Pancreatic Cancer is More Frequently Early Stage at Diagnosis in Surgically Resected Intraductal Papillary Mucinous Neoplasms With Preoperative Surveillance.

Background and Aims: Management of intraductal papillary mucinous neoplasms (IPMNs) relies on clinical and imaging features to select patients for either pancreatectomy or periodic image-based surveillance. We aimed to compare outcomes in patients with IPMNs who underwent surgery at diagnosis with those who underwent surgery after a period of surveillance and identify preoperative clinical and imaging features associated with advanced neoplasia. Methods: Patients with surgically resected IPMN (n = 450) were divided into 2 groups: "immediate surgery": resection within 6 months of IPMN detection, and "surveillance surgery": resection after surveillance >6 months. Survival was analyzed with Kaplan-Meier estimates and Cox proportional hazard models. Results: Pancreatic cancers in the surveillance surgery group (n = 135) was more frequently stage I compared with the immediate surgery group (9/13, 69.2% vs 41/110, 37.3%; P = .027). Among Fukuoka "worrisome features," only main pancreatic duct dilation 5-9 mm (odds ratio [OR] = 3.12, 95% confidence interval [CI]: 1.72-5.68; P < .001) and serum CA 19-9≥ 35 U/mL (OR = 2.82, 95% CI: 1.31-6.06; P = .008) were significantly associated with advanced neoplasia. In addition, smoking history was associated with increased risk of advanced neoplasia (OR = 2.05, 95% CI: 1.23-3.43). Occurrence of future cancer was 16-fold higher in IPMN with high-grade dysplasia when compared with low-grade dysplasia (hazard ratio: 16.5; 95% CI: 4.19-64.7). Conclusion: Surveillance-detected pancreatic cancers in patients with IPMNs are more frequently stage I, and IPMN-HGD on surgical pathology is associated with significant risk of future pancreatic cancer. In addition to known "high-risk" features, main pancreatic duct dilation 5-9 mm, CA 19-9 elevation, and smoking history are significantly associated with advanced neoplasia.

Determining age and sex-specific distribution of pancreatic whole-gland CT attenuation using artificial intelligence aided image segmentation: Associations with body composition and pancreatic cancer risk.

BACKGROUND & AIMS: Increased intrapancreatic fat is associated with pancreatic diseases; however, there are no established objective diagnostic criteria for fatty pancreas. On non-contrast computed tomography (CT), adipose tissue shows negative Hounsfield Unit (HU) attenuations (-150 to -30 HU). Using whole organ segmentation on non-contrast CT, we aimed to describe whole gland pancreatic attenuation and establish 5th and 10th percentile thresholds across a spectrum of age and sex. Subsequently, we aimed to evaluate the association between low pancreatic HU and risk of pancreatic ductal adenocarcinoma (PDAC). METHODS: The whole pancreas was segmented in 19,456 images from 469 non-contrast CT scans. A convolutional neural network was trained to assist pancreas segmentation. Mean pancreatic HU, volume, and body composition metrics were calculated. The lower 5th and 10th percentile for mean pancreatic HU were identified, examining the association with age and sex. Pre-diagnostic CT scans from patients who later developed PDAC were compared to cancer-free controls. RESULTS: Less than 5th percentile mean pancreatic HU was significantly associated with increase in BMI (OR 1.07; 1.03-1.11), visceral fat (OR 1.37; 1.15-1.64), total abdominal fat (OR 1.12; 1.03-1.22), and diabetes mellitus type 1 (OR 6.76; 1.68-27.28). Compared to controls, pre-diagnostic scans in PDAC cases had lower mean whole gland pancreatic HU (-0.2 vs 7.8, p = 0.026). CONCLUSION: In this study, we report age and sex-specific distribution of pancreatic whole-gland CT attenuation. Compared to controls, mean whole gland pancreatic HU is significantly lower in the pre-diagnostic phase of PDAC.

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.

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.

High-Grade Dysplasia in Resected Main-Duct Intraductal Papillary Mucinous Neoplasm (MD-IPMN) is Associated with an Increased Risk of Subsequent Pancreatic Cancer.

BACKGROUND: There is lack of consensus on post-operative surveillance for resected non-invasive intraductal papillary neoplasms (IPMNs). In this study we explored risk factors for subsequent PC in patients with MD-IPMN undergoing partial pancreatectomy. METHODS: We searched the Mayo Clinic surgical pathology database for all cases of resected MD-IPMN between 1997 and 2014. Cases with histologically confirmed main pancreatic duct involvement either isolated or in a mixed pattern with branch-duct involvement were included. Outcomes of PC in the remnant pancreas, and death related to MD-IPMN were assessed with survival analyses (Kaplan-Meier and Cox regression). RESULTS: Among the 179 patients with resected MD-IPMN the incidence of concomitant PC and high-grade dysplasia (HGD) in the resected specimen was 23 and 14%, respectively. The mean duration of follow-up was 4.31 years (range 0.12-13.5 years). Excluding 28 subjects who either underwent initial total pancreatectomy or partial pancreatectomy with surgical margins positive for PC/HGD, the 5-year incidence of subsequent PC was 12%, including 60.6% and 15.6% in those with initial PC and HGD, respectively. The 10-year incidence of PC was 21.2% overall, 60.6% for PC, 38.3% for HGD, and 3.0% for LGD. Risk of subsequent PC was significantly higher for those with initial PC compared with HGD (HR = 4.95, 95% CI: 1.63-15.03, p = 0.005 and for HGD compared with LGD (HR = 11.30, 95% CI: 1.55-82.26, p = 0.017). CONCLUSIONS: Patients with MD-IPMN with PC or HGD undergoing segmental pancreatectomy are at higher risk of subsequent PC and may benefit from post-operative surveillance. The post-operative surveillance intervals in resected MD-IPMNs need to be tailored based on dysplasia grade.

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.

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.

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.

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.

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.

Clinical profiles and outcomes in idiopathic duct-centric chronic pancreatitis (type 2 autoimmune pancreatitis): the Mayo Clinic experience.

OBJECTIVE: Idiopathic duct-centric chronic pancreatitis (IDCP), also known as type 2 autoimmune pancreatitis (AIP), is an uncommon subtype of AIP. International Consensus Diagnostic Criteria for IDCP propose that the diagnosis requires pancreatic histology and/or concurrent IBD. We examined our experience with IDCP (type 2 AIP) to assess the appropriateness of these criteria, and identify unique characteristics in patients presenting with acute pancreatitis. DESIGN: We reviewed the Mayo Clinic AIP database through May 2014 to identify subjects with either definitive (n=31) or probable (n=12) IDCP. We compared demographic and clinical factors based on strength of diagnostic confidence (definitive versus probable), presence of IBD, and acute pancreatitis as the presenting manifestation. Relapse-free survival was determined using the Kaplan-Meier method. RESULTS: The clinical profiles were similar irrespective of the diagnostic criteria fulfilled. Common clinical presentations included acute pancreatitis (n=25, 58.1%, 12 of whom (27.9%) had recurrent pancreatitis) and pancreatic mass/obstructive jaundice (n=15, 34.9%). The cumulative relapse rate was 10.6% at 3 years (median follow-up 2.9 years). Relapse-free survival was similar for the different diagnostic categories, but was decreased in those initially presenting with acute pancreatitis (p=0.047) or treated with steroids (vs surgery, p=0.049). CONCLUSIONS: The current diagnostic classification of probable IDCP and the inclusion of IBD as a supportive criterion appear valid, because patients have similar clinical profiles and disease-related outcomes to those with definitive IDCP. Concurrent IBD, especially in young patients, may suggest when IDCP is the underlying cause of recurrent acute pancreatitis, but additional studies are needed for validation.

EUS-guided ethanol lavage does not reliably ablate pancreatic cystic neoplasms (with video).

BACKGROUND: 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. METHODS: 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. RESULTS: 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% versus <80% 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. CONCLUSIONS: 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. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT02158039.).

The string sign for diagnosis of mucinous pancreatic cysts.

BACKGROUND AND STUDY AIMS: Pancreas cyst fluid analysis does not provide optimal discrimination between mucinous and nonmucinous cysts. The aim of this study was to assess the performance characteristics of the "string sign" - a test performed at the time of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), for the diagnosis of mucinous pancreatic cysts (branch duct intraductal papillary mucinous neoplasms [bIPMN] and mucinous cystic neoplasms). PATIENTS AND METHODS: Patients undergoing EUS-FNA of pancreatic cystic lesions at one referral center between 2003 and 2012 were included. The string sign was performed prospectively, and was considered positive if ≥ 1 cm string formed in cyst fluid and lasted for ≥ 1 second. Performance characteristics of the string sign and a sequential cyst fluid test interpretation model were assessed. RESULTS: For 98 histologically proven cases, the sensitivity, specificity, positive predictive value, and negative predictive value of the string sign for diagnosis of mucinous cysts were 58 % (95 % confidence interval [CI] 44 % - 70 %), 95 % (83 % - 99 %), 94 % (81 % - 99 %), and 60 % (46 % - 72 %), respectively. When string sign results and carcinoembryonic antigen (CEA) concentration (≥ 200 ng/mL) were combined, diagnostic accuracy improved from 74 % and 83 %, respectively, to 89 % (P ≤ 0.03). Among bIPMN, a positive string sign was associated with gastric and intestinal epithelial subtypes. The sequential cyst fluid test interpretation model (including cytology, mucin stain, CEA, and string sign) yielded an overall sensitivity for mucinous lesions of 96 %, with a specificity of 90 %. CONCLUSIONS: The string sign is highly specific for diagnosis of mucinous pancreatic cysts, and improves overall diagnostic accuracy of pancreatic cyst fluid analysis. Sequential cyst fluid test interpretation yields high diagnostic sensitivity and specificity for mucinous cysts.

Impact of celiac neurolysis on survival in patients with pancreatic cancer.

BACKGROUND: Pancreatic cancer (PC) often produces pain that is difficult to control. Celiac neurolysis (CN) is performed with the goal of improving pain control and quality of life while reducing opioid-related side effects. OBJECTIVE: We aimed to evaluate whether CN provides a survival advantage for PC patients. DESIGN: Retrospective case-control study. SETTING: Single tertiary-care referral center. PATIENTS: Review of a prospectively maintained database identified patients with unresectable PC who underwent CN over a 12-year period. Each patient was matched to 2 control patients with unresectable PC. INTERVENTION: CN, which included both celiac plexus neurolysis (CPN) and celiac ganglia neurolysis (CGN). MAIN OUTCOME MEASUREMENTS: Median survival in Kaplan-Meier curves and hazard ratios. RESULTS: A total of 417 patients underwent CN and were compared with 840 controls with PC. Baseline characteristics were similar except the CN group had greater weight loss and pain requiring opioids. A mean of 16.6 ± 5.8 mL of alcohol was administered. For patients who underwent CN, the median survival from the time of presentation was shorter compared with controls (193 vs 246 days; hazard ratio 1.32; 95% confidence interval, 1.13-1.54). There was no difference in survival with unilateral or bilateral injection. However, EUS-guided CN was associated with longer survival compared with non-EUS approaches, and those who received CPN had longer survival compared with CGN. LIMITATIONS: Single center, retrospective. CONCLUSION: Our study suggests that CN is an independent predictor of shortened survival in PC patients. A prospective study is needed to verify the findings and determine whether shortened survival results from CN or from other features such as performance status and tumor-related characteristics. It is also imperative to verify our finding that EUS-guided CN provides a survival advantage over other approaches and whether CPN prolongs survival compared with CGN.

EUS-guided pancreatic duct intervention: outcomes of a single tertiary-care referral center experience.

BACKGROUND: EUS can provide access to the main pancreatic duct (MPD) for therapeutic intervention. The long-term clinical success of EUS-guided MPD interventions is unknown. OBJECTIVE: To determine technical and clinical success rates, predictors of success, and long-term outcomes of EUS-guided MPD intervention. DESIGN: Retrospective, single-center study. SETTING: Tertiary-care referral center. PATIENTS: Forty-five patients. INTERVENTION: EUS-guided MPD stent retrieval or placement. MAIN OUTCOME MEASUREMENTS: Technical and clinical success rates, adverse events, and long-term clinical outcomes. RESULTS: Among the 45 patients, 37 had undergone failed ERCP, and 29 had surgically altered anatomy. Median follow-up after initial EUS-guided intervention was 23 months. Two patients underwent EUS for stent removal, and EUS-guided MPD stent placement was attempted in 43 patients. Technical success was achieved in 32 of 43 patients (74%) with antegrade (n = 18) or retrograde (n = 14) stent insertion. Serious adverse events occurred in 3 patients (6%). Patients underwent a median of 2 (range 1-6) follow-up procedures for revision or removal of stents, without adverse events. Complete symptom resolution occurred in 24 of 29 patients (83%) while stents were in place, including all 6 with nondilated ducts. Stents were removed in 23 patients, who were then followed for an additional median of 32 months; 4 patients had recurrent symptoms. Among the 11 failed cases, most had persistent symptoms or required surgery. LIMITATIONS: Retrospective study design, individualized patient management. CONCLUSION: EUS-guided MPD intervention is feasible and safe, with long-term clinical success in the majority of patients. EUS provides important treatment options, particularly in patients who would otherwise undergo surgery.

IgG4-related paratesticular pseudotumor in a patient with autoimmune pancreatitis and retroperitoneal fibrosis: an extrapancreatic manifestation of IgG4-related disease.

In this report, we describe the first case of a patient with an IgG4-related paratesticular pseudotumor. He had histologically proven autoimmune pancreatitis, then later developed a scrotal mass. The orchiectomy specimen revealed that this was a paratesticular pseudotumor with histopathologic and immunohistochemistry findings characteristic of IgG4-related disease. Paratesticular pseudotumors are uncommon causes of intrascrotal masses and have an unexplained pathogenesis. A variety of genitourinary manifestations of IgG4-related disease including IgG4-related tubulointerstitial nephritis, IgG4-related ureteral pseudotumors, and IgG4-related prostatitis has been previously reported. The current case highlights the need to have a high index of suspicion for IgG4-tissue infiltration in patients with known autoimmune pancreatitis, particularly those with a pseudotumor.