Circulating immune signatures across clinical stages of chronic pancreatitis: a pilot study.

OBJECTIVE: This pilot study seeks to identify serum immune signatures across clinical stages of patients with chronic pancreatitis (CP). METHODS: We performed a cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies-study. CP subjects were categorised into three clinical stages based on the presence/absence of metabolic complications: (1) CP with no diabetes and exocrine pancreatic dysfunction (EPD), (2) CP with either diabetes or EPD, and (3) CP with diabetes and EPD. Blinded samples were analysed using an 80-plex Luminex assay of cytokines/chemokines/adhesion molecules. Group and pairwise comparisons were performed to characterise immune signatures across CP subgroups. RESULTS: A total of 135 CP subjects (evenly distributed between clinical stages) and 50 controls were studied. Interleukin-6 (IL-6), interleukin-8 (IL-8), and soluble intercellular adhesion molecule 1 (sICAM-1) were significantly elevated in CP subjects compared to controls. The levels of IL-6 and IL-8 increased with advancing disease stages, with the highest levels observed in CP with diabetes and EPD (clinical stage 3). Furthermore, hepatocyte growth factor and macrophage-derived chemokine were significantly increased in clinical stage 3 compared to controls. CONCLUSION: Our study reveals a progressive elevation in pro-inflammatory cytokines and chemokines with advancing clinical stages of CP. These findings indicate potential targets for the development of disease-modifying interventions.

Utility of Urgent Endoscopic Retrograde Cholangiopancreatography in Patients with Predicted Mild Acute Pancreatitis and Cholestasis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) within 72 h is suggested for patients presenting with acute biliary pancreatitis (ABP) and biliary obstruction without cholangitis. This study aimed to identify if urgent ERCP (within 24 h) improved outcomes compared to early ERCP (24-72 h) in patients admitted with predicted mild ABP. METHODS: Patients admitted for predicted mild ABP defined as a bedside index of severity in acute pancreatitis score < 3 and underwent ERCP for biliary obstruction within 72 h of presentation during the study period were included. Patients with prior biliary sphincterotomy or surgically altered anatomy preventing conventional ERCP were excluded. The primary outcome was the development of moderately severe or severe pancreatitis based on the revised Atlanta classification. Secondary outcomes were the length of hospital stay, the need for ICU admission, and ERCP-related adverse events (AEs). RESULTS: Of the identified 166 patients, baseline characteristics were similar between both the groups except for the WBC count (9.4 vs. 8.3/µL; p < 0.044) and serum bilirubin level (3.0 vs. 1.6 mg/dL; p < 0.0039). Biliary cannulation rate and technical success were both high in the overall cohort (98.8%). Urgent ERCP was not associated with increased development of moderately severe pancreatitis (10.4% vs. 15.7%; p = 0.3115). The urgent ERCP group had a significantly shorter length of hospital stay [median 3 (IQR 2-3) vs. 3 days (IQR 3-4), p < 0.01]. CONCLUSION: Urgent ERCP did not impact the rate of developing more severe pancreatitis in patients with predicted mild ABP but was associated with a shorter length of hospital stay and a lower rate of hospital readmission.

Quantitative MRI of chronic pancreatitis: results from a multi-institutional prospective study, magnetic resonance imaging as a non-invasive method for assessment of pancreatic fibrosis (MINIMAP).

PURPOSE: To determine if quantitative MRI techniques can be helpful to evaluate chronic pancreatitis (CP) in a setting of multi-institutional study. METHODS: This study included a subgroup of participants (n = 101) enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study (NCT03099850) from February 2019 to May 2021. MRI was performed on 1.5 T using Siemens and GE scanners at seven clinical centers across the USA. Quantitative MRI parameters of the pancreas included T1 relaxation time, extracellular volume (ECV) fraction, apparent diffusion coefficient (ADC), and fat signal fraction. We report the diagnostic performance and mean values within the control (n = 50) and CP (n = 51) groups. The T1, ECV and fat signal fraction were combined to generate the quantitative MRI score (Q-MRI). RESULTS: There was significantly higher T1 relaxation time; mean 669 ms (± 171) vs. 593 ms (± 82) (p = 0.006), ECV fraction; 40.2% (± 14.7) vs. 30.3% (± 11.9) (p < 0.001), and pancreatic fat signal fraction; 12.2% (± 5.5) vs. 8.2% (± 4.4) (p < 0.001) in the CP group compared to controls. The ADC was similar between groups (p = 0.45). The AUCs for the T1, ECV, and pancreatic fat signal fraction were 0.62, 0.72, and 0.73, respectively. The composite Q-MRI score improved the diagnostic performance (cross-validated AUC: 0.76). CONCLUSION: Quantitative MR parameters evaluating the pancreatic parenchyma (T1, ECV fraction, and fat signal fraction) are helpful in the diagnosis of CP. A Q-MRI score that combines these three MR parameters improves diagnostic performance. Further studies are warranted with larger study populations including patients with acute and recurrent acute pancreatitis and longitudinal follow-ups.

Perception versus reality: A National Cohort Analysis of the surgery-first approach for resectable pancreatic cancer.

INTRODUCTION: Although surgical resection is necessary, it is not sufficient for long-term survival in pancreatic ductal adenocarcinoma (PDAC). We sought to evaluate survival after up-front surgery (UFS) in anatomically resectable PDAC in the context of three critical factors: (A) margin status; (B) CA19-9; and (C) receipt of adjuvant chemotherapy. METHODS: The National Cancer Data Base (2010-2015) was reviewed for clinically resectable (stage 0/I/II) PDAC patients. Surgical margins, pre-operative CA19-9, and receipt of adjuvant chemotherapy were evaluated. Patient overall survival was stratified based on these factors and their respective combinations. Outcomes after UFS were compared to equivalently staged patients after neoadjuvant chemotherapy on an intention-to-treat (ITT) basis. RESULTS: Twelve thousand and eighty-nine patients were included (n = 9197 UFS, n = 2892 ITT neoadjuvant). In the UFS cohort, only 20.4% had all three factors (median OS = 31.2 months). Nearly 1/3rd (32.7%) of UFS patients had none or only one factor with concomitant worst survival (median OS = 14.7 months). Survival after UFS decreased with each failing factor (two factors: 23 months, one factor: 15.5 months, no factors: 7.9 months) and this persisted after adjustment. Overall survival was superior in the ITT-neoadjuvant cohort (27.9 vs. 22 months) to UFS. CONCLUSION: Despite the perceived benefit of UFS, only 1-in-5 UFS patients actually realize maximal survival when known factors highly associated with outcomes are assessed. Patients are proportionally more likely to do worst, rather than best after UFS treatment. Similarly staged patients undergoing ITT-neoadjuvant therapy achieve survival superior to the majority of UFS patients. Patients and providers should be aware of the false perception of 'optimal' survival benefit with UFS in anatomically resectable PDAC.

Predicting the Need for Step-Up Therapy After EUS-Guided Drainage of Pancreatic Fluid Collections With Lumen-Apposing Metal Stents.

BACKGROUND & AIMS: A significant proportion of individuals with pancreatic fluid collections (PFCs) require step-up therapy after endoscopic drainage with lumen-apposing metal stents. The aim of this study is to identify factors associated with PFCs that require step-up therapy. METHODS: A retrospective cohort study of patients undergoing endoscopic ultrasound-guided drainage of PFCs with lumen-apposing metal stents from April 2014 to October 2019 at a single center was performed. Step-up therapy included direct endoscopic necrosectomy, additional drainage site (endoscopic or percutaneous), or surgical intervention after the initial drainage procedure. Multivariable logistic regression was performed using a backward stepwise approach with a P ≤ .2 threshold for variable retention to identify factors predictive for the need for step-up therapy. RESULTS: One hundred thirty-six patients were included in the final study cohort, of whom 69 (50.7%) required step-up therapy. Independent predictors of step-up therapy included: collection size measuring ≥10 cm (odds ratio [OR], 8.91; 95% confidence interval [CI], 3.36-23.61), paracolic extension of the PFC (OR, 4.04; 95% CI, 1.60-10.23), and ≥30% solid necrosis (OR, 4.24; 95% CI, 1.48-12.16). In a sensitivity analysis of 81 patients with walled-off necrosis, 51 (63.0%) required step-up therapy. Similarly, factors predictive of the need for step-up therapy for walled-off necrosis included: collection size measuring ≥10 cm (OR, 6.94; 95% CI, 1.76-27.45), paracolic extension of the PFC (OR, 3.79; 95% CI, 1.18-12.14), and ≥30% solid necrosis (OR, 7.10; 95% CI, 1.16-43.48). CONCLUSIONS: Half of all patients with PFCs drained with lumen-apposing metal stents required step-up therapy, most commonly direct endoscopic necrosectomy. Individuals with PFCs ≥10 cm in size, paracolic extension, or ≥30% solid necrosis are more likely to require step-up therapy and should be considered for early endoscopic reintervention.

Utilisation of artificial intelligence for the development of an EUS-convolutional neural network model trained to enhance the diagnosis of autoimmune pancreatitis.

OBJECTIVE: The diagnosis of autoimmune pancreatitis (AIP) is challenging. Sonographic and cross-sectional imaging findings of AIP closely mimic pancreatic ductal adenocarcinoma (PDAC) and techniques for tissue sampling of AIP are suboptimal. These limitations often result in delayed or failed diagnosis, which negatively impact patient management and outcomes. This study aimed to create an endoscopic ultrasound (EUS)-based convolutional neural network (CNN) model trained to differentiate AIP from PDAC, chronic pancreatitis (CP) and normal pancreas (NP), with sufficient performance to analyse EUS video in real time. DESIGN: A database of still image and video data obtained from EUS examinations of cases of AIP, PDAC, CP and NP was used to develop a CNN. Occlusion heatmap analysis was used to identify sonographic features the CNN valued when differentiating AIP from PDAC. RESULTS: From 583 patients (146 AIP, 292 PDAC, 72 CP and 73 NP), a total of 1 174 461 unique EUS images were extracted. For video data, the CNN processed 955 EUS frames per second and was: 99% sensitive, 98% specific for distinguishing AIP from NP; 94% sensitive, 71% specific for distinguishing AIP from CP; 90% sensitive, 93% specific for distinguishing AIP from PDAC; and 90% sensitive, 85% specific for distinguishing AIP from all studied conditions (ie, PDAC, CP and NP). CONCLUSION: The developed EUS-CNN model accurately differentiated AIP from PDAC and benign pancreatic conditions, thereby offering the capability of earlier and more accurate diagnosis. Use of this model offers the potential for more timely and appropriate patient care and improved outcome.

Impact of disconnected pancreatic duct syndrome on endoscopic ultrasound-guided drainage of pancreatic fluid collections.

BACKGROUND: Endoscopic intervention for pancreatic fluid collections (PFCs) with disconnected pancreatic duct syndrome (DPDS) has been associated with failures and increased need for additional endoscopic and non-endoscopic interventions. The primary aim of this study was to determine the outcomes of endoscopic ultrasound (EUS)-guided transmural drainage of PFCs in patients with DPDS. METHODS: In patients undergoing EUS-guided drainage of PFCs from January 2013 to January 2018, demographic profiles, procedural indications and details, adverse events, outcomes, and subsequent interventions were retrospectively collected. Overall treatment success was determined by PFC resolution on follow-up imaging or stent removal without recurrence. RESULTS: EUS-guided drainage of PFCs was performed in 141 patients. DPDS was present in 57 of them (40 %) and walled-off necrosis was the most frequent type of PFC (55 %). DPDS was not associated with lower clinical success, increased number of repeat interventions, or increased time to PFC resolution. Patients with DPDS were more likely to be treated with permanent transmural plastic double-pigtail stents (odds ratio [OR] 6.4; 95 % confidence interval [CI] 2.5 - 16.5; P < 0.001). However, when stents were removed, DPDS was associated with increased PFC recurrence after stent removal (OR 8.0; 95 %CI 1.2 - 381.8; P = 0.04). CONCLUSIONS: DPDS frequently occurs in patients with PFCs but does not negatively impact successful resolution. DPDS is associated with increased PFC recurrence after stent removal.

Safety, Diagnostic Accuracy, and Effects of Endoscopic Ultrasound Fine-Needle Aspiration on Detection of Extravascular Migratory Metastases.

BACKGROUND & AIMS: Tumor cells can migrate via diminutive perivascular cuffing to distant sites along blood vessels to form extravascular migratory metastases (EVMM). These metastases usually are identified during surgery or autopsies. We aimed to evaluate the feasibility and safety of endoscopic ultrasound fine-needle aspiration (EUS-FNA) of perivascular soft-tissue cuffs to detect EVMM. We compared findings from EUS with those from noninvasive cross-sectional imaging (reference standard) of patients who underwent EUS-FNA to assess suspected EVMM and studied the effects on pancreatic tumor staging and determination of resectability. METHODS: We performed a retrospective analysis of 253 patients (mean age, 62 ± 12 y) who underwent EUS-FNA of 267 vessels for evaluation of suspected EVMM, from April 2001 through May 2018. EUS findings were compared with those from computed tomography (CT) and magnetic resonance imaging (MRI) as the reference standard. Lesions were considered to be malignant based on cytology analysis of FNA samples, histology analyses of surgical or biopsy specimens, or vascular abnormalities detected by CT or MRI that clearly indicate EVMM. RESULTS: Thirty patients were found to have benign lesions. The remaining 223 patients who had malignancies (166 with pancreatic ductal adenocarcinomas [PDACs]), underwent further analyses. A median of 4 FNAs (range, 1-20 FNAs) were obtained from 4-mm perivascular soft-tissue cuffs (range, 2-20 mm). FNA and cytology analysis showed malignant cells in 163 vessels (69.4%) from 157 patients (70.4%). CT or MRI did not detect EVMM in 44 patients (28%) with malignancies, including 24 patients (24%) with newly diagnosed PDAC. Detection of EVMM by EUS-FNA resulted in upstaging of 15 patients and conversion of 14 patients with PDAC from resectable (based on CT or MRI) to unresectable. No adverse events were reported during a follow-up period of 3.9 months (range, 0-117 mo). CONCLUSIONS: EUS-FNA and cytologic analysis of perivascular soft-tissue cuffs can detect EVMM that were not found in 28% of patients by CT or MRI. Detection of EVMM affects tumor staging and determination of tumor resectability.

Combined Celiac Ganglia and Plexus Neurolysis Shortens Survival, Without Benefit, vs Plexus Neurolysis Alone.

BACKGROUND & AIMS: Pancreatic cancer produces debilitating pain that opioids often ineffectively manage. The suboptimal efficacy of celiac plexus neurolysis (CPN) might result from brief contact of the injectate with celiac ganglia. We compared the effects of endoscopic ultrasound-guided celiac ganglia neurolysis (CGN) vs the effects of CPN on pain, quality of life (QOL), and survival. METHODS: We performed a randomized, double-blind trial of patients with unresectable pancreatic ductal adenocarcinoma and abdominal pain; 60 patients (age 66.4±11.6 years; male 66%) received CPN and 50 patients (age 66.8±10.0 years; male 56%) received CGN. Primary outcomes included pain control and QOL at week 12 and survival (overall median and 12 months). Secondary outcomes included morphine response, performance status, secondary neurolytic effects, and adverse events. RESULTS: Rates of pain response at 12 weeks were 46.2% for CGN and 40.4% for CPN (P = .84). There was no significant difference in improvement of QOL between the techniques. The median survival time was significantly shorter for patients receiving CGN (5.59 months) compared to (10.46 months) (hazard ratio for CGN, 1.49; 95% CI, 1.02-2.19; P = .042), particularly for patients with non-metastatic disease (hazard ratio for CGN, 2.95; 95% CI, 1.61-5.45; P < .001). Rates of survival at 12 months were 42% for patients who underwent CPN vs 26% for patients who underwent CGN. The number of adverse events did not differ between techniques. CONCLUSION: In a prospective study of patients with unresectable pancreatic ductal adenocarcinoma and abdominal pain, we found CGN to reduce median survival time without improving pain, QOL, or adverse events, compared to CPN. The role of CGN must be therefore be reassessed. Clinicaltrials.gov no: NCT01615653.

Recurrent Acute Pancreatitis: International State-of-the-Science Conference With Recommendations.

Recurrent acute pancreatitis (RAP) is a clinically significant problem globally. The etiology remains unclear in approximately 10% to 15% of patients despite a thorough workup. Data on natural history and efficacy of treatments are limited. We aimed to establish criteria for diagnosis, evaluate the causative factors, and arrive at a consensus on the appropriate workup and management of patients with RAP. The organizing committee was formed, and a set of questions was developed based on the current evidence, controversies, and topics that needed further research. After a vetting process, these topics were assigned to a group of experts from around the world with special interest in RAP. Data were presented as part of a workshop on RAP organized as a part of the annual meeting of the America Pancreatic Association. Pretest and Posttest questions were administered, and the responses were tabulated by the current Grades of Recommendation Assessment, Development and Evaluation system. The consensus guidelines were established in the format of a diagnostic algorithm. Several deficiencies were identified with respect to data on etiology, treatment efficacies, and areas that need immediate research.

Risk of Pancreatic Cancer in Patients With Pancreatic Cysts and Family History of Pancreatic Cancer.

BACKGROUND & AIMS: A diagnosis of pancreatic cancer in a first-degree relative increases an individuals' risk of this cancer. However, it is not clear whether this cancer risk increases in individuals with pancreatic cystic lesions who have a first-degree relative with pancreatic cancer. The Fukuoka criteria are used to estimate risk of pancreatic cancer for patients with pancreatic cystic lesions: individuals with cysts with high risk or worrisome features (Fukuoka positive) have a higher risk of pancreatic cancer than individuals without these features (Fukuoka negative). We aimed to compare the risk of pancreatic cancer and surgery based on presence or absence of pancreatic cystic lesions and a first-degree relative with pancreatic cancer. METHODS: We performed a retrospective study of patients seen at the Mayo Clinic in Rochester, Minnesota, from January 1, 2000, through December 31, 2012. We identified individuals with: pancreatic cystic lesions and first-degree relative with pancreatic cancer (group 1, n = 269), individuals with pancreatic cystic lesions but no first-degree relative with pancreatic cancer (group 2, n = 1195), and individuals without pancreatic cystic lesions but with a first-degree relative with pancreatic cancer (group 3, n = 720). We compared, among groups, as well among patients with cysts classified according to Fukuoka criteria, proportions of individuals who developed pancreatic cancer or underwent pancreatic surgery within a 5-year period. RESULTS: A significantly higher proportion of individuals in group 1 developed pancreatic cancer during the 5-year period than in group 3 (6.64% vs 1.69%; P = .03); there was no significant difference between the percentage of individuals in group 1 vs group 2 who developed pancreatic cancer (6.64% vs 4.05%; P = .41). There was no significant difference in pancreatic cancer development among individuals with Fukuoka-positive cysts with vs without a family history of pancreatic cancer (P = .39). There was no significant difference in the proportion of patients in group 1 vs group 2 who underwent pancreatic surgery for their pancreatic cyst over the 5-year period (14.37% vs 11.80%; P = .59). Among patients with Fukuoka-negative cysts, a significantly higher proportion underwent surgery in group 1 than in group 2 (10.90% vs 5.90%; P = .03). However, among patients with Fukuoka-positive cysts, there was no difference in proportions of patients who underwent surgery between groups 1 and 2 (P = .66). CONCLUSIONS: In a retrospective study of patients with pancreatic cysts and/or cancer, we found that a family history of pancreatic cancer does not affect 5-year risk of pancreatic cancer in patients with pancreatic cystic lesions. Despite this, among patients with Fukuoka-negative cysts, a higher proportion of those with a family history of pancreatic cancer undergo surgery than patients without family history of pancreatic cancer.

Large-caliber metal stents versus plastic stents for the management of pancreatic walled-off necrosis.

BACKGROUND AND AIMS: Symptomatic pancreatic walled-off necrosis (WON) may be managed by endoscopic transmural drainage and endoscopic transmural necrosectomy, with stent placement at endoscopic drainage sites. The optimal stent choice is yet to be determined. We compared outcomes after endoscopic management of WON using either large-caliber fully covered self-expandable metal stents (LC-SEMSs) or double-pigtail plastic stents (DPPSs). METHODS: We performed a retrospective comparison of outcomes among patients who received LC-SEMSs or DPPSs before endoscopic transmural necrosectomy for WON. RESULTS: Among 94 patients included, WON resolution rates did not differ between the DPPS (36 patients) and LC-SEMS (58 patients) groups, whether concomitant percutaneous drainage was considered a failure (75% vs 82.8%; P = .36) or not (91.7% vs 94.8%; P = .55). Of 75 patients (80%) successfully treated without percutaneous drainage, 37 (49%) underwent endoscopic transmural drainage without subsequent endoscopic transmural necrosectomy. WON was more likely to resolve without subsequent endoscopic transmural necrosectomy in the LC-SEMS group than the DPPS group (60.4% vs 30.8%; P = .01). WON resolution without subsequent endoscopic transmural necrosectomy remained more likely with LC-SEMSs (odds ratio, 4.5 [95% confidence interval, 1.5-15.5]) after adjusting for patient age and size and location of WON. Rates of adverse events were similar except for clinically significant bleeding requiring endoscopic intervention, which was higher with DPPSs than LC-SEMSs (14% vs 2%; P = .02). CONCLUSION: Management of pancreatic WON with LC-SEMSs appears to decrease both the need for repeated necrosectomy procedures and the risk of intervention-related hemorrhage.

Metal stents versus plastic stents for the management of pancreatic walled-off necrosis: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Endoscopic transluminal drainage of symptomatic walled-off necrosis (WON) is a good management option, although the optimal choice of drainage site stent is unclear. We performed a systematic review and meta-analysis to compare metal stents (MSs) and plastic stents (PSs) in terms of WON resolution, likelihood of resolution after 1 procedure, and adverse events. METHODS: An expert librarian queried several databases to identify studies that assessed WON management, and selection was according to a priori criteria. Publication bias, heterogeneity, and study quality were evaluated with the appropriate tools. We performed single and 2-arm meta-analyses for noncomparative and comparative studies using event rate random-effects model and odds ratio (OR)/difference in means, respectively. RESULTS: We included 41 studies involving 2213 patients. In 2-arm study meta-analysis, WON resolution was more likely with MSs compared with PSs (OR, 2.8; 95% confidence interval, 1.7-4.6; P < .001). Resolution with a single endoscopic procedure was similar between stents (47% vs 44%), although for those cases requiring more than 1 intervention, the MS group had fewer interventions, favored by a mean difference of -.9 procedures (95% CI, -1.283 to -.561). In single-arm study meta-analysis, when compared with PSs, MS use was associated with lower bleeding (5.6% vs 12.6%; P = .02), a trend toward lower perforation and stent occlusion (2.8% vs 4.3%, P = .2, and 9.5% vs 17.4%, P = .07), although with higher migration (8.1% vs 5.1%; P = .1). CONCLUSION: Evidence suggests that MSs are superior for WON resolution, with fewer bleeding events, trend toward less occlusion and perforation rate, but increased migration rate compared with PSs.

An Investigation of Bayes Algorithm and Neural Networks for Identifying the Breast Cancer.

CONTEXT: Breast cancer is a biggest threat to women. X-ray mammography is the most effective method for early detection and screening of breast cancer. It is a tough challenge for the radiologist in reading mammography since it does not provide consistent result every time. AIM: To improve the primary sign of this disease, computer-aided diagnosis schemes have been developed. Using monitor, digital images of mammography are displayed and they can be lightened or darkened before they are printed on the film. Time factor is important to identify the abnormality in body such as breast cancer and lung cancer. Hence, to detect the tissues and treatment stages, image-processing techniques are improved in several medical areas. In this project, using low-level preprocessing techniques and image segmentation, the breast cancer detection is done. METHODS: With the help of Bayes algorithm and neural networks (NNs), the type of the mammogram and stages is identified. For segmentation process, region-growing algorithm is used, which helps to find the affected portion, i.e., region of interest. Gray-level co-occurrence matrix (GLCM) and texture feature are used for feature extraction. RESULTS: Bayes algorithm is used for probability of identification, whereas NNs is used to reduce the probability level from 0-1000 to 0-1 in case of classification.

Fukuoka criteria accurately predict risk for adverse outcomes during follow-up of pancreatic cysts presumed to be intraductal papillary mucinous neoplasms.

OBJECTIVE: Fukuoka consensus guidelines classify pancreatic cystic lesions (PCLs) presumed to be intraductal papillary mucinous neoplasms (IPMNs) into Fukuoka positive (FP) (subgroups of high-risk (HR) and worrisome features (WFs)) and Fukuoka negative (FN) (non-HR feature/WF cysts). We retrospectively estimated 5-year risk of pancreatic cancer (PC) in FN, WF and HR cysts of patients with PCL-IPMN. DESIGN: From Mayo Clinic databases, we randomly selected 2000 patients reported to have a PCL; we excluded inflammatory or suspected non-IPMN cysts and those without imaging follow-up. We re-reviewed cross-sectional imaging and abstracted clinical and follow-up data on PCL-IPMNs. The study contained 802 patients with FN cysts and 358 with FP cysts. RESULTS: Patients with PCL-IPMN had median (IQR) follow-up of 4.2 (1.8-7.1) years. Among FN cysts, 5-year PC risk was low (2-3%) regardless of cyst size (p=0.67). After excluding events in the first 6 months, 5-year PC risk remained low (0-2%) regardless of cyst size (p=0.61). Among FP cysts, HR cysts (n=66) had greater 5-year PC risk than WF cysts (n=292) (49.7% vs 4.1%; p<0.001). In HR cysts, 3-year PC risk was greatest for obstructive jaundice versus enhancing solid component or main pancreatic duct >10 mm (79.8% vs 37.3% vs 39.4%, respectively; p=0.01). CONCLUSIONS: Fukuoka guidelines accurately stratify PCL-IPMNs for PC risk, with FN cysts having lowest and HR cysts having greatest risk. After 6-month follow-up, WF and FN cysts had a low 5-year PC risk. Surveillance strategies should be tailored appropriately.

Endoscopic Ultrasound Fine-Needle Aspiration Diagnosis of Synchronous Primary Pancreatic Adenocarcinoma and Effects on Staging and Resectability.

Synchronous primary pancreatic adenocarcinoma, defined as the simultaneous presence of 2 or more newly identified and anatomically separate primary adenocarcinomas within the pancreas, is reported rarely. We compared endoscopic ultrasound (EUS) and computed tomography (CT) and magnetic resonance imaging (MRI) findings from patients with synchronous primary pancreatic adenocarcinoma and their effects on cancer staging and treatment. We performed a retrospective analysis of the EUS database at the Mayo Clinic, from September 2008 through May 2016, to collect EUS, CT, MRI, and clinical data from patients with synchronous primary pancreatic adenocarcinoma. EUS and separate fine-needle aspiration of both tumors detected synchronous primary pancreatic adenocarcinoma in 11 patients (70.9 ± 10.4 y; 64% men). Of the 22 cancers, CT (n = 9) and MRI (n = 2) detected 9 (41%) cancers; in only 2 patients did CT detect both cancers. EUS increased cancer stage for 7 of the 11 (64%) patients and changed the status from resectable to unresectable for 3 of the 9 (33%) patients, compared with CT or MRI. EUS findings altered the likely extent of surgical resection for 3 patients. Synchronous primary pancreatic adenocarcinoma is reported rarely and may be undetected by CT or MRI; this could account for the false presumption of early tumor recurrence, rather than actual residual second tumor, leading to incomplete resection.

Remote malignant intravascular thrombi: EUS-guided FNA diagnosis and impact on cancer staging.

BACKGROUND AND AIMS: Malignant vascular invasion usually results from gross direct infiltration from a primary tumor and impacts cancer staging, prognosis, and therapy. However, patients may also develop a remote malignant thrombi (RMT), defined as a malignant intravascular thrombus located remote and noncontiguous to the primary tumor. Our aim was to compare EUS, CT, and magnetic resonance imaging (MRI) findings of RMT and to explore the potential impact on cancer staging. METHODS: Patients with RMT were identified from a prospectively maintained EUS database. Retrospective chart review was performed to obtain EUS, CT/MRI, clinical, and outcome data. RESULTS: A median of 3 FNAs (range, 1-8) was obtained from RMT in 17 patients (60 ± 14.1 years, 56% men) between April 2003 and August 2016, with the finding of malignant cytology in 12 patients (70.6%; 10 positive, 2 suspicious). CT/MRI detected the RMT in 5 patients (29.4%), 4 of whom had positive or suspicious EUS-FNA cytology. Among the 8 newly diagnosed pancreatic adenocarcinoma (PaC) patients, CT did not detect the RMT in 5 (63%), of whom 3 patients had positive or suspicious intravascular EUS-FNA cytology. For newly diagnosed PaC patients (n = 8), the EUS-FNA diagnosis of a biopsy specimen-proven RMT upstaged 3 patients (37.5%) and converted 2 patients (25%) from CT resectable to unresectable disease. No adverse events were reported. The mean follow-up was 18.9 ± 27.7 months. CONCLUSIONS: Our study demonstrates the ability and potential safety of intravascular FNA to detect radiographically occult RMT, which substantially impacts cancer staging and resectability.

Pancreatic cyst epithelial denudation: a natural phenomenon in the absence of treatment.

BACKGROUND AND AIMS: The presence and significance of epithelial denudation among treatment-naïve pancreatic cystic lesions (PCLs) remain undetermined. The aims of this study were to determine the prevalence, extent, and predictors of epithelial denudation in treatment-naïve PCLs. METHODS: Single-center retrospective study including patients who underwent EUS preceded by cross-sectional imaging and who subsequently underwent surgical resection of treatment-naïve PCLs. Surgically resected PCLs were reviewed by a pathologist in a fashion that allowed evaluation from evenly distributed regions of the cyst. RESULTS: A total of 140 patients were identified (60% female, mean age 63 years). Eighty-five cysts (60.7%) were classified as intraductal papillary mucinous neoplasms (IPMNs), 33 (23.5%) as main duct IPMNs (m-IPMNs), 11 (7.9%) as serous cystadenomas (SCAs), and 11 (7.9%) were composed of other cyst subtypes. A greater extent of epithelial denudation was seen in mucinous cystic neoplasm (MCN) compared with IPMN and SCA (mean percentage of denuded epithelium 45.1%, 10.8%, and 22.4%, respectively [P < .0001]). An association existed between the extent of denuded epithelium and degree of cyst epithelial dysplasia for IPMN and MCN combined (mean percentage of denuded epithelium for low-, moderate-, and high-grade dysplasia being 23.3%, 4.5%, and 1.2%, respectively; P = .02). PCLs resected from the neck and/or body and/or tail of the pancreas were associated with a greater extent of mean percentage of denuded epithelium than PCLs resected from the head and/or uncinate of the pancreas (23.9% vs 13.4%; P = .035). CONCLUSIONS: The presence and extent of cyst epithelial denudation of treatment-naïve PCLs vary with cyst histology and other factors. The observation of denudation after intracystic ablative therapy may not provide an adequate metric of successful intervention. Further studies are needed to validate these findings.