Ann M. Chen

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 Barretts 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 Barretts esophagus is ongoing.

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.

Diagnostic accuracy of cyst fluid amphiregulin in pancreatic cysts

BackgroundAccurate 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.MethodsA single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed.ResultsAmong 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%).ConclusionCyst 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.

229 A Prospective, Randomized Trial of Adenoma Miss Rates At Colonoscopy Associated With 3-Minute vs. 6-Minute Withdrawal Time

Introduction: A minimum withdrawal time for screening colonoscopy of 6 minutes has been proposed, based on an observational study. The 6-minute withdrawal time remains controversial and has not been compared in a standardized fashion to alternate withdrawal times. Aim: To perform a prospective, randomized trial to compare adenoma miss rates (AMR) associated with withdrawal times of 6 minutes vs. 3 minutes. Methods: Consecutive patients undergoing colonoscopy at Stanford University and Palo Alto Veterans Administration Hospital were randomized to undergo either a 3-minute or 6-minute withdrawal (1st pass), followed immediately by a tandem 6-minute withdrawal (2nd pass). AMR was defined as the number of adenomas detected on the 2nd pass divided by total number of adenomas found. A chi-square statistic was used to directly compare AMR. A z-statistic was used to determine effect of polyp size/location on AMR. A mixed-effects logistic regression model was then created to compare AMR, controlling for endoscopist, size/location of adenoma, and patient. Finally, a Cochrane-Armitage test for trend was used to evaluate the trend of adenoma detection associated with increasing withdrawal time. Results: 200 subjects were enrolled (99 in the 3-minute group, 101 in the 6-minute group). Demographics and indications for colonoscopy were similar between the two groups (Table 1). AMR was significantly higher in the 3-minute withdrawal group compared to the 6-minute withdrawal group (48.5% vs 21.8%; p≤0.0001). Adenomas were significantly more likely to be missed in the 3-minute withdrawal group in all 3 locations of the colon (right, transverse and left colon). AMR was higher in the 3-minute withdrawal group among adenomas that were ≤5mm; there was no significant difference in AMR for adenomas that were 6-9mm or ≥10mm. After controlling for endoscopist, size/location of the polyp/adenoma, and the patient, AMR remained significantly higher in the 3-minute withdrawal group compared to the 6-minute withdrawal group (OR 2.92, 95% CI=1.54-5.55) (Table 1). Adenoma detection rate (ADR) was similar between both 3 and 6 minute withdrawal groups (38.4% vs 40.6%, p=0.75); however, this study was not powered to detect differences in ADR. There was a significant trend towards higher total number of adenomas detected as withdrawal time increased (52 at 3 minutes, 87 at 6 minutes, 101 at 9 minutes, and 111 at 12 minutes; p<0.001) (Figure 1). Conclusions: A 3-minute withdrawal time leads to an unacceptably high AMR. A 6minute withdrawal time is more appropriate for colorectal cancer screening. Location did not affect AMR; however, adenomas that were ≤5mm were more likely to be missed in the 3-minute withdrawal group. Further research into the optimal withdrawal time, including evaluation of withdrawal times longer than 6 minutes, is warranted.

Locally Advanced Gastric Cancer Complicated by Mesenteric Invasion and Intestinal Malrotation

A 67-year-old female immigrant from India without significant medical history was initially evaluated in the emergency department with complaints of 2 months of progressive epigastric pain, early satiety, nausea, and recurrent emesis associated with a 5-kg weight loss. On physical examination, a firm epigastric mass was noted. Extensive circumferential thickening of the gastric antrum and pylorus accompanied by gastric distention, and the presence of a malrotated and dilated duodenum which was entirely located right of the midline was noted in the abdominal computed tomography (CT) report (Fig. 1). The patient was admitted to the hospital for expedited diagnosis. Esophagogastroduodenoscopy (EGD) demonstrated hypertrophic antral folds with hyperemia and friability, and a dilated proximal duodenum with an abrupt, angular transition point at the third segment (Fig. 2a, b). Numerous biopsies of the antrum and pylorus were interpreted as having extensive lymphocytic inflammatory cell infiltration, but no malignant cells. Endoscopic ultrasound (EUS) confirmed the presence of circumferential hypertrophy in the antrum consistent with suspected tissue invasion (Fig. 3). Following nasogastric tube gastric decompression, a naso-duodenal feeding tube was advanced past the area of antral obstruction. Due to ongoing signs of obstruction with continued intolerance to oral intake and a high suspicion for malignancy, exploratory laparotomy was performed. At operation, a hard and thick antral mass suggestive of malignancy was immediately visible, with white plaque overlying the gastric serosa, suggestive of malignant serosal invasion (Fig. 4a). When the stomach and transverse mesocolon were lifted, tumor invasion into the root of the mesentery and into the serosa of the third and fourth segments of the duodenum was apparent, tethering the third and fourth portions of the duodenum to the ligament of Treitz (Fig. 4b). There was no evidence of obvious metastatic disease. Resection was deferred given that the locally advanced nature of the tumor would have required a subtotal gastrectomy, en bloc extended right hemicolectomy, and en bloc resection of the third and fourth portions of the duodenum. Instead, a loop gastro-jejunostomy and a feeding jejunostomy were performed for nutritional support, and the abdomen was closed, leaving open the possibility of later resection after neo-adjuvant therapy. Biopsies of the invaded gastric mucosa demonstrated scattered dyscohesive clusters of cells exhibiting signet ring morphology which stained positively for CDX2, CK7, and CK20, providing support for a primary gastric cancer. The tumor cells were diffusely infiltrative and not densely aggregated as a mass, consistent with the diffuse thickening seen on laparotomy, which also helped to explain the difficulty in obtaining a tissue diagnosis at endoscopic biopsy. The patient recovered uneventfully from surgery, and began neo-adjuvant chemotherapy. R. J. Huang (&) A. M. Chen U. Ladabaum Department of Medicine, Stanford University Medical Center, Stanford, CA, USA e-mail: rjhuang@stanford.edu