Darwin L. Conwell

Diagnosis of Exocrine Pancreatic Insufficiency

Opinion statementThe accurate diagnosis of exocrine pancreatic insufficiency (EPI) helps identify those in need of pancreatic enzyme replacement therapy. Conversely, ruling out EPI identifies those in which additional evaluation should be pursued to explain their symptoms. There are many available tests that can be used to diagnose EPI; however, the tests must be tailored to each clinical scenario. Tests that are convenient but less accurate (e.g., fecal elastase-1, qualitative fecal fat determination) are best suited for patients with a high pretest probability of EPI. In contrast, tests that are highly accurate but more cumbersome (e.g., endoscopic pancreatic function testing, 72-h fecal fat collection) are favored in patients suspected to have mild EPI or an early stage of chronic pancreatitis. Additional research is needed to identify a more convenient means of accurately diagnosing at all stages of EPI.

Complications of Chronic Pancreatitis

Chronic pancreatitis is a disease that leads to irreversible changes in the pancreatic morphology and function. The loss of function can lead to diabetes mellitus and exocrine pancreatic insufficiency. The inflammation and fibrosis can also lead to other complications including a chronic abdominal pain syndrome, metabolic bone disease, and pancretic cancer. This article reviews our current understanding of the mechanisms and management of these complications of chronic pancreatitis.

Validation of diagnostic characteristics of needle based confocal laser endomicroscopy in differentiation of pancreatic cystic lesions

Background and aims: Endoscopic ultrasound (EUS)-guided needle-based Confocal Laser Endomicroscopy (nCLE) characteristics of pancreatic cystic lesions (PCLs) have been identified in studies where the gold standard surgical histopathology was available in a minority of patients. There are diverging reports of interobserver agreement (IOA) and paucity of intraobserver reliability (IOR). Thus, we sought to validate current EUS-nCLE criteria of PCLs in a larger consecutive series of surgical patients. Methods: A retrospective analysis of patients who underwent EUS-nCLE at a single center was performed. For calculation of IOA (Fleiss’ kappa) and IOR (Cohen’s kappa), blinded nCLE-naïve observers (nu200a=u200a6) reviewed nCLE videos of PCLs in two phases separated by a 2-week washout period. Results: EUS-nCLE was performed in 49 subjects, and a definitive diagnosis was available in 26 patients. The overall sensitivity, specificity, and accuracy for diagnosing a mucinous PCL were 94u200a%, 82u200a%, and 89u200a%, respectively. The IOA for differentiating mucinous vs. non-mucinous PCL was “substantial” (κu200a=u200a0.67, 95u200a%CI 0.57, 0.77). The mean (± standard deviation) IOR was “substantial” (κu200a=u200a0.78u200a±u200a0.13) for diagnosing mucinous PCLs. Both the IOAs and mean IORs were “substantial” for detection of known nCLE image patterns of papillae/epithelial bands of mucinous PCLs (IOA κu200a=u200a0.63; IOR κu200a=u200a0.76u200a±u200a0.11), bright particles on a dark background of pseudocysts (IOA κu200a=u200a0.71; IOR κu200a=u200a0.78u200a±u200a0.12), and fern-pattern or superficial vascular network of serous cystadenomas (IOA κu200a=u200a0.62; IOR κu200a=u200a0.68u200a±u200a0.20). Three (6.1u200a% of 49) patients developed post-fine needle aspiration (FNA) pancreatitis. Conclusion: Characteristic EUS-nCLE patterns can be consistently identified and improve the diagnostic accuracy of PCLs. These results support further investigations to optimize EUS-nCLE while minimizing adverse events. Study registration: NCT02516488

Inhibition of Jak/STAT signaling reduces the activation of pancreatic stellate cells in vitro and limits caerulein-induced chronic pancreatitis in vivo.

Chronic pancreatitis (CP) is a fibro-inflammatory disease leading to pain, maldigestion, and pancreatic insufficiency. No therapeutic options exist due to a limited understanding of the biology of CP pathology. Recent findings implicate pancreatic stellate cells (PSC) as prominent mediators of inflammatory and fibrotic processes during CP. Here, we utilized primary and immortalized PSC obtained from mice and patients with CP or pancreatic cancer to examine the effect of Jak/STAT and MAPK pathway inhibition in vitro. The well-characterized caerulein model of CP was used to assess the therapeutic efficacy of Jak1/2 inhibition in vivo. Treatment of cultured PSC with the Jak1/2 inhibitor ruxolitinib reduced STAT3 phosphorylation, cell proliferation, and expression of alpha-smooth muscle actin (α-SMA), a marker of PSC activation. Treatment with the MAPK inhibitor, MEK162, had less consistent effects on PSC proliferation and no impact on activation. In the caerulein-induced murine model of CP, administration of ruxolitinib for one week significantly reduced biomarkers of inflammation and fibrosis. These data suggest that the Jak/STAT pathway plays a prominent role in PSC proliferation and activation. In vivo treatment with the Jak1/2 inhibitor ruxolitinib reduced the severity of experimental CP, suggesting that targeting Jak/STAT signaling may represent a promising therapeutic strategy for CP.

Needle-based confocal laser endomicroscopy for the diagnosis of pancreatic cystic lesions: an international external interobserver and intraobserver study (with videos)

BACKGROUND AND AIMSnEUS-guided needle-based confocal laser endomicroscopy (nCLE) characteristics of common types of pancreatic cystic lesions (PCLs) have been identified; however, surgical histopathology was available in a minority of cases. We sought to assess the performance characteristics of EUS nCLE for differentiating mucinous from non-mucinous PCLs in a larger series of patients with a definitive diagnosis.nnnMETHODSnSix endosonographers (nCLE experience >30 cases each) blinded to all clinical data, reviewed nCLE images of PCLs from 29 patients with surgical (nxa0= 23) or clinical (nxa0= 6) correlation. After 2 weeks, the assessors reviewed the same images in a different sequence. A tutorial on available and novel nCLE image patterns was provided before each review. The performance characteristics of nCLE and the κ statistic for interobserver agreement (IOA, 95% confidence interval [CI]), and intraobserver reliability (IOR, mean ± standard deviation [SD]) for identification of nCLE image patterns were calculated. Landis and Koch interpretation of κ values was used.nnnRESULTSnA total of 29 (16 mucinous PCLs, 13 non-mucinous PCLs) nCLE patient videos were reviewed. The overall sensitivity, specificity, and accuracy for the diagnosis of mucinous PCLs were 95%, 94%, and 95%, respectively. The IOA and IOR (mean ± SD) were κxa0= 0.81 (almost perfect); 95% CI, 0.71-0.90; and κxa0= 0.86 ± 0.11 (almost perfect), respectively. The overall specificity, sensitivity, and accuracy for the diagnosis of serous cystadenomas (SCAs) were 99%, 98%, and 98%, respectively. The IOA and IOR (mean ± SD) for recognizing the characteristic image pattern of SCA were κxa0= 0.83 (almost perfect); 95% CI, 0.73-0.92; and κxa0= 0.85 ± 0.11 (almost perfect), respectively.nnnCONCLUSIONSnEUS-guided nCLE can provide virtual histology of PCLs with a high degree of accuracy and inter- and intraobserver agreement in differentiating mucinous versus non-mucinous PCLs. These preliminary results support larger multicenter studies to evaluate EUS nCLE. (Clinical trial registration number: NCT02516488.).

Effects of Bariatric Surgery on Outcomes of Patients With Acute Pancreatitis

BACKGROUND & AIMSnThe prevalence of obesity and number of patients undergoing bariatric surgery are increasing. Obesity has adverse effects in patients with acute pancreatitis (AP). We investigated whether bariatric surgery affects outcomes of patients with AP.nnnMETHODSnWe performed a retrospective study, collecting data from the US Nationwide Inpatient Samplexa0(2007-2011) on all adult inpatients (≥18 years) with a principal diagnosis of AP (nxa0=xa01,342,681). We compared primary clinical outcomes (mortality, acute kidney injury, and respiratory failure) and secondary outcomes related to healthcare resources (hospital stay and charges) among patient groups using univariate and multivariate analyses. We performed a propensity score-matched analysis to compare outcomes of patients with versus without bariatric surgery.nnnRESULTSnOf patients admitted to the hospital with a principal diagnosis of AP, 14,332 (1.07%) had undergone bariatric surgery. The number of patients that underwent bariatric surgery doubled, from 1801 in 2007 to 3928 in 2011 (P < .001). AP in patients that had undergone bariatric surgery was most frequently associated with gallstones. Multivariate analysis associated prior bariatric surgery with decreased mortality (odds ratio, 0.41; 95% confidence interval, 0.18-0.92), shorter duration of hospitalization (0.65 days shorter; P < .001), and lower hospital charges (

The Impact of Obesity on Gallstone Disease, Acute Pancreatitis, and Pancreatic Cancer

3558 lower) than in patients with AP not receiving bariatric surgery (P < .001). A propensity score-matched cohort analysis found that mortality and odds of acute kidney injury were similar between patients with versus without history of bariatric surgery, whereas respiratory failure was less frequent in patients who received bariatric surgery (1.34% vs 4.42%; P < .001).nnnCONCLUSIONSnPrior bariatric surgery in patients hospitalized with AP is not adversely associated with in-hospital mortality, development of organ failure, or healthcare resource use. Bariatric surgery may mitigate the obesity-associated adverse prognostication in AP. These observations are pertinent for future research, because the prevalence of obesity and AP-related hospitalizations is increasing.

Left Ventricular Assist Devices Impact Hospital Resource Utilization Without Affecting Patient Mortality in Gastrointestinal Bleeding

Obesity is a well-recognized risk factor for gallstone formation and increases the risk for gallstone-related complications. Pancreatic diseases are impacted adversely by obesity. Although weight loss surgery increases the risk of gallstone disease, evidence suggests that bariatric surgery mitigates the obesity-associated adverse prognostication in acute pancreatitis. Obesity is also a significant risk factor for pancreatic cancer. Obesity is a global epidemic and is increasing worldwide and among all age groups. There is an urgent need for focused health policies aimed at reducing the incidence and prevalence of obesity. This article summarizes the current literature highlighting the association between obesity and the pathophysiology and outcome of gallstone disease, pancreatitis, and pancreatic cancer.

Novel technique for diagnosis of mucinous cystic neoplasms: in vivo and ex vivo confocal laser endomicroscopy

BackgroundLeft ventricular assist devices (LVADs) are being utilized for management of end-stage heart failure and require systemic anticoagulation. Gastrointestinal bleeding (GIB) is one of the most common adverse events following LVAD implantation.AimTo investigate the impact of continuous-flow (CF) LVAD implants on outcomes of patients admitted with GIB.MethodsThis is a cross-sectional study utilizing the Nationwide Inpatient Sample in the CF-LVAD era from 2010 to 2012. All adult admissions with a primary diagnosis of GIB were included. Among hospitalizations with GIB, patients with (cases) and without (controls) CF-LVAD implants were compared using univariate and multivariate analyses. The main outcome measurements were in-hospital mortality, length of stay, and hospitalization costs.ResultsAmong 1,002,299 hospitalizations for GIB, 1112 (0.11%) patients had CF-LVADs. Bleeding angiodysplasia accounted for a majority of GIB in CF-LVAD patients (35.4% of 1112). Multivariate analysis adjusting for demographic, hospital and etiological differences, site of GIB, and patient comorbidities revealed that CF-LVADs were not adversely associated with mortality in GIB (OR 0.53, 95% CI 0.07–4.15). However, CF-LVADs independently accounted for prolonged hospitalization (3.5xa0days, 95% CI 2.6–4.6) and higher hospital charges (

Diagnostic performance of endoscopic ultrasound for detection of pancreatic malignancy following an indeterminate multidetector CT scan: a systemic review and meta-analysis

37,032, 95% CI