Endoscopic Ultrasound-Guided Fine Needle Biopsy Needles Provide Higher Diagnostic Yield Compared to Endoscopic Ultrasound-Guided Fine Needle Aspiration Needles When Sampling Solid Pancreatic Lesions: A Meta-Analysis.

BACKGROUND/AIMS: Studies comparing the utility of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for solid pancreatic lesions have been inconclusive with no clear superiority. The aim of this meta-analysis was to compare the diagnostic accuracy and safety between the two sampling techniques. METHODS: We performed a systematic search of randomized controlled trials published between 2012 and 2019. The primary outcome was overall diagnostic accuracy. Secondary outcomes included adverse event rates, cytopathologic and histopathologic accuracy, and the mean number of passes required to obtain adequate tissue between FNA and FNB needles. Fixed and random effect models with pooled estimates of target outcomes were developed. RESULTS: Eleven studies involving 1,365 participants were included for analysis. When compared to FNB, FNA had a significant reduction in diagnostic accuracy (81% and 87%, p=0.005). In addition, FNA provided reduced cytopathologic accuracy (82% and 89%, p=0.04) and an increased number of mean passes required compared to FNB (2.3 and 1.6, respectively, p<0.0001). There was no difference in adverse event rate between FNA and FNB needles (1.8% and 2.3% respectively, p=0.64). CONCLUSION: FNB provides superior diagnostic accuracy without compromising safety when compared to FNA. FNB should be readily considered by endosonographers when evaluating solid pancreatic masses.

Clinical significance of recurrent gastroesophageal junction intestinal metaplasia after endoscopic eradication of Barrett's esophagus.

BACKGROUND AND AIMS: After endoscopic eradication of Barrett's esophagus (BE), recurrence of intestinal metaplasia at the gastroesophageal junction (GEJIM) is common. The clinical significance of this finding is unclear. We assessed whether recurrent GEJIM is associated with increased risk of subsequent dysplasia and whether endoscopic treatment lowers this risk. METHODS: A retrospective, multicenter, cohort study was performed of treated BE patients who achieved complete eradication of intestinal metaplasia (IM). Postablation follow-up was performed at standard intervals. Recurrent GEJIM was defined as nondysplastic IM on gastroesophageal junction biopsy specimens without endoscopic evidence of BE. Patients were categorized as "never-GEJIM," "GEJIM-observed," or "GEJIM-treated." Endoscopic treatment for recurrent GEJIM was at the endoscopists' discretion. The primary outcome was dysplasia recurrence. Analyses were performed using log-rank tests and Cox proportional hazards modeling. RESULTS: Six hundred thirty-three patients were analyzed; median follow-up was 47 months (interquartile range, 24-69). Most patients (81%) had high-grade dysplasia or intramucosal adenocarcinoma before treatment. Dysplasia recurrence was 2.2% per year. GEJIM-observed patients had the lowest rate of recurrence (.6%/y) followed by GEJIM-treated (2.2%/y) and never-GEJIM (2.6%/y) (log-rank P = .07). In multivariate analyses, compared with never-GEJIM, the risk of dysplasia recurrence was significantly lower in GEJIM-observed patients (adjusted hazard ratio, .19; 95% confidence interval, .05-.81) and not different in GEJIM-treated patients (adjusted hazard ratio, .81; 95% confidence interval, .39-1.67). Older age and longer initial BE length were independently associated with recurrence. CONCLUSIONS: Recurrent GEJIM after endoscopic eradication of BE was not associated with an increased risk of subsequent dysplasia. Future studies are warranted to determine if observation is appropriate for this finding.

New onset diabetes predicts progression of low risk pancreatic mucinous cysts.

BACKGROUND: Patients with low-risk lesions require ongoing surveillance since the rate of progression to pancreatic cancer (PC), while small, is much greater than in the general population. Our objective was to study the relationship between new onset diabetes (NODM) and progression in patients with low risk mucinous cysts. METHODS: We evaluated a prospectively maintained cohort of 442 patients with a suspected mucinous cyst without worrisome features (WF) or high-risk stigmata (HRS). Multivariable Cox models were developed for progression to WF and HRS, with diabetes status formulated as both time independent and dependent covariates. The adjusted cumulative risk of progression was calculated using the corrected group prognosis method. RESULTS: The 5-year cumulative progression rates to WFs and HRS were 12.8 and 3.6%, respectively. After controlling for other risk factors, the development of NODM was strongly associated with progression to HRS (HR = 11.6; 95%CI, 3.5-57.7%), but not WF. Among patients with the smallest cysts (<10 mm) at baseline, those who developed NODM had a 5-year adjusted cumulative risk of progression to HRS of 8.6% (95%CI, 0.0%-20.2%), compared to only 0.8% (95%CI, 0.0%-2.3%) for patients without NODM. Among patients with the largest cysts (20-29 mm), those who developed NODM during surveillance had a 5-year adjusted cumulative risk of progression of 53.5% (95%CI, 19.6%-89.9%) compared to only 7.5% (95%CI, 1.6%-15.2%) for patients without NODM. CONCLUSION: New onset diabetes may predict progression in patients with low risk mucinous cysts. Pending validation with large-scale studies, these findings support regular diabetes screening among patients surveilled for suspected IPMNs or MCNs.

The Role of Endoscopic Ultrasound-Guided Ki67 in the Management of Non-Functioning Pancreatic Neuroendocrine Tumors.

BACKGROUND/AIMS: The management of small, incidentally discovered nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has been a matter of debate. Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is a tool used to identify and risk-stratify PNETs. This study investigates the concordance rate of Ki67 grading between EUS-FNA and surgical pathology specimens in NFPNETs and whether certain NF-PNET characteristics are associated with disease recurrence and disease-related death. METHODS: We retrospectively reviewed the clinical history, imaging, endoscopic findings, and pathology records of 37 cases of NFPNETs that underwent pre-operative EUS-FNA and surgical resection at a single academic medical center. RESULTS: There was 73% concordance between Ki67 obtained from EUS-FNA cytology and surgical pathology specimens; concordance was the highest for low- and high-grade NF-PNETs. High-grade Ki67 NF-PNETs based on cytology (p=0.028) and histology (p=0.028) were associated with disease recurrence and disease-related death. Additionally, tumors with high-grade mitotic rate (p=0.005), tumor size >22.5 mm (p=0.104), and lymphovascular invasion (p=0.103) were more likely to have poor prognosis. CONCLUSION: NF-PNETs with high-grade Ki67 on EUS-FNA have poor prognosis despite surgical resection. NF-PNETs with intermediate-grade Ki67 on EUS-FNA should be strongly considered for surgical resection. NF-PNETs with low-grade Ki67 on EUSFNA can be monitored without surgical intervention, up to tumor size 20 mm.

Diagnosis of Pancreatic Cystic Lesions by Virtual Slicing: Comparison of Diagnostic Potential of Needle-Based Confocal Laser Endomicroscopy versus Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

BACKGROUND: 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: To determine the diagnostic utility of in vivo nCLE and EUS-FNA in the diagnosis and histologic characterization of pancreatic cystic lesions (PCL). MATERIALS AND METHODS: 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: A total of n=32 patients were included in this study, which consisted of n=13 serous cystadenoma (SCA), n=7 intraductal papillary mucinous neoplasms (IPMN), n=2 mucinous cystic neoplasms (MCN), n=3 well-differentiated neuroendocrine tumors, n=2 cysts, n=2 benign pancreatic lesions, n=1 adenocarcinoma, n=1 gastrointestinal stromal tumor (GIST) and n=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: 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.

Shorter time to achieve endoscopic eradication is not associated with improved long-term outcomes in Barrett's esophagus.

Quality indicators have been proposed for endoscopic eradication therapy of Barrett's esophagus (BE). One such measure suggests that complete eradication of intestinal metaplasia (CE-IM) should be achieved within 18 months of starting treatment. The aim of this study was to assess whether achievement of CE-IM within 18 months is associated with improved long-term clinical outcomes. This was a retrospective cohort study of BE patients who underwent endoscopic eradication. Time to CE-IM was recorded and categorized as ≤ or > 18 months. The main outcome measures were recurrence of IM and of dysplasia after CE-IM, defined as a single endoscopy without endoscopic evidence of BE or histologic evidence of intestinal metaplasia. Recurrence was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards modeling. A total of 290 patients were included in the analyses. The baseline histology was high-grade dysplasia or intramucosal carcinoma in 74.2% of patients. CE-IM was achieved in 85.5% of patients, and 54.1% of the cohort achieved CE-IM within 18 months. Achieving CE-IM within 18 months was not associated with reduced risk of recurrence of IM or dysplasia in both unadjusted and adjusted analyses. In this cohort, older age and increased BE length were associated with IM recurrence, and increased hiatal hernia size was associated with dysplasia recurrence. Compared to longer times, achieving CE-IM within 18 months was not associated with a reduced risk of recurrence of IM or dysplasia. Alternative evidence-based quality metrics for endoscopic eradication therapy should be identified.

The Utility of Endoscopic Ultrasound in Patients with Isolated Elevations in Serum Amylase and/or Lipase.

BACKGROUND/AIMS: 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: 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.

The Role of Endotherapy in Recurrent Acute Pancreatitis.

Patients with recurrent acute pancreatitis (RAP) have few treatment options available to them to manage their symptoms or prevent progression to chronic pancreatitis. At present, endotherapy is typically pursued as a means to achieve symptom remission and reduce rates of recurrence, hospitalization, abdominal pain, narcotic use, and surgical intervention. However, evidence that endotherapy effectively alters the natural history of disease remains limited. This article reviews the recent literature on the efficacy of endoscopic intervention in the treatment RAP with a focus on high-quality prospective randomized controlled studies. Additional studies are needed to corroborate these findings.

Predictors of Progression Among Low-Risk Intraductal Papillary Mucinous Neoplasms in a Multicenter Surveillance Cohort.

OBJECTIVES: Our aim was to identify baseline characteristics associated with disease progression and malignant transformation in low-risk suspected intraductal papillary mucinous neoplasms (IPMNs). METHODS: This is a retrospective cohort study of prospectively maintained databases of pancreatic cysts at 3 international, academic institutions. Five hundred fifty-nine adult patients with clinically suspected asymptomatic IPMN evaluated by radiologic studies or endoscopic ultrasound between 2003 and 2013 without worrisome features and under surveillance for 12 months or longer were included. We evaluated the relationship of baseline demographics and cyst features to disease progression (size increase, development of worrisome features, or high-grade dysplasia/cancer). RESULTS: After a median of 44 months follow-up, 269 (48%) patients experienced cyst size increase, 68 (12%) developed worrisome features, and 11 (2%) developed high-grade dysplasia/cancer. In multivariable Cox-regression analysis, no baseline characteristics were associated with size increase. An initial cyst size of 2 cm or greater, multifocality, history of prostate cancer, and smoking were the strongest predictors of development of new worrisome features. Univariable analysis found male sex, diabetes, and recent weight loss associated with development of high-grade dysplasia/cancer. CONCLUSIONS: Our study demonstrates that low-risk suspected IPMNs carry a small but clinically relevant risk of disease progression and provides data on baseline characteristics that may help in risk stratification.

Comparison of Endoscopic Ultrasound-Fine-Needle Aspiration and Endoscopic Ultrasound-Fine-Needle Biopsy for Solid Lesions in a Multicenter, Randomized Trial.

BACKGROUND & AIMS: Endoscopic ultrasound with fine-needle aspiration (FNA) is the standard of care for tissue sampling of solid lesions adjacent to the gastrointestinal 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 6 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%), and 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 with 88.5% for FNB (P = .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. CONCLUSIONS: FNA and FNB obtained a similar diagnostic yield with a comparable number of needle passes. On the basis of these results, there is no significant difference in the performance of FNA compared with FNB in the cytologic diagnosis of solid lesions adjacent to the gastrointestinal tract. ClinicalTrials.gov identifier: NCT01698190.

Comparison of the diagnostic accuracy of three current guidelines for the evaluation of asymptomatic pancreatic cystic neoplasms.

Asymptomatic pancreatic cysts are a common clinical problem but only a minority of these cases progress to cancer. Our aim was to compare the accuracy to detect malignancy of the 2015 American Gastroenterological Association (AGA), the 2012 International Consensus/Fukuoka (Fukuoka guidelines [FG]), and the 2010 American College of Radiology (ACR) guidelines.We conducted a retrospective study at 3 referral centers for all patients who underwent resection for an asymptomatic pancreatic cyst between January 2008 and December 2013. We compared the accuracy of 3 guidelines in predicting high-grade dysplasia (HGD) or cancer in resected cysts. We performed logistic regression analyses to examine the association between cyst features and risk of HGD or cancer.A total of 269 patients met inclusion criteria. A total of 228 (84.8%) had a benign diagnosis or low-grade dysplasia on surgical pathology, and 41 patients (15.2%) had either HGD (n = 14) or invasive cancer (n = 27). Of the 41 patients with HGD or cancer on resection, only 3 patients would have met the AGA guideline's indications for resection based on the preoperative cyst characteristics, whereas 30/41 patients would have met the FG criteria for resection and 22/41 patients met the ACR criteria. The sensitivity, specificity, positive predictive value, negative predictive value of HGD, and/or cancer of the AGA guidelines were 7.3%, 88.2%, 10%, and 84.1%, compared to 73.2%, 45.6%, 19.5%, and 90.4% for the FG and 53.7%, 61%, 19.8%, and 88% for the ACR guidelines. In multivariable analysis, cyst size >3 cm, compared to ≤3 cm, (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.11, 4.2) and each year increase in age (OR = 1.07, 95% CI = 1.03, 1.11) were positively associated with risk of HGD or cancer on resection.In patients with asymptomatic branch duct-intraductal papillary mucinous neoplasms or mucinous cystic neoplasms who underwent resection, the prevalence rate of HGD or cancer was 15.2%. Using the 2015 AGA criteria for resection would have missed 92.6% of patients with HGD or cancer. The more "inclusive" FG and ACR had a higher sensitivity for HGD or cancer but lower specificity. Given the current deficiencies of these guidelines, it will be important to determine the acceptable rate of false-positives in order to prevent a single true-positive.

A Multicenter Study of a Fluorescence In Situ Hybridization Probe Set for Diagnosing High-Grade Dysplasia and Adenocarcinoma in Barrett's Esophagus.

BACKGROUND AND AIMS: Preliminary single-institution data suggest that fluorescence in situ hybridization (FISH) may be useful for detecting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EA) in patients with Barrett's esophagus (BE). This multicenter study aims to validate the measurement of polysomy (gain of at least two loci) by FISH as a way to discriminate degrees of dysplasia in BE specimens. METHODS: Tissue specimens were collected from four different hospitals and read by both the local pathology department ("Site diagnosis") and a single central pathologist ("Review diagnosis") at a separate institution. The specimens then underwent FISH analysis using probes 8q24 (MYC), 9p21 (CDKN2A), 17q12 (ERBB2), and 20q13 (ZNF217) for comparison. A total of 46 non-BE, 42 non-dysplastic specialized intestinal metaplasia (SIM), 23 indefinite-grade dysplasia (IGD), 10 low-grade dysplasia (LGD), 29 HGD, and 42 EA specimens were analyzed. RESULTS: We found that polysomy, as detected by FISH, was the predominant chromosomal abnormality present as dysplasia increased. Polysomy was also the best predictor for the presence of dysplasia or EA when comparing its area under the curve to that of other FISH abnormalities. We observed that if at least 10% of cells had polysomy within a specimen, the FISH probe was able to differentiate between EA/HGD and the remaining pathologies with a sensitivity of 80% and a specificity of 88%. CONCLUSIONS: This study demonstrates that using FISH to determine the percentage of cells with polysomy can accurately and objectively aid in the diagnosis of HGD/EA in BE specimens.

Mutation Profile and Fluorescence In Situ Hybridization Analyses Increase Detection of Malignancies in Biliary Strictures.

BACKGROUND & AIMS: It is a challenge to detect malignancies in biliary strictures. Various sampling methods are available to increase diagnostic yield, but these require additional procedure time and expertise. We evaluated the combined accuracy of fluorescence in situ hybridization (FISH) and polymerase chain reaction-based DNA mutation profiling (MP) of specimens collected using standard brush techniques. METHODS: We performed a prospective study of 107 consecutive patients treated for biliary strictures by endoscopic retrograde cholangiopancreatography from June 2012 through June 2014. We performed routine cytology and FISH analyses on cells collected by standard brush techniques, and analyzed supernatants for point mutations in KRAS and loss-of-heterozygosity mutations in tumor-suppressor genes at 10 loci (MP analysis was performed at Interpace Diagnostics). Strictures were determined to be nonmalignant based on repeat image analysis or laboratory test results 12 months after the procedure. Malignant strictures were identified based on subsequent biopsy or cytology analyses, pathology analyses of samples collected during surgery, or death from biliary malignancy. We determined the sensitivity and specificity with which FISH and MP analyses detected malignancies using the exact binomial test. RESULTS: Our final analysis included 100 patients; 41% had biliary malignancies. Cytology analysis identified patients with malignancies with 32% sensitivity and 100% specificity. Addition of FISH or MP results to cytology results increased the sensitivity of detection to 51% (P < .01) without reducing specificity. The combination of cytology, MP, and FISH analyses detected malignancies with 73% sensitivity (P < .001). FISH identified an additional 9 of the 28 malignancies not detected by cytology analysis, and MP identified an additional 8 malignancies. FISH and MP together identified 17 of the 28 malignancies not detected by cytology analysis. CONCLUSIONS: Addition of FISH and mutation analyses to cytology analysis significantly increased the level of sensitivity with which we detected malignancy in biliary strictures, with 100% specificity. These techniques can be performed using standard brush samples collected during endoscopic retrograde cholangiopancreatography, with mutations detected in free DNA in supernatant fluid of samples. The tests are complementary and therefore should be used sequentially in the diagnostic evaluation of biliary strictures.

Endoscopic Therapy With Lumen-apposing Metal Stents Is Safe and Effective for Patients With Pancreatic Walled-off Necrosis.

BACKGROUND & AIMS: Endoscopic ultrasound-guided transmural drainage and necrosectomy have become the standard treatment for patients with pancreatic walled-off necrosis (WON). Lumen-apposing metal stents (LAMS) have shown success in the management of pancreatic fluid collections. However, there are few data on their specific roles in management of WON. We investigated the efficacy and safety of LAMS in treatment of WON. METHODS: We performed a retrospective multicenter case series of 124 patients with WON who underwent endoscopic transmural drainage by using LAMS at 17 tertiary care centers from January 2014 through May 2015. Patients underwent endoscopic ultrasound-guided cystogastrostomy or cystoenterostomy with placement of an LAMS into the WON collection. At the discretion of the endoscopist, we performed direct endoscopic necrosectomy, irrigation with hydrogen peroxide, and/or nasocystic drain placement. We performed endoscopic retrograde cholangiopancreatography with pancreatic duct stent placement when indicated. Concomitant therapies included direct endoscopic debridement (n = 78), pancreatic duct stent placement for leak (n = 19), hydrogen peroxide-assisted necrosectomy (n = 38), and nasocystic irrigation (n = 22). We collected data for a median time of 4 months (range, 1-34 months) after the LAMS placement. The primary outcomes were rates of technical success (successful placement of the LAMS), clinical success (resolution of WON, on the basis of image analysis, without need for further intervention via surgery or interventional radiology), and adverse events. RESULTS: The median size of the WON was 9.5 cm (range, 4-30 cm). Eight patients had 2 LAMS placed for multiport access, all with technical success (100%). Clinical success was achieved in 107 patients (86.3%) after 3 months of follow-up. Thirteen patients required a percutaneous drain, and 3 required a surgical intervention to manage their WON. The stents remained patent in 94% of patients (117 of 124) and migrated in 5.6% of patients (7 of 124). The median number of endoscopic interventions was 2 (range, 1-9 interventions). CONCLUSIONS: On the basis of a retrospective analysis of 124 patients, endoscopic therapy of WON by using LAMS is safe and effective. Creation of a large and sustained cystogastrostomy or cystoenterostomy tract is effective in the drainage and treatment of WON.

Progression of Incidental Intraductal Papillary Mucinous Neoplasms of the Pancreas in Liver Transplant Recipients.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are premalignant pancreatic cysts commonly found incidentally. Immunosuppression accelerates carcinogenesis.Thus, we aimed to compare IPMN progression in liver transplant (LT) recipients on chronic immunosuppression to progression among an immunocompetent population. METHODS: We retrospectively assessed adult LT recipients between 2008 and 2014 for imaging evidence of IPMN. Diagnosis of IPMN was based on history, imaging, and cyst fluid analysis. The immunocompetent control group consisted of nontransplant patients from our pancreatic cyst surveillance program with IPMN under surveillance for greater than 12 months between 1997 and 2013. Four hundred fifty-four patients underwent LT in the study period and had cross-sectional imaging. RESULTS: The prevalence of suspected IPMN was 6.6% (30 of 454). Compared with 131 controls, the transplant cohort was younger, with increased prevalence of diabetes and smoking. The prevalence of other risk factors for IPMN progression (history of pancreatitis, family history of pancreatic cancer) was similar. After an average follow-up of 31 months, most cysts increased in diameter, with a similar increase of dominant cyst (0.4 cm vs 0.5 cm; P = 0.6). Type of immunosuppression was not associated with the increased rate of cyst growth. CONCLUSIONS: Our findings suggest that LT recipients with incidental IPMN can be managed under similar guidelines as immunocompetent patients.

The role of molecular analysis in the diagnosis and surveillance of pancreatic cystic neoplasms.

CONTEXT: Molecular analysis of pancreatic cyst fluid obtained by EUS-FNA may increase diagnostic accuracy. We evaluated the utility of cyst-fluid molecular analysis, including mutational analysis of K-ras, loss of heterozygosity (LOH) at tumor suppressor loci, and DNA content in the diagnoses and surveillance of pancreatic cysts. METHODS: We retrospectively reviewed the Columbia University Pancreas Center database for all patients who underwent EUS/FNA for the evaluation of pancreatic cystic lesions followed by surgical resection or surveillance between 2006-2011. We compared accuracy of molecular analysis for mucinous etiology and malignant behavior to cyst-fluid CEA and cytology and surgical pathology in resected tumors. We recorded changes in molecular features over serial encounters in tumors under surveillance. Differences across groups were compared using Student's t or the Mann-Whitney U test for continuous variables and the Fisher's exact test for binary variables. RESULTS: Among 40 resected cysts with intermediate-risk features, molecular characteristics increased the diagnostic yield of EUS-FNA (n=11) but identified mucinous cysts less accurately than cyst fluid CEA (P=0.21 vs. 0.03). The combination of a K-ras mutation and ≥2 loss of heterozygosity was highly specific (96%) but insensitive for malignant behavior (50%). Initial data on surveillance (n=16) suggests that molecular changes occur frequently, and do not correlate with changes in cyst size, morphology, or CEA. CONCLUSIONS: In intermediate-risk pancreatic cysts, the presence of a K-ras mutation or loss of heterozygosity suggests mucinous etiology. K-ras mutation plus ≥2 loss of heterozygosity is strongly associated with malignancy, but sensitivity is low; while the presence of these mutations may be helpful, negative findings are uninformative. Molecular changes are observed in the course of cyst surveillance, which may be significant in long-term follow-up.

Strategies for improving diagnostic accuracy of biliary strictures.

BACKGROUND: Brush cytology is the initial intervention when evaluating biliary strictures. Biliary brush cytology is known for its low sensitivity (but high specificity) and may be accompanied by biopsies and/or fluorescent in situ hybridization (FISH) to improve diagnostic yield. This study aimed to identify features to enhance cytological sensitivity, and assess which sampling method(s) improve identification of pancreatobiliary adenocarcinomas (PBCa). METHODS: Seventy-three biliary stricture cases were retrieved (38 PBCa and 35 control benign strictures). Biliary brushings, FISH, and biopsies were reviewed. Cytology specimens were evaluated for cellularity and presence of drunken honeycomb (DH), loosely cohesive clusters of round cells (LCCRC), large atypical cells with foamy cytoplasm (LACF), and single vacuolated malignant cells (SCs). Biopsies were examined for the presence of stromal invasion (SI). RESULTS: Biliary brushings were scantly cellular in 47.4% of PBCa and 51.4% of controls, resulting in 69.6% nondiagnostic/false-negative cytology diagnoses. DH, LACF, and SCs were significantly associated with adenocarcinoma (P < .00001, .0033, and .00002, respectively). By univariate analysis, SCs and LACF were predictors of malignancy in brushings (P = .0002 and .05). By multivariate analysis, only SCs were predictive of malignancy (P = .002). SI facilitated the diagnosis in 9 biopsies. Sensitivity/specificity of brush cytology, FISH, and biopsy were 39.5%/94.3%, 63.9%/94.3%, and 84.2%/100%, respectively. CONCLUSIONS: The low sensitivity of biliary brushings results from limited cellularity. Identification of LACF, DH, and SCs improves sensitivity. Sampling of stromal tissue may facilitate PBCa diagnosis. Concurrent biopsies and FISH are helpful in enhancing the diagnostic yield of PBCa.

Esophageal Stenting With Sutures: Time to Redefine Our Standards?

BACKGROUND AND STUDY AIMS: Migration is the most common complication of the fully covered metallic self-expanding esophageal stent (FCSEMS). Recent studies have demonstrated migration rates between 30% and 60%. The aim of this study was to determine the effect of fixation of the FCSEMS by endoscopic suturing on migration rate. PATIENT AND METHODS: Patients who underwent stent placement for esophageal strictures and leaks over the last year were captured and reviewed retrospectively. Group A, cases, were patients who underwent suture placement and group B, controls, were patients who had stents without sutures. Basic demographics, indications, and adverse events (AEs) were collected. Kaplan-Meier analysis and Cox regression modeling were conducted to determine estimates and predictors of stent migration in patients with and without suture placement. RESULTS: Thirty-seven patients (18 males, 48.65%), mean age 57.2 years (±16.3 y), were treated with esophageal FCSEMS. A total of 17 patients received sutures (group A) and 20 patients received stents without sutures (group B). Stent migration was noted in a total of 13 of the 37 patients (35%) [2 (11%) in group A and 11 (55%) in group B]. Using Kaplan-Meier analysis and log-rank analysis, fixation of the stent with suturing reduced the risk of migration (P=0.04). There were no AEs directly related to suture placement. CONCLUSIONS: Anchoring of the upper flare of the FCSEMS with endoscopic sutures is technically feasible and significantly reduces stent migration rate when compared with no suturing, and is a safe procedure with very low AEs rates.

Demographic features and natural history of intermediate-risk multifocal versus unifocal intraductal papillary mucinous neoplasms.

OBJECTIVES: This study compares the progression of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs) to unifocal (UF) lesions. METHODS: We performed a retrospective review of demographics, risk factors, and cyst characteristics of a prospectively maintained database of 999 patients with pancreatic cysts. Patients included had IPMN under surveillance for 12 months or more. Those with high-risk stigmata were excluded. Cyst size progression and development of worrisome features were compared between MF and UF cohorts. We evaluated whether the dominant cyst in MF-IPMN had more significant growth than did the other cysts. RESULTS: Seventy-seven patients with MF-IPMN and 54 patients with UF-IPMN, with mean follow-up of 27 and 34 months, met the criteria. There were no significant differences between demographics, risk factors, or initial cyst sizes. Fifty-seven percent of MF dominant cysts and 48% of UF cysts increased in size (P = 0.31). Progression in MF was more likely in the dominant cyst (P < 0.05). There were no significant differences in the development of mural nodules or increase in cyst size to more than 3 cm. CONCLUSIONS: Demographics of both cohorts were similar, as was the overall incidence of worrisome features. Because meaningful size progression primarily occurred in the dominant cyst, our findings support surveillance based on the dominant cyst in MF disease.