Timothy Kinney

Endoscopic ultrasound rendezvous for bile duct access using a transduodenal approach: cumulative experience at a single center. A case series

Endoscopic ultrasound (EUS)-assisted biliary access is utilized when conventional endoscopic retrograde cholangiopancreatography (ERCP) fails. We report a 10-year experience utilizing a transduodenal EUS rendezvous via a transpapillary route without dilation of the transduodenal tract, followed by immediate ERCP access. Patients included all EUS-guided rendezvous procedures for biliary access that were performed following ERCP failure. EUS-assisted bile duct puncture was performed via a transduodenal approach and a guide wire was advanced through the papilla without any dilation or bougienage of the tract; ERCP was performed immediately afterwards. EUS-assisted biliary rendezvous was attempted in 15 patients (mean age 66 +/- 18.2 years; malignant = 10, benign = 5). Mean diameter of measured bile ducts was 14.3 +/- 5.17 mm (range 4-23 mm). The reasons for initial ERCP failure were tumor infiltration or edema (n = 9), intradiverticular papilla (n = 2), pre-existing duodenal stent (n = 1), and anatomic anomalies (n = 3). Successful EUS-guided bile duct puncture and wire passage were achieved in all 15 patients (100 %), with drainage being successful in 12 / 15 (80 %). Failures occurred in three patients due to inability to traverse the biliary stricture (n = 2) or dissection of a choledochocele with the guide wire (n = 1); all were subsequently drained via percutaneous methods. Stents placed were metallic in eight patients and plastic in four. Complications consisted of moderate pancreatitis after a difficult ERCP attempt in one patient, and bacteremia after percutaneous biliary drainage in another. There were no instances of perforation, extraluminal air or fluid collections. EUS-assisted biliary drainage utilizing a transduodenal rendezvous approach demonstated a high success rate without any complications directly attributable to the EUS access. Advantages over percutaneous biliary and other methods of EUS biliary access include performance under the same anesthesia, and a very small-caliber needle puncture similar to EUS/fine-needle aspiration.

Impact of experience with a retrograde-viewing device on adenoma detection rates and withdrawal times during colonoscopy: the Third Eye Retroscope study group

BACKGROUNDnColonoscopy has been adopted as the preferred method to screen for colorectal neoplasia in the United States. However, lesions can be missed because of numerous factors, including location on the proximal aspect of folds or flexures, where they may be difficult to detect with the forward-viewing colonoscope. The Third Eye Retroscope (TER) is a disposable device that is passed through the instrument channel of a standard colonoscope to provide a retrograde view that complements the forward view of the colonoscope during withdrawal.nnnOBJECTIVEnTo evaluate whether experience with the TER affects polyp detection rates and procedure times in experienced endoscopists who had not previously used the equipment.nnnDESIGN, SETTING, PATIENTSnThis was an open-label, prospective, multicenter study at 9 U.S. sites, involving 298 patients presenting for colonoscopy, evaluating the use of the TER in combination with a standard colonoscope.nnnINTERVENTIONSnAfter cecal intubation, the TER was inserted through the instrument channel of the colonoscope. During withdrawal, the forward and retrograde video images were observed simultaneously on a wide-screen monitor.nnnMAIN OUTCOME MEASUREMENTSnPrimary outcome measures were the number and size of adenomas and all polyps detected with the standard colonoscope and with the colonoscope combined with the TER. Secondary outcome measures were withdrawal phase time and total procedure time. Each endoscopist examined 20 subjects, divided into quartiles according to the order of their procedures, and results were compared among quartiles.nnnRESULTSnOverall, 182 polyps were detected with the colonoscope and 27 additional polyps with the TER, a 14.8% increase (P < .001). A total of 100 adenomas were detected with the colonoscope and 16 more with the TER, a 16.0% increase (P < .001). For procedures performed after each endoscopist had completed 15 procedures while using the TER, the mean additional detection rates with the TER were 17.0% for all polyps (P < .001) and 25.0% for adenomas (P < .001). For lesions 6 mm or larger, the overall additional detection rates with the TER for all polyps and for adenomas were 23.2% and 24.3%, respectively. For lesions 10 mm or larger, the overall additional detection rates with the TER for all polyps and for adenomas were 22.6% and 19.0%, respectively. The mean withdrawal times in the first and fourth quartiles were 10.6 and 9.2 minutes, respectively (P = .044).nnnLIMITATIONSnThere was no randomization or separate control group. The endoscopists judged whether each lesion could have been detected with the colonscope alone by using their standard technique.nnnCONCLUSIONSnPolyp detection rates improved significantly with the TER, especially after 15 procedures, when the mean additional detection rate for adenomas was 25.0%. Additional detection rates with the TER for medium-size and large adenomas were greater than for smaller lesions. These results suggest that, compared with a colonoscope alone, a retrograde-viewing device can increase detection rates for clinically significant adenomas without detriment to procedure time or procedure complications. (nnnCLINICAL TRIAL REGISTRATION NUMBERnNCT00969124.).

Evidence-Based Imaging of Pancreatic Malignancies

A high-quality pancreatic protocol computed tomography (CT) is the primary imaging modality for diagnosing and staging pancreatic malignancy. The main limitation of CT is the lack of sensitivity for early pancreatic lesions. Endoscopic ultrasound (EUS) provides an excellent complement to CT for both diagnosis and staging of pancreatic cancer, and allows easy access for needle aspiration and tissue diagnosis. Magnetic resonance (MR) can be helpful for evaluating small hepatic nodules or cystic lesions of the pancreas, but in general, the role of MR and positron emission tomography remains limited to special situations when the results of CT and EUS are equivocal.

Therapeutic pancreatic endoscopy after Whipple resection requires rendezvous access

Chronic pancreatic complications after pancreaticoduodenectomy, including strictured pancreaticojejunostomy and pancreatic fistulas, may be amenable to endoscopic therapy. To date there is no published series focusing on pancreatic endotherapy in this group of patients. We report our experience performing pancreatic therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in 10 patients after pancreaticoduodenectomy. All patients had evidence of pancreatic anastomotic obstruction by endoscopic ultrasound (EUS) or secretin-enhanced magnetic resonance cholangiopancreatography. Technical endoscopic success and clinical outcomes were measured. Technically successful endoscopic access and therapy was ultimately achieved by ERCP in eight of the 10 patients. Although a duodenoscope or pediatric colonoscope could be advanced up the afferent limb in all patients, initial unassisted pancreatic cannulation and therapy was successful in only one patient. Rendezvous techniques, either percutaneous or EUS-guided, were required for endoscopic access in the other 9 patients. Complications included moderate pancreatitis with retroperitoneal air after percutaneous rendezvous access in 1 patient, and fever in 1 patient. Therapeutic pancreatic ERCP for chronic complications after Whipple pancreaticoduodenectomy is feasible but quite challenging. Endoscopic access through a stenotic pancreaticojejunal anastomosi generally requires either EUS or percutaneous rendezvous assistance.

Epitope-specific immunotherapy targeting CD4-positive T cells in coeliac disease: two randomised, double-blind, placebo-controlled phase 1 studies

BACKGROUNDnA gluten-free diet is the only means to manage coeliac disease, a permanent immune intolerance to gluten. We developed a therapeutic vaccine, Nexvax2, designed to treat coeliac disease. Nexvax2 is an adjuvant-free mix of three peptides that include immunodominant epitopes for gluten-specific CD4-positive T cells. The vaccine is intended to engage and render gluten-specific CD4-positive T cells unresponsive to further antigenic stimulation. We assessed the safety and pharmacodynamics of the vaccine in patients with coeliac disease on a gluten-free diet.nnnMETHODSnWe did two randomised, double-blind, placebo-controlled, phase 1 studies at 12 community sites in Australia, New Zealand, and the USA, in HLA-DQ2·5-positive patients aged 18-70 years who had coeliac disease and were on a gluten-free diet. In the screening period for ascending dose cohorts, participants were randomly assigned (1:1) by central randomisation with a simple block method to a double-blind crossover, placebo-controlled oral gluten challenge. Participants with a negative interferon γ release assay to Nexvax2 peptides after the screening oral gluten challenge were discontinued before dosing. For the biopsy cohorts, the screening period included an endoscopy, and participants with duodenal histology who had a Marsh score of greater than 1 were discontinued before dosing. Participants were subsequently randomly assigned to either Nexvax2 or placebo in ascending dose cohorts (2:1) and in biopsy cohorts (1:1) by central randomisation with a simple block method. In the three-dose study, participants received either Nexvax2 60 μg, 90 μg, or 150 μg weekly, or placebo over 15 days; in a fourth biopsy cohort, patients received either Nexvax2 at the maximum tolerated dose (MTD) or placebo. In the 16-dose study, participants received Nexvax2 150 μg or 300 μg or placebo twice weekly over 53 days; in a third biopsy cohort, patients also received either Nexvax2 at the MTD or placebo. In the 4-week post-treatment period, ascending dose cohorts underwent a further double-blind crossover, placebo-controlled oral gluten challenge, which had a fixed sequence, and biopsy cohorts had a gastroscopy with duodenal biopsies and quantitative histology within 2 weeks without oral gluten challenge. Participants, investigators, and study staff were masked to the treatment assignment, except for the study pharmacist. The primary endpoint was the number and percentage of adverse events in the treatment period in an intention-to-treat analysis. Both trials were completed and closed before data analysis. Trials were registered with the Australian New Zealand Clinical Trials Registry, numbers ACTRN12612000355875 and ACTRN12613001331729.nnnFINDINGSnParticipants were enrolled from Nov 28, 2012, to Aug 14, 2014, in the three-dose study, and from Aug 3, 2012, to Sept 10, 2013, in the 16-dose study. Overall, 62 (57%) of 108 participants were randomly assigned after oral gluten challenge and 20 (71%) of 28 participants were randomly assigned after endoscopy. In the three-dose study, nine participants were randomly allocated to Nexvax2 60 μg and three to placebo (first cohort), nine were allocated to Nexvax2 90 μg and four to placebo (second cohort), eight were allocated to Nexvax2 150 μg and four to placebo (third cohort), and three were allocated to Nexvax2 150 μg and three to placebo (biopsy cohort). In the 16-dose study, eight participants were randomly allocated to Nexvax2 150 μg and four to placebo (first cohort), ten were allocated to Nexvax2 300 μg and three to placebo (second cohort), and seven were allocated to Nexvax2 150 μg and seven to placebo (biopsy cohort). The MTD for Nexvax2 was 150 μg because of transient, acute gastrointestinal adverse events with onset 2-5 h after initial doses of the vaccine, similar to those caused by gluten ingestion. In the ascending dose cohorts in the three-dose study, six (55%) of 11 placebo recipients, five (56%) of nine who received Nexvax2 60 μg, seven (78%) of nine who received Nexvax2 90 μg, and five (63%) of eight who received Nexvax2 150 μg had at least one treatment-emergent adverse event, as did all three (100%) placebo recipients and one (33%) of three Nexvax2 150 μg recipients in the biopsy cohort. In the ascending dose cohorts of the 16-dose study, five (71%) of seven placebo-treated participants, six (75%) of eight who received Nexvax2 150 μg, and all ten (100%) who received Nexvax2 300 μg had at least one treatment-emergent adverse event, as did six (86%) of seven placebo recipients and five (71%) of seven Nexvax2 150 μg recipients in the biopsy cohort. Vomiting, nausea, and headache were the only treatment-emergent adverse events that occurred in at least 5% of participants in either study. Among participants given the MTD, eight gastrointestinal treatment-emergent adverse events occurred in four (50%) of eight participants in the third cohort and none (0%) of three participants in the biopsy cohort in the three-dose study, and five events occurred in five (63%) of eight participants in the first cohort and three events in two (29%) of seven participants in the biopsy cohort of the 16-dose study. Median villous height to crypt depth ratio in distal duodenal biopsies was not significantly different between those who received the vaccine at the MTD on either schedule and those who received placebo. Of the participants who completed the post-treatment oral gluten challenge per protocol, interferon γ release assay to Nexvax2 peptides was negative (responders to treatment) in two (22%) of nine placebo-treated participants in the three-dose study versus two (33%) of six who received Nexvax2 60 μg, five (63%) of eight who received Nexvax2 90 μg, and six (100%) of six who received Nexvax2 150 μg (p=0·007); in the 16-dose study, none (0%) of five placebo-treated participants had a negative assay versus six (75%) of eight who received Nexvax2 150 μg (p=0·021).nnnINTERPRETATIONnThe MTD of Nexvax2 was 150 μg for twice weekly intradermal administration over 8 weeks, which modified immune responsiveness to Nexvax2 peptides without deterioration in duodenal histology. The gastrointestinal symptoms that followed the first intradermal administration of the vaccine resembled those associated with oral gluten challenge. These findings support continued clinical development of this potential therapeutic vaccine for coeliac disease.nnnFUNDINGnImmusanT.

Pancreatic imaging: current state of the art.

Radiologic imaging is an important component in the evaluation of pancreatic disease. Recent improvements in computed tomography (CT) have led to unprecedented imaging quality. With the addition of magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS), the clinician can detect neoplasms at an earlier stage, and often find an etiology of “idiopathic” pancreatitis. Certain problematic imaging scenarios remain, such as the detection of occult neoplasms in the setting of acute or chronic pancreatitis, accuracy of preoperative surgical staging of pancreatic malignancy, and assessment of early chronic pancreatitis and pancreatic function. New technologies including sonographic elastography, contrast enhanced or 3-dimensional (3D) ultrasound, secretin-stimulated MRCP, and other methods of pancreatic imaging are under investigation and may soon become a standard part of our clinical armamentarium. This article briefly reviews some recent advances in traditional imaging technology and discusses some of the emerging research in pancreatic imaging.

A multicenter, prospective study of a new fully covered expandable metal biliary stent for the palliative treatment of malignant bile duct obstruction.

Background and Study Aims. Endoscopic placement of self-expanding metal stents (SEMSs) is indicated for palliation of inoperable malignant biliary obstruction. A fully covered biliary SEMS (WallFlex Biliary RX Boston Scientific, Natick, USA) was assessed for palliation of extrahepatic malignant biliary obstruction. Patients and Methods. 58 patients were included in this prospective, multicenter series conducted under an FDA-approved IDE. Main outcome measurements included (1) absence of stent occlusion within six months or until death, whichever occurred first and (2) technical success, need for reintervention, bilirubin levels, stent patency, time to stent occlusion, and adverse events. Results. Technical success was achieved in 98% (57/58), with demonstrated acute removability in two patients. Adequate clinical palliation until completion of followup was achievedin 98% (54/55) of evaluable patients, with 1 reintervention due to stent obstruction after 142 days. Mean total bilirubin decreased from 8.9u2009mg/dL to 1.2u2009mg/dL at 1 month. Device-related adverse events were limited and included 2 cases of cholecystitis. One stent migrated following radiation therapy. Conclusions. The WallFlex Biliary fully covered stent yielded technically successful placement with uncomplicated acute removal where required, appropriate reduction in bilirubin levels, and low rates of stent migration and occlusion. This SEMS allows successful palliation of malignant extrahepatic biliary obstruction.

⁎3341 Single-use biopsy forceps: does sterility upon insertion prevent contamination at time of biopsy?

Background: It has been suggested that single-use biopsy forceps will prevent inter-patient transmission of infection during endoscopy. Passage of sterile forceps through the biopsy channel can lead to contamination, however, if the endoscope is inadequately reprocessed.We prospectively evaluated the potential for contamination of single-use biopsy forceps at various stages of endoscope reprocessing. Methods: A total of forty disposable biopsy forceps (Microvasive Inc., Natick, MA) were passed through the biopsy channels of ten colonoscopes at various stages of reprocessing. Ten forceps were passed through the channels prior to use on patients to establish a baseline of high-level disinfection. Ten forceps were passed directly after colonoscopy to confirm contamination with use. Ten forceps were passed after manual cleaning and flushing of the biopsy channel to evaluate the effectiveness of manual cleaning to reduce bioburden. Finally ten were passed through the biopsy channel after either a 2- or 20-minute soak in 2% glutaraldehyde (Cidex™, Johnson & Johnson, Arlington, TX). The forceps were then sealed in sterile plastic bags and 15 ml of soy broth was added. The suspension was passed through a 0.2-micron filter, and the filters were cultured. All cultures were incubated more than 48 hours. Results: Biopsy forceps underwent a total of 40 aerobic and 40 anaerobic cultures. TNTC gastrointestinal flora grew on 19 of 20 plates from biopsy forceps passed through colonoscopes immediately after use (one plate grew only 3 colonies). Persistent gastrointestinal flora was noted on 5 of 20 plates from forceps passed through colonoscopes after manual cleaning alone. No gastrointestinal flora was found on forceps after the colonoscopes were exposed to gluteraldehyde soaks of 2 or 20 minutes. Nonpathogenic organisms including diptheroids, staphylococcus, and streptococcus grew on 16 plates. Conclusions: 1) Disposable biopsy forceps are highly susceptible to contamination from passage through the biopsy channels of improperly cleaned endoscopes. 2) High-level disinfection of the colonoscopes in this study prevented contamination of the forceps with pathogenic organisms. 3) Proper endoscope reprocessing may be the most important factor in preventing inter-patient infection, whether new biopsy forceps or sterilized reusable forceps are utilized.

3416 Photodynamic therapy probes: can they be reused?

Background: Fiber optic diffuser probes used in photodynamic therapy (PDT) are marketed as single-use disposable items. The relatively simple design of these probes (i.e. no moving parts, no open lumens) suggests that they might be safely sterilized and reused, without significant degradation in function.We prospectively evaluated PDT probes for sterility and loss of function in vivo and in vitro. Methods: Three patients underwent a total of five PDT treatments for esophageal cancer, with treatment time averaging 19 minutes per session. PDT probes were reused on two patients, but never shared between patients. Light transmission was evaluated prior to each treatment. After use, the PDT probe was cultured and sent for manual cleaning and sterilization using the STERIS system (Steris Corp., Mentor, Ohio). The probes were then recultured to assess sterility, and light transmission was measured to test for degradation in function. All cultures were incubated aerobically and anaerobically for more than 48 hours. To further evaluate the potential for sterilization and reuse, a separate probe was exposed in vitro to a suspension of 2.1 × 10 7 B. Stearothermophilus spores. The probe was cultured to ensure contamination by the spores. After manual cleaning and sterilization, the probe was recultured and tested for light transmission. This procedure was repeated five times. Results: Cultures of PDT probes following treatment in vivo grew numerous colonies of oropharyngeal flora. Culture of the probe exposed to B. Stearothermophilus spores grew numerous colonies of this organism. After sterilization, all probe cultures showed no growth, including eradication of B. Stearothermophilus spores. Light transmission did not change significantly in any probes following two treatments in vivo and up to five sterilizations in vitro. Conclusions: 1) Sterilization of PDT probes was achieved by manual cleaning followed by STERIS system reprocessing. 2) Reuse and reprocessing of PDT probes did not affect light transmission or probe function after up to five sterilizations. 3) The number of procedures which may be performed before significant deterioration in probe function has yet to be determined.