Management of Patients With Pancreatic Cysts: Analysis of Possible False-Negative Cases of Malignancy.

GOALS: To examine the utility of integrated molecular pathology (IMP) in managing surveillance of pancreatic cysts based on outcomes and analysis of false negatives (FNs) from a previously published cohort (n=492). BACKGROUND: In endoscopic ultrasound with fine-needle aspiration (EUS-FNA) of cyst fluid lacking malignant cytology, IMP demonstrated better risk stratification for malignancy at approximately 3 years' follow-up than International Consensus Guideline (Fukuoka) 2012 management recommendations in such cases. STUDY: Patient outcomes and clinical features of Fukuoka and IMP FN cases were reviewed. Practical guidance for appropriate surveillance intervals and surgery decisions using IMP were derived from follow-up data, considering EUS-FNA sampling limitations and high-risk clinical circumstances observed. Surveillance intervals for patients based on IMP predictive value were compared with those of Fukuoka. RESULTS: Outcomes at follow-up for IMP low-risk diagnoses supported surveillance every 2 to 3 years, independent of cyst size, when EUS-FNA sampling limitations or high-risk clinical circumstances were absent. In 10 of 11 patients with FN IMP diagnoses (2% of cohort), EUS-FNA sampling limitations existed; Fukuoka identified high risk in 9 of 11 cases. In 4 of 6 FN cases by Fukuoka (1% of cohort), IMP identified high risk. Overall, 55% of cases had possible sampling limitations and 37% had high-risk clinical circumstances. Outcomes support more cautious management in such cases when using IMP. CONCLUSIONS: Adjunct use of IMP can provide evidence for relaxed surveillance of patients with benign cysts that meet Fukuoka criteria for closer observation or surgery. Although infrequent, FN results with IMP can be associated with EUS-FNA sampling limitations or high-risk clinical circumstances.

Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts.

BACKGROUND AND STUDY AIMS: Current diagnostic testing is inadequate to determine the malignant potential of pancreatic cysts, resulting in overcautious patient management. Integrated molecular pathology (IMP) testing combines molecular analysis with first-line test results (cytology, imaging, and fluid chemistry) to assess the malignant potential of pancreatic cysts. This multicenter study aimed to determine the diagnostic accuracy of IMP for pancreatic adenocarcinoma, and the utility of IMP testing under current guideline recommendations for managing pancreatic cysts. PATIENTS AND METHODS: Patients who had undergone previous IMP testing as prescribed by their physician and for whom clinical outcomes were available from retrospective record review were included (n = 492). Performance was determined by correlation between clinical outcome and previous IMP diagnosis ("benign"/"statistically indolent" vs. "statistically higher risk [SHR]"/ "aggressive") or an International Consensus Guideline (Sendai 2012) criteria model for "surveillance" vs. "surgery." The Cox proportional hazards model determined hazard ratios for malignancy. RESULTS: Benign and statistically indolent IMP diagnoses had a 97 % probability of benign follow-up for up to 7 years and 8 months from initial IMP testing. SHR and aggressive diagnoses had relative hazard ratios for malignancy of 30.8 and 76.3, respectively (both P < 0.0001). Sendai surveillance criteria had a 97 % probability of benign follow-up for up to 7 years and 8 months, but for surgical criteria the hazard ratio was only 9.0 (P < 0.0001). In patients who met Sendai surgical criteria, benign and statistically indolent IMP diagnoses had a > 93 % probability of benign follow-up, with relative hazard ratios for SHR and aggressive IMP diagnoses of 16.1 and 50.2, respectively (both P < 0.0001). CONCLUSION: IMP more accurately determined the malignant potential of pancreatic cysts than a Sendai 2012 guideline management criteria model. IMP may improve patient management by justifying more relaxed observation in patients meeting Sendai surveillance criteria. IMP can more accurately differentiate between the need for surveillance or surgery in patients meeting Sendai surgical criteria.

Applied principles of neurogastroenterology: physiology/motility sensation.

Many of the symptoms prominent in the functional gastrointestinal disorders (FGIDs) are consistent with dysfunction of the sensory and/or motor apparatus of the digestive tract. Assessment of these phenomena in man can be undertaken by using a wide variety of invasive and noninvasive techniques, some well established and others requiring further validation. By using such techniques, alterations in both sensory and motor function have been reported in the FGIDs; various combinations of such dysfunction occur in different regions of the digestive tract in the FGIDs. Our understanding of the origins of this gut sensorimotor dysfunction is gradually increasing. Thus, inflammatory, immunologic, and other processes, as well as psychosocial factors such as stress, can alter the normal patterns of sensitivity and motility through alterations in local reflex activity or via altered neural processing along the brain-gut axis. In this context, a potential role of genetic factors, early-life influences, enteric flora, dietary components, and autonomic dysfunction also should be considered in the disease model. A firm relationship between sensorimotor dysfunction and the production of symptoms, however, has been difficult to show, and so the clinical relevance of the former requires continuing exploration. Based on the conceptual framework established to date, a number of recommendations for further progress can be made.

Cognitive therapy for irritable bowel syndrome is associated with reduced limbic activity, GI symptoms, and anxiety.

This study sought to identify brain regions that underlie symptom changes in severely affected IBS patients undergoing cognitive therapy (CT). Five healthy controls and 6 Rome II diagnosed IBS patients underwent psychological testing followed by rectal balloon distention while brain neural activity was measured with O-15 water positron emission tomography (PET) before and after a brief regimen of CT. Pre-treatment resting state scans, without distention, were compared to post-treatment scans using statistical parametric mapping (SPM). Neural activity in the parahippocampal gyrus and inferior portion of the right cortex cingulate were reduced in the post-treatment scan, compared to pre-treatment (x, y, z coordinates in MNI standard space were -30, -12, -30, P=0.017; 6, 34, -8, P=0.023, respectively). Blood flow values at these two sites in the controls were intermediate between those in the pre- and post-treatment IBS patients. Limbic activity changes were accompanied by significant improvements in GI symptoms (e.g., pain, bowel dysfunction) and psychological functioning (e.g., anxiety, worry). The left pons (-2, -26, -28, P=0.04) showed decreased neural activity which was correlated with post-treatment anxiety scores. Changes in neural activity of cortical-limbic regions that subserve hypervigilance and emotion regulation may represent biologically oriented change mechanisms that mediate symptom improvement of CT for IBS.

Overview of functional gastrointestinal disorders: dysfunction of the brain-gut axis.

Functional gastrointestinal disorders are common and incompletely understood. The gut is controlled by a complex interaction of sensory and motor neurons in the local enteric nervous system. Inputs from the central nervous system modify gut function, whereas inputs from the gut to the brain mediate symptoms. Dysfunction at one or more sites in the brain-gut axis is likely to produce the various functional gastrointestinal syndromes. Therapies likewise can be directed at one or more levels.