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Background and Aims Advances in imaging technology have improved the annual detection rate of pancreatic cystic lesions (PCLs), but the preoperative diagnosis of PCLs remains unclear. Thus, the usefulness of single-operator cholangioscopy (SOC) as a diagnostic imaging tool for PCLs is worth investigating. We performed an intracystic visual examination of PCLs using SOC to determine the diagnostic value of SOC for PCLs. Methods In this retrospective observational study, PCLs were confirmed using a diagnostic imaging modality. Patients who underwent an EUS-guided through-the-needle fiberoptic pancreatic cystoscopy and SOC examination and those whose lesion type was definitively diagnosed were included (n = 43). If the cystic fluid was turbid, a physiologic saline solution was injected into the cyst, and a SOC fiberoptic probe was inserted through a 19-gauge needle to observe the wall of the intracystic cavity and its contents. The characteristics were recorded, and the cystic fluid and biopsy specimens were further assessed by performing liquid-based cytologic and histopathologic examinations. Particularly, histopathologic examinations were performed in patients who underwent surgery. Results Intracystic characteristics of the confirmed cases of PCLs (43 patients) were identified through intracystic visual examination with SOC. The clarity of cyst fluid is a prerequisite for imaging by SOC. The tree-like branching pattern of blood vessel distribution may be a serous cystic neoplasm–specific characteristic. Intracystic papilla-like structure is an important characteristic for diagnosing mucinous cystic neoplasms. Conclusions The identified imaging characteristics such as blood vessel distribution on the intracystic wall and the contents of different PCLs observed under the SOC probe can provide useful information for diagnosing PCLs. SOC could be an important ancillary imaging test of PCLs by EUS.

Background and Aims Management of branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains challenging. We determined factors associated with malignancy in BD-IPMNs and long-term outcomes. Methods This retrospective cohort study included all patients with established BD-IPMNs by the International Consensus Guidelines (ICG) 2012 and/or pathologically confirmed BD-IPMNs in a tertiary care referral center between 2001 and 2013. Main outcome measures were the association between high-risk stigmata (HRS)/worrisome features (WFs) of the ICG 2012 and malignant BD-IPMNs, performance characteristics of EUS-FNA for the diagnosis of malignant BD-IPMNs, and recurrence and long-term outcomes of BD-IPMN patients undergoing surgery or imaging surveillance. Results Of 364 BD-IPMN patients, 229 underwent imaging surveillance and 135 underwent surgery. Among the 135 resected BD-IPMNs, HRS/WFs on CT/magnetic resonance imaging (MRI) were similar between the benign and malignant groups, but main pancreatic duct (MPD) dilation (5-9 mm) was more frequently identified in malignant lesions. On EUS-FNA, mural nodules, MPD features suspicious for involvement, and suspicious/positive malignant cytology were more frequently detected in the malignant group with a sensitivity, specificity, and accuracy of 33%, 94%, and 86%; 42%, 91%, and 83%; and 33% 91%, and 82%, respectively. Mural nodules identified by EUS were missed by CT/MRI in 28% in the malignant group. Patients with malignant lesions had a higher risk of any IPMN recurrence during a mean follow-up period of 131 months ( P = .01). Conclusions Among HRS and WFs of the ICG 2012, an MPD size of 5 to 9 mm on CT/MRI was associated with malignant BD-IPMNs. EUS features including mural nodules, MPD features suspicious for involvement, and suspicious/malignant cytology were accurate and highly specific for malignant BD-IPMNs. Our study highlights the incremental value of EUS-FNA over imaging in identifying malignant BD-IPMNs, particularly in patients without WFs and those with smaller cysts. Benign IPMN recurrence was observed in some patients up to 8 years after resection.

Certain pancreatic cysts (mucinous cystic neoplasm and side branch intraductal papillary mucinous neoplasm [IPMN]) have malignant potential and require surveillance. However, whether patients with pancreatic cysts have a higher long-term risk of pancreatic cancer (PaCa) has still not been established.This was a retrospective study of Veterans Administration patients. Patients noted to have pancreatic cysts on CT/magnetic resonance imaging (n = 1050) were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Patients aged 15 years (n = 425), patients with 1 year of follow-up (n = 13,259), and patients diagnosed to have PaCa within 1 year of identification of a pancreatic cyst (n = 102) or within 1 year of follow-up in the remaining patients in the database (n = 200) were excluded. Patients with pancreatic cystic lesions (group A, n = 755) and the remaining patients in the database without cysts (group B, n = 520,215) were followed from 1998 to 2007.During the study period, in group A and B PaCa was diagnosed in 17 and 1206 patients, respectively, and the incidence rate of PaCa was 5.08 and .32 per 1000 patient-years, respectively. The hazard ratio of PaCa in all patients with cysts was 19.64 (95% CI, 12.12-31.82; P .0001) when compared with the rest of the patients without cysts. In the subset of patients with cysts, without a history of acute or chronic pancreatitis (n = 241), the hazard ratio of PaCa (n = 5) was 18.80 (95% CI, 7.80-45.31; P .0001).Patients with pancreatic cysts have a significantly higher overall risk of PaCa. The etiologic distribution of cysts in our study patients is not available. Patients with mucinous cystic neoplasm and side branch IPMN are likely to have a higher risk of PaCa than our estimation of risk based on all etiologies.

Background and Aims The tissue acquisition and diagnostic yield of cyst fluid cytology is low-to-moderate and rarely provides a specific diagnosis. The aim of this study was to compare the tissue acquisition and diagnostic tissue yield of microforceps biopsy (MFB) with cyst fluid cytology. Methods In this multicenter study, data of 42 patients who had cysts both aspirated by EUS-guided FNA (EUS-FNA) and biopsy specimens were then obtained with an MFB device, were collected. Cytology analysis of cyst fluid and histologic analysis of biopsy specimens were done. Acquisition yield was defined as percentage of patients with tissue present in the aspirate or biopsy. Diagnostic tissue yield was evaluated at 3 levels: the ability of differentiation between mucinous and/or nonmucinous cysts, detection of high risk for malignancy, and specific cyst type diagnosis. Results The mean patient age was 69 years. Sixteen pancreatic cysts (38.1%) were located in the head, 17 (40.5%) in the body, and 9 (21.4%) in the tail. The mean cyst size was 28.2 mm (12-60 mm); 25 of 42 (60%) were septated. The EUS-FNA tissue (fluid) acquisition yield was 88.1% (37/42). The MFB tissue acquisition yield was 90.4% (38/42). The diagnostic cytology yield to differentiate between mucinous and/or nonmucinous cysts was 47.6% (20/42), and the MFB histologic yield to differentiate between mucinous and/or nonmucinous cysts was 61.9% (26/42) ( P = .188). The percentage of cysts at high risk for malignancy by cytology was 54.7% (23/42), and MFB was 71.5% (30/42) ( P = .113). However, the ability of MFB to provide a specific cyst type diagnosis was 35.7% (15/42), and that for cytology was 4.8% (2/42) ( P = .001). Surgical histology was concordant with that of MFB in 6 of 7 patients (85%), and with that of cytology in 1 of 7 patients (15%). Conclusion The cyst tissue acquisition yield for MFBs was 90%. Although cytology of cyst fluid and MFB were comparable in distinguishing mucinous and nonmucinous cysts and detecting cysts at high risk for malignancy, MFB was far superior to cytology for providing a specific cyst diagnosis.

Background Differentiation between benign and malignant branch-duct type intraductal papillary mucinous neoplasms (IPMNs) remains challenging. Objective To examine the usefulness of pancreatic duct lavage cytology with cell block method for discriminating benign and malignant branch-duct type IPMNs. Patients and Methods Between December 2007 and April 2011, patients with branch-duct type IPMNs having mural nodules on EUS were examined by pancreatic duct lavage cytology by using the cell block method. Cell block sections underwent hematoxylin and eosin staining and mucin immunostainings (MUCs 1, 2, 5AC, and 6). Design Single-center, prospective study. Setting Academic medical center. Main Outcome Measurements The sensitivity and specificity of cytology were assessed. The agreement between cytological and histological results for MUC was also examined. Results Cytology with this method was investigated in 44 patients. Cell block diagnosis was cancer positive (class V or IV) in 11 patients and negative (classes I, II, III, and noninformative) in 33. The sensitivity, specificity, and positive and negative predictive values of this method were 92%, 100%, 100%, and 97%, respectively. The cytological and histological results of MUCs 1, 2, 5AC, and 6 agreed in 88% (15/17), 94% (16/17), 88% (15/17), and 100% (17/17), respectively. Limitations Single center and small number of patients. Conclusions Pancreatic duct lavage cytology with the cell block method may be useful to differentiate between benign and malignant IPMNs preoperatively and as well as to determine their mucin type.

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.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.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).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.

Characterization of pancreatic cysts by using EUS-FNA includes chemical and cytologic analysis.To evaluate whether material obtained from FNA of the cyst wall increases diagnostic yield.Prospective series.Tertiary referral center.Consecutive patients with pancreatic cysts referred for EUS-FNA between March 2010 and March 2011.FNA was performed with aspiration of cyst fluid for carcinoembryonic antigen (CEA) and cytology, followed by cyst wall puncture (CWP). CWP is defined as puncturing the far wall of the cyst and moving the needle back and forth through the wall to sample the wall epithelium.The diagnostic yield for mucinous cystic pancreatic neoplasms by CEA and cytology obtained from cyst fluid compared with cytology obtained from CWP. CEA ≥192 ng/mL was considered mucinous.A total of 69 pancreatic cysts from 66 patients were included. Adequate amounts of fluid were aspirated for CEA, amylase, and cytology in 60 cysts (81%). Cellular material adequate for cytologic assessment from CWP was obtained in 56 cysts (81%). Ten (30%) of 33 cysts with CEA192 ng/mL and negative results of cyst fluid cytology had a mucinous diagnosis from CWP; 6 of 9 (67%) cysts with an insufficient amount of fluid for CEA analysis and cyst fluid cytology had a mucinous diagnosis from CWP. Furthermore, 4 malignant cysts were independently diagnosed by CWP cytology. The incremental diagnostic yield of CWP for mucinous or malignant cysts was therefore 29% (20 of 69 cysts, P = .0001). An episode of pancreatitis (1.45%) occurred.Lack of surgical criterion standard.CWP during EUS-FNA is a safe and effective technique for improving the diagnostic yield for premalignant and malignant pancreatic cysts.

An asymptomatic 72-year-old woman underwent EUS-guided FNA of an incidental side-branch intraductal papillary mucinous neoplasm (SB-IPMN) in the head of the pancreas at an outside facility. Forty-eight hours after the procedure, she presented to our institution with severe epigastric pain, fever, jaundice, leukocytosis, and elevated lipase consistent with acute pancreatitis. CT of the abdomen andpelvis with contrast medium showed multiple peripancreatic fluid collections (PFC) around the pancreatic head. EUS showed a large PFC in the head region compressing the distal common bile duct (Fig. 1) and a pancreatic duct leak in the neck region. Because the PFC was causing obstructive jaundice, it was aspirated, revealing hemorrhagic fluid. ERCP was then performed to evaluate the pancreatic duct. A leak from a side branch in the head region was demonstrated on pancreatogram, which was bridged with a 4F 10-cm stent (Video 1, available online at www.giejournal.org). The patient also underwent jejunal feeding for 4 weeks through a nasojejunal tube, with resultant clinical improvement and resolution of the PFC on follow-up CT at 30 days. The risk of acute pancreatitis after EUS-FNA of pancreatic lesions is highest with SB-IPMN at 8%. Despite the lack of data, the use of indomethacin before EUS-FNA for pancreatitis prophylaxis can be considered in high-risk patients.

The true efficacy of EUS-guided ethanol lavage (EEL) of pancreatic cystic neoplasms is unclear. This study aimed to assess long-term outcomes and adverse events of EEL by using a standardized protocol.Single-center, prospective, pilot study in which participants with suspected mucinous cyst neoplasms or branch duct intraductal papillary mucinous neoplasms ≥1 cm in maximum diameter underwent EEL with 80% ethanol. Follow-up cross-sectional imaging was obtained to assess for changes in cyst volume.Twenty-three patients underwent EEL (57% male, mean age 70 years). Mean duration of follow-up was 40 months (range 9-82 months). Mean calculated final concentration of ethanol achieved in treated cysts was 50% (range 0%-79%). Complete resolution of pancreatic cystic neoplasms occurred in 2 participants (9%). When stratified into those participants who achieved ≥80% versus80% reduction in cyst volume, no statistically significant differences were seen with regard to patient demographics, cyst characteristics, or final concentration of ethanol achieved in the treated cyst. Greater decreases in cyst volume were seen in presumed nonmucinous cysts compared with presumed mucinous cysts (P = .006). Two early adverse events occurred. Five participants died during the study follow-up period (4 from nonpancreatic causes), including 1 participant who was diagnosed with pancreatic adenocarcinoma thought to have arisen from the treated branch duct intraductal papillary mucinous neoplasm 41 months after undergoing EEL.As performed in this study, EEL therapy does not appear to be a promising method for prevention of malignancy in pancreatic cysts. Endoscopic methods that effectively and completely ablate pancreatic cystic neoplasms are needed. (NCT02158039.).