Endoscopic mucosal resection results in change of histologic diagnosis in Barrett's esophagus patients with visible and flat neoplasia: a multicenter cohort study.

BACKGROUND: There are limited data on the effect of endoscopic mucosal resection (EMR) on changes of histopathologic diagnosis for Barrett's esophagus (BE) patients undergoing endoscopic eradication therapy (EET); especially those without visible lesions. AIM: To compare the frequency of changes of diagnosis by EMR compared with pre-EMR biopsy diagnosis for patients with and without visible lesions. METHODS: In this multicenter outcomes project, patients with Barrett's-related neoplasia undergoing EET at three tertiary-care centers were included. Patients undergoing biopsies followed by EMR within six months were included. The main outcome measures were frequency of overall change of histopathologic diagnosis, change based on pre-EMR biopsy diagnosis, and change based on the presence of visible lesions. RESULTS: One-hundred and thirty-eight BE patients (low-grade dysplasia (LGD) 15 (10.9 %), high-grade dysplasia (HGD) 87 (63 %), esophageal adenocarcinoma (EAC) 36 (26.1 %)) were included; 114 (82.6 %) patients had visible lesions. EMR resulted in a change of diagnosis for 43 (31.1 %) patients (upgrade 14 (10.1 %); downgrade 29 (21 %)). For HGD patients, EMR downstaged dysplasia grade for 17 (19.5 %) cases and upstaged it to EAC for nine (10.3 %) cases. There was a change of diagnosis for 26 (29.9 %) HGD patients, irrespective of the presence or absence of visible lesions (p = 0.76). For EAC patients, EMR downstaged dysplasia grade in 10 (27.8 %) cases. There was a change of diagnosis for 10 (27.8 %) EAC patients, irrespective of the presence or absence of endoscopically visible lesions (p = 0.48). CONCLUSIONS: EMR results in a change of diagnosis for approximately 30 % of BE patients with early neoplasia (with and without visible lesions) referred for EET.

Physician recommendations and patient adherence after inadequate bowel preparation on screening colonoscopy.

BACKGROUND AND AIMS: It has been suggested that bowel preparation quality may influence decision-making about appropriate follow-up interval after screening colonoscopy. We sought: (1) to assess physician recommendations for timing of subsequent colonoscopy in average-risk patients with inadequate bowel preparation on initial screening, and (2) to measure the association between physician recommendations and patient adherence to repeat colonoscopy. METHODS: Patients undergoing average-risk screening colonoscopy from 2004 to 2009 found to have inadequate bowel preparation were identified. Physician recommendations for timing of subsequent colonoscopy and patient adherence to repeat colonoscopy were assessed through examination of endoscopy records. Data from repeat colonoscopies were collected through August 2010. RESULTS: There were 373 patients with inadequate bowel preparation on initial screening colonoscopy. There was a wide range of physician recommendations for timing of repeat colonoscopy: next day (4.6 % of patients), 2 days to 6 months (9.9 %), 7 months to 1 year (34.0 %), 2-5 years (38.3 %), 6-10 years (5.1 %), and timing not specified (8.0 %). Physicians were significantly more likely to recommend repeat colonoscopy within 1 year if any polyps were detected (OR = 2.2, p = 0.001). Patients instructed to have next day follow-up were significantly more likely to adhere to the recommendation compared to patients who were instructed to return after longer intervals (OR 4.4, p = 0.005). CONCLUSIONS: Patients with inadequate bowel preparation on screening colonoscopy were subject to a wide range of physician recommendations for follow-up. Patient adherence to physician recommendations was significantly higher when repeat colonoscopy was recommended the next day.

Long-term outcomes after single-balloon enteroscopy in patients with obscure gastrointestinal bleeding.

BACKGROUND: Limited data exists on the long-term outcomes of patients with obscure gastrointestinal bleeding (OGIB) following single-balloon enteroscopy (SBE). AIM: To examine the long-term outcomes of patients undergoing SBE for OGIB. METHODS: Consecutive patients undergoing SBE for OGIB at a tertiary care center between 2008 and 2010 were retrospectively identified. Clinical data and SBE findings were extracted from the medical record. Recurrence of OGIB during follow-up through 2012 was assessed by a combination of chart review and telephone interviews. RESULTS: One hundred and forty-seven patients were included in the study. The overall diagnostic yield of SBE was 64.6% (95/147 patients). Findings of SBE included vascular lesions (VLs, 53.7%), small bowel neoplasm (2.7%), inflammatory lesions (4.8%), and normal SBE (35.4%). One hundred and ten patients (56.4% female, mean age 70.6±11.3 years) were followed for an average 23.9 months after initial SBE. During follow-up, OGIB recurred in 39.5% of patients in whom a source of OGIB was identified on SBE and 55.9% of patients with normal findings on SBE. OGIB recurred in 47.6% of patients in whom small bowel VLs were treated endoscopically. None of the 13 patients in whom a non-VL lesion was identified as the source of bleeding on SBE experienced recurrent bleeding (p=0.019). CONCLUSIONS: SBE is a safe and valuable method for managing patients with OGIB. More than 50% of patients experienced no recurrent bleeding during 2 years of follow-up after SBE. The long-term management of OGIB due to small bowel VLs remains challenging.

Learning curves for EUS by using cumulative sum analysis: implications for American Society for Gastrointestinal Endoscopy recommendations for training.

BACKGROUND: American Society for Gastrointestinal Endsocopy (ASGE) guidelines for assessing minimal competence in EUS are based on expert opinion and retrospective studies. OBJECTIVE: To prospectively define learning curves in EUS among advanced endoscopy trainees (AETs). DESIGN: Prospective trial. SETTING: Three tertiary-care referral centers. PATIENTS: AETs with no prior EUS experience. INTERVENTION: AETs were evaluated by attending endosonographers at intervals of 10 EUS examinations (beginning at the 25th examination) during a 12-month training period. A standardized data collection form was used to grade examination of EUS anatomic stations and, when applicable, lesion of interest, accurate uTNM staging, wall layer origin of subepithelial lesions, and technical success with FNA. MAIN OUTCOME MEASUREMENTS: Cumulative sum analysis was applied to assess competency and produce a learning curve for each trainee for overall performance and for each anatomic station. Acceptable and unacceptable failure rates of 10% and 20%, respectively, were used. RESULTS: Five AETs were included, with a total of 1412 EUS examinations (AET1-225, T2-175, T3-402, T4-315, T5-295). Two AETs crossed the threshold for acceptable performance at cases number 255 and 295, two AETs showed a trend toward acceptable performance after 225 and 196 cases but needed ongoing training, and 1 AET demonstrated the need for ongoing training after 402 cases. Similar variable results were noted for individual stations. LIMITATIONS: Results from this study may not be generalizable to other centers' AETs. CONCLUSION: We observed substantial variability in achieving competency and a consistent need for more supervision in all AETs than current recommendations (150 cases). Future studies should focus on standardization of trainee performance, definition of competency, and widespread applicability of AET evaluation.

Diagnostic yield of malignancy during EUS-guided FNA of solid lesions with and without a stylet: a prospective, single blind, randomized, controlled trial.

BACKGROUND: Use of a stylet during EUS-guided FNA (EUS-FNA) is believed to improve the quality and diagnostic yield of specimens. OBJECTIVE: To compare samples obtained by EUS-FNA with (S+) and without (S-) a stylet for diagnostic yield of malignancy and cytological characteristics. DESIGN: Randomized, controlled trial. SETTING: Tertiary referral center. PATIENTS: Consecutive patients referred for EUS-FNA of solid lesions. INTERVENTION: EUS-FNA; the number of passes was determined by lesion site (6 pancreas/others and 4 lymph nodes). MAIN OUTCOME MEASUREMENTS: Diagnostic yield of malignancy and degree of cellularity, specimen adequacy, contamination, and amount of blood. RESULTS: One hundred patients were prospectively enrolled in this randomized, controlled trial and the sites of EUS-FNA were the pancreas, 58; lymph node, 25; and other, 17. The overall diagnosis was malignancy in 56, benign in 30, suspicious/atypical in 7, and inadequate specimen in 7 lesions. There were 550 passes made (275 with a stylet and 275 without a stylet). Interim analysis demonstrated no difference in the diagnostic yield of malignancy (94 passes with a stylet [34.2%] vs 110 without a stylet [40%], P = .2) and in the proportion of inadequate specimens (57 with a stylet [20.7%] vs 64 without a stylet [23.3%], P = .2). There was no difference with regard to cellularity (P = .83), contamination (P = .31), number of cells (P = .25), and amount of blood (P = .6). Similar results were noted in a subgroup analysis based on lesion site. Applying the rules of futility, the study was terminated. LIMITATIONS: Subjectivity in cytopathologists' assessment, endosonographer not blinded. CONCLUSIONS: There was no difference in the diagnostic yield of malignancy or proportion of inadequate specimens between passes with and without a stylet. These results suggest that the use of a stylet does not confer any advantage during EUS-FNA.

Use of a pancreatic duct stent or guidewire facilitates bile duct access with low rates of precut sphincterotomy: a randomized clinical trial.

BACKGROUND AND STUDY AIMS: Among cases of difficult biliary cannulation, alternatives include use of a pancreatic duct stent (PDS) or guidewire (PDW) to facilitate access. We compared the effectiveness of a PDS versus a PDW to facilitate common bile duct (CBD) cannulation. PATIENTS AND METHODS: We conducted a randomized, crossover trial at two endoscopy referral centers, limited to patients undergoing ERCP without a history of biliary sphincterotomy. After meeting predefined criteria for difficult cannulation, patients were randomized to using a PDS or PDW to facilitate CBD cannulation. Outcomes included cannulation rate within 6 min, overall cannulation rate, frequency of precut, and complication rates. RESULTS: Among 442 eligible patients, 87 (19.7 %) met criteria for difficult cannulation. Forty two were randomized to PDW, 54 to PDS (including 9 PDW patients crossed over to PDS). The rate of CBD cannulation within 6 min was similar in the PDW (38.1 %) and PDS (51.9 %) groups (p = 0.18). In a secondary analysis limited to patients who successfully underwent PDW or PDS deployment, the rate was also comparable (PDW 59.3 %, PDS 65.1 %; p = 0.62). The overall frequency of CBD cannulation was 66.7 % in PDW and 90.7 % in PDS patients. Precut was required in 9.5 % of PDW and 25.9 % of PDS patients. Complication rates were similar, with 4 (4.6 %) patients having post-ERCP pancreatitis and 1 (1.1 %) having post-ERCP pain without confirmation of pancreatitis. CONCLUSIONS: Use of a PDS or PDW facilitates CBD cannulation while maintaining a low complication rate and reducing the need for precut sphincterotomy in the majority of cases.

Prevalence of missed adenomas in patients with inadequate bowel preparation on screening colonoscopy.

BACKGROUND: The prevalence of missed polyps in patients with inadequate bowel preparation on screening colonoscopy is unknown. OBJECTIVE: To determine the prevalence of missed adenomas in average-risk patients presenting for screening colonoscopy who are found to have inadequate bowel preparation. DESIGN: Retrospective chart review. Endoscopy and pathology reports were examined to determine the characteristics of polyps. Data from repeat colonoscopies were collected through 2010. SETTING: Outpatient endoscopy center at an academic medical center. PATIENTS: This study involved patients who underwent outpatient average-risk screening colonoscopy between 2004 and 2009 documented to have inadequate bowel preparation and who had colonoscopy to the cecum. MAIN OUTCOME MEASUREMENTS: Initial adenoma detection rate and adenoma detection rate on follow-up examination. RESULTS: Inadequate bowel preparation was reported on 373 patients, with an initial adenoma detection rate of 25.7%. Of 133 patients who underwent repeat colonoscopy, 33.8% had at least 1 adenoma detected, and 18.0% had high-risk states detected (≥ 3 adenomas, 1 adenoma ≥ 1 cm, or any adenoma with villous features or high-grade dysplasia). Per-adenoma miss rate was 47.9%. Among patients with at least 1 adenoma on repeat colonoscopy, 31.1% had no polyps on initial colonoscopy; mean time between colonoscopies was 340 days. Among patients with high-risk states, 25.0% had no polyps seen on initial colonoscopy; mean time between colonoscopies was 271 days. LIMITATIONS: Retrospective design. CONCLUSION: Adenomas and high-risk lesions were frequently detected on repeat colonoscopy in patients with inadequate bowel preparation on initial screening colonoscopy, suggesting that these lesions were likely missed on initial colonoscopy.

Obesity as a risk factor for sedation-related complications during propofol-mediated sedation for advanced endoscopic procedures.

BACKGROUND: There are limited data on the safety of anesthesia-assisted endoscopy by using propofol-mediated sedation in obese individuals undergoing advanced endoscopic procedures (AEPs). OBJECTIVE: To study the association between obesity (as measured by body mass index [BMI]) and the frequency of sedation-related complications (SRCs) in patients undergoing AEPs. DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS: A total of 1016 consecutive patients undergoing AEPs (BMI <30, 730 [72%]; 30-35, 159 [16%]; >35, 127 [12%]). INTERVENTION: Monitored anesthesia sedation with propofol alone or in combination with benzodiazepines and/or opioids. MAIN OUTCOME MEASUREMENTS: SRCs, airway maneuvers (AMs), hypoxemia, hypotension requiring vasopressors, and early procedure termination were compared across 3 groups. RESULTS: There were 203 AMs in 13.9% of patients, hypoxemia in 7.3%, need for vasopressors in 0.8%, and premature termination in 0.6% of patients. Increasing BMI was associated with an increased frequency of AMs (BMI <30, 10.5%; 30-35, 18.9%; >35-26.8%; P < .001) and hypoxemia (BMI <30, 5.3%; 30-35, 9.4%; >35, 13.4%; P = .001); there was no difference in the frequency of need for vasopressors (P = .254) and premature termination of procedures (P = .401). On multivariable analysis, BMI (odds ratio [OR] 2.0; 95% CI, 1.3-3.1), age (OR 1.1; 95% CI, 1.0-1.1), and American Society of Anesthesiologists class 3 or higher (OR 2.4; 95% CI, 1.1-5.0) were independent predictors of SRCs. In obese individuals (n = 286), there was no difference in the frequency of SRCs in patients receiving propofol alone or in combination (P = .48). LIMITATIONS: Single tertiary center study. CONCLUSIONS: Although obesity was associated with an increased frequency of SRCs, propofol sedation can be used safely in obese patients undergoing AEPs when administered by trained professionals.

Training in EUS-Guided Fine Needle Aspiration: Safety and Diagnostic Yield of Attending Supervised, Trainee-Directed FNA from the Onset of Training.

Background. The optimal time to initiate hands-on training in endoscopic ultrasound fine needle aspiration (EUS-FNA) is unclear. We studied the feasibility of initiating EUS-FNA training concurrent with EUS training. Methods. Three supervised trainees were instructed on EUS-FNA technique and allowed hands-on exposure from the onset of training. The trainee and attending each performed passes in no particular order. During trainee FNA, the attending provided verbal instruction as needed but no hands-on assistance. A blinded cytopathologist assessed the adequacy (cellularity) and diagnostic yield of individual passes. Primary outcomes compared cellularity and diagnostic yield of attending versus fellow FNA passes. Results. We analyzed 305 FNA sites, including pancreas (51.2%), mediastinal/upper abdominal lymph node (LN) (28.5%) and others (20.3%). The average proportion of fellow passes with AC was similar to attending FNA-pancreas: 70.3 versus 68.8%; LN: 79.0 versus 81.7%; others 65.5 versus 68.7%; P > 0.05); these did not change significantly during the training period. Among cases with confirmed malignancy (n = 179), the sensitivity of EUS-FNA was 78.8% (68.4% fellow-only versus 69.6% attending only). There were no EUS-FNA complications. Conclusions. When initiated at the onset of EUS training, attending-supervised, trainee-directed FNA is safe and has comparable performance characteristics to attending FNA.

Randomized, controlled trial of standard-definition white-light, high-definition white-light, and narrow-band imaging colonoscopy for the detection of colon polyps and prediction of polyp histology.

BACKGROUND: Missing adenomas and the inability to accurately differentiate between polyp histology remain the main limitations of standard-definition white-light (SD-WL) colonoscopy. OBJECTIVE: To compare the adenoma detection rates of SD-WL with those of high-definition white-light (HD-WL) and narrow-band imaging (NBI) as well as the accuracy of predicting polyp histology. DESIGN: Multicenter, prospective, randomized, controlled trial. SETTING: Two academic medical centers in the United States. PATIENTS: Subjects undergoing screening or surveillance colonoscopy. INTERVENTION: Subjects were randomized to undergo colonoscopy with one of the following: SD-WL, HD-WL, or NBI. MAIN OUTCOME MEASUREMENTS: The proportion of subjects detected with adenomas, adenomas detected per subject, and the accuracy of predicting polyp histology real time. RESULTS: A total of 630 subjects were included. The proportion of subjects with adenomas was 38.6% with SD-WL compared with 45.7% with HD-WL and 46.2% with NBI (P = .17 and P = .14, respectively). Adenomas detected per subject were 0.69 with SD-WL compared with 1.12 with HD-WL and 1.13 with NBI (P = .016 and P = .014, respectively). HD-WL and NBI detected more subjects with flat and right-sided adenomas compared with SD-WL (all P values <.005). NBI had a superior sensitivity (90%) and accuracy (82%) to predict adenomas compared with SD-WL and HD-WL (all P values <.005). LIMITATIONS: Academic medical centers with experienced endoscopists. CONCLUSIONS: There was no difference in the proportion of subjects with adenomas detected with SD-WL, HD-WL, and NBI. However, HD-WL and NBI detected significantly more adenomas per subject (>60%) compared with SD-WL. NBI had the highest accuracy in predicting adenomas in real time during colonoscopy. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT 00614770.).

A screening instrument for sleep apnea predicts airway maneuvers in patients undergoing advanced endoscopic procedures.

BACKGROUND & AIMS: Among patients undergoing advanced endoscopy, unrecognized obstructive sleep apnea (OSA) could predict sedation-related complications (SRCs) and the need for airway maneuvers (AMs). By using an OSA screening tool, we sought to define the prevalence of patients at high risk for OSA and to correlate OSA with the frequency of AMs and SRCs. METHODS: We enrolled 231 consecutive patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) (n = 176) and endoscopic ultrasound (n = 55). Propofol-based sedation and patient monitoring were performed by a nurse anesthetist and an anesthesiologist. A previously validated screening tool for OSA (STOP-BANG) was used to identify patients at high risk for OSA (score, > or =3 of 8; SB+) or low risk (SB-). AMs were defined as a chin lift, modified mask ventilation, nasal airway, bag-mask ventilation, and endotracheal intubation. SRCs were defined as any duration of pulse oximetry less than 90%, systolic blood pressure less than 90 mm Hg, apnea, or early procedure termination. RESULTS: The prevalence of SB+ was 43.3%. The frequency of hypoxemia was significantly higher among patients with SB+ than SB- (12.0% vs 5.2%; relative risk [RR], 1.83; 95% confidence interval [CI], 1.32-2.54). The rate of AMs was also significantly higher among SB+ (20.0%) compared with SB- (6.1%) patients (RR, 1.8; 95% CI, 1.3-2.4). These rates remained significant after adjusting for American Society of Anesthesiologists class 3 or higher (RR, 1.70; 95% CI, 1.28-2.2 for AMs; RR, 1.63; 95% CI, 1.19-2.25 for hypoxemia). Each element of the STOP-BANG was reported more commonly in SB+ patients (P < .0001 for each comparison). CONCLUSIONS: A significant number of patients undergoing advanced endoscopic procedures are at risk for OSA. AMs and hypoxemia occur at an increased frequency in these patients.

The antimicrobial efficacy of sustained release silver-carbene complex-loaded L-tyrosine polyphosphate nanoparticles: characterization, in vitro and in vivo studies.

The pressing need to treat multi-drug resistant bacteria in the chronically infected lungs of cystic fibrosis (CF) patients has given rise to novel nebulized antimicrobials. We have synthesized a silver-carbene complex (SCC10) active against a variety of bacterial strains associated with CF and chronic lung infections. Our studies have demonstrated that SCC10-loaded into L-tyrosine polyphosphate nanoparticles (LTP NPs) exhibits excellent antimicrobial activity in vitro and in vivo against the CF relevant bacteria Pseudomonas aeruginosa. Encapsulation of SCC10 in LTP NPs provides sustained release of the antimicrobial over the course of several days translating into efficacious results in vivo with only two administered doses over a 72 h period.

Synthesis and in vitro Efficacy Studies of Silver Carbene Complexes on Biosafety Level 3 Bacteria.

A series of N-heterocyclic carbene silver complexes have been synthesized and tested against the select group of bio-safety level 3 bacteria Burkholderia pseudomallei, Burkholderia mallei, Bacillus anthracis, methicillin-resistant Staphylococcus aureus and Yersinia pestis. Minimal inhibitory concentrations, minimal bactericidal and killing assays demonstrated the exceptional efficacy of the complexes against these potentially weaponizable pathogens.

Synthesis, stability, and antimicrobial studies of electronically tuned silver acetate N-heterocyclic carbenes.

A series of methylated imidazolium salts with varying substituents on the 4 and 5 positions of the imidazole ring were synthesized. These salts were reacted with silver acetate to afford their corresponding silver N-heterocyclic carbene (NHC) complexes. These complexes were then evaluated for their stability in water as well as for their antimicrobial efficacy against a variety of bacterial strains associated with cystic fibrosis and chronic lung infections.

Synthesis from caffeine of a mixed N-heterocyclic carbene-silver acetate complex active against resistant respiratory pathogens.

The bis(N-heterocyclic carbene) (NHC) silver complex, 3, with a methyl carbonate anion was formed from the reaction of the iodide salt of methylated caffeine, 1, with silver (I) oxide in methanol. Attempts to crystallize this complex from a mixture of common alcohols and ethyl acetate led to the formation of an NHC-silver acetate complex, 4. The more direct synthesis of 4 was accomplished by the in-situ deprotonation of 1 by silver acetate in methanol. Complex 4 demonstrated antimicrobial activity against numerous resistant respiratory pathogens from the lungs of cystic fibrosis (CF) patients including members of the Burkholderia cepacia complex that cause a high rate of mortality in patients with cystic fibrosis (CF). Application of this NHC silver complex to primary cultures of murine respiratory epithelial cells followed by microarray analysis showed minimal gene expression changes at the concentrations effective against respiratory pathogens. Furthermore, methylated caffeine without silver showed some antibacterial and antifungal activity.