Differential Outcomes and Clinical Challenges of NAFLD With Extreme Obesity.

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. The prevalence of extreme obesity, defined as body mass index (BMI) of 50 kg/m2 or higher, is rising more rapidly than overall obesity. We aimed to compare the clinical outcomes and performance of noninvasive fibrosis assessment tools in NAFLD with or without extreme obesity. A retrospective analysis was performed in 304 patients with NAFLD with extreme obesity and compared them to patients with NAFLD with BMI of 40 kg/m2 or less, matched for age, gender, race, and liver fibrosis stage. The mean age of the NAFLD with extreme obesity cohort was 55.9 years, BMI 55 kg/m2, and 49.7% had cirrhosis at initial evaluation. Baseline cirrhosis and coronary artery disease were associated with increased risk of death, and dyslipidemia with decreased risk of mortality. Age, insulin use, hypertension, albumin and platelet count were associated with cirrhosis. Fifteen percent of patients had weight-loss surgery, but this was not associated with survival or risk of cirrhosis. Of the 850 abdominal ultrasound scans performed in 255 patients, 24.1% were deemed suboptimal for hepatocellular carcinoma screening. The mean NAFLD fibrosis score (NFS) in the extreme obesity cohort, versus a propensity-matched cohort with BMI of 40 kg/m2 or less, was significantly different for both low fibrosis (F0-F2) (0.222 vs. -1.682, P < 0.0001) and high fibrosis (F3-F4) (2.216 vs. 0.557, P < 0.001). Conclusion: NAFLD with extreme obesity is associated with increased risk of liver-related and overall mortality. Accurate noninvasive assessment of liver fibrosis, low rates of weight loss surgery, and high failure rate of ultrasound were identified as clinical challenges in this population.

Evaluation of the 2015 AGA guidelines on pancreatic cystic neoplasms in a large surgically confirmed multicenter cohort.

Background and study aims The American Gastroenterological Association (AGA) recently published guidelines for the management of asymptomatic pancreatic cystic neoplasms (PCNs). We aimed to evaluate the diagnostic characteristics of the AGA guidelines in appropriately recommending surgery for malignant PCNs. Patients and methods A retrospective multicenter study was performed of patients who underwent endoscopic ultrasound (EUS) for evaluation of PCNs who ultimately underwent surgical resection from 2004 - 2014. Demographics, EUS characteristics, fine-needle aspiration (FNA) results, type of resection, and final pathologic diagnosis were recorded. Patients were categorized into 2 groups (surgery or surveillance) based on what the AGA guidelines would have recommended. Performance characteristics for the diagnosis of cancer or high-grade dysplasia (HGD) on surgical pathology were calculated. Results Three hundred patients underwent surgical resection for PCNs, of whom the AGA guidelines would have recommended surgery in 121 (40.3 %) and surveillance in 179 (59.7 %) patients. Among patients recommended for surgery, 45 (37.2 %) had cancer, whereas 76 (62.8 %) had no cancer/HGD. Among patients recommended for surveillance, 170 (95.0 %) had no cancer/HGD; however, 9 (5.0 %) patients had cancer that would have been missed. For the finding of cancer/HGD on surgical pathology, the AGA guidelines had 83.3 % sensitivity (95 % CI 70.7 - 92.1), 69.1 % specificity (95 % CI 62.9 - 74.8), 37.2 % positive predictive value (95 % CI 28.6 - 46.4), 95.0 % negative predictive value (95 % CI 90.7 - 97.7), and 71.7 % accuracy (95 % CI 67.4 - 74.6). Conclusions The 2015 AGA guidelines would have resulted in 60 % fewer patients being referred for surgical resection, and accurately recommended surveillance in 95 % of patients with asymptomatic PCNs. Future prospective studies are required to validate these guidelines. Meeting presentations: Presented in part at Digestive Diseases Week 2016.

Oropharyngeal pH Testing Does Not Predict Response to Proton Pump Inhibitor Therapy in Patients with Laryngeal Symptoms.

OBJECTIVES: Predicting response to proton pump inhibitor (PPI) therapy in patients with laryngeal symptoms is challenging. The Restech Dx-pH probe is a transnasal catheter that measures oropharyngeal pH. In this study, we aimed to investigate the prognostic potential of oropharyngeal pH monitoring to predict responsiveness to PPI therapy in patients with laryngeal symptoms. METHODS: We conducted a physician-blinded prospective cohort study at a single academic institution between January 2013 and October 2014. Adult patients with Reflux Symptom Index scores (RSI) ≥13 off PPI therapy were recruited. Patients underwent video laryngoscopy and 24-h oropharyngeal pH monitoring, followed by an 8- to 12-week trial of omeprazole 40 mg daily. Prior to and following PPI therapy, patients completed various symptom questionnaires. The primary outcome was the association between PPI response and oropharyngeal pH metrics. PPI response was separated into three subgroups based on the post-treatment RSI score and % RSI response: non-response=RSI ≥13; partial response=post-treatment RSI <13 and change in RSI <50%; and complete response=post-treatment RSI <13 and change in RSI ≥50%. The primary analysis utilized a multinomial logistic regression controlling for the pre-treatment RSI score. A secondary analysis assessed the relationship between the change in RSI (post-pre) and oropharyngeal pH metrics via ordinary least square regression. RESULTS: Thirty-four patients completed the study and were included in final analysis. Symptom response to PPI therapy was as follows: 50% no response, 15% partial response, and 35% complete response. Non-responders had a higher pre-treatment RSI (P<0.01). There were no significant differences in oropharyngeal acid exposure (below pH of 4.0, 5.0, 5.5, 6.0, and RYAN scores) between responder types. The secondary analysis noted a trend between lower PPI response and a greater total percent time below pH of 5.0 (P=0.03), upright percent time below pH of 5.0 (P=0.07), and RYAN supine (corrected; P=0.03), as well as an association between PPI response and greater decreases in the Anxiety Sensitivity Inventory (P<0.01), Brief Symptom Inventory-18 (P<0.01), and Negative Affect Scale (P<0.01). CONCLUSIONS: Oropharyngeal pH testing did not predict laryngeal symptom response to PPI therapy. Contrary to hypothesis, our study signaled that the degree of oropharyngeal acid exposure is inversely related to PPI response. In addition, reduction in negative affect and psychological distress parallels PPI response.

Abilities of Oropharyngeal pH Tests and Salivary Pepsin Analysis to Discriminate Between Asymptomatic Volunteers and Subjects With Symptoms of Laryngeal Irritation.

BACKGROUND & AIMS: It has been a challenge to confirm the association between laryngeal symptoms and physiological reflux disease. We examined the ability of oropharyngeal pH tests (with the Restech Dx-pH system) and salivary pepsin tests (with Peptest) to discriminate between asymptomatic volunteers (controls) and subjects with a combination of laryngeal and reflux symptoms (laryngeal ± reflux). METHODS: We performed a physician-blinded prospective cohort study of 59 subjects at a single academic institution. Adult volunteers were recruited and separated into 3 groups on the basis of GerdQ and Reflux Symptom Index scores: controls (n = 20), laryngeal symptoms (n = 20), or laryngeal + reflux symptoms (n = 19). Subjects underwent laryngoscopy and oropharyngeal pH tests and submitted saliva samples for analysis of pepsin concentration. Primary outcomes included abnormal acid exposure and composite (RYAN) score for oropharyngeal pH tests and abnormal mean salivary pepsin concentration that was based on normative data. RESULTS: Complete oropharyngeal pH data were available from 53 subjects and complete salivary pepsin data from 35 subjects. We did not observe any significant differences between groups in percent of time spent below pH 4.0, 5.0, 5.5, 6.0, or RYAN scores or percent of subjects with positive results from tests for salivary pepsin (53% vs 40% vs 75%; P = .50, respectively). The laryngeal + reflux group had a significantly higher estimated mean concentration of salivary pepsin (117.9 ± 147.4 ng/mL) than the control group (32.4 ± 41.9 ng/mL) or laryngeal symptom group (7.5 ± 11.2 ng/mL) (P = .01 and P = .04, respectively). CONCLUSIONS: By using current normative thresholds, oropharyngeal pH testing and salivary pepsin analysis are not able to distinguish between healthy volunteers and subjects with a combination of laryngeal and reflux symptoms.

Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study.

BACKGROUND AND AIMS: The exact cutoff value at which pancreatic cyst fluid carcinoembryonic antigen (CEA) level distinguishes pancreatic mucinous cystic neoplasms (MCNs) from pancreatic nonmucinous cystic neoplasms (NMCNs) is unclear. The aim of this multicenter retrospective study was to evaluate the diagnostic accuracy of cyst fluid CEA levels in differentiating between MCNs and NMCNs. METHODS: Consecutive patients who underwent EUS with FNA at 3 tertiary care centers were identified. Patients with histologic confirmation of cyst type based on surgical specimens served as the criterion standard for this analysis. Demographic characteristics, EUS morphology, FNA fluid, and cytology results were recorded. Multivariate logistic regression analysis to identify predictors of MCNs was performed. Receiver-operating characteristic (ROC) curves were generated for CEA levels. RESULTS: A total of 226 patients underwent surgery (mean age, 61 years, 96% white patients, 39% female patients) of whom 88% underwent Whipple's procedure or distal pancreatectomy. Based on surgical histopathology, there were 150 MCNs and 76 NMCNs cases. The median CEA level was 165 ng/mL. The area under the ROC curve for CEA levels in differentiating between MCNs and NMCNs was 0.77 (95% confidence interval, 0.71-0.84, P < .01) with a cutoff of 105 ng/mL, demonstrating a sensitivity and specificity of 70% and 63%, respectively. The cutoff value of 192 ng/mL yielded a sensitivity of 61% and a specificity of 77% and would misdiagnose 39% of MCN cases. CONCLUSIONS: Cyst fluid CEA levels have a clinically suboptimal accuracy level in differentiating MCNs from NMCNs. Future studies should focus on novel cyst fluid markers to improve risk stratification of pancreatic cystic neoplasms.