Adenoma miss rates associated with a 3-minute versus 6-minute colonoscopy withdrawal time: a prospective, randomized trial.

BACKGROUND AND AIMS: The 6-minute withdrawal time for colonoscopy, widely considered the standard of care, is controversial. The skill and technique of endoscopists may be as important as, or more important than, withdrawal time for adenoma detection. It is unclear whether a shorter withdrawal time with good technique yields an acceptable lesion detection rate. Our objective was to evaluate a 3-minute versus a 6-minute withdrawal time by using segmental tandem colonoscopy. METHODS: We performed a prospective, randomized trial by using 4 expert endoscopists. Patients were randomized to a 3-minute or a 6-minute initial withdrawal, each followed by a tandem second 6-minute withdrawal. All polyps were removed. The primary outcomes were adenoma miss rates (AMRs), adenomas per colonoscopy (APC) rates, and adenoma detection rates (ADRs). RESULTS: A total of 99 and 101 patients were enrolled in the 3-minute and 6-minute withdrawal groups, respectively. The AMR was significantly higher in the 3-minute withdrawal group (48.0% vs 22.9%; P = .0001). After controlling for endoscopist, patient age and/or sex, Boston Bowel Preparation Scale score, and size and/or location and/or morphology of adenoma, the AMR remained significantly higher in the 3-minute withdrawal group (odds ratio, 2.78; 95% confidence interval, 1.35-5.15; P = .0001). The ADR was similar between both groups (39.2% vs 40.6%; P = .84). However, the mean APC rate was significantly lower in the 3-minute withdrawal group (0.55 vs 0.80; P = .0001). CONCLUSIONS: The AMR was significantly higher, and the APC rate was significantly lower in the 3-minute withdrawal group versus the 6-minute withdrawal group. Despite expert technique, a shorter withdrawal time is associated with an unacceptably high AMR and low APC rate. (Clinical trial registration number: NCT01802008.).

Cyst Fluid Glucose is Rapidly Feasible and Accurate in Diagnosing Mucinous Pancreatic Cysts.

OBJECTIVES: Better diagnostic tools are needed to differentiate pancreatic cyst subtypes. A previous metabolomic study showed cyst fluid glucose as a potential marker to differentiate mucinous from non-mucinous pancreatic cysts. This study seeks to validate these earlier findings using a standard laboratory glucose assay, a glucometer, and a glucose reagent strip. METHODS: Using an IRB-approved prospectively collected bio-repository, 65 pancreatic cyst fluid samples (42 mucinous and 23 non-mucinous) with histological correlation were analyzed. RESULTS: Median laboratory glucose, glucometer glucose, and percent reagent strip positive were lower in mucinous vs. non-mucinous cysts (P<0.0001 for all comparisons). Laboratory glucose<50 mg/dl had a sensitivity of 95% and a specificity of 57% (LR+ 2.19, LR- 0.08). Glucometer glucose<50 mg/dl had a sensitivity of 88% and a specificity of 78% (LR+ 4.05, LR- 0.15). Reagent strip glucose had a sensitivity of 81% and a specificity of 74% (LR+ 3.10, LR- 0.26). CEA had a sensitivity of 77% and a specificity of 83% (LR+ 4.67, LR- 0.27). The combination of having either a glucometer glucose<50 mg/dl or a CEA level>192 had a sensitivity of 100% but a low specificity of 33% (LR+ 1.50, LR- 0.00). CONCLUSIONS: Glucose, whether measured by a laboratory assay, a glucometer, or a reagent strip, is significantly lower in mucinous cysts compared with non-mucinous pancreatic cysts.

Predictive factors for surgery among patients with pancreatic cysts in the absence of high-risk features for malignancy.

BACKGROUND: Without a reliable biopsy technique for pancreatic cysts, consensus-based guidelines are used to guide surgical utilization. The primary objective of this study was to characterize the proportion of operations performed outside of these guidelines. METHODS: A 5-year retrospective review between July 1, 2007, and June 30, 2012, was performed of consecutive patients seen at a single tertiary medical center for a pancreatic cyst. Manual chart review for relevant clinical variables and cyst characteristics was performed. RESULTS: During this period, 148 patients underwent surgery, and of these, 23 (16 %) patients had no high-risk criteria by the 2006 Sendai criteria. None of these harbored high-grade dysplastic or cancerous lesions. A high cyst carcinoembryonic antigen (CEA) level (35 %), patient anxiety (26 %), and physician concern (22 %) were explicit reasons to proceed to surgery. An elevated cyst CEA level >192 ng/ml was the most significant predictor (OR 5.14 (95 % confidence interval (CI) 1.47-18.0) for surgery without high-risk criteria. CONCLUSION: A high cyst CEA level was significantly associated with the decision to operate outside of consensus-based guidelines. The misuse of cyst CEA in the management of pancreatic cysts negatively impacts patient anxiety, increases physician uncertainty, and leads to surgery with minimal benefit.

Variation in Aptitude of Trainees in Endoscopic Ultrasonography, Based on Cumulative Sum Analysis.

BACKGROUND & AIMS: Studies have reported substantial variation in the competency of advanced endoscopy trainees, indicating a need for more supervised training in endoscopic ultrasound (EUS). We used a standardized, validated, data collection tool to evaluate learning curves and measure competency in EUS among trainees at multiple centers. METHODS: In a prospective study performed at 15 centers, 17 trainees with no prior EUS experience were evaluated by experienced attending endosonographers at the 25th and then every 10th upper EUS examination, over a 12-month training period. A standardized data collection form was used (using a 5-point scoring system) to grade the EUS examination. Cumulative sum analysis was applied to produce a learning curve for each trainee; it tracked the overall performance based on median scores at different stations and also at each station. Competency was defined by a median score of 1, with acceptable and unacceptable failure rates of 10% and 20%, respectively. RESULTS: Twelve trainees were included in the final analysis. Each of the trainees performed 265 to 540 EUS examinations (total, 4257 examinations). There was a large amount of variation in their learning curves: 2 trainees crossed the threshold for acceptable performance (at cases 225 and 245), 2 trainees had a trend toward acceptable performance (after 289 and 355 cases) but required continued observation, and 8 trainees needed additional training and observation. Similar results were observed at individual stations. CONCLUSIONS: A specific case load does not ensure competency in EUS; 225 cases should be considered the minimum caseload for training because we found that no trainee achieved competency before this point. Ongoing training should be provided for trainees until competency is confirmed using objective measures.

Metabolomic-derived novel cyst fluid biomarkers for pancreatic cysts: glucose and kynurenine.

BACKGROUND: Better pancreatic cyst fluid biomarkers are needed. OBJECTIVE: To determine whether metabolomic profiling of pancreatic cyst fluid would yield clinically useful cyst fluid biomarkers. DESIGN: Retrospective study. SETTING: Tertiary-care referral center. PATIENTS: Two independent cohorts of patients (n = 26 and n = 19) with histologically defined pancreatic cysts. INTERVENTION: Exploratory analysis for differentially expressed metabolites between (1) nonmucinous and mucinous cysts and (2) malignant and premalignant cysts was performed in the first cohort. With the second cohort, a validation analysis of promising identified metabolites was performed. MAIN OUTCOME MEASUREMENTS: Identification of differentially expressed metabolites between clinically relevant cyst categories and their diagnostic performance (receiver operating characteristic [ROC] curve). RESULTS: Two metabolites had diagnostic significance-glucose and kynurenine. Metabolomic abundances for both were significantly lower in mucinous cysts compared with nonmucinous cysts in both cohorts (glucose first cohort P = .002, validation P = .006; and kynurenine first cohort P = .002, validation P = .002). The ROC curve for glucose was 0.92 (95% confidence interval [CI], 0.81-1.00) and 0.88 (95% CI, 0.72-1.00) in the first and validation cohorts, respectively. The ROC for kynurenine was 0.94 (95% CI, 0.81-1.00) and 0.92 (95% CI, 0.76-1.00) in the first and validation cohorts, respectively. Neither could differentiate premalignant from malignant cysts. Glucose and kynurenine levels were significantly elevated for serous cystadenomas in both cohorts. LIMITATIONS: Small sample sizes. CONCLUSION: Metabolomic profiling identified glucose and kynurenine to have potential clinical utility for differentiating mucinous from nonmucinous pancreatic cysts. These markers also may diagnose serous cystadenomas.

Pancreatic neuroendocrine tumors: radiographic calcifications correlate with grade and metastasis.

BACKGROUND: Studies to identify preoperative prognostic variables for pancreatic neuroendocrine tumor (PNET) have been inconclusive. Specifically, the prevalence and prognostic significance of radiographic calcifications in these tumors remains unclear. METHODS: From 1998 to 2009, a total of 110 patients with well-differentiated PNET underwent surgical resection at our institution. Synchronous liver metastases present in 31 patients (28%) were addressed surgically with curative intent. Patients with high-grade PNET were excluded. The presence of calcifications in the primary tumor on preoperative computed tomography was recorded and correlated with clinicopathologic variables and overall survival. RESULTS: Calcifications were present in 16% of patients and were more common in gastrinomas and glucagonomas (50%), but never encountered in insulinomas. Calcified tumors were larger (median size 4.5 vs. 2.3 cm, P=0.04) and more commonly associated with lymph node metastasis (75 vs. 35%, P=0.01), synchronous liver metastasis (62 vs. 21%, P<0.01), and intermediate tumor grade (80 vs. 31%, P<0.01). On multivariate analysis of factors available preoperatively, calcifications (P=0.01) and size (P<0.01) remained independent predictors of lymph node metastasis. Overall survival after resection was significantly worse in the presence of synchronous liver metastasis (5-year, 64 vs. 86%, P=0.04), but not in the presence of radiographic calcifications. CONCLUSIONS: Calcifications on preoperative computed tomography correlate with intermediate grade and lymph node metastasis in well-differentiated PNET. This information is available preoperatively and supports the routine dissection of regional lymph nodes through formal pancreatectomy rather than enucleation in calcified PNET.

Diagnostic accuracy of cyst fluid amphiregulin in pancreatic cysts.

BACKGROUND: Accurate tests to diagnose adenocarcinoma and high-grade dysplasia among mucinous pancreatic cysts are clinically needed. This study evaluated the diagnostic utility of amphiregulin (AREG) as a pancreatic cyst fluid biomarker to differentiate non-mucinous, benign mucinous, and malignant mucinous cysts. METHODS: A single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed. RESULTS: Among the cyst fluid samples, the median (IQR) AREG levels for non-mucinous (n = 6), benign mucinous (n = 15), and cancerous cysts (n = 15) were 85 pg/ml (47-168), 63 pg/ml (30-847), and 986 pg/ml (417-3160), respectively. A significant difference between benign mucinous and malignant mucinous cysts was observed (p = 0.025). AREG levels greater than 300 pg/ml possessed a diagnostic accuracy for cancer or high-grade dysplasia of 78% (sensitivity 83%, specificity 73%). CONCLUSION: Cyst fluid AREG levels are significantly higher in cancerous and high-grade dysplastic cysts compared to benign mucinous cysts. Thus AREG exhibits potential clinical utility in the evaluation of pancreatic cysts.

Cryotherapy for Barrett's esophagus: Who, how, and why?

Cryotherapy is a noncontact ablation method that has long been used clinically in the treatment of a wide variety of malignant and premalignant diseases. The relative ease of use and unique mechanisms of cellular destruction make cryotherapy particularly attractive for the eradication of dysplastic Barrett's esophagus. Currently, liquid nitrogen and carbon dioxide are the most common cryogens used. Preliminary data with these agents have shown high efficacy in the reversal of dysplastic Barrett mucosa and excellent safety profiles. Intense investigation on cryotherapy ablation of Barrett's esophagus is ongoing.