1, cannulation was achieved in 1 of 13 patients (7.7%) after the placebo was given and in 13 of 16 patients (81.3%) after synthetic porcine secretin was given (p < 0.0001). In phase 2, cannulation was achieved in 12 of 12 patients (100%) after synthetic porcine secretin was given and in 0 of 3 patients (0%) after the placebo was given (p = 0.0022). Overall, cannulation was successful in 25 of 28 patients (89.3%) who received synthetic porcine secretin and in 1 of 16 (6.3%) who received the placebo (p < 0.0001). Mean time to cannulation was significantly greater for the placebo than for the synthetic porcine secretin (4.75 min vs. 2.63 min; p = 0.0001). No adverse events directly attributable to synthetic porcine secretin administration were documented. CONCLUSIONS: This study confirmed the use and safety of synthetic porcine secretin in facilitating cannulation of the minor papilla in patients with pancreas divisum in whom cannulation was difficult. Use of this agent has the potential to further increase the cannulation success rate in this group of patients.