Faculty Bibliography

BACKGROUND:Risk stratification is a critical element for the successful implementation of cytopathology reporting systems. To the authors' knowledge, there are limited prior studies regarding risk stratification for The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSCPC). In the current study, the authors reported on a single-institution experience on 3-year prospective PSCPC regarding risk of malignancy (ROM) and the overall risk of malignancy (OROM). METHODS:A computerized search was performed from August 2014 to December 2017 for all pancreatic fine-needle aspiration (FNA) samples. Pathology from surgical resections and biopsies and relevant radiologic and clinical follow-up data were collected. The ROM and the OROM were calculated. The OROM was based on the total number of FNA samples in each category. RESULTS:A total of 1017 pancreatic FNA cases were identified, with surgical and/or clinical follow-up data available for 548 cases. The cytopathologic diagnoses included 242 nondiagnostic (category I), 162 benign (category II), 142 atypical (category III), 20 neoplastic-benign (category IV: benign), 133 neoplastic-other (category IV: other), 28 suspicious (category V), and 290 malignant (category VI) cases. A total of 364 malignancies were documented in 11 cases, 4 cases, 36 cases, 0 cases, 36 cases, 21 cases, and 255 cases, respectively, from categories I, II, III, IV: benign, IV:other, V, and VI. The ROM was 25%, 17.4%, 41.8%, 0%, 34.3% (95.2%), 95.5%, and 99.6%, respectively, and the OROM was 4.5%, 2.5%, 25.3%, 0%, 27.1% (83.3%), 75%, and 87.9%, respectively, for categories I, II, III, IV: benign, IV: other (with high-grade dysplasia), V, and VI. CONCLUSIONS:The true ROM for PSCPC is likely between the ROM and OROM for the benign and indeterminate categories. In the neoplastic-other category (category IV: other), identifying high-grade dysplasia is important for its association with malignancy and a higher ROM.

BACKGROUND/OBJECTIVES/OBJECTIVE:For the currently recommended pancreatic cyst surveillance to be feasible, participant adherence is a prerequisite. Our objective was to evaluate the psychological burden of pancreatic cyst surveillance from a participant's perspective. METHODS:The present participant survey is part of an international cohort study (PACYFIC study, www.pacyfic.net), which prospectively records the outcome of surveillance of asymptomatic pancreatic cysts. Participants are invited to complete questionnaires before and during cyst surveillance. RESULTS:109 participants, 31 enrolled before and 78 during surveillance (median time since cyst diagnosis 16.5 (IQR 36) months), returned a total of 179 questionnaires. The majority indicated that surveillance reduces concerns of developing pancreatic cancer (82%), gives a sense of certainty (81%) and is a good method to detect cancer (91%). Participants already undergoing surveillance reported more negative aspects than those still to commence, like sleeping worse (30% vs 13%, P = 0.035), postponing plans (32% vs 13%, P = 0.031), and finding the follow-up burdensome (33% vs 13%, P = 0.044). Overall, the vast majority (94%) deemed advantages to outweigh disadvantages. Anxiety and depression scores were low (median Hospital Anxiety and Depression Scale 4 for anxiety (IQR 6), 2 for depression (IQR 5)). CONCLUSION/CONCLUSIONS:The psychological burden of pancreatic cyst surveillance is low. Therefore, participant adherence is expected to be high and annual surveillance seems feasible.

BACKGROUND:Because most pancreatic intraductal papillary mucinous neoplasms (IPMNs) will never become malignant, currently advocated long-term surveillance is low-yield for most individuals. AIM:To develop a score chart identifying IPMNs at lowest risk of developing worrisome features or high-risk stigmata. METHODS:We combined prospectively maintained pancreatic cyst surveillance databases of three academic institutions. Patients were included if they had a presumed side-branch IPMN, without worrisome features or high-risk stigmata at baseline (as defined by the 2012 international Fukuoka guidelines), and were followed ≥ 12 months. The endpoint was development of one or more worrisome features or high-risk stigmata during follow-up. We created a multivariable prediction model using Cox-proportional logistic regression analysis and performed an internal-external validation. RESULTS:875 patients were included. After a mean follow-up of 50 months (range 12-157), 116 (13%) patients developed worrisome features or high-risk stigmata. The final model included cyst size (HR 1.12, 95% CI 1.09-1.15), cyst multifocality (HR 1.49, 95% CI 1.01-2.18), ever having smoked (HR 1.40, 95% CI 0.95-2.04), history of acute pancreatitis (HR 2.07, 95% CI 1.21-3.55), and history of extrapancreatic malignancy (HR 1.34, 95% CI 0.91-1.97). After validation, the model had good discriminative ability (C-statistic 0.72 in the Mayo cohort, 0.71 in the Columbia cohort, 0.64 in the Erasmus cohort). CONCLUSION:In presumed side branch IPMNs without worrisome features or high-risk stigmata at baseline, the Dutch-American Risk stratification Tool (DART-1) successfully identifies pancreatic lesions at low risk of developing worrisome features or high-risk stigmata.

Pancreatic cysts are identified at an increasing frequency. Although mucinous cystic neoplasms represent a pre-malignant condition, the majority of these lesions do not progress to cancer. Over the last 10 years several societies have established guidelines for the diagnosis, initial evaluation and surveillance of these lesions. Here we provide an overview of five commonly used guidelines: 2015 American Gastroenterological Association, 2017 International Association of Pancreatology, American College of Gastroenterology 2018, European Study Group and American College of Radiology. We describe the similarities and differences between the methods used to formulate these guidelines, the population they target and their approaches towards initial evaluation and surveillance of cystic lesions.

Background: Gastrointestinal bleeding (GIB)is a common complication of left ventricular assist device (LVAD)therapy. Previously, we retrospectively reviewed the endoscopic evaluation and outcomes of GIB in LVAD recipients in our center and proposed an endoscopic management algorithm (Figure)to eliminate low yield procedures. Herein, we aimed to prospectively validate this algorithm.
Method(s): We prospectively tested the algorithm in LVAD recipients who presented with GIB between June 2017 and August 2018. We compared the diagnostic and therapeutic yield of endoscopy, healthcare costs, and re-bleeding rates between conventional GIB management (our retrospective cohort)and our algorithm (our prospective cohort).
Result(s): Prospectively, we identified 33 LVAD patients with GIB. Presentation was consistent with upper GIB in 20 (61%), lower GIB in 5 (15%), and occult GIB in 8 (24%)patients. In total, 41 endoscopies localized a source in 23 (56%)resulting in 14 (36%)interventions at a median LOS of 8 days. Of 18 lesions identified, AVMs were the most common (9, 50%)and the small bowel was the most common location (11, 48%). Despite non-adherence to the algorithm in 7 of 33 patients (21%), algorithm implementation in comparison to our retrospective cohort increased the diagnostic yield by 70% (p<0.01)and therapeutic yield by 125% (p=0.01), and reduced the number of procedures per patient by 24% (p<0.01), length of stay by 33% (p<0.01), and estimated costs by 18% (p<0.01). In assessing the safety of our algorithm, we found the same median number of packed red blood cell transfusions and observed no increase in re-bleeding events in the prospective cohort as compared to our retrospective cohort.
Conclusion(s): Our endoscopic management algorithm for GIB in LVAD patients was effective in reducing low yield endoscopic procedures, improving the diagnostic and therapeutic yield of endoscopy, and decreasing healthcare resource utilization costs while not increasing the risk of re-bleeding. [Figure presented][Figure presented]
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BACKGROUND AND AIMS:We determined the incremental predictive value of pancreatic cyst fluid molecular analysis to assessing malignancy risk over long-term follow-up of a well-characterized cohort, given the underlying predictive value of imaging parameters routinely used to triage such patients. METHODS:Patients who lacked initial cytologic malignancy in cyst fluid and had final pathology or a follow-up period of more than 2 years were included. Patient outcomes determined the malignancy-free survival of patients with high-risk stigmata (HRS), worrisome features (WFs), and DNA abnormalities. DNA analysis included 3 abnormalities: loss of heterozygosity mutations among a panel of tumor suppressor genes, Kras mutation, and elevated DNA quantity. RESULTS:Included were 478 patients; 209 had surgical pathology-derived outcomes and 269 had clinical follow-up of >2 years. Eleven percent had malignant outcome. Forty-two patients had HRS, 272 lacked both HRS and WFs, and 164 lacked HRS but had WFs. DNA abnormalities did not statistically change long-term malignancy risk in patients with HRS or in patients lacking both HRS and WFs. Among patients with WFs, the presence of ≥2 DNA abnormalities significantly increased malignancy risk (relative risk, 5.2; P = .002) and the absence of all DNA abnormalities significantly decreased risk (relative risk, .4; P = .040). Sensitivity analysis confirmed results of survival analysis over differing baseline malignancy probabilities. CONCLUSIONS:Our study defines the clinical characteristic of patients in which DNA abnormality testing has the greatest impact on patient outcomes. Use of DNA abnormality testing is supported in a carefully selected patient population limited to cysts with WFs.

BACKGROUND/AIMS/OBJECTIVE:The aim of this study was to describe the diagnostic yield of endoscopic ultrasound (EUS) in patients with isolated elevated levels of amylase and/or lipase. METHODS:A retrospective chart review was conducted at a large academic medical center from 2000 to 2016. Patients were selected based on having elevated amylase, lipase, or both, but without a diagnosis of pancreatitis or known pancreatobiliary disease. Patients were excluded if they had abnormal liver function tests or abnormal imaging of the pancreas. RESULTS:Of 299 EUS procedures performed, 38 met inclusion criteria. Symptoms were present in 31 patients, most frequently abdominal pain (87%). In 20 patients (53%), initial EUS most commonly found chronic pancreatitis (n=7; 18%), sludge (5; 13%), or new diagnosis of pancreas divisum (3; 8%). In the asymptomatic patients (7), 3 had a finding on EUS, most importantly sludge (2), stone (1), and pancreas divisum (1). No patients were diagnosed with a mass or pancreatic cyst. During the follow up period, 6 patients (22%) had cholecystectomy. CONCLUSION/CONCLUSIONS:In our study of patients with isolated elevations in amylase and/or lipase without acute pancreatitis who underwent EUS, approximately 50% had a pancreatobiliary finding, most commonly chronic pancreatitis or biliary sludge.

Background/UNASSIGNED:Pancreatic cystic lesions are often challenging entities for diagnosis and management. EUS-FNA diagnostic accuracy is limited by paucicellularity of cytology specimens and sampling errors. Needle-based confocal laser endomicroscopy (nCLE) provides real-time imaging of the microscopic structure of the cystic lesion and could result in a more accurate diagnosis. Aims and Objectives/UNASSIGNED:nCLE and EUS-FNA in the diagnosis and histologic characterization of pancreatic cystic lesions (PCL). Materials and Methods/UNASSIGNED:All patients diagnosed with PCL who had undergone nCLE and FNA over a 10-year period within a major urban teaching hospital were included in this study. All gastroenterology reports of the nCLE images and corresponding pathologist findings from the EUS-FNA were collected and compared with, a final diagnosis prospectively collected from clinicopathological and imaging data. Results/UNASSIGNED:=1 lymphangioma. The overall diagnostic rate was higher in nCLE (87.5%) vs. EUS-FNA (71.9%) While the diagnostic accuracy of nCLE and EUS-FNA were comparable in characterization of benign vs. malignant lesions, the nCLE diagnosis demonstrated higher accuracy rate in identifying mucinous cystic neoplasms compared to EUS-FNA. Conclusion/UNASSIGNED:nCLE is a useful companion diagnostic tool for pancreatic cystic lesions and could assist the cytopathologist to better triage the sample for required ancillary testing and treatment planning. The combination of nCLE and EUS-FNA may be especially helpful in reducing the proportion of cases categorized as non-diagnostic.

Cyst fluid biomarkers may be used to identify pancreatic cyst subtypes. Biomarkers are selected based on their ability to accurately distinguish mucinous from nonmucinous cysts and to risk stratify cysts based on malignant potential. Biomarkers of interest include but are not limited to amylase, oncogenes, DNA analysis, and epigenetic markers. The introduction of next-generation sequencing and molecular panels has aided in improved diagnostic accuracy and risk stratification. This review presents the diagnostic performance of currently available biomarkers and proposes an algorithm to incorporate their use in the diagnosis of pancreatic cysts.

BACKGROUND & AIMS: Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) is the standard of care for tissue sampling of solid lesions adjacent to the GI tract. Fine needle biopsy (FNB) may provide higher diagnostic yield with fewer needle passes. The aim of this study was to assess the difference in diagnostic yield between FNA and FNB. METHODS: This is a multicenter, prospective randomized clinical trial from six large tertiary care centers. Patients referred for tissue sampling of solid lesions were randomized to either FNA or FNB of the target lesion. Demographics, size, location, number of needle passes, and final diagnosis were recorded. RESULTS: After enrollment, 135 patients were randomized to FNA (49.3%) and 139 patients were randomized to FNB (50.7%).The following lesions were sampled: mass (n=210; 76.6%), lymph nodes (n=46, 16.8%), submucosal tumors (n=18, 6.6%). Final diagnosis was malignancy (n=192, 70.1%), reactive lymphadenopathy (n=30, 11.0%), and spindle cell tumors (n=24, 8.8%). FNA had a diagnostic yield of 91.1% compared to 88.5% for FNB (p=0.48). There was no difference between FNA and FNB when stratified by the presence of on-site cytopathology or by type of lesion sampled A median of 1 needle pass was needed to obtain a diagnostic sample for both needles. CONCLUSION: FNA and FNB obtained a similar diagnostic yield with a comparable number of needle passes. Based on these results, there is no significant difference in the performance of FNA compared to FNB in the cytological diagnosis of solid lesions adjacent to the GI tract. (ClincalTrials.gov identifier: NCT01698190).